Assisted manual injector devices and methods

Various embodiments disclosed herein relate to needle-based injectors that incorporate a power assembly comprising a stored energy source and a rate control assembly. The power assembly may be further configured to allow the injection to be performed with more force than a user may be capable of delivering, while also allowing the user to maintain control of the injection process after the stored energy source has been released and the injection has begun, such the user may increase or decrease the rate of injection, or stop the injection, during the injection process. In various embodiments, the power assembly may comprise spring- or gas-based stored energy sources, and/or may comprise friction- or tension-based rate control assemblies. Described herein are also methods for injecting an agent using embodiments of the devices described here.

FIELD

Described here are power-assisted injection devices that allow a user to selectively increase or decrease the injection rate, and to pause or stop the injection, as desired.

BACKGROUND

The injection of therapeutic agents in hospital, clinic, and home-based settings is a common procedure, but can sometimes be complex and difficult to perform, even for experienced healthcare providers. Drawing a therapeutic agent into a syringe and injecting it into a patient requires a certain level of manual dexterity and strength, in addition to sufficient visual and mental acuity to perform the procedural steps. The risk of needlestick injury also exists throughout all of the steps of a manual injection procedure. In home-based settings, these challenges could lead to reduced patient compliance with treatment regimens.

Nevertheless, as reliance upon home-based injection regimens continues to expand, the challenges with syringe injection have become more diversified. For example, patients with physical or cognitive impairment may need to perform such injections, without assistance from in-home care providers. Also, some injections require more force than users are capable of delivering, for instance if the injected substance has a high viscosity. Furthermore, for some medications, the injection process can cause discomfort related to the rate of injection. In some instances, a user may want to increase the rate of injection, in order to accomplish the injection in a shorter time, or may want to decrease the rate of injection or stop the injection, for example to mitigate injection-related pain. There is therefore a need for a power-assisted injection device, which allows the user to both control a stored energy source and also provide some amount of user supplied power to the injection, and thus increase or decrease the injection rate, or stop the injection, at will.

BRIEF SUMMARY

Various embodiments disclosed herein relate to needle-based injectors that incorporate a power assembly comprising a stored energy source and a rate control assembly. The power assembly may be further configured to allow the injection to be performed with more force than a user may be capable of delivering, while also allowing the user to maintain control of the injection process after the stored energy source has been released and the injection has begun, such the user may increase or decrease the rate of injection, or stop the injection, during the injection process. In various embodiments, the power assembly may comprise spring- or gas-based stored energy sources, and may comprise friction- or tension-based rate control assemblies. Described herein are also methods for injecting an agent using embodiments of the devices described here.

A particular embodiment comprises a device for injecting an agent, comprising a syringe comprising a syringe cavity, a plunger element slidably received in the syringe cavity, and a hollow needle in fluid communication with the syringe cavity, wherein the plunger element is configured to move from a proximal position to a distal position, a power assembly configured to transmit force to the plunger element, and a user-actuated brake assembly that is configured to reversibly resist movement of the plunger element in at least one intermediate position between the proximal position and the distal position. The brake assembly may be biased to resist movement of the plunger element when in an inactivated state, and may permit movement of the plunger element when in an activated state. The brake assembly may be biased by a brake spring to resist movement of the plunger element. The power assembly may comprise a mechanical spring. The plunger element may be further configured to simultaneously receive user-applied force that moves the plunger element toward the distal position. The device may further comprise a housing wherein the syringe is located in the housing. The housing may be coupled to the plunger element. The housing may be configured to transmit user-applied force to the plunger element. The brake assembly may comprise a flexible, elongate brake cord. The brake cord may comprise a releasable friction fit to reversibly resist movement of the plunger element. The releasable friction fit may be provided by releasable tension in the brake cord. The brake assembly may comprise a rigid friction element. The brake assembly may act on an outer surface of the syringe to reversibly resist movement of the plunger element. The brake assembly may act on a surface fixed relative to the syringe to reversibly resist movement of the plunger element. The brake assembly may comprise an opening in which the syringe resides. The power assembly may be configured to pull the plunger element toward the distal position. The power assembly may be configured to push the plunger element toward the distal position. The power assembly may be further configured to push and pull the plunger element toward the distal position. The syringe may be slidably located in the housing and the syringe is configured to move from a retracted position where a distal tip of the needle lies within the housing, toward an extended position where the distal tip of the needle extends distal to the housing. The device may further comprise an extendable needle shroud, wherein the needle shroud may be configured with a releasably locked, retracted state relative to the syringe, and an unlocked state that may permit movement toward an extended position relative to the syringe. The device may further comprise an extendable needle shroud, wherein the needle shroud is configured with a releasably locked, retracted state relative to the syringe, and an unlocked state that permits movement toward an extended position relative to the syringe, and wherein the needle shroud is further configured to change to the unlocked state before the distal tip of the needle extends distal to the housing. The needle shroud may be further configured to relock when the needle shroud reaches the extended state. In other variations the device may comprise an extendable needle shroud, wherein the needle shroud is configured with an unlocked extended state that permits movement toward a retracted position relative to the syringe and a locked extended state. The needle shroud may be configured to enter the locked extended state when the needle shroud extends from a retracted state.

A particular embodiment comprises a device for injecting an agent, comprising a syringe comprising a syringe cavity containing a formulation comprising the agent, and a power assembly configured to act upon the syringe to cause the formulation to be displaced from the syringe cavity, wherein the power assembly comprises a stored energy source and a rate control assembly, wherein the rate control assembly resists the stored energy source acting on the syringe when in a first configuration and allows the stored energy source to act on the syringe when in a second configuration. The rate control assembly may partially resist the stored energy source acting on the syringe in a third configuration. The device may further comprise a housing, wherein the syringe and power assembly are at least partially located within the housing. The rate control assembly may be configured to be changed from the first configuration to the second configuration by application of distal force on the housing. The change from the first configuration to the second configuration may be reversible. The rate control assembly may be configured to be changed from the second configuration to the first configuration by removing or reducing the application of distal force on the housing. The change from the second configuration to the first configuration may be reversible. The housing may comprise a proximal housing and a distal housing, and wherein the application of distal force on the housing may be to the proximal housing. The distal housing may comprise a distal end and a nose located at the distal end, and wherein the nose has a flared shape. The syringe may further comprise a plunger slidable within the syringe cavity and a needle having a lumen in fluid communication with the syringe cavity, wherein the syringe may be configured such that distal movement of the plunger within the syringe cavity may cause the formulation to be displaced from the syringe cavity through the lumen of the needle. In the first configuration, the rate control assembly may resist distal movement of the plunger within the syringe cavity. In the second configuration, the rate control assembly may allow distal movement of the plunger within the syringe cavity. The stored energy source may comprise a spring. The rate control assembly may comprise a longitudinal axis and the housing may comprise a longitudinal axis, and the rate control assembly may be configured to be reversibly moved from the first configuration to the second configuration by moving the longitudinal axis of the rate control assembly toward the longitudinal axis of the housing. The stored energy source may comprise a composite spring, wherein the composite spring may comprise a coaxially arranged compression spring and extension spring. The rate control assembly may comprise a cord comprising at least two portions capable of being under differing amounts of tension. The stored energy source may comprise a compressed gas or liquid propellant in a supercritical state. The device is configured such that the rate at which the formulation is able to be displaced from the syringe cavity may be able to be selectively increased, decreased, or stopped after the plunger has moved distally relative to an initial position within the syringe cavity. The device may be configured such that movement of the plunger distally within the syringe cavity may require application of distal force by a user during the movement.

A particular embodiment comprises a device for injecting an agent, comprising a syringe comprising a syringe cavity containing a formulation comprising the agent to be injected by application of distal force on the device by a user, and a power assembly configured to act upon the syringe, wherein the power assembly is configured to amplify the application of distal force by the user, such that the agent is able to be injected with more distal force than is applied by the user to the device, and wherein the power assembly is configured to reduce the rate of injection of the agent if the distal force is reduced. The power assembly may be configured to stop the injection of the agent if the user stops applying distal force to the device. The formulation may be a liquid formulation. The formulation may be a colloidal formulation.

A particular embodiment comprises a device for injecting an agent, comprising a syringe comprising a syringe cavity, a plunger element slidably received in the syringe cavity, and a hollow needle in fluid communication with the syringe cavity, wherein the plunger is configured to move from a proximal position to a distal position, a pressurized gas assembly with a user-actuated valve opening biased to a closed state, and a flow path between the valve opening and a pressurization region, wherein the flow path is non-linear. The pressurized gas assembly may be configured to apply force to a surface at a fixed position relative to the plunger to move the plunger from the proximal position to the distal position. The plunger may be further configured to simultaneously receive user-applied force that moves the plunger element toward the distal position. The device may further comprise a housing wherein the syringe may be at least partially located in the housing. The housing may be configured to transmit user-applied force to the plunger. The housing may be configured to transmit user-applied force to the valve opening. The valve opening may be configured to be opened by user-applied force to the housing. The syringe may be slidably located in the housing and the syringe may be configured to move from a retracted position where a distal tip of the needle lies within the housing, toward an extended position where the distal tip of the needle extends distal to the housing. The device may further comprise an extendable needle shroud, wherein the needle shroud may be configured with a releasably locked, retracted state relative to the syringe, and an unlocked state that may permit movement toward an extended position relative to the syringe. The device may further comprise an extendable needle shroud, wherein the needle shroud may be configured with a releasably locked, retracted state relative to the syringe, and an unlocked state that may permit movement toward an extended position relative to the syringe, and wherein the needle shroud maybe further configured to change to the unlocked state before the distal tip of the needle extends distal to the housing. The needle shroud may be further configured to relock when the needle shroud reaches the extended state. The pressurization region may be configured to have a variable volume.

A particular embodiment comprises a device for injecting an agent, comprising a housing, and a syringe located within the housing, wherein the housing comprises a needle shroud having activated and inactivated configurations, wherein when the needle shroud is in an activated configuration, it is biased from a retracted position toward an extended position, and wherein the needle shroud is switched from the inactivated configuration to the activated configuration by distal motion of the syringe relative to at least a portion of the housing. The syringe may comprise a needle and the syringe may be slidably located in the housing and may be configured to move from a retracted position where a distal tip of the needle lies within the housing, toward an extended position where the distal tip of the needle extends distal to the housing. The needle shroud may be switched from the inactivated configuration to the activated configuration before the distal tip of the needle extends distal to the housing. The needle shroud may be configured to be maintained in a retracted position by proximal force on the needle shroud after being switched to an activated configuration. The needle shroud may be further configured to be locked in an extended position once moved to an extended position.

A particular embodiment comprises a device for injecting an agent, comprising a housing having a longitudinal axis, a syringe containing the agent located within the housing, a plunger slidable within the syringe, configured to be moveable between a proximal position and a distal position, wherein moving the plunger toward the distal position displaces the agent from the syringe, a biter having a longitudinal axis and comprising a lumen through which the syringe is located, wherein the biter is configured to be moveable between a first configuration wherein the longitudinal axis of the biter is offset from the longitudinal axis of the housing, and a second configuration wherein the longitudinal axis of the biter is less offset from the longitudinal axis of the housing than in the first configuration, and a spring in contact with the biter configured to bias the plunger toward the distal position via the biter when the biter is in the second configuration. The spring may bias the biter toward the first configuration. The syringe may be configured to be moveable between a proximal position and a distal position relative to the housing. The biter may be configured to be moveable between the first configuration and the second configuration by moving an actuation rod between a first position not in contact with the biter and a second position in contact with the biter. The biter may configured to be moveable between the first configuration and the second configuration by application of distal force on the housing. The spring may apply a distal force on the biter. The distal force on the biter from the spring may be opposed by a proximal frictional force when the biter is in the first configuration. The device may further comprise a retractable needle shroud configured to be moveable between a retracted position and an extended position. The device may further comprise an end-of-dose indicator moveable between an inactivated and an activated configuration.

A particular embodiment may comprise a device for injecting an agent, comprising a housing, a syringe located within the housing, wherein the syringe comprises the agent, a plunger configured to move slidably within the syringe between a proximal and a distal position, a spring configured to bias the plunger toward the distal position, and a cord configured to be reversibly changed between a tensioned configuration and an reduced-tension configuration, wherein the cord is configured to bias the plunger toward the proximal position when in the tensioned configuration. The plunger may be configured to remain fixed relative to the syringe when the cord is in a tensioned configuration. The plunger may be configured to move toward the distal position when the cord is in a reduced-tension configuration. The plunger may comprise a distal end, and the cord may be configured to apply proximal force to the distal end of the plunger when the cord is in the tensioned configuration. The spring may be configured to pull the plunger toward the distal position.

A particular embodiment may comprise a device for injecting an agent, comprising a housing, a syringe located within the housing, and an end-of-dose indicator, wherein the end-of-dose indicator has an inactivated configuration and an activated configuration, and wherein the visual appearance of the end-of-dose indicator through the housing is different in the inactivated and activated configurations. The syringe may further comprise a syringe cavity and a plunger slidably received in the syringe cavity, and a hollow needle in fluid communication with the syringe cavity, wherein the plunger may be configured to move from a proximal position to a distal position, and wherein the end-of-dose indicator is moved from the inactivated configuration to the activated configuration by movement of the plunger toward the distal position.

A particular embodiment may comprise a method for injecting an agent using a device comprising a syringe comprising a syringe cavity, a housing wherein the syringe is located in the housing, a plunger slidably received in the syringe cavity, and a hollow needle in fluid communication with the syringe cavity, wherein the plunger is configured to move from a proximal position to a distal position, a power assembly configured to transmit force to the plunger, and a user-actuated brake assembly that is configured to reversibly resist movement of the plunger in at least one intermediate position between the proximal position and the distal position, comprising applying force to the housing, wherein the force causes the power assembly to transmit force to the plunger to move the plunger toward the distal position, and reducing the applied force to the housing when the plunger is in an intermediate position, wherein reducing the applied force causes the brake assembly to reduce the force transmitted to the plunger by the power assembly. The housing may comprise a proximal housing and a distal housing, and wherein applying force to the housing comprises applying distal force to the proximal housing. The force applied to the housing may further cause the brake assembly to move from an inactivated state to an activated state, wherein the brake assembly may be biased to resist movement of the plunger element when in the inactivated state, and may permit movement of the plunger element when in the activated state. The method may further comprise reapplying force to the housing, wherein the force may cause the power assembly to transmit force to the plunger to move the plunger toward the distal position.

A particular embodiment comprises a device for injecting an agent, comprising a housing having a longitudinal axis, a syringe containing the agent within a syringe cavity, wherein the syringe is located within the housing, a plunger slidable within the syringe, configured to be moveable between a proximal position and a distal position, wherein moving the plunger toward the distal position displaces the agent from the syringe, and a spring in contact with the plunger configured to bias the plunger toward the distal position, wherein the plunger comprises a braking pad configured to be reversibly moveable between a first configuration and a second configuration, wherein the braking pad generates friction to resist movement of the plunger in the second configuration. The braking pad may be configured to be moveable from the first configuration to the second configuration by radially outward movement. The device may further comprise a stopper located within the plunger and movable between a proximal position and a distal position within the plunger, wherein the stopper is configured such that moving the stopper from the distal position to the proximal position moves the braking pad from the first configuration to the second configuration. The stopper may be biased toward the proximal position. The stopper may be configured to be moveable between the proximal position and distal position by application of distal force on the housing. The device may further comprise a retractable needle shroud configured to be moveable between a retracted position and an extended position. The device may further comprise an end-of-dose indicator moveable between an inactivated and an activated configuration.

DETAILED DESCRIPTION

Generally, the injection devices described herein may comprise a housing, which may contain a syringe and a power assembly. In general, the housing may comprise a proximal housing and a distal housing. The proximal and distal housings may be configured to fit slidably together to form a cavity of variable size. The syringe and power assembly may be located within the cavity formed by the proximal and distal housings, and force applied to the housing may be translated into force on the syringe and/or power assembly to cause an injection to proceed. In some variations, the housing may comprise certain safety features, such as a retractable needle safety assembly, to limit accidental needlesticks, and/or indicators to indicate the progress or completion of the injection.

The syringe may reside within the housing and may comprise a syringe body defining a syringe cavity, and a seal slidably disposed within the syringe cavity defining a reservoir that may hold a formulation comprising a therapeutic or diagnostic agent, a ram comprising a plunger that may fit slidably within the syringe cavity, and a needle at the distal end of the syringe body. The needle may be configured to pierce the tissue of a patient receiving an injection, and may have a lumen therethrough to deliver the contents of the reservoir to the patient's tissue. Movement of the seal within the syringe cavity distally may cause the contents of the reservoir to be displaced through the lumen of the needle.

The power assembly may comprise a stored energy source and a rate control assembly. The stored energy source, when released, may be configured to transmit force to displace the contents of reservoir of the syringe through the lumen of the needle and into the patient. In some variations, the user's input force onto the device may work in conjunction with the stored energy source to also provide force to displace the reservoir contents. In some further variations, the stored energy source may be configured to do so by contributing to the distal motion of the plunger or seal within the syringe cavity. The rate control assembly may limit or restrict the stored energy source from contributing to the displacement of the contents of the reservoir of the syringe. In some variations, the rate control assembly may be configured to do so by limiting or restricting the distal movement of a plunger or seal within the syringe cavity. The rate control assembly may be selectively and reversibly moved between open and closed configurations; in a closed configuration, the rate control assembly may limit or restrict the stored energy source from contributing to the distal movement of the seal within the syringe cavity. Together, the stored energy source and the rate control assembly of the power assembly may allow a user (a patient or another person) to direct the injection process in an intuitive way by directing the injection by pressing the injection device against a patient's skin, but the power assembly may supply a supplemental injection force (or in some variations, the full injection force), such that the user does not need to provide the full force needed to carry out the injection.

As used throughout this specification, the term “proximal” refers to the direction away from the needle of the syringe. The term “distal” refers to the direction of the needle of the syringe.

One embodiment of an injection device100is depicted inFIGS. 1 and 2A-2N, comprising a housing102which contains a syringe104and a power assembly106. In some embodiments, the housing102may comprise a proximal housing108and a distal housing110. As described above, the proximal housing108and distal housing110may be configured to fit slidably together to form a cavity146. The syringe104and power assembly106may be located within the cavity146. It should be appreciated that while the distal housing110is shown to fit slidably within the proximal housing108inFIGS. 1 and 2A-2N, in other variations the proximal housing may fit slidably within the distal housing. In still other variations, the housing may only comprise a proximal housing, with a syringe projecting distally from the proximal housing, or only distal housing, with a plunger or other actuator projecting distally or otherwise found on the proximal end of the distal housing. The housing102may be configured to be moved between an extended configuration (shown inFIGS. 1 and 2A-2D), through a range of intermediate configurations (for example, the configuration shown inFIGS. 2G-2J), and to a compressed configuration, or toward a compressed configuration (shown inFIGS. 2K-2N) by moving the proximal housing108distally relative to the distal housing110. In a retracted configuration, the proximal housing108is pushed over the distal housing110, or otherwise overlaps or telescopes with the distal housing110, and achieves a shorter overall housing length. In some variations, when in an extended configuration, the length of the housing102may be less than about 150 mm, about 160 mm, about 170 mm, about 180 mm, about 190 mm, or about 200 mm. In other variations, the length of the housing102may be greater than about 200 mm. In some variations, when in an extended configuration, the length of the housing102may be about 150 mm to 155 mm, about 155 mm to 160 mm, about 160 mm to 165 mm, or about 165 mm to about 170 mm.

In some variations, the housing102may comprise one or more elements for preventing or resisting the housing102from being moved back toward an extended configuration once initial compression has begun. For example, the housing102may comprise a one-way ratchet mechanism between proximal housing108and distal housing110. As another example, the distal housing110may comprise a groove (not shown) extending around its circumference. The groove which may have a distal face orthogonal to the surface of the distal housing110, and a proximally angled proximal face. An elastomer loop (e.g., an O-ring) (not shown) may reside in the groove. Due to the shape of the groove, if the proximal housing108moves proximally relative to the distal housing110(i.e., the housing102is moved towards an extended configuration), the elastomer loop may be pulled along the proximal face, preventing further motion. As yet another example, the injection device100may comprise a sharp prong (not shown) fixed relative to the distal housing110and angled distally, which may travel along the inside of the proximal housing108. In some variations, the sharp prong may travel along a groove on the inside of the proximal housing108. The sharp prong may be configured to travel proximally relative to the proximal housing108as the proximal housing108moves distally, but the sharp prong may not be able to move distally relative to the proximal housing108, and thus may resist movement of the housing102toward an extended configuration. In some variations, the sharp prong may be attached to or integral to the syringe sleeve430(described below). In some of these variations, the sharp prong may be attached to or integral to the proximal lip454of the syringe sleeve430(described below). In some variations, the proximal housing108and/or distal housing110may comprise one or more elements to resist rotation of the proximal housing108and distal housing110relative to each other, such as the clocking mechanisms described in more detail below. In other variations, the proximal housing108and distal housing110may be able to be rotated relative to each other.

The distal housing110may further comprise a nose116at the distal end114, which may have a tapered shape as shown inFIGS. 1 and 2A-2N, but need not. In still other variations, the nose may generally maintain the same size and/or shape as the rest of the distal housing, along its longitudinal length. Or, the nose may have a flared shape wherein the nose has a larger cross-sectional shape than the rest of the distal housing and/or proximal housing. In some variations, the flared shape may help the user maintain the injection device100in a perpendicular position with respect to the surface of the injection site, slippage of the injection device100as download pressure is being applied by the user, and/or may help allow the tissue to remain relatively flat during the injection process. In some variations, the flared shape may be a gradual outward flaring of the nose, a schematic example of which is shown inFIG. 25A; in other variations, the nose may comprise a flat portion at its distal end having a larger cross-sectional shape than the rest of the distal housing and/or proximal housing (e.g., a flat, disk, oval, ellipse, or the like), a schematic example of which is shown inFIG. 25B. These portions of the nose may be symmetric about the distal housing, or in other variations it may be asymmetric about the distal housing. Additionally or alternatively, the proximal housing may comprise a flared portion at its distal end, having a larger cross-sectional shape than the rest of the proximal housing, a schematic example of which is shown inFIG. 25C. This may assist the user grip and/or apply force to the proximal housing.

The nose116may comprise a distal opening112at its distal end158, through which the needle406of the syringe104may be extended, as described below. In some variations, the nose116may be a separate component of distal housing110, while in other variations it may be integral to distal housing110. Similarly, the proximal housing108may have an end cap118at its proximal end120. In some variations, the end cap118may be a separate component of proximal housing108, while in other variations it may be integral to proximal housing108. The proximal housing108may optionally further comprise a grip (not shown), which may be configured to enhance a user's ability to hold onto or press the proximal housing108. In some variations, the grip may have an ergonomic shape and/or a material that may enhance a user's ability to hold onto or press the proximal housing108, such as a rubber grip. While shown inFIGS. 1 and 2A-2Nas each having a substantially cylindrical shape, the proximal housing108and distal housing110may have any suitable shape (e.g., having an elliptical cross-section, oblong cross-section, ovoid cross-section, square cross-section, rectangular cross-section, triangular cross-section, etc.). In some variations, the maximum diameter (or maximum distance transverse to the longitudinal axis) of the housing102may be less than about 20 mm, about 22 mm, about 24 mm, about 26 mm, about 28 mm, about 30 mm, about 32 mm, about 34 mm, about 36 mm, about 38 mm, or about 40 mm. In some variations, the maximum diameter (or maximum distance transverse to the longitudinal axis) of the housing may be about 20 mm to 25 mm, about 25 mm to 30 mm, about 30 mm to 35 mm, or about 35 mm to about 40 mm. In some embodiments, the proximal housing108and/or distal housing110may optionally comprise one or more anti-roll elements (not shown). In some variations, the anti-roll elements may comprise a planar region on the outside of proximal housing108. In some variations, rolling of the housing102may be resisted by the housing102having a non-circular cross-sectional shape, such as an elliptical shape or other non-circular shape discussed above, or by the rigid needle shield (discussed below) having an asymmetric shape. The proximal housing108and distal housing110may comprise any suitable materials, such as but not limited to one or more plastic or metal materials.

In some variations, at least a portion of the distal housing110may comprise a viewing region124allowing the syringe104to be seen from outside the housing102. In some variations, this may allow the user to visually monitor the progress or completion of the injection (e.g., in variations in which the syringe body also comprises a viewing region or is otherwise transparent or translucent (e.g. as a result of being comprise of a transparent or translucent materials, such as a glass or plastic), by visualizing the position of the plunger or seal within the syringe cavity). In other variations, both the proximal housing108and distal housing110may comprise a viewing region, only the proximal housing108may comprise a viewing region, or neither the proximal housing108nor the distal housing110may comprise a viewing region. The viewing region(s) (e.g., viewing region124) may comprise a translucent or transparent material, such as but not limited to a glass or plastic. In other variations, the viewing region(s) (e.g., viewing region124) may be an opening (e.g., an opening in the distal housing110). In some other variations, a viewing region may be used as an opening (open or covered) to replace the syringe component of the device for re-use. In some variations, the viewing region(s) may extend around the full circumference of the proximal housing108and/or distal housing110, as shown inFIG. 1. In some variations, the viewing region(s) may comprise substantially all of the distal housing110, excluding the nose116, as shown inFIG. 1. In other variations, the viewing region(s) may extend around a portion of the circumference of the proximal housing and/or distal housing.

In some variations, the housing102may optionally further comprise a cap.FIGS. 2A-2Bshow two orthogonal cross-sectional views of the injection device100before use with a cap148attached. The cap148may be configured to fit slidably over the distal housing110and may cover the distal opening112of nose116. The cap148may be removed by applying force to separate the cap148and the remainder of the housing102. In some variations, this can be done by holding the proximal housing108with one hand and the cap148with another hand and pulling in opposite directions. In some variations, the cap148may further serve to remove the rigid needle shield422. The cap148may be connected to the rigid needle shield422in any suitable manner, such that removing the cap may also remove the rigid needle shield422. For example, the cap148may comprise an inside proximal protrusion that may fit around the outside of the rigid needle shield422. The proximal protrusion may be substantially cylindrical, but may have other shapes. The proximal protrusion may comprise an inwardly facing lip or lips that may fit into a recess or hook (or recesses or hooks) on the outside of the rigid needle shield422. When the cap148is separated from the remainder of the housing102, the rigid needle shield422may also be separated from the syringe104due to force on the rigid needle shield422from the inwardly facing lip. In some variations, the proximal protrusion may be flexible (e.g., due to a cut-out) to allow the cap to be installed over the distal housing110and rigid needle shield422. In some variations, the cap may comprise a viewing region, which may coincide with the viewing region of the distal housing, when the cap is attached to the remainder of the housing.

FIGS. 2A-2Ndepict longitudinal cross-sectional views of the injection device100ofFIG. 1in various stages during use.FIGS. 2A-2Bshow two orthogonal cross-sectional views of the device before use.FIGS. 2C-2Dshow two orthogonal cross-sectional views of the device with the rigid needle shield and cap removed.FIGS. 2E-2Fshow two orthogonal cross-sectional views of the device with the syringe partially moved toward an extended position.FIGS. 2G-2Hshow two orthogonal cross-sectional views of the device with the syringe in an extended position.FIGS. 2I-2Jshow two orthogonal cross-sectional views of the device with the plunger partially moved toward a distal position within the syringe cavity.FIGS. 2K-2Ltwo orthogonal cross-sectional views of the device with the plunger moved to the distal position within the syringe cavity.FIGS. 2M-2Nshow two orthogonal cross-sectional views of the device with the needle shroud extended. The nose116may comprise a needle safety assembly200. In some variations, the needle safety assembly200may comprise an extendable needle shroud202that protects the needle406after the injection is completed or terminated, a biasing element218, and a locking assembly226. The needle safety assembly200may be movable between a retracted position (shown inFIGS. 1, 2A-2L, and 3A-3D) and an extended position (shown inFIGS. 2M-2N and 3E-3F). In the retracted position, the needle shroud202may allow the needle406of the syringe104to be exposed when the syringe104is in an extended position, as described in detail below. Thus, in the retracted position, the distal end212of the needle shroud202may be located proximally to the distal tip424of the needle406when the syringe104is in an extended position. In an extended position, the needle shroud202may shield the needle406from exposure when the syringe104is in an extended position; for example, the needle shroud202may resist insertion of the needle406in a patient's tissue or resist contact between the needle406and tissue. Thus, in an extended position, the distal end212of the needle shroud202may be located distally to the distal tip424of the needle406when the syringe104is in an extended position. In some variations, the displacement of the needle shroud202between retracted and extended positions may be about 6 mm to 8 mm, about 8 mm to 10 mm, about 10 mm to 12 mm, about 12 mm to 14 mm, or about 14 mm to 16 mm.

As shown inFIGS. 3A-3D, the needle shroud202may fit slidably within the nose116. In the variations shown inFIGS. 3A-3F, when the needle safety assembly200is in a retracted position, the distal end212of the needle shroud202may be flush with the distal end158of the nose116, while in an extended position, the distal end212of the needle shroud202may be distal to the distal end158of the nose116. It should be appreciated that in other variations, in a retracted position, the distal end212of the needle shroud202may be proximal to the distal end158of the nose116, or in other variations, it may be distal to the distal end158of the nose116in a retracted position.

The needle shroud202may have a proximal opening204and a distal opening206, with a lumen208extending between the proximal opening204and distal opening206. The needle shroud202may have a longitudinal axis210aligned with the longitudinal axis144of the housing102. While the needle shroud202is shown as having a cylindrical shape inFIGS. 3A-3F, it should be appreciated that the needle shroud may have other shapes (e.g. an elliptical cross-section, oblong cross-section, ovoid cross-section, square cross-section, rectangular cross-section, triangular cross-section, or the like). In some variations, the needle shroud202may optionally comprise a stop (not shown) to resist the needle shroud202being disconnected from the nose116(e.g., to resist the needle shroud202sliding distally away from and disengaging with the nose116). Additionally or alternatively, the needle shroud202may comprise a distal lip216to hold the biasing element218, described below. In some variations, the needle shroud202may comprise a plastic material, but it should be appreciated that the needle shroud202may comprise any suitable material. The needle shroud202may be optically opaque, translucent, or transparent. The needle shroud may also optionally comprise apertures or cutouts to permit partial visualization of the needle during or after the injection procedure.

The biasing element218may be configured to bias the needle safety assembly200toward an extended position. The biasing element218may have a compressed configuration and an expanded configuration. The biasing element218may be in a compressed configuration when the needle safety assembly200is in a retracted configuration, and the biasing element218may be in an expanded configuration when the needle safety assembly200is in an extended position. In some variations, the biasing element218may comprise a compression spring220. When the compression spring220is in a compressed configuration, the compression spring220at its proximal end222may be connected to or in contact with a portion of the distal housing110or nose116, and at its distal end224may be connected to or in contact with a portion of the needle shroud202. The biasing element218(e.g., compression spring220) may thus bias the needle shroud202distally away from the distal housing110and nose116through the distal opening112of the nose116. In the variation shown inFIGS. 3A-3F, the compression spring220may have a cylindrical shape and may fit within the lumen208of the needle shroud202. The proximal end222of the compression spring220may contact a ledge156extending radially inward from the distal end114of the distal housing110, and the distal end224of the compression spring220may contact the lip216extending radially inward from the needle shroud202. While the lip216is shown as located at the distal end212of needle shroud202inFIGS. 3A-3F, it should be appreciated that in other variations a lip may extend from a location proximal to the distal end212of the needle shroud202. In some variations, the proximal end222of the compression spring220may be fixedly attached to the distal end114of distal housing110, but it need not be (e.g., it may rest against the distal end114of the distal housing110but be unattached). Similarly, in some variations, the distal end224of the compression spring220may be fixedly attached to the needle shroud202, but it need not be (e.g., it may rest against a portion of the needle shroud202but be unattached). It should be appreciated that in other variations the biasing element218may not comprise a compression spring220and may instead comprise other forms of biasing elements (e.g., an extension spring, torsion spring, or the like) configured so as to bias the needle shroud202distally away from the distal housing110. In some variations, the biasing element218may provide about 1 N, about 2 N, about 3 N, about 4 N, about 5 N, about 6 N, about 7 N, or about 8 N of biasing force.

The locking assembly226may hold the needle shroud202in a retracted position and/or in an extended position. In some variations, the locking assembly226may comprise one or more latches228that may be configured to connect the needle shroud202to the syringe104. While in the embodiment ofFIGS. 3A-3F, the locking assembly226may comprise four latches228evenly spaced around the needle shroud202, it should be appreciated that in other variations, the locking assembly226may comprise fewer or more latches and may have different positioning (e.g., one, two, three, five, or six latches, etc., which may or may not be evenly spaced from each other). In some variations, the latches228may be integral to the needle shroud202. The latches228may each comprise an elongate portion230extending proximally from the needle shroud202, and a tab234extending from the elongate portion230. In some variations, the elongate portions230may have different lengths. The elongate portion230may extend proximally from the proximal opening204of the needle shroud202, and the tab234may extend inwardly from the proximal end of the elongate portion230. As shown inFIGS. 3A-3B, the latches228may be configured to mate with the syringe sleeve430(described below), such that when mated, the latches228resist motion of the needle shroud202relative to the distal housing110. The syringe sleeve430may comprise four proximal slots168, which may be located on the syringe sleeve430such that when the tabs234of the latches228are mated with the proximal slots168, the needle shroud202may be located in a retracted position. When the tabs234are mated with the proximal slots168, the elongate portion230of the latches228may be flush against the outer surface458of the syringe sleeve430, while the tabs234of the latches228may be inserted radially into the proximal slots168. The locking assembly226may resist distal motion due to a biasing force from the biasing element218because of the proximally oriented force applied to the distal surface of the tabs234by the distal surface of the proximal slots168.

As shown inFIGS. 3C-3D, the locking assembly226may be configured such that the needle shroud202may be unlocked from a retracted position (e.g., the locking assembly226may no longer hold the needle shroud202in a retracted position) by distal motion of the syringe104. In some variations, the tabs234may be configured such that they can be released from the proximal slots168by distal movement of the syringe104relative to the syringe sleeve430. For example, in the variation shown inFIGS. 3A-3F, the tabs234may have a triangular, proximally tapering shape. Thus, as the syringe104is moved distally within the syringe sleeve430, the distal end418of the outer surface468of the syringe body402may engage the inner surface236of the tabs234protruding through the proximal slots168. As the outer surface468of the syringe body402continues to slide distally along the inner surface460of the syringe sleeve430(described below), the outer surface468of the syringe body402gradually pushes the tabs234further radially out of the proximal slots168. Once the outer surface468of the syringe body402has fully pushed the tabs234radially out of the proximal slots168, the tabs234may no longer be mated with the proximal slots168and may no longer resist distal motion of the needle shroud202relative to the distal housing110. It should be appreciated that while the latches in the embodiment ofFIGS. 3A-3Fare connected (or integral) to the needle shroud202and fit into slots in the syringe sleeve430, in other variations, the latches may be connected (or integral) to the syringe sleeve and may fit into slots in the needle shroud. For example, the inner surface of the syringe sleeve may comprise inwardly facing tabs, which may extend inwardly through slots in the needle shroud, such that they may protrude radially within the inner surface of the syringe sleeve. As in the embodiment inFIGS. 3A-3F, distal movement of the syringe may cause the outer surface of the syringe body to push the tabs radially outward through the slots to an extent sufficient to cause the tabs to no longer resist distal motion of the needle shroud relative to the distal housing.

When the needle shroud202is unlocked from a retracted position, if a force is then applied that is configured to urge the needle shroud202from a retracted position to an extended position (e.g., a biasing force from the biasing element218), the needle shroud202may move from a retracted position to an extended position. However, the force configured to urge the needle shroud202from a retracted position to an extended position may be counterbalanced or partially or completely opposed by a proximally directed force on the needle shroud202. For example, in the variation shown inFIGS. 3A-3F, the distal end212of the needle shroud202is configured to be pressed against a patient's tissue during an injection. Thus, the tissue may apply a force to the distal end212of the needle shroud202, partially or fully counteracting the biasing force from the biasing element218(e.g., compression spring220) while the injection device100is pressed against the tissue. This may resist the needle shroud202moving from a retracted position to an extended position, even when the needle shroud202is unlocked from a retracted position. However, if the injection device100is then moved away from the tissue, there may no longer be a force from the tissue to counteract the biasing force from the biasing element218, and as a result, the needle shroud202may move from a retracted position to an extended position, as shown inFIGS. 3E-3F.

In some variations, such as the variation ofFIGS. 3A-3F, the locking assembly226may be configured such that the needle shroud202may be unlocked from a retracted position just before the distal tip424of the needle406of the syringe104extends from the distal end158of the nose116, as shown inFIGS. 3C-3D. Thus, at any time the needle406is exposed such that it is capable of piercing or otherwise contacting a patient's tissue, the needle shroud202is unlocked from a retracted position. The exposure of the needle406for injection may therefore only be maintained by maintaining a proximal force on the distal end212of the needle shroud202to hold it in a retracted position (e.g. by pressing the distal end212of the needle shroud202against a patient's tissue); once the proximal force is removed (e.g., by moving the injection device100away from a patient's tissue), the needle shroud202may move into an extended position, which may resist piercing of a patient's tissue by the needle406or resist contact between the needle406and a patient's tissue.

In some variations, the needle shroud202of the needle safety assembly200may additionally or alternatively be configured to be locked in an extended position once moved to an extended position. That is, the needle shroud202may be configured such that once it enters an extended position, it may be unable to return to a retracted position. In some variations wherein the locking assembly comprises one or more latches, the same latches may be used to lock the needle shroud202in an extended position. In some of these variations, as shown inFIGS. 3E-3F, the syringe sleeve430may comprise four distal slots176configured to mate with the tabs234of the latches228of the locking assembly226. The distal slots176may be located on the syringe sleeve430to coincide with the position of the tabs234when the needle shroud202is in an extended position. When the needle shroud202moves into an extended position, the tabs234on the latches228may mate with the distal slots176. When the tabs234on the latches228are mated with the distal slots176, the locking assembly226may resist motion of the needle shroud202relative to the syringe sleeve430, and in turn, may cause the locking assembly226to resist motion of the needle shroud202relative to the distal housing110. Once locked in an extended position, the needle shroud202may, for example, resist proximal force on the distal end212of the needle shroud202(e.g., from tissue pressed against the distal end212of the needle shroud202) tending to urge the needle shroud202proximally toward a retracted position, and/or the needle shroud202may resist distal force applied to it (e.g., from the biasing element218) tending to urge the needle shroud202further away from the distal housing110. In variations of the injection device configured to lock in an extended position, this feature may limit the ability of a needle to extend from the distal end of the nose to pierce or otherwise contact tissue or other surfaces after the injection device has been removed from a patient's tissue. This may make the injection device safer for the user and/or patient by limiting accidental needlesticks after injection has been fully or partially completed. However, it should be appreciated that in other variations, the needle shroud may not be configured to lock when in an extended position (e.g., in some variations, the needle shroud202may retract from an extended position in response to distal force).

In some variations, the needle safety assembly200may provide feedback to the user. In some variations, this feedback may include a biohazard indicator, such as a biohazard symbol located on the outside surface of the needle shroud202, which may be visible when the needle shroud202is in an extended position. Additionally or alternatively, all or a portion of the needle shroud202may be colored (e.g. red, yellow, orange, green, magenta, blue, or the like) in order to indicate or signal to the user that the injection device100has been used.

The housing102may comprise an indicator to indicate the progress or completion of the injection. In one variation, the indicator may have a range of configurations corresponding to various levels of progress of the injection. In some such variations, the configurations may have different visual, tactile, or auditory perceptions, such as but not limited to color, numerical, or ordinal cues or indicia, or the position of the proximal housing108relative to the distal housing110. In the same or other variations, the transition between the inactivated configuration and the activated configuration, and/or the transition between the configurations, may produce visual, tactile, or auditory alerts, such as but not limited to color, numerical, or ordinal cues or indicia, or the position of the proximal housing108relative to the distal housing110.

In some variations, the indictor may alert the user that the full dose has been displaced from the reservoir414of the syringe104and/or that the seal410has traveled the full length of the reservoir414to the distal end462of the syringe cavity404(described below). Additionally or alternatively, the end-of-dose indicator may alert the user that nearly (e.g., greater or equal to about 85%, greater or equal to about 90%, greater or equal to about 95%, or more) the full dose has been displaced from the reservoir414of the syringe104and/or that the seal410has traveled nearly (e.g., greater or equal to about 85%, greater or equal to about 90%, greater or equal to about 95%, or more, or within about 1 mm of full displacement, about 2 mm of full displacement, about 3 mm of full displacement, or about 4 mm of full displacement, etc.) the full length of the reservoir414to the distal end462of the syringe cavity404.

FIGS. 4A-4Cillustrate longitudinal cross-sectional views of a proximal portion of the injection device ofFIG. 1, showing the end-of-dose indicator300having a different visual appearance associated with the inactivated (FIG. 4A) and activated (FIG. 4C) configurations. The indicator300may be seen through the housing102in the activated configuration, while not seen through the housing102in the inactivated configuration. In some variations, at least a portion of the housing102may be translucent, transparent, or comprise an opening to allow the visual appearance of the indicator300to be different between the activated and inactivated configurations. For example, the indicator300may be seen when in an activated configuration through the end cap118of the proximal housing108, which may comprise a transparent or translucent material. While in the variation ofFIGS. 4A-4Cthe transparent or translucent region is in end cap118, it should be appreciated that in other variations the indicator300may be seen through other portions of the housing102.

In the variation shown inFIGS. 4A-4C, the indicator300may comprise a main body302, a release member308, and a biasing element320. The main body302and end cap118of the proximal housing108may be configured such that when the main body302is adjacent to the inner surface186of the end cap118, at least a portion of the main body302may be seen from outside the end cap118through a viewing portion. In some variations, at least a portion of the main body302may have a color or pigment that may be capable of being more easily noticed, such as but not limited to red, yellow, orange, green, magenta, blue, and the like. In order for the main body302to be seen through at least a portion of end cap118, in some variations, at least a portion of the end cap118may be translucent. In variations in which a portion of the end cap118is translucent, the level of translucency may be such that the coloring of the main body302may be perceived through the end cap118only when the main body302is adjacent or nearly adjacent to the viewing portion. In other variations, the end cap118may comprise a transparent or open region configured such that the main body302is only visible through the viewing portion when the main body302is adjacent to the transparent or open region, for example, because of the viewing angle. For instance, in some such variations, the viewing portion may comprise a transparent region around the circumference of the end cap118, and the main body302of the indicator300may only be visible through the viewing portion when aligned adjacent to the viewing portion. The main body302of the indicator300may also comprise a lumen304therethrough to allow a portion of the ram502(described below) to pass through the main body302.

The biasing element320may be configured to bias the indicator300toward an activated configuration. The biasing element320may have a compressed configuration and an expanded configuration. The biasing element320may be in a compressed configuration when the indicator300is in an inactivated configuration, and the biasing element320may be in an expanded configuration when the indicator300is in an activated configuration. As shown inFIGS. 4A-4C, in some variations the biasing element320may comprise a compression spring322. The proximal end324of the compression spring322may be connected to or in contact with the main body302of the indicator300, and the distal end326of the compression spring322may be connected to or in contact with the interlocker436(described below). The biasing element320may thus bias the main body302of the indicator300away from the ram502.

As shown inFIG. 4A, the release member308may hold the indicator300in an inactivated configuration until released. The release member308may comprise an elongate portion312and a locking portion310. The elongate portion312may connect the main body302and the locking portion310, and the locking portion310may extend radially outward from the distal end of the elongate portion312. When the indicator300is in an inactivated configuration, the radially outer tip of the locking portion310may fit within an indicator recess328in the interlocker436. Radially outward pressure from the plunger510on the inner end of the locking portion310may resist the locking portion310from moving radially inward to emerge or disengage from the recess328. The protrusion of the outer tip of the locking portion310into the indicator recess328may result in a distally directed force on the locking portion310from the proximal surface of the recess328, which may counteract the biasing force of the compression spring322, and which may thus hold the indicator300in an inactivated configuration.

When the release member308is released, the indicator300may no longer be held in an inactivated configuration, as shown inFIG. 4B. The release member308may be released by the distal motion of the ram502as the injection proceeds (as described in more detail below). As the ram502moves distally relative to the interlocker436, the plunger510may move distally relative to the locking portion310of the release member308, until the plunger510may be fully distal to the locking portion310, as shown inFIG. 4B. At this point, the plunger510may no longer contact the inner end of the locking portion310to resist the locking portion310from moving radially inward to emerge or disengage from the recess328. As a result, the locking portion310may move radially inward to emerge or disengage from the recess328, and the proximal surface of the recess328may no longer provide a distally directed force on the locking portion310to counteract the biasing force from the compression spring322, thus releasing the release member308. Once released, the biasing force from the compression spring322may cause the indicator300to move proximally relative to the interlocker436and toward an activated configuration, as shown inFIG. 4C.

FIGS. 4D-4Eillustrate cut-away elevational side views of a proximal portion of another embodiment of an injection device showing another example of an end-of-dose indicator in inactivated (FIG. 4D) and activated configurations (FIG. 4E). In the embodiment ofFIGS. 4D-4E, the indicator300may, like the embodiment ofFIGS. 4A-4C, comprise a main body2302, a release member2308, and a biasing element2320, but the proximal end2324of the compression spring2322may be connected to or in contact with an inner lip2306on the main body2302of the indicator2300, and the distal end2326of the compression spring2322may be connected to or in contact with the arms506of the ram2502. The release member2308may comprise one or more latches2310that may mate with a slot or other form of recess in the arm2506of the ram2502. When the latches2310are mated with the slots or recesses, the release member2308may resist distal motion of the main body2302of the indicator2300relative to the ram502(e.g., due to a biasing force from the biasing element2320). If the latches2310are released from the slots or recesses, a force from the biasing element2320may cause the indicator2300to move into an activated configuration, as shown inFIG. 4E. In the embodiment shown inFIGS. 4D-4E, for example, the release member2308may comprise two latches2310. Each latch2310may extend distally from the main body2302of the indicator2300. Each latch2310may be configured to mate with an indentation ridge2524on the outer surface of an arm2506of the ram2502. When the latches2310are mated with the indentation ridge2524, the proximal side of the indentation ridge may resist proximal motion of the latch2310and thus of the main body2302of the indicator2300due to the biasing force from the compression spring2322. If the latches2310are released from the indentation ridges2524, however, the biasing force from the compression spring2322may urge apart the ram2502and the indicator2300, moving the main body2302of the indicator2300towards the end cap2118of the proximal housing2108, which may cause the indicator2300to be visible through the end cap2118. The tabs2103may be configured to be released from the indentation ridge2524by distal movement of the ram2502relative to the proximal housing2108and end cap2118. When the ram2502has moved distally such that the full dose has been displaced from the reservoir of the syringe and/or nearly the full dose has been displaced from the reservoir of the syringe the latches2310may be pushed out of the indentation ridges2524, moving the indicator2300to an activated configuration, as shown inFIG. 4E.

While the indicators inFIGS. 4A-4Eare end-of-dose indicators, in other variations, the indicator may be configured to convey the progress of the injection at one or more points throughout the injection. For example, in some variations, the proximal housing108and/or distal housing110may comprise a viewing region (e.g., a transparent or transparent region, or an opening) such that the location of the interlocker436(described below) may be viewed through the viewing region. The location of the interlocker436relative to the housing102may indicate the progress of the injection. In some of these variations, the interlocker436may be colored or comprise a colored region to be more easily visible through the viewing region. In other variations, a separate component, which may also be colored or comprise a colored region, may be attached to the interlocker436, which may be seen through the viewing region.

As described briefly above, in general, the syringe104may comprise a syringe body defining a syringe cavity, a seal slidably disposed within the lumen of the syringe cavity defining a reservoir that may hold a formulation comprising a therapeutic or diagnostic agent, a ram comprising a plunger that may fit slidably within the syringe cavity, and a needle at the distal end of the syringe body. The needle may be configured to pierce the tissue of a patient receiving an injection, and may have a lumen therethrough to deliver the contents of the reservoir to the patient's tissue. Movement of the seal within the syringe cavity distally may cause the contents of the reservoir to be displaced through the lumen of the needle.

Returning toFIGS. 2A-2N, the syringe104may comprise, as briefly mentioned above, a syringe body402, which may define a syringe cavity404. The syringe cavity404may be in fluid communication with the lumen408of the needle406, described in more detail below. A seal410may be slidably disposed within the syringe cavity404and may form an airtight seal with the inner surface412of the syringe body402. The inner surface412of the syringe body402and the seal410may form a reservoir414configured to contain a formulation, such as a solution, comprising a therapeutic or diagnostic agent. The seal410may limit the contents of the syringe cavity404from flowing or otherwise moving proximally to the seal410. If the seal410is moved distally relative to and within the syringe cavity404, the volume of the reservoir414may be decreased. Thus, distal motion of the seal410relative to and within the syringe cavity404may cause the contents of the reservoir414to be displaced through the lumen408of the needle406. In some variations, the reservoir414may be configured to contain a maximum volume of about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL. In other variations, the reservoir414may be configured to contain a maximum volume of about 0.1 mL to 1 mL, 1 mL to 2 mL, 2 mL to 3 mL, 3 mL to 5 mL, 5 mL to 10 mL, 10 mL to 15 mL, 15 mL to 20 mL, 20 mL to 25 mL, or more. While the syringe104is shown as having a circular cross-section, and thus the syringe body402forms a barrel, in other variations, the syringe104and its component parts may have any suitable shape (e.g., having an elliptical cross-section, oblong cross-section, ovoid cross-section, square cross-section, rectangular cross-section, triangular cross-section, etc.).

The reservoir414formed by the inner surface412of the syringe body402and the seal410may contain a formulation comprising one or more therapeutic or diagnostic agents. In some variations, the therapeutic or diagnostic agent may be a substance such as but not limited to a large molecule, small molecule, or a biologic. In some variations, the formulation may further comprise one or more solvents, diluents, and/or adjuvants. The formulation may have any suitable viscosity. Generally, the formulation may have a viscosity of up to 10 cP, up to 20 cP, up to 30 cP, up to 40 cp, up to 50 cP, up to 60 cP, up to 70 cP, up to 80 cP, up to 90 cP, or up to 100 cP. In some instances, the formulation may have a higher viscosity, such as up to 1,000 cP, up to 10,000 cP, or up to 50,000 cP. Examples of higher viscosity injectates include certain dermal fillers used for cosmetic or tissue bulking procedures, such as the treatment of urinary incontinence. In some instances the formulation may have a significantly higher viscosity (e.g., an even higher viscosity, such as up to 500,000 cP or higher.

In some variations, the formulation may comprise a therapeutically effective amount of a protein or proteins, such as but not limited to growth hormone, including human growth hormone and bovine growth hormone; growth hormone releasing factor; parathyroid hormone; thyroid stimulating hormone; lipoproteins; α-1-antitrypsin; insulin A-chain; insulin B-chain; proinsulin; follicle stimulating hormone; calcitonin; luteinizing hormone; glucagon; clotting factors such as factor VIIIC, factor IX, tissue factor, and von Willebrands factor; anti-clotting factors such as Protein C; atrial natriuretic factor; lung surfactant; a plasminogen activator, such as urokinase or tissue-type plasminogen activator (t-PA, e.g., Activase®, TNKase®, Retevase®); bombazine; thrombin; tumor necrosis factor-α and -β; enkephalinase; RANTES (regulated on activation normally T-cell expressed and secreted); human macrophage inflammatory protein (MIP-1-α); serum albumin such as human serum albumin; mullerian-inhibiting substance; relaxin A-chain; relaxin B-chain; prorelaxin; mouse gonadotropin-associated peptide; DNase; inhibin; activin; vascular endothelial growth factor (VEGF); receptors for hormones or growth factors; an integrin; protein A or D; rheumatoid factors; a neurotrophic factor such as bone-derived neurotrophic factor (BDNF), neurotrophin-3, -4, -5, or -6 (NT-3, NT-4, NT-5, or NT-6), or a nerve growth factor such as NGF-P; platelet-derived growth factor (PDGF); fibroblast growth factor such as aFGF and bFGF; epidermal growth factor (EGF); transforming growth factor (TGF) such as TGF-α and TGF-β, including TGF-(31, TGF-β2, TGF-β3, TGF-β4, or TGF-β5; insulin-like growth factor-I and -II (IGF-I and IGF-II); des(1-3)-IGF-I (brain IGF-I); insulin-like growth factor binding proteins; CD proteins such as CD3, CD4, CD8, CD19 and CD20; erythropoietin (EPO); thrombopoietin (TPO); osteoinductive factors; immunotoxins; a bone morphogenetic protein (BMP); an interferon such as interferon-α, -β, and -γ; colony stimulating factors (CSFs), e.g., M-CSF, GM-CSF, and G-CSF; interleukins (ILs), e.g., IL-1 to IL-10; superoxide dismutase; T-cell receptors; surface membrane proteins; decay accelerating factor (DAF); a viral antigen such as, for example, a portion of the AIDS envelope; transport proteins; homing receptors; addressins; regulatory proteins; immunoadhesins; antibodies; and biologically active fragments or variants of any of the above-listed polypeptides. By “protein” is meant a sequence of amino acids for which the chain length is sufficient to produce the higher levels of tertiary and/or quaternary structure. In some of these variations, the protein which is formulated may be essentially pure and essentially homogeneous (i.e., free from contaminating proteins). “Essentially pure” protein means a composition comprising at least about 90% by weight of the protein, based on total weight of the composition, preferably at least about 95% by weight. “Essentially homogeneous” protein means a composition comprising at least about 99% by weight of protein, based on total weight of the composition.

Although the formulations comprising one or more therapeutic or diagnostic agents are described above with respect to syringe104of injection device100, it should be appreciated that the formulations described above may be injected with any of the variations of injection devices described herein, including injection devices700and1300described below.

The syringe body402and seal410and/or plunger may comprise any suitable materials, such as but not limited to glass (e.g., Type 1 glass), a polymer (e.g. a rubber, such as putyl rubber), a metal, or the like. In some variations, the material or materials of the syringe body402and/or seal410may have properties so as to not substantially interact with the therapeutic or diagnostic agent, resisting adhesion, and/or promoting stability and/or sterility or sterilizability of the formulation. In some variations, the syringe body may comprise a coating. In some variations, the coatings may comprise silicone oils, fluoropolymers (e.g., perfluoropolyether-based chemical coatings, polytetrafluoroethylene (TEFLON®)), or the like. For example, the syringe body may comprise glass that may be siliconized on the inside surface. In some variations, the syringe body402and/or seal410may comprise materials that limit light transmission to the therapeutic or diagnostic agent (i.e., materials that reflect or absorb light), such as but not limited to materials that block UV light and/or light at given visible wavelengths (e.g., amber-tinted materials), black-out materials blocking all light, and foil linings. The material(s) may be selected for their specific colors, color change resistance (due to aging, due to exposure to the formulation, or due sterilization), leach resistance, in regard to some general or specific formulation characteristics. In some variations, the syringe body402may comprise a translucent or transparent material, such that the contents of the syringe body402can be viewed through the material. In some variations, the shelf life of the therapeutic or diagnostic agent within the injection device100may be up to about 1 year, about 2 years, about 3 years, about 4 years, or about 5 years.

The needle406of the syringe104may be attached to the distal end of the syringe body402of the syringe104. The proximal end416of the needle406may be secured to the distal end418of the syringe body402, such that the proximal end416of the lumen408of the needle406is in fluid communication with a distal opening420at the distal end418of the syringe body402. The distal end418of the needle406may have a pointed shape configured to pierce tissue. The needle406may thus be configured allow the formulation within the reservoir414to flow out through the distal opening420in the syringe body402, through the lumen408of the needle406, and into tissue, when the needle406is inserted into tissue. The length and gauge of the needle406may be appropriate for the intended use. For example, in some variations the syringe104may comprise needle sizes up to, or including but not limited to 7 gauge, 9 gauge, 11 gauge, 13 gauge, 15 gauge, 17 gauge, 19 gauge, 21 gauge, 23 gauge, 25 gauge, 27 gauge, 29 gauge, 31 gauge, and 33 gauge needles, and lengths including those up to about 3 mm, 4 mm, 6 mm, 8 mm, 10 mm, 15 mm, 20 mm, 30 mm, 40 mm or more. The needle may comprise any suitable material, including but not limited to stainless steel. In other variations, the device may be provided without a needle. In some variations, the needleless devices are intended to be attached to a pre-existing needle (e.g., a lumbar puncture needle or a central line catheter).

As shown inFIG. 1, the syringe104may further comprise a rigid needle shield422. In some variations, the injection device100may comprise a deshielder configured to allow easy removal of the rigid needle shield422. In some variations, the deshielder or rigid needle shield422may comprise an interlock to resist motion of the syringe104within the distal housing110before removal of the rigid needle shield422. In some variations, the deshielder may be integrated with a cap148that may fit over the distal housing110, as described in more detail above. In some variations, the rigid needle shield422may be asymmetric to resist rolling of the housing102when attached to the injection device100.

The syringe104may be configured to move longitudinally relative to the distal housing110from a retracted position (shown inFIGS. 2A-2D and 3A-3B) to an extended position (shown inFIGS. 2G-2N and 3E-3F). In a retracted position, the distal tip424of the needle406may be shielded from exposure (e.g. the needle406may be protected from piercing or otherwise contacting tissue), and thus the distal tip424of the needle406may be proximal to the distal end of the housing102(e.g., the distal end114of the distal housing110). The syringe104may be held in a retracted position (i.e., it may resist distal motion relative to the syringe104) by a restraining element. In some variations, the restraining element may comprise one or more flexures428, described below. The syringe104may be moved toward an extended position by a distal force sufficient to overcome the resistance of the flexures428, as described below. In an extended position, the distal tip424of the needle406may be exposed (e.g., the distal tip424of the needle406may be capable of piercing or other otherwise contacting tissue), and thus the distal tip424of the needle406may be distal to the distal end of the housing102(e.g., the distal end114of the distal housing110). When the syringe104is in an extended position, if the needle shroud202of the needle safety assembly200is in a retracted position, the distal tip424of the needle406may extend beyond the distal end of the distal housing110and the needle shroud202to pierce tissue to a desirable depth, as shown inFIGS. 2G-2L. In some variations, the distal tip424of the needle406may move about 6 mm to 8 mm, about 8 mm to 10 mm, about 10 mm to 12 mm, or about 12 mm to 14 mm between retracted and extended positions. In some variations, the distal tip424of the needle406may be about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, or about 7 mm proximal to the distal end114of the distal housing110in a retracted position. In some variations, the distal tip424of the needle406may be about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, or about 10 mm distal to the distal end114of the distal housing110in an extended position.

FIG. 5depicts an exploded perspective view of the injection device100. In some variations, the injection device100may comprise a syringe sleeve430, as mentioned above, but need not. In these variations, the syringe104may be slidably disposed with the syringe sleeve430. The syringe sleeve430may comprise a distal portion432and a proximal portion434. The distal portion432may be configured to fit slidably around the syringe body402. The proximal portion434may have a larger diameter (or maximum distance transverse to the longitudinal axis) than the distal portion432, and may be configured to hold the power assembly106in place, as described in more detail below. The syringe sleeve430may be fixed relative to the distal housing110, and may have a longitudinal axis aligned with the longitudinal axis of the housing102. The syringe sleeve may comprise any suitable material, and in some variations, the syringe sleeve430may comprise a deep drawn metal.

The distal portion432of the syringe sleeve430may also have attached to it an interlocker436. As shown inFIGS. 6A-6B, the interlocker436may comprise a main body438that may be fixed within the proximal portion434of the syringe sleeve430. The interlocker436may have a proximal opening440, a distal opening442, and a lumen444therethrough. At least a portion of the ram502(described below) may fit through the proximal opening440of the interlocker436, and the syringe body402of the syringe104may fit through the distal opening442of the interlocker436. The interlocker436may further comprise one or more flexures428to resist distal movement of the syringe104, and a biter interlock448to hold the biter608of the power assembly106in place, both of which will be described in more detail below.

Returning toFIGS. 2A-2N, the ram502may be directly or indirectly connected to the proximal housing108, such that movement of the proximal housing108can be transmitted to the ram502. The ram502may be configured to transmit distal force on the proximal housing108into different motions, depending on the stage of the injection process. In a first stage, distal force on the proximal housing108may be transmitted into distal motion of the syringe104relative to the distal housing110. In a second stage, distal force on the proximal housing108may be transmitted into displacement of the contents of the reservoir414of the syringe104(e.g., a fluid or formulation comprising a therapeutic or diagnostic agent) through the lumen408of the needle406.

In some variations, the ram502may be configured such that the effects of distal force on the proximal housing108may occur in the order described above. That is, the ram502may be configured such that distal force on the proximal housing108may be transmitted first into distal motion of the syringe104relative to the distal housing108, and then transmitted second into displacement of the contents of the reservoir414(e.g., a formulation comprising a therapeutic agent) through the lumen408of the needle406. This may be desirable, for example, because it may allow the syringe104to move distally such that the needle406may pierce a patient's tissue before the contents of the reservoir414are displaced through the lumen408of the needle406.

In some variations, the ordering of effects of distal force on the proximal housing108may be due to different amounts of force that are required for each motion. For example, the ram502may transmit distal force on the proximal housing108into distal motion of the syringe104relative to the distal housing110when the force on the proximal housing108is above a first threshold (e.g., above about 1 N, above about 2 N, above about 3 N, above about 4 N, above about 5 N, above about 6 N, above about 7 N, or higher); and the ram502may transmit distal force on the proximal housing108into displacement of the contents of the reservoir414through the needle406when the force on the proximal housing108is above a second higher threshold (e.g., above about 1 N, above about 2 N, above about 4 N, above about 6 N, above about 8 N, above about 10 N, above about 12 N, above about 14 N, or higher). These thresholds may in some cases be desirable for other or additional reasons. For example, it may be desirable that the force threshold to initiate distal motion of the syringe be higher than the amount of force required to insert the needle through the skin. It may also be desirable that the force threshold to initiate distal motion of the syringe be high enough to discourage accidental distal motion. Indeed, in some variations, it may be desirable that the force threshold to initiate distal motion of the syringe be high enough so as to force rapid needle insertion. In some variations, the thresholds may be due to the proximal forces from friction on the syringe104and ram502, respectively. In other variations, the thresholds may be due to the proximal forces from other sources on the syringe104and ram502, respectively, such as proximal forces from a flexure or spring. In other variations, one or more of the thresholds may be due to the proximal forces from friction and other sources on the syringe104, and ram502, respectively. It should be appreciated that in some other variations, the ram502may transmit distal force on the proximal housing108into different motions in different orders and by different mechanisms. For example, in some variations the effect of the distal force may be chosen by a mechanism for manual selection by the user. In should also be appreciated that the ram may have fewer or more motions into which it may transmit distal force on the proximal housing108.

As shown inFIGS. 2A-2N, the ram502may comprise a central portion504and two arms506extending from opposite sides of the central portion504. The central portion504may be divided in a proximal central portion comprising a connector rod508, and a distal central portion comprising a plunger510. The two arms506may extend from the central portion504at the dividing point512between the plunger510and the connector rod508. The connector rod508may be slidable within a portion of the actuation rod636(described in detail below), which may in turn be fixedly attached to the end cap118of the proximal housing. However, in other variations (not shown), the connector rod may be configured to directly connect the ram to the proximal housing. In those variations, the connector rod may fit at least partially into a receiving cup on the inner surface of the end cap of the proximal housing. The receiving cup may be located at the center of the end cap and may be configured to hold the ram in a position aligned with the longitudinal axis of the housing.

The plunger510may be configured to be slidable within the syringe cavity404of the syringe104. The distal end516of the plunger510may be configured to engage with the seal410of the syringe104. If the plunger510is moved distally relative to and within the syringe cavity404, the plunger510may push the seal410distally relative to and within the syringe cavity404. This movement of the seal410may decrease the volume of the reservoir414containing the formulation comprising a therapeutic or diagnostic agent. Thus, distal motion of the plunger510, and in turn of the seal410, relative to and within the syringe cavity404may cause the contents of the reservoir414to be displaced through the lumen408of the needle406. The two arms506of the ram502may extend distally from opposite sides of the ram502from its dividing point512along the central portion504. The arms506may comprise a proximal curved portion518and a distal straight portion520. The straight portion520of the arms506may be radially distanced from the plunger510, such that if the plunger510is moved within the syringe cavity404, the straight portion520of the arms506may be located outside of the syringe body402. In some variations, the outer surface of the straight portion of the arms506may optionally comprise an indentation ridge for attachment of the indicator, as described above. The arms506may additionally be configured to attach to a portion of the power assembly106when the syringe104is in an extended position, as described below.

As shown inFIGS. 2E-2F, in the first stage of the injection process, distal force on the proximal housing108may be transmitted into distal movement of the syringe104relative to the syringe sleeve430from a retracted position (shown inFIGS. 2C-2D) to an extended position (shown inFIGS. 2G-2H) if the distal housing110is held in place (e.g. by pressing the distal end158of the nose116of the distal housing110against a patient's tissue) and if the distal force is above the necessary force threshold. The threshold force required may be due to the first pair of flexures428, as described above. More specifically, when the threshold distal forced is reached, the flexures428may deflect outward and over the proximal lip452of the syringe body402, at which point the flexures428may no longer resist distal movement of the syringe104. Distal force on the proximal housing108may then cause distal motion of the ram502, which may in turn cause distal motion of the syringe104, via the plunger510located within the syringe cavity404, toward the extended position. The syringe104may move distally within the syringe sleeve430, which may move the needle406of the syringe104distally toward the distal end of the nose116of the distal housing110. As the distal tip424of the needle406approaches the distal end158of the nose116(shown inFIGS. 2E-2F), the needle shroud202of the needle safety assembly200may be unlocked from a retracted position, as described in detail above. As the distal tip424of the needle406moves to extend beyond the distal end158of the nose116, the needle406may pierce tissue pressed against the distal end158of the nose116. The syringe104may continue to move distally relative to the syringe sleeve430until the syringe104has reached an extended position (shown inFIGS. 2G-2H). At an extended position, the distal tip424of the needle406may have reached the desired depth, as described above. The forward motion of the syringe104beyond the extended position may be limited by the proximal lip452contacting the distal end of the proximal portion434of the syringe sleeve430. Because the proximal portion434of the syringe sleeve430may have a larger diameter (or maximum distance transverse to the longitudinal axis) than the distal portion432, as described above, the proximal lip452of the syringe body402may fit within the proximal portion434but may not fit within the distal portion432. In some variations, the injection device100may comprise a cushioning element (e.g., a rubber or elastomer overmold on the interlocker436or other rubber or elastomer element) with which the proximal lip452may come into contact when it reaches its fully proximal position. Additionally or alternatively, the injection device100may comprise a damping element, such as but not limited to a rubber or elastomer seal on the outside surface of the syringe body402. In some variations, the injection device100may comprise an insertion detent, which may cause the movement of the distal tip424of the needle406to occur at a specific rate, in order to achieve a desired insertion speed into tissue.

It should be noted that the syringe104may move distally with the ram502, rather than the ram502moving distally relative to the syringe104(e.g., due to the plunger510moving distally relative to and within the syringe cavity404) in response to application of distal force on the proximal housing108, due to the relative amounts of force required to move the syringe104relative to the syringe sleeve430and to move the ram502relative to the syringe104, as described above, and due to mechanisms that may resist distal motion of the ram502relative to the syringe104. More specifically, the amount of force required to overcome the first set of flexures428that may hold the syringe104in place relative to the interlocker436, as described above, may be less than the amount of force to overcome the rate control assembly604of the power assembly106(described below) and/or the locking portion of the indicator that resists distal motion of the plunger510within the syringe cavity404of the syringe104, as described in more detail below. If the distal force on the proximal housing108is released while the syringe104is moving from a retracted position to an extended position, the syringe104may stay in place relative to the syringe sleeve430.

In the variation shown inFIGS. 2A-2N, distal motion of the plunger510within the syringe cavity404may be resisted before the syringe104is in an extended configuration due to the locking portion of the indicator300, described above. Until the syringe104is in an extended configuration, a protrusion316on the inner edge of locking portion310may be mated with a recess330in the plunger510, as shown inFIGS. 2A, 2C, and 2E. Inward pressure on the outer tip of the locking portion310from the inner surface of the interlocker436may resist radially outward movement of the locking portion310out of the recess330, thus keeping the locking portion310and the plunger510mated. While mated, the indicator300, the plunger502, and the syringe104may be fixed relative to each other and may move distally together as the syringe104is moved toward an extended configuration. Once the syringe104is in an extended configuration, as shown inFIG. 2G, the locking portion310may align with the indicator recess328(described in more detail above). When distal force is applied to the plunger510via the proximal housing108, pressure on the inner edge of the locking portion310from the plunger510may push the locking portion310radially outward and into the indicator recess328. The locking portion310and the plunger510may thus no longer be mated, allowing the plunger510to move distally.

After the syringe104has moved distally relative to the syringe sleeve430such that the syringe104is in an extended position and the distal tip424of the needle406is at the desired depth, additional distal force on the proximal housing108may be transmitted into distal motion of the ram502relative to the syringe cavity404, if the force is above the necessary force threshold. When the force is above the necessary force threshold, the plunger510and seal410may be moved distally within the syringe cavity404, as shown inFIGS. 2I-2J, which may decrease the volume of the reservoir414and displace the contents of the reservoir414through the lumen408of the needle406, as described above. Distal force on the proximal housing108may continue to cause the contents of the reservoir414to be displaced through the lumen408of needle408until the seal410has traveled to the distal end462of the syringe cavity404(shown inFIGS. 2K-2L), at which time the full dosage of the therapeutic or diagnostic agent may have been injected into the patient. In some variations, the total displacement of the plunger510during distal motion of the ram502relative to the syringe cavity404may be about 20 mm to 25 mm, about 25 mm to 30 mm, about 30 mm to 35 mm, about 35 mm to 40 mm, about 40 mm to 45 mm, about 45 mm to 50 mm, about 50 mm to 55 mm, about 55 mm to 60 mm, about 60 mm to 65 mm, about 65 mm to 70 mm, or about 70 mm to 75 mm. In some variations, the threshold force required to move the plunger510and seal410distally within the syringe cavity404, once the locking portion310and the plunger510are no longer mated, may be due to the rate control assembly604of the power assembly106, as described below.

The power assembly may comprise a stored energy source and a rate control assembly. The stored energy source may be configured to provide force to displace the contents of reservoir of the syringe. In some variations, the stored energy source may be configured to do so by contributing to the distal motion of the plunger or seal within the syringe cavity. In some variations, the power assembly may allow a user (a patient or another person) to direct the injection process in an intuitive way by directing the injection by pressing the injection device against a patient's skin, but the power assembly may supply additional supplemental injection force, such that the user does not need to provide the full force needed to carry out the injection. In addition, the power assembly may in some variations assist with providing a desirable user experience. This may include smooth operation, particularly when transitioning between static, slow, and fast injection states. While in the injection device100the power assembly supplies an injection force supplemental to the user-supplied injection force, it should be appreciated that in other embodiments, the power assembly may supply the full injection force. It should also be appreciated that in some variations, injection device may not provide a supplemental injection force.

The injection force provided by the power assembly may thus be sufficient (alone or in addition to injection force supplied by the user) to inject a given volume of a given formulation through a given size needle in a given time. In some variations, for example, the power assembly may be capable of 2 mL of 19 cP solution in 10 seconds through a 27 gauge thin-wall needle 17 mm in length. In some variations, the power assembly may provide supplementary injection forces of up to about 5 N, about 10 N, about 15 N, about 20 N, about 25 N, about 30 N, about 35 N, about 40 N, about 45 N, about 50 N, about 55 N, about 60 N, about 65 N, about 70 N, about 75 N, about 80 N, about 85, or about 90 N at the beginning of the injection.

In some variations, it may be desirable for the power assembly to deliver a substantially constant force for the duration of the injection. In some variations, a substantially constant force for the duration of the injection may be achieved, for example, using a long spring with a low spring rate. In some of these variations, the spring fade may be about 5-10%, about 10-15%, about 15-20%, about 20-25%, about 25-30%, about 30-35%, or about 35-40% over the course of the injection. In other variations, a substantially constant force for the duration of the injection may be achieved, for example, with a spring having a shorter total length by mounting an extension spring to a compression spring (as described in more detail with respect to the embodiment of the injection device shown inFIG. 10). In other embodiments, a substantially constant force for the duration of the injection may be achieved, for example, with a pressure from a liquid propellant in a supercritical state (as described in more detail with respect to the embodiment of the injection device shown inFIG. 18). In some other variations, the power assembly may provide a varying force for the duration of the injection.

In some variations, the rate control assembly may comprise a braking assembly that may limit or restrict the stored energy source from contributing to the displacement of the contents of the reservoir of the syringe. In some variations, the rate control assembly may be configured to do so by limiting or restricting the distal movement of a plunger or seal within the syringe cavity.

FIG. 7depicts a perspective view of an example of the stored energy source602of the injection device100. The stored energy source602may comprise a compression spring606. The compression spring606may be directly or indirectly attached or in contact with a first surface fixed relative to the distal housing110on one end, and may be directly or indirectly attached or in contact with the a second surface fixed relative to the plunger510of the ram502on the other end. Thus, the force from the compression spring606on the first and second surfaces may bias the first and second surfaces away from each other, which may in turn bias the plunger601distally relative to the syringe cavity404. More specifically, the compression spring606may be sized to fit within the distal housing110and around the proximal portion434of the syringe sleeve430. The compression spring606may be housed by a spring sleeve610, but need not be. In variations having a spring sleeve610, the spring sleeve610may be substantially cylindrical and configured to fit around the compression spring606. The spring sleeve610may be moveable relative to the syringe sleeve430, and may have an inwardly extending distal lip612. The distal end616of the compression spring606may be attached or connected to the distal lip612. The proximal end614of the compression spring606may be attached or connected to an inwardly extending proximal lip454on the proximal portion432of the syringe sleeve430, which may in turn be fixed relative to the distal housing110, as described above.

The force from the compression spring606against the distal lip612of the spring sleeve610may be transmitted into distal motion of the ram502by a biter608, as shown inFIGS. 8A-8B. Alternatively, in some variations not having a syringe sleeve, the compression spring may press directly against the biter. As shown inFIGS. 8A-8B, the biter608may comprise a main body618. The main body618may be configured to fit within the distal housing110and may have a lumen626therethrough. The biter608may comprise one or more inner projections628extending inward into the lumen626, described in more detail below. In some variations, the biter608may comprise two attachment ports622, which may be configured to engage with the distal ends538of the straight portions520of the arms506of the ram502when the syringe104reaches an extended position, as shown inFIG. 2H. In some variations, the distal ends538of the ram502may engage with the attachment ports622by deflecting radially outward as the distal ends538come into contact with the attachment ports622as the ram502moves distally, and then snapping into place onto the attachment ports622. The engagement between the attachment ports622and the distal ends538is such that the biter608may rotate relative to ram502, as described in more detail below.

As shown inFIG. 7, the lumen626of the biter608may be configured to fit slidably around the distal portion432of the syringe sleeve430. While the lumen626is shown as having a substantially circular cross-section, it should be appreciated that the lumen626may have any suitable shape (e.g., having an elliptical cross-section, oblong cross-section, ovoid cross-section, square cross-section, rectangular cross-section, triangular cross-section, etc.), depending in part on the cross-section of the syringe104and/or syringe sleeve430. As shown inFIG. 7, the distal lip612of the spring sleeve610may press distally against the proximal projection620of the biter608. The compression spring606may therefore bias the biter608distally away from the proximal end614of the spring sleeve610. This may in turn bias the arms506of the ram502distally away from the proximal end614of the spring sleeve610, which may bias the plunger510of the ram502distally relative to the syringe sleeve430and within the syringe cavity404.

The compression spring606may be made of any suitable material, such as but not limited to music wire, stainless steel, and spring steel. The spring rate of the compression spring606may be chosen to deliver an appropriate force based on the formulation viscosity, needle choice, volume, and desired injection time, as described above. In some variations, for example, the compression spring606may be configured to deliver a force of up to about 5 N, about 10 N, about 15 N, about 20 N, about 25 N, about 30 N, about 35 N, about 40 N, about 45 N, about 50 N, about 55 N, about 60 N, about 65 N, about 70 N, about 75 N, about 80 N, about 85, or about 90 N when the compression spring606initially begins to expand.FIG. 21show an illustrative graph of the user force required to perform an injection using an injection device having a power assembly similar to the power assembly106of the injection device100, illustrating the initial actuation force and relatively stable spring fade. The graph represents a liquid having a viscosity of approximately 9 cP injected through a 27 gauge, thin-wall needle, with the seal displacing the contents of the reservoir at approximately 6 mm/s, which generally requires approximately 15 N of force. However, as seen in the graph, approximately 4 to 6 N of user force was required, thus representing a load multiplication factor around 3. It should be noted that this graph is merely illustrative of the force requirements for a similar device, and is not meant to indicate that the injection device100may or must conform to this representation.

As described above, the rate control assembly of the power assembly may at times comprise a braking assembly that may slow, limit, or restrict the stored energy source from providing force to displace the contents of the reservoir of the syringe. In some variations, the rate control assembly may be moveable between a closed configuration and an open configuration. When the rate control assembly is in a closed configuration, the rate control assembly may stop or reduce the displacement of the contents of the reservoir of the syringe. When the rate control assembly is in an open configuration, the rate control assembly may not limit or restrict the displacement of the contents of the reservoir of the syringe. In some variations, the rate control assembly may be configured to limit or restrict the displacement of the contents of the reservoir of the syringe by limiting or restricting the distal motion of a plunger within the syringe cavity when in a closed configuration. When in an open configuration, the rate control assembly may not limit or restrict the distal motion of a plunger within the syringe cavity, thus allowing the stored energy source to act upon the plunger to move it distally relative to and within the syringe cavity, which may move the seal of the syringe distally within the syringe cavity to displace the contents of the reservoir through the lumen of the needle.

The rate control assembly may be a braking assembly. In some variations, force generated by the rate control assembly and/or another component of the injection device100may counteract or partially or fully oppose the force from the stored energy source. In some variations, the braking assembly may be friction-based. That is, when the rate control assembly is in a closed configuration, friction between the rate control assembly and another component of the injection device100may counteract or partially or fully oppose the force from the stored energy source. In some variations, the force when the rate control element is in a closed configuration (e.g., friction between the rate control assembly in a closed configuration and another component of the injection device100) may counteract or oppose the force from the stored energy source completely, resisting distal movement of the plunger510within the syringe cavity404of the syringe104. In other variations, the force (e.g., friction between the rate control assembly in a closed configuration and another component of the injection device) may partially counteract or oppose the force from the stored energy source, damping the distal movement of the plunger within the syringe cavity due to the stored energy source. In some variations, when the rate control assembly is in an open configuration, there may not be a force (e.g., friction between the rate control assembly and another component of the injection device100) opposing the stored energy source, which may allow the stored energy source to cause the plunger510to be moved distally within the syringe cavity404of the syringe104. In other variations, there may be a force (e.g., friction between the rate control assembly and another component of the injection device100) opposing the stored energy source, but the force may be less than is required to fully resist the stored energy source from acting on the plunger510.

As shown inFIG. 9, the rate control assembly604may comprise the biter608discussed above. The biter608may be reversibly and selectively moved between open and closed configurations. When the biter608is in a closed configuration, friction between the biter608and the syringe sleeve430may counteract or partially or fully oppose the distal force from the compression spring606. The friction may be due to contact between the inner projections628of the biter608and the syringe sleeve430. The inner projections628may be configured such that when the biter608is tipped such that the longitudinal axis630through the lumen626is displaced from the longitudinal axis144of the housing102(and thus displaced from the longitudinal axis470of the syringe sleeve430), the inner projections628come into contact with the syringe sleeve430with a force sufficient to create enough friction to counteract or partially or fully oppose the distal force from the compression spring606. WhileFIGS. 8A-8Bshow the biter608as comprising three inner projections628approximately equally spaced around the circumference of the lumen626, it should be appreciated that in other variations, the biter may comprise other numbers of inner projections and/or arrangements. For example, in some variations, the biter may comprise two or four inner projections equally spaced around the circumference of the lumen.

When the biter608is in an open configuration, the longitudinal axis630through the lumen626of the main body618of the biter608may be rotated from the open configuration toward a position parallel to the longitudinal axis144of the housing102(and thus toward a position parallel to the longitudinal axis470of the syringe sleeve430). While in some cases the biter608may rotate such that the longitudinal axis630may be parallel to the longitudinal axis144of the housing, the longitudinal axis630need not rotate so far as to be parallel to the longitudinal axis144in order to be in an open configuration. Once rotated into an open configuration, the inner projections628may not be in contact with the syringe sleeve430. Thus, there may not be friction between the biter608and the syringe sleeve430. In some variations, the biter608may also, but need not, have an intermediate configuration (not shown), wherein there is friction between the biter608and the syringe sleeve430, but the friction between the biter608and the syringe sleeve430may be less than the distal force from the compression spring606. It should be appreciated that some variations of the injection devices described here may not have a syringe sleeve, and in those variations, when the biter is in a closed configuration, there may be friction between the inner projections628and the outer surface512of the syringe body402. While the force in the embodiment shown inFIG. 9is due to friction, it should also be appreciated that in other variations the force may be due to another form of interaction between the braking assembly and another component of the injection device. For example, in some variations, a biter may comprise one or more features (e.g., ridges or teeth) that are configured to mechanically interact or interface with one or more features of a syringe sleeve (e.g., ridges or teeth), which may generate a force that may partially or fully oppose the force from the stored energy source.

In some variations, the rate control assembly604may be biased toward a closed configuration, such as by a distal force on the biter608that acts radially asymmetrically on the biter608. In the power assembly106, the biter608may be biased toward a closed configuration by the compression spring606. The force from the compression spring606biasing the distal lip612of the spring sleeve610away from the proximal lip454of the syringe sleeve430may cause the distal lip612of the spring sleeve610to push distally against the proximal projection620of the biter608, as described above. The proximal projection620of the biter608may extend around less than 180 degrees of the main body618of the biter608on a first side632, and therefore the distal force on the proximal projection620of the biter608from the distal lip612of the spring sleeve610may cause the biter608to tilt such that the first side632may move distally relative to the other second side634of the biter608. The longitudinal axis630through the lumen626of the biter608may thus be rotated relative to the longitudinal axis144of the housing102. This may cause the biter608to move into a closed configuration and the inner projections628of the biter608to contact the syringe sleeve430, as described above. It should be appreciated that while in the embodiment of the biter608shown inFIGS. 8A-8Bthe proximal projection620extends approximately 40 degrees around the main body618of the biter608and is approximately 8 mm in width, in other embodiments, the proximal projection620may extend less or more around the biter608(e.g., about 10 degrees, about 20 degrees, about 40 degrees, about 60 degrees, about 80 degrees).

The rate control assembly604may further have, in addition to open and closed configurations, an inactivated configuration (shown inFIG. 7). In the inactivated configuration, the biter608may be held by the interlocker436, such that it resists movement relative to the interlocker436. The interlocker436may comprise a biter interlock448, which may comprise a tab466that may extend inwardly from the distal end of the biter interlock448. The tab466may be configured to mate with a projection676of the biter608. When the tab466is mated with the projection676, the biter interlock448may resist motion of the biter608relative to the interlocker436. As shown inFIG. 8A, the projection676may comprise a U-shaped hook, through which the tab466may attach, as shown inFIG. 7. The tab466may resist distal motion of the projection676, and in turn of the biter608relative to the interlocker436. The rate control assembly604may be released from the inactivated configuration by distal movement of the syringe104. In the variation shown inFIG. 7, the biter608may be released from the interlocker436by the proximal lip452of the syringe body402. As the proximal lip452moves distally relative to the interlocker436as the syringe104moves toward an extended configuration, the proximal lip452may press against the tab466of the biter interlock448, pushing it radially outward. When the tab466is pushed radially outward, it may move outward through the opening in the U-shaped hook of projection676and may disengage from the projection676. The biter608may thus no longer be held in place by interlocker436. While the variation shown inFIG. 7comprises two biter interlocks448configured to mate with two projections676, it should be appreciated that in other variations, the interlocker436may comprise fewer (e.g., zero or one) or more (e.g., three, four, five, or more) biter interlocks and/or projections.

The biter608may be moved into an open configuration by rotating the biter608such that the longitudinal axis630through the lumen626of the main body618of the biter608is moved toward a position parallel to the longitudinal axis144of the housing102(and thus toward a position parallel to the longitudinal axis470of the syringe sleeve430). As described above, while in some cases the biter608may rotate such that the longitudinal axis630may be parallel to the longitudinal axis144of the housing, the longitudinal axis630need not rotate so far as to be parallel to the longitudinal axis144in order to be in an open configuration. In some variations, the biter608may be moved from a closed configuration to an open configuration by application of a distal force on second side634of the biter608. Such a distal force may counterbalance or partially or fully oppose the distal force on the proximal projection620of the biter608from the distal lip612of the spring sleeve610.FIG. 9shows one example of an actuation rod636that may apply this distal force. The actuation rod636may be selectively and reversibly moved between an advanced position, during which it may engage the biter608at a contact point642on the second side634to urge it toward an open configuration, and a withdrawn position, during which it may not engage the biter608, thus leaving the biter608in a closed configuration. The distal end644of the actuation rod636may be configured to engage the second side634of the biter608at the contact point642. In some variations, the contact point642may optionally comprise a concave region to assist in alignment of the actuation rod636and biter608. In some variations, the distal end644of the actuation rod636may optionally have one or more features to promote engagement with the contact point642of the biter608. When the actuation rod636presses on the biter608at the contact point642, the actuation rod636may tilt the biter608into an open configuration (described above). This may occur when the distal end644of the actuation rod636presses down on the contact point642with sufficient force to counteract or partially or fully oppose the force from the compression spring606on the proximal projection of the biter608.

When the syringe104is in an extended position (described above), the actuation rod636may be selectively and reversibly moved between advanced and withdrawn positions by applying distal force to the proximal housing108. When distal force is applied to the proximal housing108while the distal housing110is held in place (e.g., by pressing the distal end158of the nose116of the distal housing110against a patient's tissue) and the syringe104is in an extended position, the proximal housing108and the actuation rod636may be moved distally relative to the biter608. The force on the contact point642of the biter608from the distal end644of the actuation rod636may move the biter608into an open configuration as described above. When the biter608is in an open configuration, the distal force applied to the distal end of the housing and the distal force from the compression spring606may both act to urge the biter608distally. This in turn may urge the plunger510distally via the arms506of the ram502, which in turn may urge the seal410distally to displace the contents of the reservoir414through the lumen408of the needle406, as described above.

In some variations, the actuation rod636may be moveable between advanced and withdrawn positions relative to the biter608by distal force on the proximal housing108because the relative locations of the ram502and the actuation rod636may be variable. In some variations, the actuation rod636may comprise an elongate rod638having a proximal end640that is fixedly attached to the proximal housing108. While the actuation rod636is shown inFIG. 9as attaching to the inner surface186of end cap118of proximal housing108, it should be appreciated that in other variations the actuation rod636may be fixed to the proximal housing108at other locations and via other methods, or in other variations may be integral to the proximal housing108. In contrast, the ram502may have extended and retracted positions relative to the actuation rod636and/or to the proximal housing108. In one variation, the connector rod508of the ram may fit within a bore646in the actuation rod636, being slidable between an extended position and a retracted position within the bore646. In another variation (not shown), the proximal end of the ram may be slidable between an extended position and a retracted position within a receiving cup on the inside of the end cap. In some variations, the ram502may be biased toward an extended position relative to the proximal end of the proximal housing108. The biasing may be due to a compression spring526. More specifically, the compression spring526may fit slidably around the connector rod508of the ram502. The ram502may be biased toward an extended position relative to the actuation rod636by the compression spring526, which may fit slidably around the connector rod508between the plunger510and the actuation rod636. In other variations (not shown) in which the ram is connected to the end cap directly, the proximal end of the compression spring may be in contact with or attached to a portion of the end cap and the distal end of the compression spring may be in contact with a portion of the ram. Thus, the compression spring526may bias the ram502and the proximal housing108away from each other, thus biasing the ram502toward an extended position. It should be appreciated that the compression spring526may be at other locations in order to bias the ram502and the proximal housing108away from each other.

Thus, when the syringe104is in an extended position (described above), the actuation rod636may be selectively and reversibly moved between advanced and withdrawn positions by applying distal force to the proximal housing108, which may move the ram502from an extended to a retracted position relative to the actuation rod636.

If the distal force on the proximal housing108is released, the bias of the ram502toward an extended configuration relative to the actuation rod636due to the compression spring526may cause the proximal housing108and actuation rod636to move distally away from the ram502. However, the syringe104may stay in place relative to the syringe sleeve430, and the ram502may stay in place relative to the syringe104. As such, the actuation rod636may be moved from an advanced position to a withdrawn position, to move distally away from the biter608such that it no longer contacts the biter608at the contact point642. Removing the application of distal force at the contact point642may cause the biter608to return to a closed configuration, as described above. This may allow the user to selectively and reversibly start and stop, or increase or decrease the speed of, the injection process.

In some variations, but not wishing to be bound by such a theory, the amount of distal force that may be applied to the second side of the a biter having a similar design to the biter608, in order to move the biter from a closed configuration to an open configuration, may be mathematically described in a two-dimensional model as

U=S⁡(e+d2-b2⁢μ)d2+b2⁢μ+g
where U is the distal force applied, S is the force from the compression spring on the biter, μ is the coefficient of friction between the syringe sleeve and the biter, and e, g, d, t, and G represent the distances illustrated schematically inFIG. 24A. In a model having three points of contact between the biter and the syringe sleeve, the amount of distal force that may be applied to the second side of a biter to move it from a closed configuration to an open configuration may similarly be mathematically described as

U=S⁡(e+d1+cos⁢⁢θ-b(1+sec⁢θ)*μ)d-d1+cos⁢⁢θ+b(1+sec⁢⁢θ)*μ+g
where θ represents the angle of the points of contact, as illustrated schematically inFIG. 24B. It should of course be appreciated that these equations describe highly simplified models and may not represent the actual force required the move the biter608described here from a closed to an open configuration.

In some variations, the injection device100may comprise an autocomplete mechanism, which may cause the full volume of the reservoir414to be automatically displaced through the lumen408of the needle406within a certain tolerance of the total injection (e.g., within about 85% of the injection, within about 90% of the injection, within about 95% of the injection, or more, or within about 1 mm of full displacement, about 2 mm of full displacement, about 3 mm of full displacement, or about 4 mm of full displacement, etc.), regardless of a user's application of distal force to the proximal housing108. In some variations, autocompletion may be caused by the biter608and syringe sleeve430no longer generating a frictional force once the biter608moves to a particular distal point along the distal portion434of the syringe sleeve. For example, the distal portion434of the syringe sleeve430may comprise a region near its distal end having a smaller diameter (or maximum distance transverse to the longitudinal axis) smaller than the remainder of the distal portion434of the syringe sleeve430, such that when the biter608moves distally to reach this region, the biter608may no longer contact the syringe sleeve430. Thus, there may be no friction between the biter608and the syringe sleeve430, and thus no force opposing the distal force from the compression spring606. As a result, the dose may autocomplete. As another example, instead of the full diameter of the distal portion434being smaller in a region near its distal end, the distal portion434of the syringe sleeve430may comprise inward notches at the locations at which the biter608would contact the syringe sleeve430(e.g. at the locations of inner projections628), which may eliminate or reduce the friction between the biter680and syringe sleeve430to cause autocompletion.

In some variations, one or more of the elements of injection device100may optionally comprise clocking features to correctly orient the elements relative to each other. In some variations, elements of the injection device100may comprise longitudinal ribs and grooves (e.g., narrow grooves molded onto the interior of the proximal housing108and short mating ribs on the exterior of distal housing110) that may engage to provide alignment, and may also resist rotation of the elements relative to each other once engaged. In some variations, elements of the injection device100may comprise one or more (e.g., two, three, four, five, or more) teeth on a first element and a corresponding one or more (e.g., two, three, four, five, or more) slots in a second element, wherein the teeth and slots are configured to engage when the first and second slots are properly aligned.

Another embodiment of an injection device700is depicted inFIGS. 10, 11A-11B, and 12A-12F, comprising a housing702, a syringe704, and a power assembly706. The housing702may be similar to the housing102described above with respect to injection device100, and may have the same components, configurations, and functions. As shown inFIG. 10, however, the proximal housing708and distal housing710may have an elliptical cross-section, which may accommodate the power assembly706, described below. An elliptical shape may also have certain benefits, including having an ergonomic form, allowing the contents of the syringe to be easily viewed, and resisting rolling of the device when being handled or stored. In some variations, the minor axis of the cross-section of the housing702may be less than or equal to about 20 mm, about 25 mm, about 30 mm, about 35 mm, or about 40 mm. Additionally or alternatively, in some variations, the viewing region724may comprise an opening760in the distal housing110, which may have a rounded rectangular shape.

In some variations, the housing702may optionally further comprise a cap772, which may be similar to the cap148described above with respect to injection device100, and may have the same components and functions as described above.FIGS. 11A-11Bshow side views of the injection device700with a cap772attached and removed, respectively. The cap772may comprise a viewing region774, which may coincide with the viewing region724of the distal housing when the cap772is attached to the remainder of the housing702.

FIGS. 12A-12Fdepict longitudinal cross-sectional views of the injection device700in various stages during use.FIG. 12Adepicts the device before use.FIG. 12Bdepicts the device with the rigid needle shield and cap removed.FIG. 12Cdepicts the device with the syringe in an extended position.FIG. 12Ddepicts the device with the plunger moved to the distal position within the syringe cavity.FIG. 12Edepicts the device with the end-of-dose indicator in an activated configuration.FIG. 12Fdepicts the device with the needle shroud extended.FIGS. 13A-13Cshow longitudinal cross-sectional views of a distal portion of the injection device700, showing a needle shield assembly. Like the injection device100, the injection device700may comprise a needle safety assembly800that may be movable between a retracted position (shown inFIGS. 13A-13B) and an extended position (shown inFIGS. 13C-13D), as described in detail above with regard to needle safety assembly200. As shown inFIGS. 13A-13Dthe needle safety assembly800may comprise an extendable needle shroud802, a biasing element818, and a locking assembly826, having the same components, positions, and functions as described above with respect to needle safety assembly800. However, with regard to the biasing element, the biasing element818may comprise a compression spring820, which may have a cylindrical shape and may fit within the lumen808of the needle shroud802. The proximal end822of the compression spring820may contact a ledge776extending radially outward from the inner sheath762of the nose716, and the distal end824of the compression spring820may contact a lip816extending radially inward from the needle shroud802. While the lip816is shown as located at the distal end812of needle shroud802inFIGS. 13A-13D, it should be appreciated that in other variations a lip may extend from a location proximal to the distal end812of the needle shroud802. In some variations, the proximal end822of the compression spring820may be fixedly attached to the inner sheath762of nose716, but it need not be (e.g., the compression spring may rest against the nose716but may be unattached). It should also be appreciated that in other variations, the proximal end822of the compression spring820may contact or be fixedly attached a portion of the distal housing710.

In some variations, locking assembly826of the needle safety assembly800of injection device700may, like the locking assembly226of injection device100, hold the needle shroud802in a retracted position and/or in an extended position. In some variations, the locking assembly826may comprise one or more latches828, which may have the same components, positions, and functions as described above with respect to the injection device100. However, in some variations, the latches828may be configured to mate with a portion of the nose716, such that when mated, the latches828resist motion of the needle shroud802relative to the distal housing710. As shown inFIGS. 13A-13D, the nose716may comprise an inner sheath762comprising four proximal slots764. The four proximal slots764may be located on the inner sheath762such that when the tabs834of the latches828are mated with the proximal slots764, the needle shroud802may be located in a retracted position. When the tabs834are mated with the proximal slots764, the elongate portion830of the latches828may be flush against the outer surface958of the syringe sleeve930(described below), while the tabs834of the latches828may be inserted radially into the proximal slots764. The locking assembly826may resist distal motion due to a biasing force from the biasing element818because of the proximally oriented force applied to the distal surface of the tabs834by the distal surface of the proximal slots764.

The locking assembly826may be configured such that the needle shroud802may be unlocked from a retracted position (e.g., the locking assembly826may no longer hold the needle shroud802in a retracted position) by distal motion of the syringe704. In some variations, the tabs834may be configured such that they can be released from the proximal slots764by distal movement of the syringe body902of the syringe704relative to the nose716. For example, in the variation shown inFIGS. 13A-13D, the tabs834may have a triangular, proximally tapering shape. Thus, as the syringe body902of the syringe704is moved distally relative to the nose716and within the inner sheath762, the distal end of the syringe body902may engage the inner surface of the tabs834protruding through the proximal slots764. As the syringe body902of the syringe704continues to slide distally along the inner surface of the inner sheath762of the nose716, the outer surface of the syringe body902gradually pushes the tabs834further radially out of the proximal slots764. Once the outer surface of the syringe body902has fully pushed the tabs834radially out of the proximal slots764, the tabs834may no longer be mated with the proximal slots764and may no longer resist distal motion of the needle shroud802relative to the distal housing710. Like the needle shroud202of the injection device100, when the needle shroud802of the injection device700is unlocked from a retracted position, it may move to an extended position if an appropriate force is applied, or such a force may be partially or fully counterbalanced by an opposing force, as described in detail above with regard to the needle shroud202. Likewise, the needle shroud802of the injection device700may be unlocked from a retracted position just before the distal tip924of the needle906of the syringe704extends from the distal end758of the nose716, as described in detail above with regard to the needle shroud202.

Similarly, the needle shroud802of the injection device700may additionally or alternatively be configured to be locked in an extended position once moved to an extended position, as described in detail with regard to the needle shroud202. However, in the variations shown inFIGS. 13A-13D, the inner sheath762of the nose716may comprise four distal slots770configured to mate with the tabs834of the latches828of the locking assembly826. As shown inFIGS. 13C-13D, the distal slots770may be located on the inner sheath762to coincide with the position of the tabs834when the needle shroud802is in an extended position. When the needle shroud802moves into an extended position, the tabs834on the latches828may mate with the distal slots770. When the tabs834on the latches828are mated with the distal slots770, the locking assembly826may resist motion of the needle shroud802relative to the nose716.

The housing702may also comprise an indicator that, like the indicators described with respect to the injection device100, may indicate the progress or completion of the injection, as described in detail above, and may have activated and inactivated configurations.FIGS. 14A-14Bare longitudinal cross-sectional views and elevational side views, respectively, of a proximal portion of the injection device700showing an end-of-dose indicator900having a different visual appearance associated with the activated and inactivated configurations in inactivated and activated configurations. In the variation shown inFIGS. 14A-14B, the indicator900may comprise the ram crossbar1112of the ram1102, described in greater detail below. The ram crossbar1112may be configured such that when the proximal surface1118of the ram crossbar1112is adjacent to the inner surface768of the end cap718of the proximal housing708, at least a portion of the ram crossbar1112may be seen from outside the end cap718. In some variations, at least a portion of the ram crossbar1112may have a color or pigment that may be capable of being more easily noticed, such as but not limited to red, yellow, orange, green, magenta, blue, and the like. In order for the ram crossbar1112to be seen through at least a portion of end cap718, in some variations, at least a portion of the end cap718may be translucent or transparent. In variations in which at least a portion of the end cap718is translucent, the level of translucency may be such that the coloring of the ram crossbar1112may be perceived through the end cap718when the ram crossbar1112is adjacent to the viewing portion.

The indicator900may further comprise a biasing element920, which may be configured to bias the indicator900toward an inactivated configuration. As shown inFIGS. 14A-14B, in some variations, the biasing element920may comprise a locking spring1246, described in greater detail later with respect to the power assembly706of injection device700. The proximal end1258of the locking spring1246may be attached or in contact with the inner surface768of the end cap718of the proximal housing708, while the distal end1256of the locking spring1246may be attached to or in contact with a portion of the ram1102, as described in greater detail later. The locking spring1246may thus bias the ram crossbar1112away from the inner surface768of the end cap718of the proximal housing708. The bias of the ram crossbar1112away from the inner surface768of the end cap718may be overcome by distal force on the proximal housing708at the completion of the full injection of the contents of the reservoir914, when the plunger1110has traveled the full length of the syringe cavity904, as described in more detail below.

The syringe704of the injection device700may be similar to the syringe104described above with respect to injection device100, and may have the same components, positions, and functions as described above. The injection device700may further comprise a syringe sleeve930.FIG. 15depicts a perspective view of a syringe704and syringe sleeve930of the injection device700. The syringe sleeve930may attach the syringe body902of the syringe704to the ram interlock1226(described in more detail below). The proximal lip952of the syringe body902may rest on the proximal lip954of the syringe sleeve930. The proximal lip954of the syringe sleeve930may comprise four latches964, which may be configured to attach to four corresponding recesses on the distal side of the ram interlock1226(described below). Thus, when the syringe sleeve930is attached to the ram interlock1226, the proximal lip952of the syringe body902may be fixed between the proximal lip954of the syringe sleeve930and the ram interlock1226, causing the syringe body902to resist distal motion relative to the syringe sleeve930. The syringe sleeve may comprise any suitable material or materials, but in some variations, the syringe sleeve930may comprise a plastic material.

FIGS. 16A-16Bdepict cut-away side elevational and longitudinal cross-sectional views, respectively, of the ram and power assembly of the injection device ofFIG. 10. As in the ram502described with respect to the injection device100, the ram1102may be directly or indirectly connected to the proximal housing708, such that movement of the proximal housing708can be transmitted to the ram1102. The ram1102may be configured to transmit distal force on the proximal housing708into different motions, depending on the stage of the injection process. In a first stage, distal force on the proximal housing708may be transmitted into distal motion of the syringe704and power assembly706relative to the distal housing710. In a second stage, distal force on the proximal housing708may be transmitted into displacement of the contents of the reservoir914of the syringe704(e.g., a formulation comprising a therapeutic agent) through the lumen908of the needle906.

In some variations, the ram1102may be configured such that these effects of distal force on the proximal housing708may occur in the order described above. That is, the ram1102may be configured such that distal force on the proximal housing708may be transmitted first into distal motion of the syringe704and power assembly706relative to the distal housing710, and then transmitted second into displacement of the contents of the reservoir914of the syringe704(e.g., a formulation comprising a therapeutic agent) through the lumen908of the needle906. This may be desirable, for example, because it may allow the syringe704to move distally such that the needle906may pierce a patient's tissue before the contents of the syringe cavity904are displaced through the lumen908of the needle906.

In some variations, the ordering of effects of distal force on the proximal housing708may be due to different amounts of force that are required for each motion. For example, the ram1102may transmit distal force on the proximal housing708into distal motion of the syringe704and power assembly706relative to the distal housing710when the force on the proximal housing708is above a first threshold (e.g., above about 1 N, above about 2 N, above about 3 N, above about 4 N, above about 5 N, above about 6 N, above about 7 N, or higher); and the ram1102may transmit distal force on the proximal housing708into displacement of the contents of the reservoir914of the syringe704through the lumen908of needle906when the force on the proximal housing708is above a higher second threshold (e.g., above about 1 N, above about 2 N, above about 4 N, above about 6 N, above about 8 N, above about 10 N, above about 12 N, above about 14 N, or higher). In some variations, the first threshold may be due to the proximal force from flanges on the base retainer cap1126(described below) resisting distal movement of ram interlock1226, to which the syringe704is attached, as described in detail below. The second threshold may be due to the force required to overcome a second set of flanges1296(described below) and to move the rate control assembly1204of the power assembly706to an open configuration, as described in detail below. There may also be an intermediate threshold that may need to be overcome in order for the needle906to be extended beyond the distal and758of the nose cone716. In some variations, this intermediate threshold may be due to two flexures on the ram interlock1226, which may interface with two recesses in the distal housing710. In should be appreciated that in some other variations, the ram1102may transmit distal force on the proximal housing708into different motion in different orders and by different mechanisms. For example, in some variations the effect of the distal force may be chosen by manual selection by the user. In should also be appreciated that the ram may transmit distal force on the proximal housing into fewer or more different motions.

The ram1102may comprise a central portion comprising a plunger1110and a ram crossbar1112at the proximal end1114of the plunger1110. The plunger1110may be configured to be slidable within the syringe cavity904. The distal end1116of the plunger1110may be configured to engage with the seal910of the syringe704. If the plunger1110is moved distally relative to and within the syringe cavity904, the plunger1110may push the seal910distally relative to and within the syringe cavity904. This movement of the seal910may decrease the volume of the reservoir914containing the formulation comprising a therapeutic or diagnostic agent. Thus, distal motion of the plunger1110, and in turn of the seal910, relative to and within the syringe cavity904may cause the contents of the reservoir914to be displaced through the lumen908of the needle906. The ram crossbar1112may be attached on its distal side to the proximal end1114of the plunger1110. The proximal surface1118of the ram crossbar1112may be configured to be able to sit adjacent to the inner surface768of the end cap718of the proximal housing708, so that the ram crossbar1112may serve as an indicator, as described above. The ram1102may comprise a bore hole1120extending through the ram crossbar1112and plunger1110, and may have a proximal opening1122at the proximal surface1118of the ram crossbar1112and a closed distal end1124near the distal end1116of the plunger1110. The bore hole1120may be configured to house at least a distal portion of a locking spring1246(described in more detail below). The proximal end1258of the locking spring1246may be attached or in contact with the inner surface768of the end cap718of the proximal housing708, while the distal end1256of the locking spring1246may be attached to or in contact with the distal end1124of the bore hole1120of the plunger1110. The locking spring1246may thus be configured to transmit motion of the proximal housing708to the ram1102, in addition to acting as part of the rate control assembly1204of the power assembly706, as described below. The plunger1110may further comprise two recesses1140at its distal end1116. These recesses1140may be configured to engage two flanges1296extending from a central lumen1228of a ram interlock1226(described in more detail below). The flanges1296may comprise inwardly facing proximal tabs1298, which may be configured to the engage the recesses1140, which may cause the plunger1110to resist distal movement relative to the ram interlock1226.

The injection device700may further comprise a base retainer cap1126. The distal side of the base retainer cap1126may be attached to the proximal side of the ram interlock1226(described below). As shown inFIGS. 16A-16Band in more detail inFIG. 16C, the base retainer cap1126may comprise two flanges1130, located on opposite sides of the main body1132of the base retainer cap1126. The flanges1130may extend proximally and outwardly from the main body1132, and may have proximal tabs1134. The proximal tabs1134may engage recesses780on the inner surface of the proximal housing708in order to resist proximal motion of the proximal housing708relative to the distal housing710after the injection device700has been assembled. The main body1132of the base retainer cap1126may further comprise a central lumen1136and two side lumens1138. The central lumen1136may be configured to allow the plunger1110of the ram1102to move therethrough. The central lumen1136may further comprise two recesses1142configured to allow the flanges1296of ram interlock1126to move therethrough (described below). The two side lumens1138may be configured to allow a portion of the power assembly706to move therethrough, as described below. The base retainer cap1126may comprise any suitable material or materials, but in some variations, the base retainer cap1126may comprise a plastic material.

The injection device700may further comprise a ram interlock1226. The ram interlock1226, shown in more detail inFIG. 16D, may comprise a central lumen1228, configured to allow the plunger1110of the ram1102to travel therethrough, and may comprise one side lumen1236on each of two opposite sides of the central lumen1228, each configured to allow one of the two composite springs1218to travel therethrough, as described in more detail below. The ram interlock1126may further comprise two flanges1296extending from the central lumen1228, which may comprise inwardly facing proximal tabs1298. In an initial configuration, the inwardly facing proximal tabs1298of the flanges1296of the ram interlock1126may be engaged with recesses1140of the plunger1110, as described above and shown inFIG. 16B, which may cause the plunger1110to resist distal movement relative to the ram interlock1226. The flanges1296may be resisted from flexing radially outward (such that the proximal tabs1298may disengage with recesses1140of the plunger1110, which would allow the plunger1110to move distally relative to the ram interlock1226) because in the initial configuration the distal face of the base retainer cap1126is seated against the proximal face of the ram interlock1226, such that the flanges1296of the ram interlock1226are located within recesses1142of the base retainer cap1126. The base retainer cap1126may thus exert radially inward pressure on the flanges1296to resist them moving radially outward. This may create hoop stress in the central lumen1228of the ram interlock1226.

Application of distal force on the proximal housing708may cause the proximal housing708to be moved distally. If the distal housing710is held in place (e.g. by pressing the distal end758of the nose716of the distal housing710against a patient's tissue), the proximal housing708may be moved distally relative to the distal housing710. The movement of the proximal housing708may be transferred via the locking spring1246to cause the power assembly706and syringe704to slide distally relative to the distal housing710if the distal force on the proximal housing708is above the necessary force threshold. More specifically, distal force on the proximal housing708may cause distal motion of the locking spring1246, and in turn, distal motion of the power assembly706. Distal motion of the power assembly706may in turn cause distal motion of the syringe704. This may move the syringe704from a retracted position (shown inFIGS. 12A-12B) into an extended position (shown inFIG. 12D-12F), as described above with respect to syringe104of injection device100. As the distal tip924of the needle906approaches the distal opening712of the nose716, the needle shroud802of the needle safety assembly800may be unlocked from a retracted position, as described in detail above and shown inFIGS. 13A-13D. As the distal tip924of the needle906moves to extend beyond the distal end758of the nose716, the needle906may pierce tissue pressed against the distal end758of the nose716. The syringe704may continue to move distally relative to the distal housing710until the syringe704has reached an extended position, at which point distal motion of the syringe704may be stopped by engagement of the syringe sleeve930with a portion of the nose716. At an extended position, the distal tip924of the needle906may have reached the desired depth, as described above. In some variations, the injection device700may comprise an insertion detent, which may cause the movement of the distal tip924of the needle906to occur at a specific rate during insertion, in order to achieve a desired insertion speed into tissue, as described above.

It should be noted that the power assembly706and syringe704may move distally together with distal force on the proximal housing708in a particular stage of the injection process, rather than the power assembly706acting on the syringe704(e.g., by moving the plunger1110distally within the syringe cavity904to act on the seal910and displace the contents of the reservoir914), due to the relative amounts of force required to move the power assembly706and the syringe704relative to the distal housing710, and to move the ram1102relative to the syringe704. That is, the amount of force required to move the syringe704to an extended position may be less than the amount of force required to cause distal motion of the ram1102relative to the syringe704. In some variations, the ram interlock1226and base retainer cap1126may prevent distal motion of the ram1102relative to the syringe704until the syringe704is in an extended position. The flanges1296of the ram interlock1226may be located within recesses1142of the base retainer cap1126, which may exert radially inward pressure on the flanges1296to resist them flexing radially outward to disengage with recesses1140of the plunger1110, as described above. As the syringe704moves toward an extended configuration, however, the proximal housing708, power assembly706, and ram interlock1226may move distally with the syringe704relative to the distal housing710, while the base retainer cap1126may remain fixed relative to the distal housing710. The flanges1296may be configured to have a length such that they may remain constrained by the base retainer cap1126until the syringe704has reached an extended position.

After the power assembly706and syringe704have moved distally relative to the distal housing710such that the syringe704is in an extended position and the distal tip924of the needle906is at the desired depth, and, correspondingly, the flanges1296of the ram interlock1226may be no longer constrained by the base retainer cap1126, additional distal force on the proximal housing708may be transmitted into distal motion of the ram1102relative to the syringe cavity904if the force is above the necessary force threshold. When the force is above the necessary force threshold, the plunger1110and seal910may be moved distally within the syringe cavity904, which may decrease the volume of the reservoir914and displace the contents of the reservoir914through the lumen908of the needle906, as described above with respect to syringe104of injection device100. Distal force on the proximal housing708may continue to cause the contents of the reservoir914to be displaced through the lumen908of the needle906until the seal910has traveled to the distal end918of the syringe cavity904(shown inFIGS. 12D-12E). In some variations, the threshold force required to move the plunger1110and seal910distally within the syringe cavity904may be due to the flanges1296of the ram interlock1226. As described above, the ram interlock1126may comprise two flanges1296extending from the central lumen1228, which may comprise inwardly facing proximal tabs1298. In an initial configuration, the inwardly facing proximal tabs1298of the flanges1296of the ram interlock1126may be engaged with recesses1140of the plunger1110, which may cause the plunger1110to resist distal movement relative to the ram interlock1226. When a threshold force is applied, however, the flanges1296may flex radially outward such that the proximal tabs1298may disengage with recesses1140of the plunger1110, and thus may allow the plunger1110to move distally relative to the ram interlock1226, subject to the rate control assembly of the power assembly706, described below. If the distal force on the proximal housing108is released while the power assembly706and syringe704are moving from a retracted position to an extended position, the power assembly706and syringe704may stay in place relative to the distal housing710.

As described above with respect to the power assembly106of injection device100, the power assembly may provide an injection force sufficient (alone or in addition to injection force supplied by the user) to inject a given volume of a given formulation through a given size needle in a given time, as described in detail with regard to power assembly106. Like the power assembly106, power assembly706may comprise a stored energy source and a rate control assembly. As in the power assembly106described with respect to injection device100, the power assembly706may comprise a stored energy source1202, which may be configured to provide force to displace the contents of reservoir914of the syringe704through the lumen908of the needle906, and a rate control assembly1204, which may comprise a braking assembly that may limit or restrict the stored energy source1202from contributing to the displacement of the contents of the reservoir914of the syringe704through the lumen908of the needle906. Returning toFIGS. 16A-16B, the stored energy source1202may comprise one or more springs to provide injection force. In the injection device700, the springs of the stored energy source1202may pull the ram1102distally in order to cause the contents of the reservoir914of the syringe704to be displaced through the lumen908of the needle906. In some variations, the springs may be composite springs in order to decrease the total length of the spring required to produce a desired force. Such a composite spring may comprise an extension spring located coaxially within a compression spring. It should be appreciated, however, that in other embodiments, the springs may not comprise composite springs, and may instead comprise, for example, a single extension spring or a single compression spring; further, in other embodiments, an injection device may comprise only one composite spring, or may comprise more than two composite springs, such as two, three, four, or more composite springs.

The two composite springs1218of the stored energy source1202may each have a compression spring1220located coaxially about an extension spring1206. It should be appreciated that in other variations, the extension spring1206may be located coaxially within the compression spring1220. In each of the two composite springs1218, the proximal end1222of the compression spring1220may be located distally to the proximal end1214of the extension spring1206, and the proximal end1222of the compression spring1220may be attached to the ram interlock1226. The proximal end1214of the extension spring1206may be attached to the ram crossbar1112. The distal end1224of the compression spring1220and the distal end1216of the extension spring1206may be connected to each other directly or indirectly at a composite spring interface1230. In some variations, the composite spring interface1230may comprise an intermediate component, such as but not limited to a plastic bushing, that may engage the distal end1224of the compression spring1220and the distal end1216of the extension spring1206. In other variations, the distal end1216of the extension spring1206may comprise a wireformed loop having a larger diameter than the compression spring1220, and the compression spring1220may be inserted into the distal end1216of the extension spring1206to engage the compression spring1220and the extension spring1206. In yet other variations, the extension spring1206and compression spring1220may be formed as an integrated wireform using a continuous wire.

The spring rates of the extension spring1206and compression springs1220may be chosen to deliver an appropriate force based on the formulation viscosity, needle choice, volume, and desired injection time, as described above. In some variations, for example, the spring may be configured to deliver a force of up to about 5 N, about 10 N, about 15 N, about 20 N, about 25 N, about 30 N, about 35 N, about 40 N, about 45 N, about 50 N, about 55 N, about 60 N, about 65 N, about 70 N, about 75 N, about 80 N, about 85, or about 90 N when the composite spring1218is initially released. In some variations, the composite springs1218and/or the extension springs1220may comprise music wire, but it should be appreciated that the springs may be made of any suitable material or materials.

In some variations, the composite springs1218may additionally comprise a composite spring sleeve1232, but need not. In variations having composite spring sleeves, the composite spring sleeves1232may comprise a cylindrical wall1234that may separate the extension spring1206and the compression spring1220. In some variations, the composite spring sleeves1232may assist in providing spring guidance. The composite spring sleeves1232may pass through the side lumens1236on each side of the central lumen1228of the ram interlock1226, and they may pass through the two side lumens1138of the base retainer cap1126. The distal end1240of the composite spring sleeve1232may serve as the composite spring interface1230, and as such, may have both the distal end1224of the compression spring1220and the distal end1216of the extension spring1206attached to it. In some variations, the ram interlock1226and/or spring sleeves1232may comprise a plastic material, but it should be appreciated that the ram interlock1226and/or spring sleeves1232may be made of any suitable material or materials.

The extension springs1206may bias the composite spring interfaces1230and the ram crossbar1112toward each other, while the compression spring1220may bias the ram interlock1226and the composite spring interfaces1230away from each other. The joint effect of the extension springs1206and compression springs1220of the composite springs1218may therefore be to bias the ram interlock1226and the ram crossbar1112toward each other. By biasing the ram interlock1226and the ram crossbar1112toward each other, the composite springs1218may thus bias the plunger1110distally through the central lumen1228of the ram interlock1226. The plunger1110may be configured to fit slidably within the syringe cavity904and to press against the seal910, which may in turn cause the contents of the reservoir914of the syringe704to be displaced through the lumen908of the needle906, as described in detail above with respect to syringe104of injection device100.

The distal movement of the plunger1110to press against the seal910of the syringe704, however, may at times be resisted or limited by the rate control assembly1204. As described above with respect to injection device100, the rate control assembly may be moveable between a closed configuration and an open configuration. When the rate control assembly is in a closed configuration, the rate control assembly may limit or restrict the displacement of the contents of the reservoir of the syringe. When the rate control assembly is in an open configuration, the rate control assembly may not limit or restrict the displacement of the contents of the reservoir of the syringe. In some variations, the rate control assembly may be configured to limit or restrict the displacement of the contents of the reservoir of the syringe by limiting or restricting the distal motion of a plunger within the syringe cavity when in a closed configuration. When in an open configuration, the rate control assembly may not limit or restrict the distal motion of a plunger within the syringe cavity, thus allowing the stored energy source to act upon the plunger to move it distally relative to and within the syringe cavity, which may move the seal of the syringe distally within the syringe cavity to displace the contents of the reservoir through the lumen of the needle.

As shown inFIG. 16A, the rate control assembly1204may comprise a cord tensioning system1242. The cord tensioning system1242may resist the effects of the stored energy source1202described above. The cord tensioning system1242may be reversibly and selectively moved between tensioned (the “closed” configuration of the rate control assembly) and released (the “open” configuration of the rate control assembly) configurations. Generally, the cord tensioning system1242may comprise a tensioning cord1244in addition to the locking spring1246and ram interlock1226mentioned above. When the cord tensioning system1242is in a tensioned configuration, the locking spring1246may generate a tensioning force on the tensioning cord1244of sufficient magnitude to be capable of resisting distal movement of the ram1102due to the stored energy source1202. Sufficient tensioning force in the tensioning cord1244may be achieved by wrapping the tensioning cord1244around a bollard1288. In some variations, the bollard1288may comprise a portion of the ram interlock1226, as will be described in more detail below. When the cord tensioning system1242is in a released configuration, the cord tensioning system1242may allow the distal force on the ram1102from the composite springs1218to urge the plunger1110of the ram1102distally, as will be described in more detail below. In some variations, the cord tensioning system1242may optionally further comprise a float1248, a locking spring retainer1250, and a locking spring cap1252, which will be explained in more detail below.

As shown inFIGS. 16A-16B, the locking spring1246may comprise a compression spring1254. As described above, at least a distal portion of the locking spring1246may be located within the bore hole1120of the plunger1110. The distal end1256of the locking spring1246may be attached to or in contact with the distal end1124of the bore hole1120of the plunger1110. Alternatively, in some variations, at least a distal portion of the locking spring1246may be housed in a locking spring retainer1250. The distal end of the locking spring retainer1250may be located proximally to the distal end1124of the bore hole1120, or in other variations, it may be attached to or in contact with the distal end1124of the bore hole1120. In some variations, the locking spring retainer1250may comprise a deep drawn metal. In some variations, the locking spring retainer1250may comprise a hole in its distal end, which may allow flow of a viscous damping fluid located in the bore hole1120, and as such, may dampen the motion of the locking spring retainer1250under the force of the locking spring1246. The proximal end1258of the locking spring1246may be attached or in contact with the inner surface768of the end cap718the proximal housing708. The locking spring1246may thus bias the plunger1110away from the end cap718of the proximal housing708. In some variations, the locking spring1246may have a spring rate of about 0.1 N/mm to 0.2 N/mm, 0.2 N/mm to 0.3 N/mm, 0.3 N/mm to 0.4 N/mm, 0.4 N/mm to 0.5 N/mm, 0.5 N/mm to 0.6 N/mm, 0.6 N/mm to 0.7 N/mm, 0.7 N/mm to 0.8 N/mm, 0.9 N/mm to 1 N/mm, or greater. In some variations, the proximal end1258of the locking spring1246may be housed in a locking spring cap1252. The locking spring cap1252may serve to hide the proximal end1258of the locking spring1246from view through the end cap718, for example in variations in which all or a portion of the end cap718is made of a clear or translucent material.

As shown inFIG. 17, the rate control assembly1204may further comprise a tensioning cord1244. The ends of the tensioning cord1244may be attached to a float1248that may be fixedly attached to the proximal housing708(not shown), while the middle of the tensioning cord1244may be wound around the ram interlock1226at two points and attached in between those two points to the distal end1116of the plunger1110. It should be appreciated that in some variations, the tensioning cord1244may be directly attached to the proximal housing708, instead of to a float. The locking spring1246, by biasing the plunger1110away from the end cap718of the proximal housing708(not shown), may generate tension in the tensioning cord1244, thus resisting distal movement of the plunger1110. More specifically, the float1248may be attached to the proximal housing708via latches that may snap into matching recesses in the proximal housing708. In some variations, the float1248may comprise a plastic material, though it should be appreciated that the float1248may comprise any suitable material or materials.

The first end1254of the tensioning cord1244may be attached to the float1248on a first side of the plunger1110. The first end1254of the tensioning cord1244may be attached in any suitable manner to the float1248. For example, in some variations, the first end1254of the tensioning cord1244may be attached to the float1248by being encapsulated into the plastic material, for example by being insert-molded into the float1248. In other variations, the first end1254of the tensioning cord1244may be fitted with a lug or ferrule, which may in turn be attached to a receiving socket in the float1248. A first portion1272of the tensioning cord1244may extend distally from the float1248toward the ram interlock1226. The ram interlock1226may comprise one or more bollards1288that may allow the tensioning cord1244to be wrapped around the ram interlock1226in a manner generating friction between the tensioning cord1244and ram interlock1226. In some variations, the ram interlock1226may comprise a first protrusion1264and a second protrusion1266located on opposite sides of the ram interlock1226. The tensioning cord1244may have a second portion1274that may wrap around a rounded side1290of the first protrusion1264. The tensioning cord1244may have a third portion1276that may travel from the first protrusions1264to the distal end1116of the plunger1110. The distal end1116of the plunger1110may comprise one or more features that may allow the tensioning cord1244to be attached to its distal end1116. In some variations, the distal end of the plunger1110may comprise a slot1756across the distal face1754of the plunger1110, through which a fourth portion1278of the tensioning cord1244may be placed. A fifth portion1280of the tensioning cord1244may exit the slot1756of the plunger1110and extend toward the second protrusion1266(not shown). A six portion1282of the tensioning cord1244may wrap around a rounded side1292of the second protrusion1266(not shown). While in the variation shown the first protrusion1264and second protrusion1266may comprise first and second horizontal cylindrical segments1268and1270(not shown), where the first and second horizontal cylindrical segments1268and1270may be oriented with their rounded sides facing distally, it should be appreciated that first and second protrusions1264and1266of the ram interlock1226may be shaped such that the protrusions are rounded at the points of contact with the tensioning cord1244, and therefore in some variations may comprise full cylindrical segments. Finally, the tensioning cord1244may have a seventh portion1284that may extend proximally from the ram interlock1226toward the float1248, where the second end1256of the tensioning cord1244may be attached to the float1248on the second side of the plunger1110(not shown). The second end1256may be attached to the float1248in any suitable manner, including in the manners described above with respect to first end1254. In other variations, the first end1254and second end1256may be connected (e.g., the tensioning cord1244may be a closed loop, or the first and second ends1254and1256may be spliced, knotted, or welded together), and the tensioning cord1244may extend around the float1248to secure it. In some of these variations, the tensioning cord1244may sit in a receiving groove in the float1248.

By wrapping the tensioning cord1244as described through the slot1756on the distal face1754of the plunger1110, the tension in the tensioning cord1244may resist distal movement of the plunger1110through the central lumen1228of the ram interlock1226due to the biasing force from the stored energy source1202. Due to friction between the tensioning cord1244and the first and second protrusions1264and1266of the ram interlock1226, the cord tensioning system1242may be able to resist higher forces from the stored energy source1202than may be provided by the locking spring1246. Under the principle of the capstan equation (also known as Eytelwein's formula), tension on a cord (e.g., the tensioning cord1244) may be different on either side of a static cylinder (e.g., first and second protrusions1264and1266of the ram interlock1226), such that a holding force on one side of the static cylinder (e.g., the tension supplied by the locking spring1246) may carry a larger loading force (e.g., the force supplied by the composite springs1218). The relationship between the holding force and the loading force is dictated by the coefficient of friction between the cord and the static cylinder, as well as the wrap angle—the angle around which the cord contacts the static cylinder. In the cord tensioning system1242, the tensioning cord1244and ram interlock1226may comprise any materials having suitable coefficients of friction, such as but not limited to a tensioning cord1244comprising aramid fibers and first and second protrusions1264and1266comprising polycarbonate. In some variations, the coefficient of friction between these two materials may be about 0.1 to 0.2, about 0.2 to 0.3, about 0.3 to 0.4, about 0.4 to 0.5, or greater. Additionally, it may be desirable for the tensioning cord1244to comprise a material having suitable ability to hold sustained loads, as well as resist creep and stretch, such as but not limited aramid fibers. The tensioning cord1244may be wrapped around the first and second protrusions1264and1266of the ram interlock1226for wrap angles sufficient to generate the desired relationship between the holding force and the loading force. In some variations, the wrap angle may be approximately 180 degrees. In other variations, the wrap angle may be over 360 degrees, for example 720 degrees; that is, the tensioning cord1244may be wrapped multiple times around the first and second protrusions1264and1266of the ram interlock1226.

The cord tensioning system1242may be biased toward the tensioned configuration, such that when no distal force is applied to the proximal housing708, the cord tensioning system1242may resist or limit the stored energy source1202from contributing to the displacement of the contents of the reservoir914of the syringe704through the lumen908of the needle906by applying a proximal force to the distal end1116of the plunger1110of the ram1102, as described above.

Although the cord tensioning system1242may be biased toward a tensioned configuration as described above, the cord tensioning system1242may be moved toward the released configuration by reducing or releasing the tension on first portion1272and seventh portion1284of the tensioning cord1244(described above). The tension on the first portion1272and seventh portion1280of the tensioning cord1244may be reduced or released by reducing the distance between the first and second ends1254and1256of the tensioning cord1244and the first and second protrusions1264and1266of the ram interlock1226. This distance may be reduced by applying distal force to the proximal housing708. When a distal force is applied to the proximal housing708while the distal housing710is held in place (e.g. by pressing the distal end758of the nose716of the distal housing710against a patient's tissue), the proximal housing708and the float1248may be moved distally relative to the first and second protrusions1264and1266of the ram interlock1226. When the tension on the first portion1272and seventh portion1284of the tensioning cord1244is reduced, the tension that can be held by the third portion1276and the fifth portion1280of the tensioning cord1244may be correspondingly reduced, based on the capstan equation described above. As a result, the distal force on the plunger1110of the ram1102due to the stored energy source1202may no longer be able to be partially or fully opposed by the tensioning cord1244running through the slot1756on the distal face1754of the plunger1110, and the tensioning cord1244may slip around the first and second protrusions1264and1266of the ram interlock1226, which may allow the plunger1110to move distally into the syringe cavity904, as described above and shown inFIG. 12E. This may in turn urge the seal910distally to displace the contents of the reservoir914through the lumen908of the needle906, as described above.

In some variations, the tensioning cord1244may begin to slip around the first and second protrusions1264and1266of the ram interlock1226, which may allow the plunger1110to move distally into the syringe cavity904, before the tension on the first portion1272and seventh portion1284of the tensioning cord1244is reduced to zero. In such a case, a portion of the force from the composite springs1218may urge the plunger1110to move distally within the syringe cavity904. If a user applies distal force to the proximal housing708sufficient to reduce the tension on the first portion1272and seventh portion1284of the tensioning cord1244to zero (e.g., by counterbalancing the full force from the locking spring1246), the full force from the composite springs1218may urge the plunger1110to move distally within the syringe cavity904. If a user applies distal force to the proximal housing708beyond the amount needed to reduce the tension on the first portion1272and seventh portion1284of the tensioning cord1244to zero, the additional distal force on the proximal housing708may be transferred into additional force urging the plunger1110to move distally within the syringe cavity904.

If the distal force on the proximal housing708is released, the bias of the proximal housing708away from the ram interlock1226due to the locking spring1246(described above) may cause the proximal housing708to move distally away from the ram interlock1226. The float1248may in turn move distally away from the ram interlock1226, which may restore tension in the first portion1272and seventh portion1284of the tensioning cord1244and return the cord tensioning system1242to a tensioned configuration. The rate control assembly1204may then resist motion due to the stored energy source1202. This may allow the user to selectively and reversibly start and stop, or increase or decrease the speed of, the injection process.FIG. 22shows an illustrative graph of the user force required to perform an injection using an injection device having a power assembly similar to the power assembly706of the injection device700, illustrating the initial actuation force and increasing actuation force throughout the stroke during the injection process. The graph represents the applied force required to maintain substantially constant distal motion of the housing708(and thus of the plunger1110) in order to maintain a substantially constant rate of injection. As shown, the composite spring may relax during the injection stroke, therefore exerting a decreasing force; thus, to maintain a substantially constant rate of injection, the applied force may need to increase with progress of the injection (and thus increase as a function of time, as shown). However, it should be noted that the user need not maintain a substantially constant rate of injection. As shown, an applied force of approximately 4 N is required in the given configuration to sufficiently relax the tensioning cords in order to allow the injection to begin, and subsequently a lesser force may be required to continue the injection, although the resulting injection rate may be slower. It should be noted that this graph is merely illustrative of the user force required for a similar device, and is not meant to indicate that the injection device700may or must conform to this representation.

In some variations, the injection device700may comprise an autocomplete mechanism, as described with respect to injection device100. In some variations, the autocomplete mechanism may be based on a relaxation of the locking spring1246. As described above, the locking spring1246may generate a tensioning force on the tensioning cord1244. When the tension is released, the seal910may be able to move distally to displace the contents of the reservoir914through the lumen908of the needle906. Thus, the injection may autocomplete by reducing the tensioning force on the tensioning cord1244due to the locking spring1246. In some variations, the tensioning force on the tensioning cord1244due to the locking spring1246may be reduced by increasing the distance between the proximal and distal ends of the locking spring1246. In some of these variations, this can be achieved by locating the locking spring retainer1250within the bore hole1120of the ram1102such that the distal end of the locking spring retainer1250is located proximally to the distal end1124of the bore hole1120before autocompletion. Because the distal portion of the locking spring1246may be housed in the locking spring retainer1250, the distal end of the locking spring1246may thus be located proximally to the distal end1124of the bore hole1120. When autocompletion is initiated, the locking spring retainer1250may move distally within the bore hole1120, which may in turn allow the distal end of the locking spring1246to move distally within the bore hole1120, relaxing the locking spring1246. In some variations, autocompletion may be initiated by the ram interlock1226. The locking spring retainer1250may be held at a position proximally to the distal end1124of the bore hole1120by two hooks (not shown) on the locking spring retainer1250that extend outwardly and into corresponding openings (not shown) in the ram1102. When the injection has proceeded such that the ram1102has moved distally such that the openings in the bore hole1120are aligned with the inwardly facing proximal tabs1298of the flanges1296of the ram interlock1226, the tabs1298may enter the openings in the ram1102and may apply an inward force that pushes the hooks on the locking spring retainer1250such that they disconnect from the openings in the ram1102. When the hooks disconnect from the openings, the locking spring retainer1250may move distally within the bore hole1120to the distal end1124of the bore hole, due to the biasing force from the locking spring1246. As described above, when the locking spring retainer1250moves distally, the distal end of the locking spring1246may also move distally, which may in turn relax the locking spring1246and may cause the injection to autocomplete.

In some variations, one or more of the elements of injection device700may optionally comprise clocking features to correcting orient the elements relative to each other, as described above with respect to injection device100. Additionally or alternatively, in variations in which the housing702has an elliptical cross-section, the elliptical cross-section may contribute to the correct orientation of the housing elements.

In some variations, it may be desirable to assemble portions of the injection device700in a particular order. For example, in some variations, a first portion of the injection device700may be assembly by attaching the tensioning cord1244may be attached at its first end1254and second end1256to the float1248. The tensioning cord1244may then be wrapped around the bollards1288of the ram interlock1226—more specifically, the second portion1274and sixth portion1282may be wrapped around the first protrusion1264and the second protrusion1266of the ram interlock1226, respectively. The base retainer cap1126may then be placed in line with the ram interlock1226. Then, the ram1102may be put into place such that the fourth portion1278of the cord is engaged with the slot1756on the distal face1754of the plunger1110, and the ram may be secured by lowering the base retainer cap1126onto the ram interlock1226. The composite springs1218may then be installed, which may be done by inserting each composite spring1218proximally through the side lumens1236of the ram interlock1226and side lumens1138of the base retainer cap1126and attaching the proximal end of the composite spring1218to the ram crossbar1112. A second portion of the injection device700may then be assembled by attaching the nose716to the remainder of the distal housing710, such as by sonic welding. The compression spring820of the needle safety assembly800may then be snapped into the nose716of the housing710, and the locking assembly826may be snapped into the nose716via the locking assembly826. A third portion of the injection device700may be assembled by placing the syringe sleeve930around a pre-filled syringe704. The third portion may then be attached to the first portion of the injection device700by attaching the syringe sleeve930to the ram interlock1226via the latches946on the proximal lip954of the syringe sleeve930. The attached first and third portions may then be inserted into the second portion of the injection device700(comprising the distal housing710). The locking spring retainer1250, locking spring1246, and locking spring cap1252may then be inserted into the bore hole1120of the ram1102. The proximal housing702may then be attached, which may be done by snapping together the float1248and the proximal housing708via the latches1260on the float1248. The rigid needle shield922and cap772, in variations having a cap772, may also be installed. It should be appreciated that this order of assembly is only illustrative, and that the elements of the injection device700may be assembled in other orders. It should also be appreciated that the assembly process may include additional elements not included in the description above, and that not all of the elements described as being assembled need be incorporated into the device.

Another embodiment of an injection device1300is depicted inFIGS. 18 and 19A-19D, comprising a housing1302, a syringe1304, and a power assembly1306. The housing1302may be similar to the housing102, described above with respect to injection device100, and may have the same components, configurations, and functions. In some variations, this may optionally comprise a cap1348, which may be similar to the cap148described above with respect to injection device100, and may have the same components and functions as described above.

FIGS. 19A-19Gillustrate longitudinal cross-sectional views of the embodiment of an injection device ofFIG. 17in various stages during use.FIG. 19Aillustrates the device before use.FIG. 19Billustrates the device with the rigid needle shield and cap removed.FIG. 19Cillustrates the device with the syringe in a partially extended position.FIG. 19Dillustrates the device with the syringe in a fully extended position.FIG. 19Eillustrates the device with the plunger moved partially toward the distal position within the syringe cavity.FIG. 19Fillustrates the device with the plunger in the distal position within the syringe cavity.FIG. 19Gillustrates the device with the needle shroud extended. Like the injection device100, the injection device1300may comprise a needle safety assembly1400that may be movable between a retracted position (shown inFIGS. 19A-19B) and an extended position (shown inFIGS. 19D-19G), as described in detail above with regard to needle safety assembly200. The needle safety assembly1400may have the same components, positions, and functions as the needle safety200described with respect to injection device100.

The housing1302may also comprise an indicator that, like the indicators described with respect to the injection device100, may indicate the progress or completion of the injection, as described in detail above, and may have activated and inactivated configurations. In some variations of the injection device1300, the end-of-dose indicator may comprise a flag. The flag may be spring-biased and may be released by relative motion between the flag and the housing1302. When the indicator is in an activated configuration, it may be visible through the end cap1318of the proximal housing1308.

The syringe1304of the injection device1300may be similar to the syringes104and704described above with respect to injection devices100and700, and may have the same components, positions, and functions as described above.

The injection device1300may further comprise a syringe sleeve1630. The syringe sleeve1630may be attached to the distal housing1310via a set of flexures and protrusions (not shown) that may hold the syringe sleeve1630relative to the ledge1356extending radially inward from the distal end1314of the distal housing1310. The syringe1304may be slidably disposed with the syringe sleeve1630. The syringe sleeve1630may comprise a distal portion1632and a proximal portion1634. The distal portion1632may be configured to fit slidably around the syringe body1602. The proximal portion1634may have a larger diameter (or maximum distance transverse to the longitudinal axis) than the distal portion1632. In some variations, the syringe sleeve may comprise a transparent or translucent material, such as a plastic. The proximal portion1634of the syringe sleeve1630may be configured to engage with a syringe cap1836(described below). The proximal portion1634of the syringe sleeve1630may comprise recess, slot, or other indentation configured to mate with tabs on the distal end of latches on the syringe cap1836, as described below.

As in the embodiments of the injection device100and700, the ram1702of the injection device1300may be configured to transmit distal force on the proximal housing1308into different motions, depending on the stage of the injection process. In a first stage, distal force on the proximal housing1308may be transmitted into distal motion of the syringe1304and power assembly1306relative to the distal housing1310. In a second stage, distal force on the proximal housing1308may be transmitted into displacement of the contents of the reservoir1614of the syringe1304(e.g., a formulation comprising a therapeutic agent) through the lumen1608of the needle1606.

In some variations, the ram1702may be configured such that these effects of distal force on the proximal housing1308may occur in the order described above. That is, the ram1702may be configured such that distal force on the proximal housing1308may be transmitted first into distal motion of the syringe1304and power assembly1306relative to the distal housing1310, and then transmitted second into displacement of the contents of the reservoir1614of the syringe1304(e.g., a formulation comprising a therapeutic agent) through the lumen1608of the needle1606. This may be desirable, for example, because it may allow the syringe1304to move distally such that the needle1606may pierce a patient's tissue before the contents of the syringe cavity1604of the syringe1304are displaced through the lumen1608of the needle1606.

In some variations, the ordering of effects of distal force on the proximal housing1308may be due to different amounts of force that are required for each motion. For example, the ram1702may transmit distal force on the proximal housing1308into distal motion of the syringe1304and power assembly1306relative to the distal housing1310when the force on the proximal housing1308is above a first threshold (e.g., above about 1 N, above about 2 N, above about 3 N, above about 4 N, above about 5 N, above about 6 N, above about 7 N, or higher); and the ram1702may transmit distal force on the proximal housing1308into displacement of the contents of the reservoir1614of the syringe1304through the needle1606when the force on the proximal housing1308is above a higher second threshold (e.g., above about 5 N, above about 10 N, above about 15 N, above about 20 N, above about 25 N, or higher). In some variations, the thresholds may be due to the proximal forces from friction on the syringe1304and ram1702, respectively. It should be appreciated that in some other variations, the ram1702may transmit distal force on the proximal housing1308into different motions in different orders and by different mechanisms. For example, in some variations the effect of the distal force may be chosen by a mechanism for manual selection by the user. In should also be appreciated that the ram1702may have fewer or more motions into which it may transmit distal force onto the proximal housing1308.

The ram1702may comprise a plunger1710. The plunger1710may be configured to be slidable through the lumen1842of the syringe cap1836(described below), and may be configured to be slidable within the syringe cavity1604of the syringe1304. The distal end1716of the plunger1710may be configured to engage with the seal1610of the syringe1304. If the plunger1710is moved distally relative to and within the syringe cavity1604, the plunger1710may push the seal1610distally relative to and within the syringe cavity1604. This movement of the seal1610may decrease the volume of the reservoir1614containing the formulation comprising a therapeutic or diagnostic agent. Thus, distal motion of the plunger1710, and in turn the seal1610, relative to and within the syringe cavity1604may cause the contents of the reservoir1614to be displaced through the lumen1608of the needle1606. The plunger1710may comprise an inner tube1742located coaxially within an outer tube1744. The inner tube1742and outer tube1744may form an inner lumen1746within the inner tube1742, and an outer annular lumen1748between the inner tube1742and outer tube1744. In some variations, the outer annular lumen may be divided into two or more (e.g., three, four, etc.) radial segments. The inner lumen1746and outer annular lumen1748may cooperate with the power assembly1306to direct pressure flow from the stored energy source1802, as described in detail below.

Application of distal force on the proximal housing1308may cause the proximal housing1308to be moved distally. If the distal housing1310is held in place (e.g. by pressing the distal end1358of the nose1316of the distal housing1310against a patient's tissue), the proximal housing1308may be moved distally relative to the distal housing1310. The movement of the proximal housing1308may be transferred via the power assembly1306(discussed in more detail below) to cause the power assembly1306and syringe1304to slide distally from a retracted position (shown inFIGS. 19A-19B) relative to the distal housing1310if the distal force on the proximal housing1308is above the necessary force threshold. The threshold force required may be due to the friction between the outer surface of the syringe body1602and the inner surface of the syringe sleeve1630. In some variations, the friction may additionally or alternatively be generated between the syringe body1602and the inner surface of the syringe sleeve1630by a seal attached to the inner surface of the syringe sleeve1630. When the threshold distal force is reached, the power assembly1306and syringe1304may be moved distally toward the nose1316of the distal housing1310, such that the syringe1304may move toward an extended position (described above with respect to syringe104of injection device100), as shown inFIG. 19C.

As the distal tip1624of the needle1606approaches the distal opening1312of the nose1316, the shield of the needle safety assembly1400may be unlocked from a retracted position, as described in detail above with respect to injection device100. As the distal tip1624of the needle1606moves to extend beyond the distal end1358of the nose1316, the needle1606may pierce tissue pressed against the distal end1358of the nose1316. The syringe1304may continue to move distally relative to the syringe sleeve1630until the syringe1304has reached an extended position, as shown inFIG. 19D. At an extended position, the distal tip1624of the needle1606may have reached the desired depth (described above). In some variations, when the syringe1304reaches an extended position, further distal movement relative to the distal housing1310may be resisted by a proximal lip1652extending radially outward from the proximal end1650of the syringe body1602, which may be configured such that it may fit within the proximal portion1634of the syringe sleeve1630but may not be able to enter the distal portion1632of the syringe sleeve1630. Once the syringe1304reaches an extended position, the canister manifold1866(described below) may also engage with the pressure chamber1824via flexures1868on the canister manifold1866.

It should be noted that the power assembly1306and syringe1304may move distally together with distal force on the proximal housing1308, rather than the power assembly1306acting on the syringe1304(e.g., to cause the plunger1710to move distally within the syringe cavity1604to act on the seal1610and displace the contents of the reservoir1614), due to the relative amounts of force required to move the power assembly1306and syringe1304relative to the distal housing1310, and to cause the plunger1710to move distally within the syringe cavity1604. More specifically, the amount of force required to overcome the friction between the outer surface of the syringe body1602of the syringe1304and the inner surface of the syringe sleeve1630may be less than the amount of force to cause the plunger1710to move distally within the syringe cavity1604, described in detail below.

If the distal force on the proximal housing1308is released while the power assembly1306and syringe1304are moving from a retracted position to an extended position, the power assembly1306and syringe1304may stay in place in an intermediate position relative to the syringe sleeve1630.

After the power assembly1306and syringe1304have moved distally relative to the distal housing1310such that the syringe1304is in an extended position and the distal tip1624of the needle1606is at the desired depth, additional distal force on the proximal housing1308may be transmitted into distal motion of the ram1702relative to the syringe cavity1604, if the force is above the necessary force threshold. When the force is above the necessary force threshold, the plunger1710and seal1610may begin to be moved distally relative to and within the syringe cavity1604, as shown inFIG. 19E, which may decrease the volume of the reservoir1614and displace the contents of the syringe cavity1604through the lumen1608of the needle1606, as described above with respect to injection device100. The threshold force required to move the plunger1710and seal1610distally within the syringe cavity1604may be due, first, to a ridge1670extending radially inward from the inner surface1612of the syringe cavity1604. Before the seal1610has been moved within the syringe cavity1604, the ridge1670may be located distally to the seal1610. When sufficient distal force is applied to the proximal housing1308to deflect the seal1610distally over the ridge1670, the seal1610is then able to move further distally within the syringe cavity1604, if the force is sufficient to overcome friction between the seal1610and plunger1710and the inner surface1612of the syringe body1602, as well as between the plunger1710and the syringe cap1836. Additional force to move the plunger1710and seal1610distally relative to and within the syringe cavity1604may also be due to the power assembly1306, described below.

As described above with respect to the power assembly106of injection device100, the power assembly may provide an injection force sufficient (alone or in addition to injection force supplied by the user) to inject a given volume of a given formulation through a given size needle in a given time, as described in detail with regard to power assembly106. Like the power assembly106, power assembly1306may comprise a stored energy source and a rate control assembly. As in the power assembly106described with respect to injection device100, the power assembly1306may comprise a stored energy source1802, which may be configured to provide force to displace of the contents of reservoir1614of the syringe1304through the lumen1608of the needle1606, and a rate control assembly1804, which may comprise a braking assembly that may limit or restrict the stored energy source1802from contributing to the displacement of the contents of the reservoir1614of the syringe1304through the lumen1608of the needle1606. In the embodiment of the injection device1300shown, the stored energy force1802may comprise a compressed gas or liquid propellant in a supercritical state. The compressed gas or liquid propellant may be held within container, such as a canister1806(e.g., a double-crimped metal canister), which may be located at the proximal end1320of the proximal housing1308. The canister1806may be fixedly attached to the end cap1318of the proximal housing1308, such that distal motion of the proximal housing1308may cause distal motion of the canister1806. In some variations, the canister1806may be attached to the end cap1318of the proximal housing1308by a set of flexures extending distally from the inside of the end cap1318that may snap over the canister1806to retain it.

The compressed gas or liquid propellant may comprise any gas that is suitable for compression. In some variations, the compressed gas or liquid propellant may comprise a gas that is in a gaseous state at high pressures (e.g., N2, Ar, or compressed air). In these variations, when the compressed gas is released from the canister1806, the output pressure may decrease as the compressed gas leaves the canister1806. In other variations, the liquid propellant may comprise a gas that is a saturated liquid at high pressures (e.g., CO2 and R134A (also known as HF134A or HFC-R134a)). In these variations, when the liquid propellant is released from the canister1806, the output pressure may be constant, as long as some propellant in liquid form remains in the canister1806. The compressed gas or liquid propellant may have any suitable saturation pressure.

When the compressed gas or liquid propellant in a supercritical state is released from the canister1806through a valve1808(described below), it may cause the seal1610of the syringe1304to move distally relative to and within the syringe cavity1604, which may cause the contents of the reservoir1614to be displaced through the needle1606of the syringe1304. In some variations, the force from the compressed gas or liquid propellant may act directly on all or a portion of the proximal side of the seal. In other variations, the force from the compressed gas or liquid propellant may act indirectly on the seal; that is, the force may act on a surface other than the seal, which may in turn cause distal movement of the seal. In yet other variations, the force from the compressed gas or liquid propellant may act both directly and indirectly on the seal. In each of these variations, the force from the compressed gas or liquid propellant may act on surface areas (i.e., the surface area orthogonal to the longitudinal axis) of varying sizes. In some variations, the force may act on a surface having a cross-sectional surface area approximately equal to the cross-sectional surface area of the syringe cavity, for example, by acting directly on the seal. In other variations, the force may act on a surface area smaller than the cross-sectional area of the syringe cavity, for example by acting on a portion of the seal or on an annular surface area radially outside the syringe cavity having a smaller cross-sectional surface area than the syringe cavity. In yet other variations, the force from the compressed gas or liquid propellant may act on a surface area larger than the cross-sectional surface area of the syringe cavity, for example by acting on the seal and on an annular surface area radially outside of the syringe cavity, or by acting on an annular surface area radially outside of the syringe cavity having a larger cross-sectional surface area than the syringe cavity. One portion (e.g., a proximal portion) of the flow path may have the same or different cross-sectional (i.e., orthogonal to the longitudinal axis) profile as a second portion (e.g., a distal portion) of the flow path. In some variations, the flow path of the compressed gas or liquid propellant may be linear, while in other variations, the flow path may be non-linear. For example, there may be no linear flow path between two locations in the flow path of the compressed gas or liquid propellant (e.g., the proximal-most and distal-most locations), or the flow path of the compressed gas or liquid propellant may have two or more segments not parallel to each other.

In variations in which the force may act on a larger surface area, this may allow the compressed gas or liquid propellant to generate more pressure to cause the seal to move distally. The saturation pressure of the compressed gas or liquid propellant, and the cross-sectional surface area of the upon which the pressure may act, may thus be chosen in tandem to delivery an appropriate force based on the formulation viscosity, needle choice, injection volume, and desired injection time. In some variations, for example, the power assembly may be capable of injecting 1.9 mL of 39 cP solution through a 27 gauge needle in 10 seconds by applying about 52-54 N of force. For example, in some variations, the injection device1300may use a liquid propellant with a saturation pressure of about 850 PSIa (e.g., CO2) acting on a cross-sectional surface area of about 0.014 square inches, which may supply about 52 N of force. In other variations, the injection device1300may use a liquid propellant with a saturation pressure of about 85 PSIa (e.g., R134A) acting on a cross-sectional surface area of about 0.138 square inches. In other variations, the injection device1300may use a compressed gas with a typical pressure of about 2700 PSIa (e.g., N2) acting on a cross-sectional surface area of about 0.0043 square inches. In other variations, the injection device1300may use a compressed gas with a typical pressure of about 1750 PSIa (e.g., Ar) acting on a cross-sectional surface area of about 0.0067 square inches. It should be appreciated that these pressures, surface areas, and forces are merely illustrative examples; any suitable combination may be chosen to achieve a desired injection force.

As shown inFIGS. 19A-19Gand illustrated with arrows inFIG. 20A, the stored energy source1802may comprise a flow-directing assembly for directing the compressed gas or liquid propellant when released. The flow-directing assembly may direct the compressed gas or liquid propellant distally through the inner lumen1746of the plunger1710, radially outward through redirection openings, and into a pressurization region1812formed distally to a syringe cap1836. More specifically, as described above, the plunger of the ram1702may comprise an inner tube1742located coaxially within an outer tube1744. The inner tube1772and outer tube1744may form an inner lumen1746within the inner tube1772, and an outer annular lumen1748between the inner tube1772and outer tube1744. The proximal opening1750of the inner lumen1746may be connected to the proximal opening1814of the valve1808. The distal opening1752of the inner lumen1746may be in fluid communication with an inflow opening1818of a manifold1816. The inflow opening1818of the manifold1816may be in fluid communication with one or more outflow openings1820of the manifold1816. In some variations, the manifold1816may have four outflow openings1820connected to the inflow opening1818, and the outflow openings1820may be located away from the longitudinal axis of the manifold1816, such that the outflow openings1820are directed outside of the syringe body1602. The outflow openings1820of the manifold1816may be in fluid communication with the pressurization region1812.

As shown inFIG. 20Aand in more detail inFIG. 20B, the pressurization region1812may be formed within a pressure chamber1824, distally to a syringe cap1836and annularly to the syringe body1602. The pressure chamber1824may comprise a cylinder1826having a lumen1828between a proximal end1830and a distal end1832. The proximal end1830of the pressure chamber1824may be engaged with the canister manifold1866via flexures1868when the syringe1304is in an extended position, as described above. The distal end1832of the pressure chamber1824may form a seal1834around the proximal portion1634of the syringe sleeve1630, such that the proximal portion1634of the syringe sleeve1630may be located within the lumen1828of the pressure chamber1824. The syringe sleeve1630may be slidable within the seal1834. The syringe cap1836may comprise a main body1838, which may be slidably disposed within the pressure chamber1824. The syringe cap1836may create a seal1840with the inner surface of the cylinder1826of the pressure chamber1824sufficient to resist pressurized gas travelling across the seal1840between the syringe cap1836and the inner surface of the cylinder1826of the pressure chamber1824. The syringe cap1836may also have a lumen1842therethrough, which may be configured to allow the plunger1710of the ram1702to move therethrough. There may also be a seal1844between the surface of the syringe cap1836forming the lumen1842and the plunger1710sufficient to resist pressurized gas travelling across the seal1844between the syringe cap1836and the plunger1710. Extending distally from the main body1838of the syringe cap1836may be one or more latches1846. Each latch1846may comprise an elongate portion1848having a proximal portion attached to the main body1838of the syringe cap1836, and a tab1850located at the distal end of the elongate portion1848. The tab1850may be configured to fit into a recess, slot, or other indentation (e.g. recess1674) in the proximal portion1634of the syringe sleeve1630, described above. When the latches1846are engaged with the syringe sleeve1630, the position of the syringe cap1838may be fixed relative to the position of the syringe sleeve1630.

The seal1834between the pressure chamber1824and the proximal portion1634of the syringe sleeve1630, the seal1840between the syringe cap1836and the pressure chamber1824, and the seal1844between the syringe cap1836and the plunger1710may thus create a variable-volume pressurization region1812. The volume of the pressurization region1812may be at a minimum when the proximal portion1634of the syringe sleeve1630is adjacent to the distal end1832of the pressure chamber1824, as shown inFIG. 20A. As the compressed gas or liquid propellant flows into the pressurization region1812, the pressure from the compressed gas or liquid propellant may urge the distal end1832of the pressure chamber1824distally relative to the syringe sleeve1630, in order to increase the volume of the pressurization region1812. The volume of the pressurization region1812may be at a maximum when the pressure chamber1824has moved fully distally such that the distal end1832of the pressure chamber1824may be adjacent to the distal end1314of the distal housing1310, as shown inFIG. 19F.

As the pressure chamber1824is urged distally relative to the syringe sleeve1630, this may in turn urge the plunger1710distally relative to the syringe cavity1604. As the plunger1710slides distally relative to and within the syringe cavity1604, this may in turn push the seal1610distally relative to the syringe cavity1604, which may in turn decrease the volume of the reservoir1614of the syringe1304. This may cause the contents of the reservoir1614to be displaced through the lumen1608of the needle1606of the syringe1304, as described above.

As shown with arrows inFIG. 20C, the injection device1300may further comprise a venting pathway for gas at atmospheric pressure into the region1682of the syringe cavity1604proximal to the seal1610. This may limit the development of negative pressure in the region1682as the seal1610moves distally relative to and within the syringe cavity1604. Limiting the development of negative pressure in the region1682may be desirable to avoid an unpleasant force profile experience for the user as the injection proceeds, and/or may be desirable to limit the risk that any leakage from the pressurization region1812could cause direct pressurization of the seal1610, which in turn might increase the risk of leakage into the reservoir1614, in those variations of the device in which direct pressurization of the seal1610is not intended. In some variations, this venting pathway may be created by further venting openings in the manifold1816. The manifold1816may comprise one or more inflow venting openings1862in fluid communication with the region1682of the syringe cavity1604proximal to the seal1610, and one or more outflow venting openings1864in fluid communication with ambient pressure within the housing1302via the outer annular lumen1748of the plunger1710.

The distal movement of the plunger1710to press against the seal1610of the syringe1304, however, may at times be resisted or limited by the rate control assembly1804. In some variations, the rate control assembly1804may comprise a valve1808and canister manifold1866, as shown inFIGS. 19A-19G. When the valve1808is in a closed configuration, the valve1808may limit the ability of the compressed gas or liquid propellant to leave the canister1806, and thus the compressed gas or liquid propellant may not act upon the pressure chamber1824to move the pressure chamber1824distally, and therefore may not provide force causing distal movement of the plunger1710and seal1610within the syringe cavity1604of the syringe1304, as described above. When the valve1808is in an open configuration, the compressed gas or liquid propellant may be able to leave the canister1806and act upon the pressure chamber1824distally, and may therefore provide force to distally move the plunger1710and the seal1610within the syringe cavity1604to displace the contents of the reservoir1614through the lumen1608of the needle1606. In some variations, the valve1808may also have an intermediate configuration, wherein the valve1808partially restricts the flow of the compressed gas or liquid propellant, but need not have such an intermediate configuration. The canister manifold1866may create a seal between the valve1808and pressure chamber1824. The canister manifold1866may comprise any suitable material, such as but not limited to a compliant material such as plastic with an overmold of thermoplastic elastomer.

In some variations, the valve1808may be biased toward the closed configuration. The valve1808may be moved into an open configuration by applying distal force on the valve1808by the canister1806. This distal force may be applied by applying distal force to the proximal housing1308. When a distal force is applied to the proximal housing1308while the distal housing1310is held in place (e.g. by pressing the distal end1358of the nose1316of the distal housing1310against a patient's tissue), the proximal housing1308and the canister1806may be moved distally relative to the distal housing1310, as well as relative to the pressure chamber1824and canister manifold1866. This may cause the valve1808to press against the canister manifold1866, which may cause the valve1808to open. As a result, the valve1808may open, releasing the pressurized gas from the canister1806and through the valve1808, the canister manifold1866, the inner lumen1746of the plunger1710, and the manifold1816, and into the pressurization region1812, as described above. This may cause the volume of the pressurization region1812to increase, which may urge the plunger1710and seal1610distally into the syringe cavity1604of the syringe1304to displace the contents of the reservoir1614through the lumen1608of the needle1606, as described above.FIG. 23shows a graph of illustrative forces for an injection device having a power assembly similar to the power assembly1306of the injection device1300. The graph illustrates the amount of user force required to displace simulated liquids having a range of viscosities with and without a canister installed in the injection device, with the seal displacing the contents of the reservoir at a rate of approximately 6 mm/s. As can be seen, the force required with the canister installed is approximately the same for all three stimulated viscosities—about 15 to 18 N of force from the user, approximately the valve actuation force—whereas significantly higher forces are required when the canister is not installed. Thus, the graph indicates the forces that can be generated by the power assembly in order to achieve the required injection force. It should be noted that this graph is merely illustrative of the forces for a similar device, and is not meant to indicate that the injection device700may or must conform to this representation.

If the distal force on the proximal housing1308is released, the bias of the valve1808toward the closed configuration may cause the valve1808to close, stopping or reducing the inflow of pressurized gas into the pressurization region1812. When the inflow of pressurized gas into the pressurization region1812is stopped, the existing pressure in the pressurization region1812may cause the pressure chamber1824to continue to move distally relative to the syringe sleeve1630until the pressure in the pressurization region1812drops to the same level as ambient pressure. After this initial coasting period, the displacement of the contents of the reservoir1614through the needle1606may stop. This may allow the user to selectively and reversibly start and stop the injection process. In some variations, the power assembly1306may comprise a mechanism to stop the injection process without allow for a coasting period. In some such variations, such a mechanism may depressurize the pressurization region1812when distal force on the proximal housing1308is released. For example, the seal between the valve1808and the canister manifold1866may be configured to leak when the distal force on the proximal housing1308is released.

It should be appreciated that in some variations, the rate control assembly1804may comprise different type of valve or additional elements. For example, in variations of the injection device using a compressed gas or liquid propellant with high pressures, the valve may comprise a puncture mechanism and/or a pressure regulator, but need not. A puncture mechanism, such as but not limited to a spring-loaded pin with a grenade-pin type release mechanism, or a spring-loaded gas canister with a stationary pin, may release the higher pressure gas. A pressure regulator, such as but not limited to a diaphragm regulator using a spring to regulate force on a popper valve, may bring the gas down to a safe and usable pressure.

In some variations, the injection device1300may comprise an autocomplete mechanism. In some variations, the autocomplete mechanism may allow the valve1808to be locked in an open configuration. When the valve is locked in an open configuration, force from the compressed gas or liquid propellant may cause the seal to be moved distally until the injection is complete and the full contents of the reservoir have been displaced. In these variations, the injection device may further comprise a pressure relief port that may allow pressure to be released once the full contents of the reservoir have been displaced, to prevent pressure build-up after the completion of the injection.

In some variations, one or more of the elements of injection device1300may optionally comprise clocking features to correctly orient the elements relative to each other, as described above with respect to injection device100.

Another embodiment of an injection device2600is shown inFIGS. 26 and 27A-27H.FIG. 26is a perspective view of injection device2600, whileFIGS. 27A-27Hillustrate longitudinal cross-sectional views of the embodiment of an injection device2600ofFIG. 26in various stages during use. As shown there, the injection device2600may comprise a housing2602, a syringe2604, and a power assembly2606. The housing2602may be similar to the housing102, described above with respect to injection device100, and may have the same components, configurations, and functions. In some variations, this may optionally comprise a cap, which may be similar to the cap148described above with respect to injection device100, and may have the same components and functions as described above.

The syringe2604of the injection device2600may be similar to the syringe104described above with respect to injection devices100, and may have the same components, positions, and functions as described above.

In general, the injection device2600may initially be in a state having a needle safety assembly2622extending from the distal end of the housing2602, such that the syringe is fully contained within the housing2602and needle safety assembly2622, without any exposure of the needle2628of the syringe2604, as shown inFIG. 27A. In variations comprising a cap, the cap may be removed from the injection device2600before use. The distal end of the injection device2622may then be pressed against a patient's tissue. Proximal force from the patient's tissue (e.g., by the user (the patient or another person) holding the housing2602and pressing the injection device2600against the tissue) may overcome the needle safety assembly's bias toward an extended position, moving the needle safety assembly2622from an extended to a retracted position, as shown inFIG. 27B(partially retracted) andFIG. 27C(fully retracted). Retraction of the needle safety assembly2622may expose the needle2628of the syringe2604, allowing the needle2628to pierce the patient's tissue. Retraction of the needle safety assembly2622may release a locking mechanism comprising an interlock ring2634, which prevents distal motion of a plunger2614within the syringe2604before the needle safety assembly2622is retracted. Once the locking mechanism is released, as shown inFIG. 27C, a user's application of distal force on the proximal housing may cause the plunger2614to move distally to contact the seal2612of the syringe2604, as shown inFIG. 27D, and then may cause both the plunger2614and seal2612to move distally within the syringe cavity2616. This may in turn cause the contents of the reservoir2630of the syringe2604to be delivered to the patient via the needle2628. During the injection process, the injection force applied by the user may be amplified by a stored energy source, while still allowing the user to selectively start and stop the injection process at will. A power spring2652may be configured to press the plunger2614distally within the syringe cavity2616, but when no force is applied by the user, the power spring2652may be prevented from acting on the plunger2614by friction generated by braking pad(s)2658. When a user applies force to the injection device, the force may reduce or eliminate the friction generated by the braking pad(s)2658, thus allowing the power spring2652to act on the plunger. Once the plunger2614and seal2612have been depressed such that the full or nearly full dose has been delivered to the patient, the dose may autocomplete and/or an end-of-dose indicator may be activated.FIG. 27Fillustrates the device with the plunger2614and seal2612nearly in the final distal position within the syringe cavity, with the end-of-dose indicator2618in an activated configuration.FIG. 27Gillustrates the device with plunger2614and seal2612in the final distal position within the syringe cavity. After the dose is complete, if the injection device2600is removed from the patient, the needle safety assembly2622may return to the extended position as shown inFIG. 27H, where a locking ring2668may prevent the needle safety assembly2622from re-retracting.

Thus, as illustrated in the explanation above, depending on the stage of the injection process, distal force on the proximal housing2624may be transmitted into different motions. In a first stage, distal force on the proximal housing2624may be transmitted into distal motion of injection device2600relative to the needle safety assembly2622, if the needle shroud2620of the needle safety assembly2622is held in place (e.g., by pressing the distal end of the shroud2620against a patient's tissue). In a second stage, distal force on the proximal housing2624may be transmitted into displacement of the contents of the reservoir2630of the syringe2604(e.g., a formulation comprising a therapeutic agent) through the lumen of the needle2628.

In some variations, the ram2610may be configured such that these effects of distal force on the proximal housing2624may occur in the order described above. That is, the ram2610may be configured such that distal force on the proximal housing2624may be transmitted first into distal motion of injection device2600relative to the needle safety assembly2622, and then transmitted second into displacement of the contents of the reservoir2630of the syringe2604(e.g., a formulation comprising a therapeutic agent) through the lumen of the needle2628. This may be desirable, for example, because it may allow the syringe2604to move distally such that the needle2628may pierce a patient's tissue before the contents of the syringe cavity2616of the syringe2604are displaced through the lumen of the needle2628.

In some variations, the ordering of effects of distal force on the proximal housing2624may be due to different amounts of force that are required for each motion. For example, the ram2610may transmit distal force on the proximal housing2624into distal motion of the rest of the injection device2600relative to the needle safety assembly2622when the force on the proximal housing2624is above a first threshold (e.g., above about 1 N, above about 2 N, above about 3 N, above about 4 N, above about 5 N, above about 6 N, above about 7 N, or higher); and the ram2610may transmit distal force on the proximal housing2624into displacement of the contents of the reservoir2630of the syringe2604through the needle2628when the force on the proximal housing2624is above a higher second threshold (e.g., above about 5 N, above about 10 N, above about 15 N, above about 20 N, above about 25 N, or higher). It should be appreciated that in some other variations, the ram2610may transmit distal force on the proximal housing2624into different motions in different orders and by different mechanisms. For example, in some variations the effect of the distal force may be chosen by a mechanism for manual selection by the user. In should also be appreciated that the ram2610may have fewer or more motions into which it may transmit distal force onto the proximal housing2624.

As described briefly above, in some configurations application of distal force on the proximal housing2624may cause distal motion of injection device2600relative to the needle safety assembly2622. In an initial configuration before use, as shown inFIG. 27A, if the shroud2620of the needle safety assembly2622is held in place (e.g., by pressing the distal end of the shroud2620against a patient's tissue), the proximal housing2624, distal housing2632, power assembly2606(discussed in more detail below), and syringe2604may slide distally relative to the needle safety assembly2622. In effect, this may move the needle safety assembly2622from an extended position (as shown inFIG. 27A), through a partially retracted position (as shown inFIG. 27B), and finally to a fully retracted position (as shown inFIG. 27C), in which the distal end of the shroud2620is flush with the distal end of the distal housing2632. As the needle safety assembly2622retracts, the distal tip of the needle2628may move beyond the distal end of the shroud2620, and the needle2628may pierce tissue pressed against the distal end of the shroud2620. When the needle safety assembly2622is fully retracted, the distal tip of the needle2628may have reached the desired depth (described above), and further distal movement of the needle2628may be resisted by the distal end of the distal housing2632pressing against tissue.

The force required to cause retraction of the needle safety assembly2622may be determined by a biasing element that may bias the needle safety assembly2622toward the extended position. For example, as shown inFIGS. 27A-27H, the biasing element may comprise a compression spring2662. The compression spring2662may have a proximal end fixed relative to the housing2602and a distal end fixed relative to the needle safety assembly2622, therefore biasing the shroud2620distally relative to the housing2602. When the needle safety assembly2622is in an extended position, the compression spring2662may be in an extended position, as shown inFIG. 27A. As the needle safety assembly2622moves toward the fully retracted position, it may compress, as shown inFIGS. 27B-27C. The needle safety assembly2622may remain in the fully retracted position throughout the injection, as shown inFIGS. 27D-27G, until the proximal force on the shroud2620is removed (e.g., the distal end of the injection device2600is removed from a patient's tissue), as described in more detail below.

The beginning of the injection (e.g., via distal motion of a plunger2614within the syringe cavity2616) may be restricted by a locking mechanism before the needle safety assembly2622is fully retracted. In some variations, the locking mechanism may comprise an interlock ring2634. The ram housing2636may comprise one or more flexures2638configured to restrict movement of the ram2610distally relative to the syringe2604. As shown inFIG. 30, the plunger2614(described in more detail below) may comprise a notch2640at its distal end, which may extend circumferentially around the middle of a widened region2642at the distal end of the plunger2614. A wedge-shaped portion of the flexure(s)2638of the ram housing2636may fit into the notch2640in an initial locked state, as shown inFIG. 27A. When the wedge-shaped portions of the flexure(s)2638are engaged with the notch2640, they may restrict distal movement of the ram2610. In order for the ram2610to move distally, the flexure(s)2638may be flexed outward. Interlock ring2634may comprise a ring-like structure (shown isolated inFIG. 29B) shaped and sized to fit around the ram housing2636and within the proximal housing2624and/or distal housing2632. When the interlock ring2634is in its locked position (as shown inFIG. 27A), it may be located around the flexure(s)2638of the ram housing2636, which may in turn act as a hoop to restrict outward flexion of the flexure(s)2638. The flexure(s)2638may be allowed to flex outward by displacement of the interlock ring2634such that it is no longer located around the flexure2628, and thus no longer restraining it.FIG. 27Cshows such an unlocked configuration. As shown there, the flexure(s)2638may have room to flex outward when the interlock ring2634is in a proximal, unlocked position. While the embodiment of the injection device2600comprises three flexures2638, it should be appreciated that in other variations the injection device2600may comprise fewer (e.g., one or two) or more (e.g., four, five, six, or more) flexures.

The release of the locking mechanism may be tied to the retraction of the needle safety assembly2622. That is, the locking mechanism may restrict distal motion of the plunger2614(described in more detail below) until the needle safety assembly2622is fully retracted, and thus until the needle2628is at its desired depth. In some variations, retraction of the needle safety assembly2622may cause proximal displacement of the interlock ring2634. For example, the needle safety assembly2622may comprise a proximal portion configured to engage the interlock ring2634. In injection device2600, the proximal portion of the needle safety assembly2622may comprise one or more arms2644. When the arm(s)2644are in the proximal position (i.e., when the needle safety assembly2622is retracted), the arm2644may engage the interlock ring2634. InFIG. 27B, the proximal tip of arm2644can be seen about to engage the interlock ring2634. InFIG. 27C, the proximal tip of the arm2644has pressed against the distal side of the interlock ring2634, moving it proximally relative to the ram housing2636and into the unlocked configuration.

A perspective view of the needle safety assembly2622is shown inFIG. 29A. While shown as having three arms2644, it should be appreciated that the needle safety assembly2622may have fewer (e.g., zero, one, or two) arms, or more (e.g., four, fix, or six) arms.FIG. 28Ashows a cutaway perspective view of a distal end of the injection device2600, showing the needle safety assembly2622in a first configuration with the shroud2620in an initial extended position.FIG. 28Bshows the same view in a second configuration, with the shroud2620in a retracted position. As can be seen in these figures, as the shroud2620moves from the extended position to the retracted position, the needle safety assembly2622(including the arms2644) moves proximally relative to the distal housing2632, such that it may contact the interlock ring2634. A perspective view of an interlock ring2634is shown inFIG. 29B. As shown there, in some variations the interlock ring2634may comprise one or more protrusions2646on the distal surface (e.g., as shown there, three protrusions), which may correspond to the arms2644on the needle safety assembly2622and may be configured to be engaged by the arms2644.

After the needle safety assembly2622is retracted, and thus the interlock ring2634is displaced into an unlocked configuration, as shown inFIG. 27C, additional distal force on the proximal housing2624may be transmitted into the distal movement of the ram2610. The ram2610may comprise a rod2648and a plunger2614. The rod2648may be fixedly attached on its proximal end to the end cap2650of the proximal housing2624, and thus may transmit distal force on the proximal housing2624into distal force on the ram2610. The ram2610may further comprise a plunger2614. All or a proximal portion of the plunger2614may be hollow, and the distal end of the rod2648may extend through an open proximal end of the hollow plunger2614. The rod2648may be slidable within the proximal portion of the plunger2614within a limited range of motion. This range of motion may be defined by a variable gap between the end cap2650and the proximal end2676of the plunger2614, which may allow the rod2648(which is fixedly attached to the end cap2650) to slide distally within the plunger2614until the interior of the end cap2650(e.g., contacts a protruding tubular boss of the end cap) contacts the proximal end2676of the plunger2614. This range of motion may facilitate variable application of a braking force, as described in more detail below.

The plunger2614may be configured to be slidable within the syringe cavity2616of the syringe2604. The distal end of the plunger2614may be configured to engage with the seal2612of the syringe2604. Initially, distal force on the proximal housing2624may cause the ram2610to move distally, causing the flexure2638of the ram housing2636to be deflected radially outward, until the distal end of the plunger2614of the ram2610contacts the seal2612, as shown inFIG. 27D. In some variations, the initial distance between the distal end of the plunger2614and the seal may be between about 1 mm and about 10 mm. Once the distal end of the plunger2614has contacted the seal2612, additional distal force on the proximal housing2624may be transmitted distal movement of the plunger2614within the syringe cavity2616. If the plunger2614is moved distally relative to and within the syringe cavity2616, the plunger2614may push the seal2612distally relative to and within the syringe cavity2616. This movement of the seal2612may decrease the volume of the reservoir2630containing the formulation comprising a therapeutic or diagnostic agent. Thus, distal motion of the plunger2614, and in turn of the seal2612, relative to and within the syringe cavity2616may cause the contents of the reservoir2630to be displaced through the lumen of the needle2628. When the force is above a necessary force threshold, distal force on the proximal housing2624may continue to cause the contents of the reservoir2630to be displaced through the lumen of the needle2628until the seal2612has traveled to the distal end of the syringe cavity2616, at which time the full dosage of the therapeutic or diagnostic agent may have been injected into the patient, as described in more detail above with respect to injection device100.

In some variations, once the locking mechanism is unlocked (e.g., the interlock ring2634is displaced), the threshold force required to move the plunger2614and seal2612distally within the syringe cavity2616may be governed by the power assembly2606. As described above with respect to the injection device100, the power assembly2606may comprise a stored energy source and a rate control assembly. The stored energy source may be configured to provide force to displace the contents of the reservoir2630of the syringe2604by contributing to the distal motion of the plunger2614and seal2612within the syringe cavity2616. The rate control assembly may comprise a braking assembly that may limit or restrict the stored energy source from contributing to the displacement of the contents of the reservoir2630of the syringe2604.

In injection device2600, the stored energy source may comprise a power spring2652(e.g., a compression spring). The power spring2652may be directly or indirectly attached or in contact with a first surface fixed relative to the syringe2604on one end, and may be directly or indirectly attached or in contact with a second surface fixed relative to the plunger2614of the ram2610on the other end. Thus, the force from the power spring2652on the first and second surfaces may bias the first and second surfaces away from each other, which may in turn bias the plunger2614distally relative to the syringe cavity2616. In the variation shown inFIGS. 26 and 27A-27H, the power spring2652may be located within a ram housing2636and around the plunger2614of the ram2610. The ram housing2636may be located proximally to the syringe2604and fixed relative thereto. The power spring2652may be configured to fit within the syringe cavity2616when the power spring2652is in an extended configuration. A spring sleeve2654may be located between the power spring2652and the plunger2614of the ram2610. In the variation shown inFIGS. 27A-27H, the proximal end of the power spring2652may be attached or connected to a proximal lip2656of the ram housing2636, while the distal end of the power spring2652may be attached or connected to the proximal side of the widened distal portion2642of the plunger2614.

The power spring2652may be made of any suitable material, such as but not limited to music wire, stainless steel, and spring steel. The spring rate of the power spring2652may be chosen to deliver an appropriate force based on the formulation viscosity, needle choice, volume, and desired injection time, as described above. In some variations, for example, the power spring2652may be configured to deliver a force of up to about 5 N, about 10 N, about 15 N, about 20 N, about 25 N, about 30 N, about 35 N, about 40 N, about 45 N, about 50 N, about 55 N, about 60 N, about 65 N, about 70 N, about 75 N, about 80 N, about 85, or about 90 N when the power spring2652initially begins to expand.

As described above, the rate control assembly of the power assembly2606may slow, limit, or restrict the stored energy source from providing force to displace the contents of the reservoir2630of the syringe2604. In injection device2600, the rate control assembly may comprise a friction-based braking assembly. The rate control assembly may have a closed configuration where friction from the rate control assembly may counteract or partially or fully oppose the force from the stored energy source. The rate control assembly may also have an open configuration, where there is not a friction force opposing the stored energy source, or where the friction force opposes the stored energy force but is less than is required to fully resist the stored energy source from acting on the plunger2614.

In the variation ofFIG. 26, the braking assembly may comprise one or more braking pad(s)2658, which may be attached to the outer surface of the plunger2614. The portion of the plunger2614comprising the braking pad(s)2658may be hollow and flexible, such that the outward force from within the plunger2614may flex the braking pad(s)2658radially outward. For example, the braking pad(s)2658may be located on flexures2674of the plunger2614that are configured to be flexed radially outward. Flexures2674can be seen more clearly inFIG. 30, which shows a perspective view of the ram2610. The braking pad(s)2658may comprise any suitable material configured to form a high-friction interface with the spring sleeve2654. For example, the braking pad(s)2658may comprise an elastomer (e.g., rubber, thermoplastic elastomer), which may form a high friction interface with a metal spring sleeve. If outward force from within the plunger2614presses the braking pad(s)2658radially outward (e.g., by flexing the flexures2674outward) into the spring sleeve2654, friction between the braking pad(s)2658and spring sleeve2654may be created or increased. In some variations, the braking assembly may comprise two braking pads2658(e.g., located on two radially opposite flexures2674of the plunger2614). However, in other variations the braking assembly may comprise fewer (e.g., one) or more (e.g., three, four, five, six, or more) braking pads2658, although it should be appreciated that in some instances it may be desirable for the radial loads generated by the braking pads to be radially symmetric, such that unopposed radially loads are avoided.

As shown inFIGS. 27A-27H, in one variation the outward force on the braking pad(s)2658may be achieved by a wedge-shaped stopper2660. The stopper2660may be located at the distal end of the rod2648, which as described above may be located slidably within the hollow proximal portion of the plunger2614. The hollow proximal portion of the plunger2614may have a corresponding conical or wedge-shaped interior shape, located near or adjacent to the baking pad(s)2658. When the rate control assembly is in a closed configuration, the stopper2660may exert a proximal force relative to the plunger2614. This proximal force may press the stopper2660proximally against the corresponding wedge-shaped interior of the plunger2614, flexing the braking pad(s)2658outward. When the braking pad(s)2658are located adjacent to the spring sleeve2654, this may generate sufficient friction to oppose the stored energy source (i.e., the rate control assembly may be in a closed configuration). In contrast, when the stopper2660is not pressed proximally against the corresponding wedge-shaped interior of the plunger2614, and thus the braking pad(s)2658are not flexed outward, the friction between the braking pad(s)2658and the spring sleeve2654may be reduced or eliminated, such that the stored energy source (e.g., the power spring2652) may act on the plunger2614(i.e., the rate control assembly may be in an open configuration).

In some variations, the stopper2660may be proximally biased relative to the plunger2614, such that the stopper2660is biased toward a configuration in which it presses proximally against the interior surface of the plunger2614, such that the rate control assembly is in a closed configuration. This proximal bias may be generated by a biasing element configured to bias the end cap2650of the proximal housing2624and the plunger2614away from each other. As described above, the rod2648may be fixedly attached on its proximal end to the end cap2650of the proximal housing2624, while the distal end of the rod2648may extend through an open proximal end of the hollow plunger2614such that the rod2648is slidable within the plunger2614within a limited range of motion. As shown inFIGS. 27A-27H, in one variation the biasing element may comprise a compression spring2664having a proximal end fixed relative to the rod2648(e.g., attached to the interior surface of the end cap2650at a distal end) and a distal end fixed relative to the ram2610. When distal force is not being applied to the proximal housing2624, the stopper2660may thus be naturally biased proximally against the interior of the plunger2614, pressing the braking pad(s)2658outwards. In contrast, when sufficient distal force is applied to the proximal housing2624to overcome the biasing element, the stopper2660may not press against the interior of the plunger2614, and thus the braking pad(s)2658may not be pressed outwards, such that the rate control assembly is in an open configuration.

When the braking pad(s)2658are located adjacent to a surface with which they are configured to form a high-friction interface (e.g., the spring sleeve2654), outward flexion of the braking pad(s)2658toward the adjacent surface may generate friction. This friction may be sufficient to oppose the stored energy source (e.g., the power spring2652), such that the plunger2614and seal2612are not moved distally within the syringe cavity2616, and the injection does not proceed. In contrast, when the braking pad(s)2658are located adjacent to a surface with which they are configured to form a high-friction interface (e.g., the spring sleeve2654) but the braking pad(s)2658are not flexed outwards, there may be no friction force, or the friction force may be low enough, that the stored energy source (e.g., the power spring2652) can act on the plunger2614to move the plunger2614and seal2612distally within the syringe cavity2616, causing the injection to proceed.

In some variations, the friction force generated at the high-friction interface (e.g., between the braking pad(s)2658and the spring sleeve2654) may be at least 2 times the force generated by the biasing element (e.g., by compression spring2664). In some variations, the friction force generated at the high-friction interface may be at least 3 times the force generated by the biasing element. In some variations, the friction force generated at the high-friction interface may be at least 5 times the force generated by the biasing element. In some variations, the friction force generated at the high-friction interface may be at least 10 times the force generated by the biasing element. Accordingly, in these variations, the braking pad(s) may be able to resist motion of the plunger when the power spring is 2, 3, 5, or 10 times more powerful than the biasing element. For example, in one variation, the power spring2652may apply an initial force in a compressed configuration of approximately 15 N, while the biasing element may comprise a compression spring2664configured to apply a force of about 7 N-8 N.

As shown inFIGS. 27A-27C, before the plunger2614and seal2612have advanced within the syringe cavity2616, the braking pad(s)2658may be located proximal to the proximal end of the spring sleeve2654. In this position, the braking pad(s)2658may not be adjacent to another surface, and thus, may not generate any friction. As such, after the interlock ring2634is displaced to allow distal motion of the plunger2614, the power spring2652may initially act unopposed on the plunger2614, moving the plunger2614distally until the braking pad(s)2658enter the spring sleeve2654. In some variations, this may allow the initial space between the plunger2614and the seal2612to be quickly closed by distal motion of the plunger2614. It may also in some variations be desirable that the braking pad(s)2658not be located adjacent to the spring sleeve2654or another surface in an initial state, so as to avoid the braking pad(s) experiencing a compression-set. The braking pad(s)2658may thus enter the spring sleeve2654immediately after initiation of the injection.

Additional distal force applied to the proximal housing2624may cause the plunger2614and seal2612to advance distally within the syringe cavity2616, beginning to force the contents of the reservoir2630out through the lumen of the needle2628. As the plunger2614and seal2612move distally, as shown inFIG. 27E, the braking pad(s)2658may accordingly move distally relative to the spring sleeve2654. When no distal force is applied to the proximal housing2624(or when the distal force is below the threshold), the proximal bias on the stopper2660may be sufficient to oppose the power spring2652, causing the injection to stop. When instead sufficient distal force is applied to the proximal housing2624to overcome the proximal bias on the stopper2660, the rate control assembly may be in an open configuration (e.g., the braking pad(s)2658may not be pressed radially outward by the stopper2660), and the power spring2652may apply force to push the plunger2614and seal2612distally within the reservoir2630of the syringe2604. As shown inFIG. 27E, the power spring2652may press against the proximal side of the widened region2642at the distal end of the plunger2614. As the power spring2652expands during injection, the power spring2652may extend into the syringe cavity2616.

After the plunger2614and seal2612have begun to advance within the syringe cavity2616, the braking pad(s)2658may move distally to a position adjacent the interior surface of the spring sleeve2654, as shown inFIG. 27E. As such, the rate control assembly may be reversibly and selectively moved between open and closed configurations by application of distal force to the proximal housing2624. When distal force is applied to the proximal housing2624while the distal end of the injection device2600is held in place (e.g., by pressing the distal end of the injection device2600against a patient's tissue) the rate control assembly may be moved to an open configuration. More specifically, the distal force may overcome the bias of the compression spring2664. As a result, the rod2648and stopper2660may be moved distally relative to the plunger2614, which may in turn remove outward pressure on the braking pad(s)2658and reduced the friction between the braking pad(s)2658and the spring sleeve2654. This may in turn allow the power spring2652to act on the plunger2614to urge the seal2612distally to displace the contents of the reservoir2630through the lumen of the needle2628. If the distal force on the proximal housing2624is released, the bias of the rate control assembly toward a closed configuration may cause the injection to stop. When distal force is released, the biasing force on the ram2610and stopper2660may cause them to move proximally relative to the plunger2614, applying an outward force on the braking pad(s)2658. As a result, friction between the braking pad(s)2658and the spring sleeve2654may resist the force of the stored energy source.

It should be appreciated that in this configuration, the force applied to the proximal housing2624is also applied to the plunger2614. That is, the total force moving the seal2612distally within the syringe cavity2616includes both a user's force and the force generated by the stored energy source (e.g., the power spring2652). This may allow the user to increase the speed of the injection process beyond the maximum speed generated by the stored energy source alone. Similarly, the user may be able to slow the speed of the injection process by applying sufficient distal force to partially but not fully open the rate control assembly (e.g., to decrease but not eliminate the friction between the braking pad(s)2658and the spring sleeve2654). As such, the user may be able to selectively and reversibly start and stop, or increase or decrease the speed of, the injection process.FIG. 31shows an illustrative graph of the user force required to perform an injection using an injection device having a power assembly similar to the power assembly2606of the injection device2600. As shown, in one variation, the user force required is approximately 10 N with the power assembly (indicated as “Assisted”), while without the power assembly (indicated as “Baseline”), the user force required is approximately 23 N. Thus, the device may have a force multiplication factor of about 2.3. It should be noted that this graph is merely illustrative of the user force required for a similar device, and is not meant to indicate that the injection device2600may or must conform to this representation.

In some variations the injection device2600may comprise an autocomplete mechanism, which may cause the full volume of the reservoir2630to be automatically displaced through the lumen of the needle2628within a certain tolerance of the total injection (e.g., within about 85% of the injection, within about 90% of the injection, within about 95% of the injection, or more, or within about 1 mm of full displacement, about 2 mm of full displacement, about 3 mm of full displacement, or about 4 mm of full displacement, etc.), regardless of a user's application of distal force to the proximal housing2624. In some variations, autocompletion may be caused by the braking pad(s)2658no longer contacting the spring sleeve2654. For example, when the seal2612is near the distal end of the syringe cavity2616, the plunger2614may have travelled distally within the syringe cavity2616such that the braking pad(s)2658may reach the distal end of the spring sleeve2654. When the braking pad(s)2658move distally beyond the spring sleeve2654, they may no longer be in contact with the spring sleeve2654. Accordingly, there may be no friction between the braking pad(s)2658and the spring sleeve2654, and thus no force opposing the distal force from the power spring2652. As a result, the dose may autocomplete due to distal force on the plunger2614from the power spring2652.

Injection device2600may also comprise an indicator that, like the indicators described with respect to the injection device100, may indicate the progress or completion of the injection, and may have activated and inactivated configurations. In some variations of the injection device2600, the indicator may comprise an end-of-dose indicator2618to alert the user that the full dose has been displaced from the reservoir2630of the syringe2604, and/or that the seal2612has traveled the full length of the reservoir2630to the distal end of the syringe cavity2616. Additionally or alternatively, the end-of-dose indicator2618may alert the user that nearly (e.g., greater or equal to about 85%, greater or equal to about 90%, greater or equal to about 95%, or more) the full dose has been displaced and/or that the seal2612has traveled nearly (e.g., greater or equal to about 85%, greater or equal to about 90%, greater or equal to about 95%, or more, or within about 1 mm of full displacement, about 2 mm of full displacement, about 3 mm of full displacement, or about 4 mm of full displacement, etc.) the full length of the reservoir2630to the distal end of the syringe cavity2616. In variations in which the injection device has both an autocomplete mechanism and an end-of-dose indicator, these may be triggered at the same time. If the end-of-dose indicator is deployed before the dose has been fully delivered, this may reduce the likelihood that a user fails to deliver the full dose.

The end-of-dose indicator2618may have different visual appearances associated with the inactivated and activated configurations.FIGS. 27A-27Eshow the end-of-dose indicator2618in the inactivated configuration, whileFIGS. 27F-27Hshow the end-of-dose indicator2618in an activated configuration. The end-of-dose indicator2618may be seen through the housing in the activated configuration, while not seen through the housing in the inactivated configuration.

In the variation shown inFIGS. 27A-27H, the end cap2650of the proximal housing2624may be configured such that when the end-of-dose indicator2618is adjacent to the inner surface of the end cap2650, at least a portion of the end-of-dose indicator2618may be seen from outside the end cap2650through a viewing portion. In some variations, at least a portion of the end-of-dose indicator2618may have a color or pigment that may be capable of being more easily noticed, such as but not limited to red, yellow, orange, green, magenta, blue, and the like. In order for the end-of-dose indicator2618to be seen through at least a portion of end cap2650, in some variations, at least a portion of the end cap2650may be translucent. In variations in which a portion of the end cap2650is translucent, the level of translucency may be such that the coloring of the end-of-dose indicator2618may be perceived through the end cap2650only when the end-of-dose indicator2618is adjacent or nearly adjacent to the viewing portion. In other variations, the end cap2650may comprise a transparent or open region configured such that no portion of the end-of-dose indicator is visible in the inactivate configuration, and the end-of-dose indicator2618is only visible through the viewing portion when the end-of-dose indicator2618is adjacent to the transparent or open region, for example, because of the viewing angle. For instance, in some such variations, the viewing portion may comprise a transparent region around the circumference of the end cap2650, and the end-of-dose indicator2618may only be visible through the viewing portion when aligned adjacent to the viewing portion. The end-of-dose indicator2618may comprise a lumen therethrough, such that the end-of-dose indicator2618fits within the proximal housing2624and around the ram housing2636.

A biasing element may be configured to bias the end-of-dose indicator2618toward an activated configuration. The biasing element may have a compressed configuration and an expanded configuration. The biasing element may be in a compressed configuration when the end-of-dose indicator2618is in an inactivated configuration, and the biasing element may be in an expanded configuration when the end-of-dose indicator2618is in an activated configuration. In some variations, the biasing element may comprise a compression spring2666. The proximal end of the compression spring2666may be connected to or in contact with the end-of-dose indicator2618, and the distal end of the compression spring2666may be connected to or in contact with an object distal to the end-of-dose indicator2618, such as the interlock ring2634(described above). The biasing element may thus bias the end-of-dose indicator2618toward the proximal end of the proximal housing2624.

As shown inFIGS. 27A-27E, the ram housing2636may comprise one or more latch(es)2670, which may hold the end-of-dose indicator2618in an inactivated configuration until released. The latch(es)2670may each comprise a radially outward-extending lip that may press distally against the proximal surface of the end-of-dose indicator2618. This lip may resist the biasing force from the biasing element (e.g., compression spring2666) tending to push the end-of-dose indicator2618toward an activated configuration. When the end-of-dose indicator2618is released from the latch(es)2670, the indicator may no longer be held in an inactivated configuration. The end-of-dose indicator2618may be released by radially inward force on the latch(es)2670. In the variation shown inFIGS. 27A-27H, the radially inward force may be applied by a portion of the end cap2650. As shown inFIG. 27E, the end cap2650may comprise a rim2672extending distally from the interior of the end cap2650, which may in some variations have a cup shape as shown. As end cap2650moves distally relative to the latch(es)2670and ram housing2636during the injection, the rim2672may come into contact with an angled portion of the latch(es)2670, as shown inFIG. 27F. This may generate a radially inward force on the latch(es)2670. The latch(es)2670may thus be flexed inwardly, releasing the radially outward-extending lip from the proximal surface of the end-of-dose indicator2618. The ram housing2636may comprise any suitable number of latches2670, such as but not limited to one, two, three, four, five, six, or more. The rim2672may have any suitable corresponding configuration, such as but not limited to a continuous cup shape, or individual arms each configured to contact a latch2670. Once released, the biasing force from the compression spring2666may cause the end-of-dose indicator2618to move proximally toward an activated configuration, as shown inFIGS. 27F-27H. In some variations, the end-of-dose indicator2618may be configured to produce a sudden, audible, and/or tactile indication of having delivered the full or nearly full dose.

After completion of the injection, the injection device2600may be removed from the patient. When proximal force from the tissue on the shroud2620of the needle safety assembly2622is removed, a biasing element (e.g., the compression spring2662) may cause the needle shroud2620to return to an extended configuration. In some variations, the shroud2620of the needle safety assembly2622may additionally or alternatively be configured to be locked in an extended configuration after moving from a retracted configuration to an extended configuration. This feature may limit the ability of a needle2628to extend from the distal end of the nose to pierce or otherwise contact tissue or other surfaces after the injection device2600has been removed from a patient's tissue. This may make the injection device2600safer for the user and/or patient by limiting accidental needlesticks. It should be appreciated that in some variations, the needle safety assembly2622may enter the locked extended configuration if the injection2600is removed from the patient before the injection has fully completed.

FIGS. 28A-28Cshow one variation of a mechanism by which the needle safety assembly2622may be able to be initially retracted by proximal force on the shroud2620, but after having been retracted, re-extension of the needle safety assembly2622may cause it to lock into the extended position. The needle safety assembly2622may comprise a shroud locking ring2668, shown isolated inFIG. 29C. The shroud locking ring2668may sit between the proximal portion of the needle safety assembly2622and distal housing2632. The shroud locking ring2668may be movable between three configurations: a first, stable configuration when the needle safety assembly2622is initially extended; a second, unstable configuration when the needle safety assembly2622is retracted; and a third, stable configuration when the needle safety assembly2622is extended after having been retracted. The initial stable configuration is shown inFIG. 28A. As the needle safety assembly2622moves toward a retracted configuration as shown inFIG. 28B, proximal movement of the proximal end of the needle safety assembly2622may cause the shroud locking ring2668to rotate into the second, unstable configuration. As the needle safety assembly2622moves back toward a retracted configuration as shown inFIG. 28C, the distal movement of the proximal end of the needle safety assembly2622may cause the shroud locking ring2668to rotate into the third, stable configuration. Once the shroud locking ring2668has entered the third, stable configuration, it may block distal movement of the needle safety assembly2622.

More specifically, when the needle safety assembly2622is initially in the extended position, the shroud locking ring2668may sit in a first, stable configuration against an internal shoulder of the distal housing2632, and may be biased proximally toward the internal shoulder by compression spring2662. The shroud locking ring2668and internal shoulder of the distal housing2632may comprise ramped surfaces, such that the shroud locking ring2668can sit against the internal shoulder in two different stable positions. When the needle safety assembly2622retracts, a ramped surface2680on each arm2644of the needle safety assembly2622may move into contact with a tab2684of the shroud locking ring2668. As the needle safety assembly2622and arm2644move proximally, this may exert force on the tab2684that may cause the shroud locking ring2668to rotate (e.g., by between about 10 degrees and about 30 degrees, by about 15 degrees, or any suitable range). During this motion, the shroud locking ring2668may move distally relative to the internal shoulder of the distal housing2632, allowing the shroud locking ring2668to rotate over a peak formed by the ramped surfaces of the internal shoulder. After the shroud locking ring2668rotates over the peak, the compression spring2662may bias the shroud locking ring2682back against the internal shoulder of the distal housing2632. Once the needle safety assembly2622is in a fully retracted position, steps2686on the needle safety assembly2622may interface with tabs2684to prevent further rotation of the shroud locking ring2668. When the needle safety assembly2622moves back toward a retracted configuration after having been in the retracted position, the needle safety assembly2622may disengage from the shroud locking ring2682, and the shroud locking ring2682may further rotate under the bias from compression spring2662until it reaches the second, stable configuration against the internal shoulder of the distal housing2632. In this configuration, further rotation of the shroud locking ring2668may be resisted by tabs2688on the needle safety assembly2622, but preventing further retraction of the needle safety assembly2622.

While the variation of the injection device described immediately above is configured to lock in the extended configuration after having been in a retracted configuration, it should be appreciated that in other variations, the needle shroud may not be configured to lock when re-entering an extended position (e.g., in some variations, the needle shroud may continue to be able to be retracted from an extended position in response to distal force).

In some variations, one or more of the elements of injection device2600may optionally comprise clocking features to correctly orient the elements relative to each other, as described above with respect to injection device100.

While embodiments have been described and presented herein, those embodiments are provided by way of example only. Variations, changes, and substitutions may be made without departing from the embodiments provided by way of example. It should be noted that various alternatives to the exemplary embodiments described herein may be employed.