Patent Publication Number: US-10328211-B2

Title: Automatic self-dispensing accurate dose drug delivery syringes

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a national phase application of International Patent Application No. PCT/US2014/055486, filed Sep. 12, 2014, which claims priority to U.S. Provisional Application No. 61/877,723 filed Sep. 13, 2013, and U.S. Provisional Application No. 62/005,089 filed May 30, 2014, each of which is included by reference herein in their entireties for all purposes. This application is also a continuation-in-part of U.S. application Ser. No. 13/707,201 filed Dec. 6, 2012, which claims priority to U.S. Provisional Application No. 61/568,509 filed Dec. 8, 2011 , each of which is incorporated by reference in its entirety for all purposes. 
    
    
     FIELD 
     THIS INVENTION relates to accurate dose drug delivery syringes. More particularly, this invention relates to automatic accurate dose drug delivery syringes which are capable of self-dispensing upon activation by a user, the methods of operating such devices, and the methods of assembling such devices. 
     BACKGROUND 
     Various studies have shown that the accuracy of dose delivery is affected by a number of factors, including: injection methodologies employed by medical practitioners, an inability to accurately read and control plunger travel during dosing, and the loss of dosage associated with the prime step used to evacuate air from the syringe prior to the dosing step. These effects are particularly magnified by the use of drug delivery syringes that have a high dose volume to axial translation ratio (i.e., a significant quantity of drug is dispensed for even incrementally small distances of plunger depression, as may be the case for large diameter syringes); this problem is more acute when delivering microliter size doses. While these causes for error are common, the need for accurate dose syringes remains. Such syringes are of particular importance in sensitive operations, such as in intravitreal injections, and are very desirable for low dose treatments where inaccurate dosing can lead to substantial error and potential patient harm. 
     Studies have shown that the amount of treatment delivered may vary significantly depending on whether the medical practitioner chooses to deliver 5 μL (5 microliters) of the treatment by depressing the syringe plunger from 10 μL to 5 μL or by depressing the syringe from 5 μL to 0 μL. Additionally, due to the uncertainty of plunger travel limits some practitioners may depress the syringe past the natural travel limit and deliver excess treatment to the patient because of mechanical compliance between the stopper and the syringe barrel. For example, given a particular syringe barrel diameter, a practitioner may depress the plunger past the natural stop for 0 μL and erroneously deliver up to 20% more dosage than necessary. This error is magnified because of the small dose volume requirements for particular treatments. Because the dosage amount and associated plunger travel distance are small, it is very difficult for a practitioner to gauge the fill amount of the dosing chamber and to control the injection amount as the treatment is applied to the patient. This inaccuracy in dosing can lead to substantial safety risks including, among other side effects, increased pressure in the target region and altered (reduced) drug efficacy. 
     A primary cause of the dosing inaccuracy is the inability to reliably set the limits of plunger travel, and the inherent variability in the degree to which the plunger seal (or stopper) is depressed at end of delivery during dosing. Also contributing to inaccuracy is the potential variability, during syringe manufacturing, in the placement of reference markings on the syringe barrel. Endemic to these causes of inaccuracy is the high sensitivity of volume dispensed to the axial travel of the plunger, as described above. Mechanical travel limits, however, are difficult to employ in such applications because of the challenges associated with reading and controlling the plunger travel by the user over the small distance of dosing. Simply put, because the dosage amounts are so small, it is difficult for a practitioner to identify the dosage measurements on the syringe barrel and accurately control the plunger depression and dosage amount during injection. 
     In addition to improving dosing accuracy, it is useful to incorporate the functionality of a priming step into a syringe design to reduce or eliminate air bubbles within the dosing chamber. This step is very useful to minimize safety risks, improve operational hygiene, and reduce pressure in the target site. Minimizing the likelihood of air bubbles during filling helps streamline the drug delivery process for the clinician. Employing pre-filled syringes may assist in the minimization of air bubbles. However, even pre-filled syringes are not fully devoid of air captured during the filling process. 
     Accordingly, there is a substantial need for syringes which allow the user to readily identify and control the dosage amount, minimize the presence of air bubbles within the dosage chamber prior to drug delivery, and ensure accurate delivery of the required drug dose. It is preferred that such a syringe would enable pre-filling to take advantage of benefits associated with the use of such products. 
     Various syringes have been developed in attempts to address dosing inaccuracies in drug administration. For example, U.S. Application Publication 2013/0150803 A1 to Shetty et al., which is assigned to the assignee of this disclosure, discloses a syringe having a plunger rod that is externally threaded with a course pitch to a housing. A screw that engages a plunger seal is keyed to the plunger rod, and externally threaded with a fine pitch to an adapter secured to the housing. While the differences between the pitches enhance dosing accuracy, operation of the syringe is still dependent upon and subject to variability of manual administration. 
     SUMMARY 
     The present invention provides dose control mechanisms, which may allow for the accurate dosing and delivery of drug treatments, and drug delivery syringes which incorporate such control mechanisms. Such novel devices may permit the identification and control of the dosage amount, permit the syringe to be “primed” (i.e., evacuated of air bubbles) prior to drug delivery, and ensure the accurate delivery of microliter volume dosages, all within a device size that is similar to commonly used conventional syringes available in the marketplace. Such novel devices are generally safe and easy to use, and are aesthetically and ergonomically appealing for clinical practitioners. The novel devices of the present invention may provide these desirable features while minimizing problems associated with known prior art devices. 
     In accordance with an aspect of this disclosure, there is provided an automated dose control mechanism for a syringe that has a barrel and a plunger seal. The dose control mechanism includes a plunger assembly and an automatic administration assembly. The plunger assembly is adapted to be connected to the syringe to provide movement to the plunger seal. The automatic administration assembly includes an administration mechanism, a locking mechanism, and an actuator. The administration mechanism is adapted and disposed to provide selective movement to the plunger assembly. The locking mechanism is adapted to be disposed in an engaged position to prevent the administration mechanism from providing movement to the plunger assembly, and a disengaged position wherein the locking mechanism does not prevent the administration mechanism from providing movement to the plunger assembly. The actuator is disposed to selectively engage and disengage the locking mechanism with the administration mechanism. When actuator is disposed to engage the locking mechanism, the locking mechanism prevents the administration mechanism from providing administration movement to the plunger assembly. Conversely, the administration mechanism provides administration movement to the plunger assembly when the locking mechanism is disengaged without requiring further actuation. 
     According to another aspect of some embodiments, the administration mechanism can include a biasing element and a selection dial. Alternately, the administration mechanism can include a motor or any other appropriate arrangement that provides automatic movement of the plunger assembly once actuated. According another aspect of some embodiments, the locking mechanism may include a locking pin or other surface that engages or abuts a component of the administration mechanism. According to yet another aspect of some embodiments, the actuator may include a dispense button that selectively allows the locking mechanism to disengage the administration mechanism. Some embodiments may include a voice activated arrangement or a remotely actuated arrangement, such as a foot pedal. 
     In accordance with a first embodiment, there is provided an accurate dose drug delivery syringe having a dose control mechanism, a barrel, a plunger seal, and a barrel adapter assembly having a barrel tip and a needle. The control mechanism includes a plunger having a coarse pitch screw on its exterior surface, a housing having a corresponding coarse pitch guide along the interior surface of the housing, a screw having a fine pitch screw which interfaces with a fine pitch nut of an adapter, wherein the plunger has an internal annular space within which screw at least partially resides. The syringe may further include a plunger rod connected at one end to screw and at another end to plunger seal. The plunger having the coarse pitch is rotatable upon the corresponding coarse pitch guide, and wherein at least a portion of the plunger is rotationally keyed to interface with a corresponding rotationally keyed portion of screw. A pitch ratio between the coarse pitch screw and the fine pitch screw may be from approximately 1:1 to approximately 20:1, more specifically from approximately 2:1 to approximately 10:1, and more preferably from approximately 4:1 to approximately 8:1. In a currently preferred embodiment, the pitch ratio of the coarse pitch screw and the fine pitch screw is approximately 4:1. 
     The screw may further include a screw connection aspect and, optionally, a ring which function to connect the screw to the plunger seal directly or to a plunger rod. In at least one embodiment, the housing has a housing cover at its proximal end and a window to permit the user to view the location of the plunger within housing. The plunger may have one or more dose markings on the external surface of the plunger and the housing may have one or more guide markings with which to align plunger dose markings. Upon use by the user, plunger axially translates a first distance D 1  causing screw to axially translate a second distance D 2 , wherein D 1  is always greater than D 2  by a factor determined by the pitch ratio. The syringe may be a fill-at-time-of-use syringe, a pre-filled syringe, or a safety syringe, or a combination thereof. The housing of the syringe may have a housing cover at its proximal end to protect the interior of the housing from the environment and a window to permit the user to view the location of the plunger within housing. 
     In a currently preferred embodiment, the syringe further includes a locking mechanism, an activation button, and a biasing member. The biasing member may be a spring, such as a compression spring and/or a torsional spring. The activation button, biasing member, and locking mechanism are configured such that actuation of the activation button by the user manipulates the locking mechanism to permit the biasing member to move from an initial energized state to a lower energy or deenergized state. In one embodiment, when the activation button is depressed, a locking pin of the locking mechanism is manipulated to release the plunger of the syringe. The biasing member is then permitted to act on the plunger, causing it to axially translate and axially rotate, as described further herein. Torque may be transferred from the plunger to the coarse pitch screw, the fine pitch screw, and through the keyed interface of the fine pitch nut, thereby transferring force to the plunger rod. The plunger rod preferably only axially translates, i.e. the plunger rod does not axially rotate, due to the slip fit with the screw. The plunger seal is caused to translate as it is connected or adjacent to the plunger rod, thereby delivering a drug or therapy to a user through a needle or cannula. When a torsional spring, or a torsional compression spring, is utilized as the biasing member, the torque of the spring is thus utilized to translate the plunger seal for drug delivery. In a preferred embodiment, these components may be configured to operate with the dose control mechanisms as described in International Publication WO2013/086167, although without limitation thereto. 
     In an alternative currently preferred embodiment, the biasing member may be an electrical, mechanical, or electromechanical component that, for example, acts on the plunger, causing it to axially translate and axially rotate, as described further herein. Torque may be transferred from the plunger to the coarse pitch screw, the fine pitch screw, and through the keyed interface of the fine pitch nut, thereby transferring force to the plunger rod. The plunger rod in at least one embodiment only axially translates, i.e. the plunger rod does not axially rotate, due to the slip fit with the screw. The plunger seal is caused to translate as it is connected or adjacent to the plunger rod, thereby delivering a drug or therapy to a user through a needle or cannula. When an electrical, mechanical, or electromechanical component is utilized as the biasing member, the torque of such component may be utilized to translate the plunger seal for drug delivery. In a particular embodiment, an electromechanical biasing member, such as a motor, is employed to cause axial translation and axial rotation of the plunger. The motor, such as a stepper motor, may be controlled by a myriad of mechanisms or methodologies. For example, the motor, biasing member, and/or plunger may be controlled by a foot-operated actuation mechanism, a voice-activated actuation mechanism, or other such control or actuation mechanism. In at least one particular embodiment, the biasing member is controlled by a foot-operated actuation mechanism. In another particular embodiment, the biasing member is controlled by a voice-activated actuation mechanism. In a preferred embodiment, these components may be configured to operate with the dose control mechanisms as described in International Publication WO2013/086167, although without limitation thereto. 
     In a further embodiment, a method of manufacturing a syringe having a control mechanism includes the steps of: (i) mounting a barrel adapter assembly to a distal end of a syringe barrel; (ii) mounting a plunger seal through a proximal end of the syringe barrel; and (iii) mounting a control mechanism to the proximal end of the syringe barrel, wherein the control mechanism may rest in contact with the plunger seal. The method may further include, before the step of (ii) mounting a plunger seal through a proximal end of the syringe barrel, the step of: filling the barrel at least partially with a fluid substance. In at least one embodiment, the adapter may be a two component adapter having a proximal adapter portion and a distal adapter portion. The proximal adapter portion may have one or more connection prongs and the distal adapter portion may have corresponding connection ports which, when forced together, connection prongs and corresponding connection ports merge, mate, or otherwise connect to unite the two portions of the adapter. Steps (i) and (ii), and the optional step of filling the barrel at least partially with a fluid substance, may be performed in a sterile environment to maintain the container integrity and sterility of the syringe. 
     The present invention further provides methods of manufacturing syringes having dose control mechanisms, and methods of operation of such mechanisms and syringes. Such novel devices and methods permit the identification and control of the dosage amount, permit the syringe to be “primed” (i.e., evacuated of air bubbles) prior to drug delivery, and ensure the accurate delivery of microliter volume dosages, all within a device size that is similar to commonly used conventional syringes available in the marketplace. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The following non-limiting embodiments of the invention are described herein with reference to the following drawings, wherein: 
         FIG. 1  is an isometric view of an automatic drug delivery syringe, according to at least one embodiment of the present invention; 
         FIG. 2A  is a side elevational view of the automatic drug delivery syringe of  FIG. 1 ; 
         FIG. 2B  is a cross-sectional view of the automatic drug delivery syringe taken along line  2 B- 2 B in  FIG. 2A ; 
         FIG. 3A  is a cross-sectional view of the automatic drug delivery syringe of  FIGS. 1-2B  as the components may appear in a ready-to-inject stage of operation; 
         FIG. 3B  is a cross-sectional view of the automatic drug delivery syringe of  FIGS. 1-3A  as the components may appear in an end-of-dose stage of operation; 
         FIG. 4A  is an exploded view of the automatic drug delivery syringe of  FIGS. 1-3B ; 
         FIG. 4B  is the exploded view of  FIG. 4A  in cross-section; 
         FIG. 5A  is a side elevational view of the automatic drug delivery syringe of  FIGS. 1-4B  illustrating an aspect of the operation of the syringe; 
         FIG. 5B  is an enlarged fragmentary view of the plunger and screw of the automatic drug delivery syringe of  FIG. 5A  in assembly; 
         FIG. 5C  is an enlarged fragmentary view of engagement of the plunger with the housing of the automatic drug delivery syringe of  FIG. 5A ; 
         FIG. 5D  is an enlarged fragmentary view of engagement of the screw with the adapter of the automatic drug delivery syringe of  FIG. 5A  in assembly; 
         FIG. 5E  is an enlarged fragmentary view of assembly of a screw connection aspect with a plunger rod in an embodiment the automatic drug delivery syringe of  FIG. 5A ; 
         FIG. 5F  is an enlarged fragmentary view of the engagement of the distal end of the locking pin with a locking arm in an embodiment of the automatic drug delivery syringe of  FIG. 5A ; 
         FIGS. 5G-5H  are a side elevational views of the automatic drug delivery syringe of  FIG. 5A  including enlarged views of the window and plunger dose markings; 
         FIG. 6A  is an isometric view of an automatic drug delivery syringe according to a second embodiment of the present invention; 
         FIG. 6B  is an enlarged isometric view of the distal portion of the drug delivery syringe shown in  FIG. 6A ; 
         FIG. 7A  is an isometric view of an automatic drug delivery syringe according to a third embodiment of the present invention; 
         FIG. 7B  is an enlarged isometric view of the distal portion of the drug delivery syringe shown in  FIG. 7A ; 
         FIG. 8A  is an isometric view of an automatic drug delivery syringe according to a fourth embodiment of the present invention; 
         FIG. 8B  shows an enlarged isometric view of the distal portion of the drug delivery syringe shown in  FIG. 8A ; 
         FIG. 9A  shows an isometric view of an initial assembly stage of a pre-filled drug delivery syringe that may incorporate an automatic administration assembly according to at least one embodiment of the present invention; 
         FIG. 9B  shows an isometric view of the automatic drug delivery syringe shown in  FIG. 9A  after it has been assembled; 
         FIG. 9C  shows an isometric view of the automatic drug delivery syringe shown in  FIG. 9A  in a ready-to-inject stage of operation; 
         FIG. 9D  shows an isometric view of the automatic drug delivery syringe shown in  FIG. 9A  in an end-of-dose stage of operation; and 
         FIG. 10  shows an isometric view of an automatic drug delivery syringe, according to at least a sixth embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     As used herein to describe the dose control mechanisms, drug delivery syringes, or any of the relative positions of the components of the present invention, the terms “axial” or “axially” refer generally to a longitudinal axis “A” around which the control mechanisms and syringes are preferably positioned, although not necessarily symmetrically there-around. The term “radial” refers generally to a direction normal to axis “A”. The terms “proximal,” “rear,” “rearward,” “back,” or “backward” refer generally to an axial direction in the direction “P”. The terms “distal,” “front,” “frontward,” “depressed,” or “forward” refer generally to an axial direction in the direction “D”. 
     As used herein, the term “glass” should be understood to include other similarly non-reactive materials suitable for use in a pharmaceutical grade application that would normally require glass, including but not limited to certain non-reactive polymers such as cyclic olefin copolymers (COC), cyclic olefin polymers (COP), and the like. The term “plastic” may include both thermoplastic and thermosetting polymers. Thermoplastic polymers can be re-softened to their original condition by heat; thermosetting polymers cannot. As used herein, the term “plastic” refers primarily to moldable thermoplastic polymers such as, for example, polyethylene and polypropylene, or an acrylic resin, that also typically contain other ingredients such as curatives, fillers, reinforcing agents, colorants, and/or plasticizers, etc., and that can be formed or molded under heat and pressure. As used herein, the term “plastic” is not meant to include glass, non-reactive polymers, or elastomers that are approved for use in applications where they are in direct contact with therapeutic liquids that can interact with plastic or that can be degraded by substituents that could otherwise enter the liquid from plastic. The term “elastomer,” “elastomeric” or “elastomeric material” refers primarily to cross-linked thermosetting rubbery polymers that are more easily deformable than plastics but that are approved for use with pharmaceutical grade fluids and are not readily susceptible to leaching or gas migration under ambient temperature and pressure. “Fluid” refers primarily to liquids, but can also include suspensions of solids dispersed in liquids, and gasses dissolved in or otherwise present together within liquids inside the fluid-containing portions of syringes. 
     According to various aspects and embodiments described herein, reference is made to a “biasing member”, such as in the context of one or more biasing members for retraction of a needle or needle assembly. It will be appreciated that the biasing member may be any member that is capable of storing and releasing energy. Non-limiting examples include a spring, such as for example a coiled spring, a compression or extension spring, a torsional spring, and a leaf spring, a resiliently compressible or elastic band, or any other member with similar functions. In at least one embodiment of the present invention, the biasing member is a spring, preferably a compression spring and/or a torsional spring. 
     Throughout this specification, unless otherwise indicated, “comprise,” “comprises,” and “comprising,” or related terms such as “includes” or “consists of,” are used inclusively rather than exclusively, so that a stated integer or group of integers may include one or more other non-stated integers or groups of integers. As will be described further below, the embodiments of the present invention may include one or more additional components which may be considered standard components in the industry of medical devices. The components, and the embodiments containing such components, are within the contemplation of the present invention and are to be understood as falling within the breadth and scope of the present invention. 
     The novel devices of the present invention automatic self-dispensing accurate dose drug delivery syringes. Such devices may be safe and easy to use, and may be aesthetically and ergonomically appealing for clinical practitioners. The devices described herein incorporate features which may make activation, operation, and lock-out of the device simple for even untrained users. The novel devices of the present invention provide these desirable features while minimizing or eliminating problems associated with known prior art devices. Certain non-limiting embodiments of the novel drug delivery syringes and their respective components are described further herein with reference to the accompanying figures. 
     Various studies have shown that the accuracy of dose delivery using conventional syringes is affected by a number of factors, including an inability to accurately read and control plunger travel during dosing. The use of conventional drug delivery syringes that have a high dose volume to axial translation ratio (i.e., a significant quantity of drug is dispensed for even incrementally small distances of plunger depression, as may be the case for large diameter syringes) significantly magnifies this inaccuracy. With the growth of high-cost, low-volume drug treatments entering the marketplace, it is increasingly important to accurately dose and deliver such low-volume treatments to the patient. The embodiments of the present invention may overcome the challenges faced with the use of conventional syringes for the dosing and delivery of low-volume treatments by utilizing novel dose control mechanisms. As will be described further herein, the novel dose control mechanisms may permit the user to accurately read and dose the desired volume of drug treatment for delivery to the patient. 
       FIGS. 1 through 4B  show an embodiment of a novel dose control mechanism  100  for a syringe  102 , according to at least one embodiment of the present invention. The syringe  102  may be of any appropriate design and may include, for example, an elongated hollow barrel  104  having a distal end  106  and a proximal end  108 . A barrel adapter assembly  110  disposed at the distal end  106  of the barrel  104  couples a needle assembly  112  to the barrel  104 , and a plunger seal  114  is disposed within the hollow interior of the barrel  104 . 
     The barrel adapter assembly  110  may be attached, mounted, affixed, or otherwise connected to the distal end  106  of the barrel  104  by a number of known methods, such as Luer connections, interference fit connections, barrel adapter connections, or any number of other known connections. For example, a luer connection may be utilized to connect the barrel adapter assembly  110  to the syringe barrel  104 . Luer connection systems are a standard way of attaching syringes, catheters, hubbed needles, IV tubes, and the like to each other. Luer connections consist of conical/tubular male and female interlocking components slightly tapered to hold together better. Luer connections can either be a “luer slip”, as shown in  FIGS. 6A and 6B , which are luer connections with a simple pressure or twist fit; luer connections be a “luer lock”, as shown in  FIGS. 7A and 7B , which can have an additional outer rim of threading allowing them to be more secure. The type of connections described herein can be utilized regardless of the type of syringe with which they are shown. For clarity, the luer slip connection shown with the fill-at-time-of-use syringe in  FIGS. 6A and 6B  may be utilized with the pre-filled syringe in  FIGS. 7A and 7B , or any other type of connection may be used with any other type of syringe described herein. Alternatively, the connection may be facilitated by a barrel adapter connection. By way of example, the barrel adapter connection may be as described in International Publication WO2011/137488 and/or U.S. patent application Ser. No. 13/693,915, although without limitation thereto. 
     Returning to  FIG. 2A , regardless of the type of barrel adapter assembly  110  utilized, the barrel adapter assembly  110  generally comprises of a barrel tip  116  and the needle assembly  112 , which includes a needle  118 . In some configurations, the barrel tip  116  may be a pre-formed aspect at the distal end of the barrel  104 . Alternatively, the barrel tip  116  may be a separate component that is attached at the distal end of the barrel  104 , as described, for example, above. The needle  118  may be any type of fluid conduit including, for example, a flexible cannula or a rigid needle, and may be made of any number of materials, including stainless steel. 
     Similarly, the plunger seal  114  may be of any appropriate material or design. The hollow interior of the barrel  104 , along with the plunger seal  114  and the barrel adapter assembly  110  form a drug chamber  120  within the syringe  102 . Axial translation of the plunger seal  114  in the distal direction within the hollow interior of the barrel  104  forces drug fluid out of drug chamber  120 , through the needle  118  of the barrel adapter assembly  110 , for injection and delivery to the patient. 
     While the syringes of the various embodiments herein will not be described in greater detail in each of the descriptions of the embodiments below, those of skill in the art will appreciate that the syringe design utilized may be of any suitable design. 
     The dose control mechanism  100  includes a plunger assembly  122  and an automatic administration assembly  124 . While the plunger assembly  122  may include an interface for manual drug administration, the automatic administration assembly  124  may be utilized in conjunction with the plunger assembly  122  to provide an automatic, controlled administration of a drug from the drug chamber  120  when actuated. 
     In order to provide enhanced control of the volume of drug administered, the plunger assembly  122  may include structure that limits the relative speed with which a volume of drug administered as a result of travel of the plunger assembly  122 . This structure, in conjunction with the automatic administration assembly  124  provides a very controlled administration of drug from the drug chamber  120 . While the exemplary plunger assembly illustrated includes speed/volume control structure with the automatic administration assembly, it will be appreciated that alternate plunger assemblies may be utilized in conjunction with the automatic administration assembly, either with or without such speed/volume control. 
     The plunger assembly  122  of  FIGS. 2A through 4B  includes a plunger  126 , a housing  128 , an adapter  130 , and a screw  132 . The housing  128  has a substantially cylindrical axial pass-through within which the substantially cylindrical plunger  126  may at least partially reside. Housing  128  may optionally include housing cover  144  at its proximal end, for example, to close the interior of the housing  128  off from the environment and/or to axially align plunger  126  within housing  128 , and to prevent removal of the plunger rod by functioning as a mechanical stop. The housing cover  144  may be a pre-formed aspect of the housing  128  or may be a separate component from the housing  128 . 
     The distal end of the housing  128  is connected to, and/or resides partially within, a proximal portion of adapter  130 . The housing  128  may be coupled to the adapter  130  by any appropriate arrangement, such as, for example, screw threads, as illustrated in this embodiment. The proximal and distal portions of adapter  130  may be separated by an adapter flange  134  which may additionally serve as a finger flange for use by the user. Screw  132  may reside at least partially within housing  128  and plunger  126 , and extend distally beyond flange  134 . Screw  132  may have a screw connection aspect  136  to facilitate integration of the control mechanism with a drug delivery syringe  102  and to center the plunger  126 . The internal aspects of these components will be described in further detail herein below. 
     The plunger  126  is an elongated substantially cylindrical structure, and may include a button  140  for engagement by a user. The button  140  may be a pre-formed aspect of the plunger  126  or may be a separate component from the plunger  126 . For example, button  140  may be a preformed aspect at the proximal end of the plunger  126 . Alternatively, button  140  may be a separate component attached to the proximal end of plunger  126  by a snap-fit, such as in the embodiment illustrated in  FIGS. 3A-4B . In a preferred embodiment, the button  140  may be attached to plunger  126 , but allowed to axially rotate freely from plunger  126 . In this way, the button  140  may be rotationally fixed relative to the user&#39;s/clinician&#39;s finger during depression of the plunger  126  when such plunger is utilized in a manual form of operation. Regardless of the specific configuration and relationship of button  140  and plunger  126 , button  140  is intended to have a user interface surface  142  for contact and control by a user (e.g., such as with the thumb or finger tip of the user) during manual administration of a drug, as opposed to automated delivery. 
     Housing  128  may further include a window  146 , which may be an opening (e.g., an aperture) in the housing or a transmissive or translucent component. Regardless of the particular configuration of window  146 , its primary purpose is to permit the user to view the location of the plunger  126  within housing  128 . Plunger  126  may include one or more dose markings  148  on the external surface of the plunger  126 . Housing  128  may have one or more reference or guide markings  150 , such as at the window  146 , with which to align plunger dose markings  148 . The plunger dose markings  148  may correspond to the relevant dose amounts desired by the user. By employing the respective plunger and housing markings, the user can identify volumetric dose quantities desired for controlled delivery to the patient, as will be explained further herein. In another embodiment, the window  146  may be covered by a lens, such as a clear lens, that provides visual magnification. 
       FIGS. 3A and 3B  show cross-sectional views of the dose control mechanism, according to at least one embodiment of the present invention, in a ready-to-inject stage and in an end-of-dose stage, respectively. The cross-sectional views show certain other aspects of the components which are internal to the mechanism. The plunger  126  has a coarse pitch male thread  154  (visible in  FIG. 4A ) on its exterior surface which interfaces with the coarse pitch guide  156  along the interior surface of the housing  128  such that, in at least one embodiment, the pitch on guide  156  is the same as pitch on plunger thread  154  (see also  FIG. 5C ). The terms “male” and “female” are intended to describe corresponding and interfacing threads or surfaces, and can be used interchangeably to describe corresponding aspects as would be readily appreciated in the art. 
     The plunger  126  has an internal annular space  152  within which screw  132  at  10  least partially resides. Both screw  132  and plunger  126  reside, at least partially and/or at some point of operation, within housing  128 . In order impart rotational movement of the plunger  126  to the screw  132 , the plunger  126  and a proximal portion of the screw  132  are rotationally keyed to one another. The term “keyed” is used herein to mean any number of internal aspects which removably or slidably (in the axial sense) connect two or more components. For example, the plunger  126  may be a hollow cylinder having a coarse pitch screw on at least some portion of the outer surface and a spline design along at least a portion of the inner surface. The spline design is configured to mate with, and transform or relay rotation to, a complimentary spline contained at a proximal end of the screw  132 . This spline design element ensures that the plunger  126  and screw  132  are rotationally keyed. The spline or rotationally keyed aspect is visible at the proximal end  162  of screw  132 , and with its corresponding spline or rotationally keyed aspect in the annular space  152  of plunger  126  in  FIG. 2B . As shown in  FIGS. 2B and 5B , in at least one embodiment, screw  132  has a cross or plus shape in its perpendicular cross-section which is keyed to plunger  126 . This arrangement or configuration allows the two components to be rotationally keyed while allowing them to axially slip past each other. While the illustrated embodiment includes a cross or plus shape, any number of corresponding shapes may be utilized to impart a rotationally “keyed” relationship between these components such that the first component may removably or slidably engage the second component in a manner which enables the rotational keyed relationship and permits axial slip. Such components may alternatively be keyed to have the shape of, for example, a horizontal line or minus, a star, or a semi-circle shape, with the corresponding component having the inverse of the shape on an interior annular space. 
     In a manner similar to the plunger  126 , a distal portion  168  of the screw  132  includes a fine pitch thread  158  which interfaces with a fine pitch nut  160  of adapter  130  such that, in at least one embodiment, the pitch on screw thread  158  is the same as pitch on nut  160  (see also  FIG. 5D ). Also visible in  FIGS. 3A and 3B  are the proximal end  162  of screw  132  and abutment surface  164  of adapter  130 . The plunger  126  having the coarse pitch male thread  154  is rotatable upon the corresponding (e.g., “female”) coarse pitch guide  156 , which is rotationally keyed to the screw  132  having the fine pitch thread  158 . Because the plunger  126  and screw  132  are rotationally keyed, each having a respective screw pitch, rotational translation of the plunger  126  rotates and axially translates the screw  132 . The screw  132 , having the fine pitch screw thread  166 , engages the female fine pitch nut  160  of the adapter  130 . Hence, rotation of plunger  126  results in axial translation of screw  132  and the resolution of axial travel is dictated by fine pitch thread  158  of the screw  132 . 
     Fine pitch nut  160  (or simply “nut”), having the same fine pitch of the screw  132 , may be used to brace the screw  132  and facilitate the transfer of the rotational movement of the plunger  126  into axial translation of the screw  132 . The pitch ratio of the coarse pitch to the fine pitch dictates the degree or resolution of axial travel of the screw  132 , i.e., the distance that the screw  132  axially translates for each rotation of the plunger  126 . As a result, the medical practitioner is provided with an ease of operation that enables them to accurately read and set the dosage amount. The pitch ratio can be set to enable “fine tuning” of the dosage amount, which is of particular importance for low-volume dosage quantities where variance may be significantly affected by plunger travel. 
     During operation of the dose control mechanism, the user may axially rotate plunger  126  to control the desired dosage volume for injection into the patient. Axial rotation of the plunger  126  causes coarse pitch male thread  154  (visible in  FIG. 3B ) to travel within the corresponding coarse pitch guide  156  of housing  128 , as shown in  FIGS. 3A and 3B . This action causes the plunger  126  to axially translate in the distal direction thereby reducing the dosage volume within the drug chamber, as is explained in more detail herein. Because of the rotationally keyed interaction between plunger  126  and screw  132  within the annular space  152 , rotation of the plunger  126  causes screw  132  to axially rotate and translate. However, because of the pitch ratio between the plunger  126  and screw  132 , each unit measure of translation in the distal direction of the plunger  126  results in fractional (e.g., smaller, more resolved) translation of the screw  132  in the distal direction. Because of the pitch ratio between the plunger  126  and the screw  132 , as plunger  126  is depressed or axially translated in the distal direction (i.e., in the direction of solid arrow in  FIGS. 3A and 3B ), screw  132  is caused to axially translate in the distal direction only a fraction of the distance translated by the plunger  126 . This difference in axial translation distance between plunger  126  and screw  132  is visible by comparing distances D 1  and D 2  in  FIGS. 3A and 3B . D 1  is the distance that plunger  126  axially translates while D 2  is the incremental distance that screw  132  axially translates. The difference in dimensions D 1  and D 2  is also clear by the reduction in the annular space  152  within the plunger  126  above the proximal end  162  of the screw  132 . It is noted that the variable annular space  152  within the plunger  126  is related to the mechanical set-point desired by the practitioner and provides space for translation of the screw  132  during the dosage stroke. This has a number of benefits for accurate control during delivery of low-volume doses. Primarily, the pitch ratio relationship permits the user to accurately control the desired dose and delivery of a drug treatment. 
     In order to provide axial, translational movement of the screw  132  to the plunger seal  114  without the rotational movement of the screw  132 , the screw  132  may be coupled to the plunger seal  114  by any appropriate coupling structure to either directly or indirectly drive the axial translation of the plunger seal  114 . In the embodiment of  FIGS. 3A-4B , a plunger rod  170  is coupled to both the screw  132  and the plunger seal  114 . The plunger rod  170  may be connected to the screw  132  at, for example, at a screw connection aspect  136 . In this embodiment, the screw connection aspect  136  is a ball-like structure that is received within a socket  174  of the plunger rod  170  to provide a ball-and-socket joint. Optionally, a ring  138  may be provided near the distal end of the screw  132 , which may be utilized to facilitate the connection of the screw  132 , the plunger rod  170  and the plunger seal  114 . Referring the enlarged view of  FIG. 5E , in at least one embodiment, the screw connection  172  aspect is connected to the plunger rod  170  through a radial opening  176  in the plunger rod  170 . Additionally or alternatively, this connection may be a snap-fit connection, as illustrated in  FIGS. 3A-3B , an interference-fit connection, or a number of other connection methods known in the industry. In at least one other embodiment, the screw connection aspect is connected to the plunger rod through a proximal opening in the plunger rod such that the screw connection aspect sits within a proximal pocket in the plunger rod. 
     Preferably, the connection between the screw  132  and the plunger seal  114 , or screw  132  and plunger rod  170  when a plunger rod is employed, is such that the screw is permitted to axially rotate while the plunger rod  170  and/or the plunger seal  114  remain rotationally fixed. Accordingly, as the plunger  126  and screw  132  of the control mechanism  100  are axially rotated and translated, the motion is relayed to the plunger seal  114  which is also axially translated. 
     In accordance with the invention, the dose control mechanism  100  further includes automatic administration assembly  124 . By way of the automatic administration assembly  124 , the user may preselect the volume of drug to administer, then actuate the dose control mechanism  100  to deliver the drug without the user physically depressing the plunger  126 . The automatic administration assembly  124  includes an administration mechanism  182 , a locking mechanism  184 , and an actuator  186 . 
     In the embodiment illustrated in  FIGS. 1-5A , the automatic administration assembly  124  includes a biasing member  188 , a selection dial  190 , a locking pin  192 , and a dispense button  194 . In order to support the dispense button  194  and the locking pin  192 , the automatic administration assembly  124  may further include an automation housing  195 . The automation housing  195  may be formed as a separate component, or may be unitarily formed with or secured to the adapter  130 . 
     In this embodiment, the administration mechanism  182  includes the selection dial  190  and the biasing member  188 . As may best be seen in  FIGS. 1, 2A, 3A and 3B  the selection dial  190  is disposed subjacent the button  140  and is secured to the plunger  126 . Accordingly, rotation of the selection dial  190  causes a corresponding rotation of the plunger  126 . Thus, by rotating the selection dial  190 , the user may adjust the dose to be administered, viewing the selected dose by way of the plunger dose markings  148  visible in the window  146 . As shown in  FIG. 5G , for example, the plunger dose markings  148  may include a numerical value corresponding to the volume of drug to be administered. 
     The illustrated biasing member  188  of this embodiment is a torsion spring. It will be appreciated, however that the biasing member may be of an alternate design, such as a compression spring. The biasing member  188  is disposed about the plunger  126 , and includes an anchor end  196  and a rotatably mounted end  198 . As illustrated in  FIG. 2A , the anchor end  196  is coupled to the housing  128 , while the rotatably mounted end  198  is coupled to the selection dial  190 . As a result, as the selection dial  190  is rotated to provide the desired dose (as shown by the arrow in  FIG. 5A ), the rotatably mounted end  198  of the biasing member  188  rotates with the selection dial  190 , biasing the selection dial  190  to dispense the drug from the syringe  102 . 
     In order to maintain the selection dial  190  in the pre-dispensing position, the locking pin  192  is disposed against the selection dial  190 . The locking pin  192  is maintained in position against the selection dial  190  by a slidably mounted locking arm  200 . As may best be seen in  FIG. 5F , the locking arm  200  may be supported by the automation housing  195 , which may include one or more support flanges  202 . While in this embodiment the locking arm  200  extends through an aperture  204  in a wall of the automation housing  195  with a single support flange  202  above the locking arm  200 , it will be appreciated that a second support flange may be provided, for example, subjacent the locking arm  200 . It will be appreciated that the illustrated support flange  202  disposed above the locking arm  200  includes an aperture through which the locking pin  192  may extend. Referring again to  FIG. 5F , the locking arm  200  may include an abutment surface  206 , and an actuation opening  208 . In this way, when the abutment surface  206  is disposed subjacent a distal end  210  of the locking pin  192 , the locking pin  192  is held in position against the selection dial  190 . Conversely, when the actuation opening  208  is moved to a position subjacent the distal end  210  of the locking pin  192 , the locking pin  192  is permitted to move through the actuation opening  208  under the biasing force of the biasing member  188 . While the actuation opening  208  may fully correspond to the outer surface of the locking pin  192 , it will be appreciated that the actuation opening  208  may alternately be an arcuate opening, for example, in a side surface of the locking arm  200 , so long as that actuation opening  208  is of a shape and size that allows the free passage of the locking pin  192 . 
     The locking arm  200  further includes the dispense button  194  that extends from the outer surface of the automation housing  195 . Thus, by depressing the dispense button  194 , the user may move the actuation opening  208  to the position subjacent the distal end  210  of the locking pin  192 , allowing the movement of the locking pin  192  out of engagement with the selection dial  190 . In this embodiment, the dispense button  194   30  is disposed substantially adjacent the distal end of the syringe  102 , with the locking pin  192  extending substantially parallel to the syringe  102 . In order to support the locking pin  192 , an aperture may be provided through the adapter flange  134 . One or more additional support flanges  202  may be provided within the automation housing  195 . It will be appreciated that the positioning of the dispense button  194  toward the end of the syringe  102  allows a user to hold the syringe  102  much like a pen, actuating the actuator  186  only when the needle  118  is disposed in a desired position. Those of skill will further appreciate, however, that the actuator  186 , here, dispense button  194  may be alternately positioned. 
     In use, the user first selects the desired volume of drug to be delivered using the selection dial  190  (see  FIGS. 5A and 5G ). The rotation of the selection dial  190  energizes the biasing member  188 , while the locking pin  192  held between the selection dial  190  and the abutment surface  206  of the locking arm  200 , that is, the locking mechanism  184 , locks the selection dial  190  with the biasing member  188  in the energized position. Upon a desired placement of the needle  118 , the dispense button  194  (see  FIG. 5F ) is depressed to actuate dispensing of the drug. With the selection dial  190  no longer held in position, the biasing member  188  deenergizes, imparting rotation to the plunger  126 . As explained in detail above, as the plunger  126  rotates by way of its course pitch thread  154  along the course pitch guide  156  of the housing  128  (see  FIG. 5C ), the rotationally keyed screw  132  (see  FIG. 5B ) rotates along its fine pitch thread  158  engaged with the fine pitch nut  160  of the adapter  130  (see  FIG. 5D ). The translational, axial movement of the screw  132  is transmitted to the plunger seal  114 , here, by way of plunger rod  170  (see  FIG. 5E ) to dispense the drug. 
     The novel syringes of the present invention may also utilize features which provide integrated and adjustable range-of-travel limits to ensure accurate delivery of low-volume drug treatments. This may be enabled, for example, by incorporating features that prevent variable depression of the plunger seal (or stopper) (e.g., preventing the plunger from “bottoming out” during drug delivery) within a syringe. Specifically, the dose control mechanisms of the present invention utilize adjustable set mechanical end-points for the range of plunger axial travel during drug delivery. Such limits may be predefined, i.e., integrated and fixed into the syringe configuration in advance of use by the medical practitioner, or adjustable, i.e., variably controlled by a compounding pharmacist, a medical practitioner, or by a self-administering patient using an integrated dosage setting mechanism. Such mechanical set-points permit a range of axial plunger travel that are, for example, related to the priming and dosing quantities, but also prevent the user from variably depressing the plunger and plunger seal as part of the dosing stroke or from bottoming out these components within the dosing chamber of a syringe. This novel control mechanism greatly increases the accuracy of the dose delivered to the patient. Additionally, embodiments of the present invention allow the user to prime the syringe to evacuate the dosing chamber of any residual air prior to delivering the dose to the patient. The prime step may be a fixed amount or a variable amount, depending on the configuration of the low dose syringe and variation in amount of drug or liquid contained/filled in the dosing chamber. The configuration of the novel syringe allows the user to complete the prime step while maintaining, or enabling, the ability of the syringe to deliver an accurate and precise dose to the patient. 
     As stated above, the mechanical set-point limits effectively function to prevent the user from variably depressing the plunger and plunger seal or from bottoming out  10  these components within the dosing chamber of a syringe. This functionality increases the accuracy of the dose delivered to the patient because it reduces the variability of the delivered dose from the amount prescribed and intended to be delivered to the patient. The mechanical end-points may be readily identified and easily set by employing the pitch ratio between the plunger  126  having a coarse pitch thread  154  and the screw  132  having a fine pitch thread  158 . For example, in one such embodiment a pitch ratio between the coarse pitch and a fine pitch may be 4:1, such that rotationally “screwing” or turning the selection dial  190  and associated plunger  126  axially translates the plunger component four times as far as the axial translation of the screw component. Accordingly, the practitioner is provided with a significant ease of operation since they may more accurately set the required dosage amount. Such a pitch ratio may be, for example, anywhere from the range of 1:1 to 20:1, as may be necessary to obtain the required accuracy of the low-volume dosage amount. The “dialing-in” or “setting” may be facilitated by the dose markings on the plunger and guide markings on the housing described above. 
     As the biasing member  188  deenergizes, causing the rotation of the plunger  126  set the desired low-volume dosage for injection, the user can perform what is known in the art as a “priming step.” This priming step evacuates the dosing chamber of any residual air bubble captured in the dosing chamber during pre-filling, if any, and primes the attached needle (or catheter or an extension set) before delivery. After priming and setting of the dose has been completed, the dispense button  194  may be depressed allowing delivery of the drug, the plunger seal  114  advancing inject the desired dose amount to the patient. Upon drug dose delivery, the plunger  126  is caused to “bottom out” on the abutment surface  164  of the adapter  130  (as shown in  FIG. 3B ). Upon completion of the delivery, the plunger dose marking  148  appearing in the window  146  may include a representation that that delivery is complete, as, for example, the dot illustrated in  FIG. 5H . 
     Notably, the novel embodiments contemplated by the present invention effectively prevent the plunger seal from “bottoming-out” within the dosing chamber. This feature along with the automatic administration assembly  124  may pre-empt one aspect of user variability in either excess dosing by over-depression of the plunger or under dosing by under-depression of the plunger, ensuring that the quantity dosed to the patient is accurate and minimizes user error. This is of particular importance in low dosage treatments, where user-related errors can cause significant and undesirable variation and inaccuracy in the delivery of medication to the patient. The embodiments according to the present invention may prevent such occurrences and work to effectively eliminate the dosing errors associated with prior syringe configurations and delivery methodologies. Furthermore, depression of the plunger in this embodiment does not back-drive the screw. 
     It will be appreciated that the various components of the automatic administration assembly  124  may vary. For example, the administration mechanism  182 , the locking mechanism  184 , and the actuator  186  may be of alternate designs. 
     The novel dose control mechanisms  100 , and automation assemblies  124  of the present invention can be integrated into a number of drug delivery syringe configurations to provide accurate dose delivery capability to the user. They may additionally be incorporated into existing syringes, either as integral or supplemental features. For example, these components may be configured to operate with the dose control mechanisms as described in International Publication WO2013/086167, although without limitation thereto. For example, the control mechanisms may be utilized with fill-at-time-of-use syringes, pre-filled syringes, or safety syringes having integrated needle retraction or needle sheathing safety features, or a combination thereof. 
     The components utilized and shown with reference to the syringe of  FIG. 1  may similarly be utilized with the syringes of  FIGS. 6A, 7A, 8A , and/or  9 A, as would readily be appreciated by an ordinarily skilled artisan. Examples of such syringes which incorporate the novel dose control mechanisms are provided below. For ease of understanding, like components in the embodiments of  FIGS. 6A, 7A, 8A and 9A  utilize like numbers to those component within the earlier embodiment. Thus, by employing the automatic administration assembly  124  with the respective plunger  126  and, optionally, the dose markings  148  and guide markings  150 , the user can control the volumetric dose quantities within the syringe that is desired and provide automatic delivery to the patient. The plunger dose markings  148  may correspond to the relevant dose amounts desired by the user. The user may initially utilize the plunger  126 , such as by rotating the plunger  126 , to identify and select the desired dose amount by aligning the desired dose marking  148  with the guide marking  150 . Axial rotation of the plunger  126  causes the plunger  126  to axially translate, which motion is transferred by the above described mechanism to the screw  132 . Axial translation of the screw  132  in the distal direction causes drug fluid contained within the drug chamber of the syringe to be dispensed through the needle  118  of the barrel adapter assembly  110 . 
     Typically, once the desired dose has been identified and selected by the user, the remaining amount of drug fluid within the drug chamber  120  is substantially the exact amount desired to be injected. The needle  118  may then be disposed in the target tissue and by the administration mechanism  182  initiated by actuating the actuator  186  to unlock the locking mechanism  184  to deliver the drug to the target tissue. In the embodiments of the present invention intended for fill-at-time-of-use syringes, the plunger  126  and screw  132  may initially function in reverse (e.g., axially translate in the proximal direction) to draw-in drug fluid from a vial or container to fill the drug chamber of the syringe. In the embodiments of the present invention intended for retractable or safety syringes, the plunger  126  and screw  132  may function, substantially after the drug dose has been delivered, to initiate or engage a needle retraction or safety mechanism. These embodiments of the present invention are discussed in further detail below with reference to the accompanying figures. 
     Turning now to  FIG. 6A , there is illustrated an exemplary fill-at-time-of-use syringe  220  incorporating an embodiment of the dose control mechanism  100  and automatic administration assembly  124 , i.e., syringes which can be drawn back and filled with a drug treatment by the user. As with the embodiment of  FIGS. 2A-4B , the control mechanism  100  includes a plunger  126 , a housing  128 , an adapter  130 , and a screw  132  essentially as described above, including all possible modifications. The plunger  126  may include a button  140  as a unified or separate component. The housing  128  may optionally include housing cover  144  at its proximal end, for example, to close the interior of the housing  128  off from the environment and/or to axially align plunger  126  within housing  128 . The housing  128  may further include a window  146 , which may be an opening (e.g., an aperture) in the housing or a transmissive, translucent, and/or optically magnifying component. The plunger  126  may include one or more dose markings  148  on the external surface of the plunger  126 . The housing  128  may have one or more reference or guide markings, such as at the window  146 , with which to align plunger dose markings  148 . The control mechanism  100  may be attached, mounted, affixed, or otherwise connected at the proximal end of barrel  104  such that at least a portion of the screw  132  resides inside barrel  104 . 
       FIG. 6B  shows an enlarged isometric view of the distal portion of the drug delivery syringe  220  shown in  FIG. 6A . The screw  132  may be connected to plunger seal  114  either directly or indirectly to drive the axial translation of the plunger seal  114 . In the latter configuration, a plunger rod  170  may be utilized between screw  132  and plunger seal  114  to connect those components. The plunger rod  170  may be connected to the screw  132  at, for example, the screw connection aspect  136 . Optionally, a ring  138  near the distal end of the screw  132  may be utilized to facilitate the connection of the screw  132 , the plunger rod  170  and the plunger seal  114 . In this embodiment, a ring  138  is provided to facilitate integration of the control mechanism  100  with the syringe  220 , and center the distal portion  168  of the screw  132  within the barrel  104 . In at least one embodiment, the screw connection aspect  136  is coupled to the plunger rod  170  through a radial opening in the plunger rod, as illustrated in  FIGS. 6A-6B . Additionally or alternatively, this connection may be a snap-fit connection, an interference-fit connection, or a number of other connection methods known in the industry. In at least one other embodiment, the screw connection aspect is connected to the plunger rod through a proximal opening in the plunger rod such that the screw connection aspect sits within a proximal pocket in the plunger rod. Preferably, the connection between the screw  132  and the plunger seal  114 , or screw  132  and plunger rod  170  when a plunger rod is employed, is such that the screw is permitted to axially rotate while the plunger rod and/or the plunger seal remain rotationally fixed. Accordingly, as the plunger  126  and screw  132  of the control mechanism  100  are axially rotated and translated, the motion is relayed to the plunger seal  114  which is also axially translated. 
     In accordance with the invention, the dose control mechanism  100  further includes automatic administration assembly  124  substantially as described with regard to  FIGS. 2A-4B . By way of the automatic administration assembly  124 , the user may preselect the volume of drug to administer, then actuate the dose control mechanism  100  to deliver the drug without the user physically depressing the plunger  126 . The automatic administration assembly  124  includes an administration mechanism  182 , a locking mechanism  184 , and an actuator  186 . 
     In this embodiment, the automatic administration assembly  124  includes a biasing member  188 , a selection dial  190 , a locking pin  192 , and a dispense button  194 , here, further supported by an automation housing  195 , which may be formed as a separate component, or may be unitarily formed with or secured to the adapter  130 . 
     In this embodiment, the administration mechanism  182  includes the selection dial  190  and the biasing member  188 , substantially as described above. Accordingly, rotation of the selection dial  190  causes a corresponding rotation of the plunger  126 . Thus, by rotating the selection dial  190 , the user may adjust the dose to be administered, viewing the selected dose by way of the plunger dose markings  148  visible in the window  146 . 
     In order to maintain the selection dial  190  in the pre-dispensing position, the locking mechanism  184  includes the locking pin  192  is disposed against the selection dial  190  and maintained in position against the selection dial  190  by a slidably mounted locking arm  200 . Depression of the actuator  186 , that is, the dispense button  194 , moves the abutment surface  206  out of engagement with the distal end  210  of the locking pin  192 , allowing the locking pin  192  to move out of engagement with the selection dial  190 . 
     Similarly, the novel control mechanisms of the present invention may be utilized with pre-filled syringes, i.e., syringes which are filled with a drug treatment by the manufacturer and ready for injection by the user.  FIG. 7A  shows an embodiment of the dose control mechanism  100  as a component of an exemplary pre-filled drug delivery syringe  222 . As shown, the control mechanism  100  includes a plunger  126 , a housing  128 , an adapter  130 , and a screw  132 . Housing  128  may optionally include housing cover  144  at its proximal end, for example, to close the interior of the housing  128  off from the environment, to axially align plunger  126  within housing  128 , and/or to prevent the plunger  126  being accidently removed by the user/clinician. Housing  128  may further include a window  146 , which may be an opening (e.g., an aperture) in the housing or a transmissive or translucent component. Plunger  126  may include one or more dose markings  148  on the external surface of the plunger  126 . Housing  128  may have one or more reference or guide markings, such as at the window  146 , with which to align or view plunger dose markings  148 . The control mechanism  100  may be attached, mounted, affixed, or otherwise connected at the proximal end of barrel  104  such that at least a portion of the screw  132  resides inside barrel  104 . 
       FIG. 7B  shows an enlarged isometric view of the distal portion of the drug delivery syringe shown in  FIG. 7A . Screw  132  may be connected to plunger seal  236  either directly or indirectly to drive the axial translation of the plunger seal  236 . In the latter configuration, a plunger rod  234  may be utilized between screw  132  and plunger seal  236  to connect those components. The plunger rod  234  may be connected to the screw  132  at, for example, the screw connection aspect  136 . In at least one embodiment, the screw connection aspect is connected to the plunger rod through a proximal opening  10  in the plunger rod such that the screw connection aspect sits within a proximal pocket in the plunger rod. Additionally or alternatively, this connection may be a snap-fit connection such as in the embodiment illustrated in  FIGS. 7A and 7B , an interference-fit connection, or a number of other connection methods known in the industry. 
     In at least one embodiment, as is described further below with reference to  FIGS. 9A-9D , the screw, screw connection aspect  136 , and plunger rod are configured to be readily connectable after the drug chamber has been filled with a drug fluid and the plunger seal and plunger rod have been inserted into the proximal end of the barrel. Preferably, the connection between the screw  132  and the plunger seal  236 , or screw  132  and plunger rod  234  when a plunger rod is employed, is such that the screw is permitted to axially rotate while the plunger rod and/or the plunger seal remain rotationally fixed. Accordingly, as the plunger  126  and screw  132  of the control mechanism  100  are axially rotated and translated, the motion is relayed to the plunger seal  236  which is also axially translated. 
     The control mechanism  100  additionally includes an automatic administration assembly  124  substantially as described above. When utilized within a pre-filled syringe, the control mechanism  100  including the automatic administration assembly  124  is generally attached to the barrel  240  after the drug chamber  238  of barrel  240  has been filled with a drug fluid. This is often desired so that the syringe  222  may be filled and assembled in standard pharmaceutical fill-finish process lines. Once the syringe  222  has been filled and assembled, the control mechanism  100  may be utilized by the user to identify and set the selected drug dose for delivery. The user may then inject the needle into the patient and actuate the actuator  186  to cause the plunger  126  and screw  132  to axially translate. Because of the function of the control mechanism and the pitch ratio, any measure of distal translation of the plunger  126  causes only an incremental measure of distal translation of the screw  132 , permitting accurate dose delivery control by the user. Axial translation of the screw  132  causes axial translation of the plunger seal  236 . This axial motion in the distal direction of the plunger seal  236  forces drug fluid out of drug chamber  238  of barrel  240 , through the needle  254  of the barrel adapter assembly  250 , for injection and delivery to the patient. 
     It will be appreciated that the control mechanism  100  of the present invention may likewise be utilized with safety syringes, such as retractable needle safety syringes (i.e., syringes which incorporate needle safety mechanisms).  FIG. 8A  shows an embodiment of the dose control mechanism  100  as a component of an exemplary retractable drug delivery syringe  300 . As shown, the control mechanism  100  includes a plunger  126 , a housing  128 , an adapter  130 , and a screw  132 . Housing  128  may optionally include housing cover  144  at its proximal end, for example, to close the interior of the housing  128  off from the environment, to axially align plunger  126  within housing  128 , and/or to prevent accidental removal of plunger  126 . Housing  128  may further include a window  146 , which may be an opening (e.g., an aperture) in the housing or a transmissive, translucent, and/or a component providing optical magnification. Plunger  126  may include one or more dose markings  148  on the external surface of the plunger  126 . Housing  128  may have one or more reference or guide markings  150 , such as at the window  146 , with which to align or view plunger dose markings  148 . 
     The control mechanism  100  further includes the automatic administration assembly  124  substantially as described in this disclosure. The control mechanism  100  may be attached, mounted, affixed, or otherwise connected the barrel  104  such that at least a portion of the screw  132  resides inside barrel  104 . 
       FIG. 8B  shows an enlarged isometric view of the distal portion of the drug delivery syringe shown in  FIG. 8A . Screw  132  may be connected to plunger seal  336  either directly or indirectly to drive the axial translation of the plunger seal  336 . In the latter configuration, a plunger rod  334  may be utilized between screw  132  and plunger seal  336  to connect those components. The plunger rod  334  may be connected to the screw  132  at, for example, the screw connection aspect  136 . The screw connection aspect may be connected to the plunger rod in the configuration described above with reference to  FIGS. 6A and 6B , in the configuration described above with reference to  FIGS. 7A and 7B , or any number of other connection methods known in the industry. Preferably, the connection between the screw  132  and the plunger seal  336 , or screw  132  and plunger rod  334  when a plunger rod is employed, is such that the screw is permitted to axially rotate while the plunger rod and/or the plunger seal remain rotationally fixed. Accordingly, as the plunger  126  and screw  132  of the control mechanism  100  are axially rotated and translated, the motion is relayed to the plunger seal  336  which is also axially translated. The plunger  126  and screw  132  may function, substantially after the drug dose has been delivered, to initiate or engage a needle retraction or safety mechanism. 
     When utilized within a safety syringe, such as a retractable needle safety syringe, the plunger  126  of the control mechanism  100  is capable of engaging or initiating a needle safety mechanism. Suitably, the needle safety mechanism is facilitated by a biasing member such as a spring, elastic or other member capable of storing and releasing energy to facilitate needle retraction, needle sheathing, or any other method of protecting the user from accidental needle stick injuries. It will be appreciated that the safety syringe may comprise any needle safety mechanism, such as a needle retraction safety mechanism or needle sheathing safety mechanism, which is operable with the control mechanisms and syringes disclosed herein. By way of example, the needle safety mechanism may be a needle retraction safety mechanism as described in International Publication WO2006/119570, International Publication WO2006/108243, International Publication WO2009/003234, International Publication WO2011/075760, and/or U.S. patent application Ser. No. 13/693,915, although without limitation thereto. In at least one embodiment of the present invention, syringe  300  is a needle retraction safety syringe and incorporates the needle retraction safety mechanism  356  as disclosed in U.S. patent application Ser. No. 13/693,915. 
     Such a needle retraction safety mechanism  356  may be assembled to the syringe barrel  104 , for example as part of the barrel adapter assembly  350 , through the distal end of the barrel  104 . The control mechanism  100  is generally attached to the barrel  340  after the drug chamber  338  of barrel  340  has been filled with a drug fluid. This is often desired so that the syringe  300  may be filled and assembled in standard pharmaceutical fill-finish process lines. Once the syringe  300  has been filled and assembled, the control mechanism  100  may be utilized by the user to identify and set drug dose for delivery. The user may then inject the needle into the patient for drug delivery. Subsequently, the actuator  186  may be actuated to cause the plunger  126  and screw  132  to axially translate. Because of the function of the control mechanism and the pitch ratio, any measure of distal translation of the plunger  126  causes only an incremental measure of distal translation of the screw  132 , permitting accurate dose delivery control by the user. Axial translation of the screw  132  causes axial translation of the plunger seal  336 . This axial motion in the distal direction of the plunger seal  336  forces drug fluid out of drug chamber  338  of barrel  340 , through the needle  354  of the barrel adapter assembly  350 , for injection and delivery to the patient. At the end of drug delivery, the plunger seal  336  is caused to contact a component of the needle retraction safety mechanism  356  to initiate the retraction mechanism thereby causing retraction of the needle  354  into the barrel  340  of syringe  300 . The screw  132  and other components or the control mechanism  100  may be configured or adjusted to permit this additional range of axial  10  translation in the distal direction after the desired drug dose has been delivered. As the needle  354  is then retracted into the barrel  340  of syringe  300 , components of the needle retraction safety mechanism  356  bear and push against plunger seal  336  in the proximal direction. As that retraction force is continued, the user may control the rate of needle retraction by controllably reducing the force they apply on the button  140  and/or plunger  126  as the screw  132  and plunger  126  move in the proximal direction. The needle retraction safety mechanism  356  therefore provides a number of additionally desirable features to the novel syringes of the present invention. 
     As would readily be appreciated by one having ordinary skill in the art, the barrel adapter assembly may be attached, mounted, affixed, or otherwise connected to the distal end of the barrel by a number of known methods. For example, a luer connection may be utilized to connect the barrel adapter assembly to the syringe barrel. Luer connection systems are a standard way of attaching syringes, catheters, hubbed needles, IV tubes, and the like to each other. Luer connections consist of conical/tubular male and female interlocking components slightly tapered to hold together better. Luer connections can either be a “luer slip”, as shown in  FIGS. 6A and 6B , which are luer connections with a simple pressure or twist fit; or luer connections be a “luer lock”, as shown in  FIGS. 7A and 7B , which can have an additional outer rim of threading allowing them to be more secure. Alternatively, the connection may be facilitated by a barrel adapter connection. By way of example, the barrel adapter connection may be as described in International Publication WO2011/137488 and/or U.S. patent application Ser. No. 13/693,915, although without limitation thereto. Luer connections, interference fit connections, barrel adapter connections, or any number of other known connections may be utilized to attach the barrel adapter assembly to the barrel while remaining within the breadth and scope of the present invention. Regardless of the type of barrel adapter assembly utilized, the barrel adapter assembly generally comprises of a barrel tip  116 ,  252 ,  352  and a needle  118 ,  254 ,  354 , respectively. In some configurations, the barrel tip  116 ,  252 ,  352  may be a pre-formed aspect at the distal end of the barrel. Alternatively, the barrel tip  116 ,  252 ,  352  may be a separate component that is attached at the distal end of the barrel. The needle  118 ,  254 ,  354  may be any type of fluid conduit including, for example, a flexible cannula or a rigid needle, and may be made of any number of materials, including stainless steel. The type of connections described herein can be utilized regardless of the type of syringe with which they are shown. For clarity, the luer slip connection shown with the fill-at-time-of-use syringe in  FIGS. 6A and 6B  may be utilized with the pre-filled syringe in  FIGS. 7A and 7B , or any other type of connection may be used with any other type of syringe described herein. 
     As noted above, the dose control mechanism  100  of each of syringes  220 ,  222 ,  300 , further includes automatic administration assembly  124  substantially as described in this disclosure. The automatic administration assembly  124  includes an administration mechanism  182 , a locking mechanism  184 , and an actuator  186 . By way of the automatic administration assembly  124 , the user may preselect the volume of drug to administer, then actuate the dose control mechanism  100  to deliver the drug without the user physically depressing the plunger  126 . Thus, in use of each of the syringes  220 ,  222 ,  300 , the user first selects the desired volume of drug to be delivered using the selection dial  190 . The rotation of the selection dial  190  energizes the biasing member  188 , while the locking pin  192  held between the selection dial  190  and the abutment surface  206  of the locking arm  200 , that is, the locking mechanism  184 , locks the selection dial  190  with the biasing member  188  in the energized position. Upon a desired placement of the needle  118 , the dispense button  194  is depressed to actuate dispensing of the drug. With the selection dial  190  no longer held in position, the biasing member  188  deenergizes, imparting rotation to the plunger  126 . As explained in detail above, as the plunger  126  rotates by way of its course pitch thread  154  along the course pitch guide  156  of the housing  128 , the rotationally keyed screw  132  rotates along its fine pitch thread  158  engaged with the fine pitch nut  160  of the adapter  130 . The translational, axial movement of the screw  132  is transmitted to the plunger seal  114 , here, by way of plunger rod  170  to dispense the drug. 
     It will be appreciated from the foregoing that the novel dose control mechanisms and syringes disclosed herein provide an efficient and easily operated system for the accurate dose setting and delivery of drug treatments. Such devices are safe and easy to use, and are aesthetically and ergonomically appealing for clinical practitioners. The embodiments of the present invention overcome the challenges faced with the use of conventional syringes for the dosing and delivery of low-volume treatments by utilizing novel dose control mechanisms. The novel dose control mechanisms permit the user to accurately read and dose the desired volume of drug treatment for delivery to the patient. 
     Assembly and/or manufacturing of control mechanism  100 , syringe  102 , syringe  220 ,  222 ,  300  or syringe  400 , or any of the individual components may utilize a number of known materials and methodologies in the art. For example, a number of known cleaning fluids such as isopropyl alcohol and hexane may be used to clean the components and/or the devices. A number of known adhesives or glues may similarly be employed in the manufacturing process. For example, a glue or adhesive may be utilized to connect the distal end of the housing  128  to the proximal end of adapter  130 . Similarly, a glue or adhesive may be utilized to connect the distal end of adapter  130  to  15  the proximal end of the barrel. Additionally, known siliconization fluids and processes may be employed during the manufacture of the novel components and devices. Furthermore, known sterilization processes may be employed at one or more of the manufacturing or assembly stages to ensure the sterility of the final product. 
     In one embodiment, a method of assembling the control mechanism includes the steps of:
     (i) threading a fine pitch screw at least partially through a fine pitch nut of an adapter;   (ii) inserting a plunger through a selection dial and a biasing member,   (iii) threading the plunger, the plunger having a coarse pitch screw on its outer surface and an annular space within its inner surface, at least partially through an interior axial pass-through of a housing, wherein the housing interior has a corresponding coarse pitch guide;   (iv) inserting at least a proximal portion of the screw into the annular space of the plunger through a distal portion of the plunger;   (v) attaching the outer distal portion of the housing to a proximal aspect of the adapter;   (vi) disposing a locking pin between the selection dial and a locking arm; and   (vii) providing an actuator operatively connected to the locking arm.   

     The control mechanism may be utilized as a component of a syringe. In one embodiment, the method of manufacturing a syringe comprising a control mechanism includes the steps of:
     (i) mounting a barrel adapter assembly to a distal end of a syringe barrel;   (ii) mounting a plunger seal through a proximal end of the syringe barrel; and   (iii) mounting a control mechanism to the proximal end of the syringe barrel, wherein a portion of the control mechanism rests in contact with the plunger seal.   

     The method of manufacturing a syringe may further comprise, before the step of (ii) mounting a plunger seal through a proximal end of the syringe barrel, the step of: filling the barrel at least partially with a fluid substance. Step (iii) may further require the step of connecting a screw connection aspect of a screw of the control mechanism directly to the plunger or indirectly through a plunger rod which is connected at the proximal end of the plunger seal. The connection between the plunger rod and the plunger seal may be any number of connections including, but not limited to, screw-type connection, snap-fit connections, interference connections, capture connections, and the like. In at least one embodiment, the screw connection aspect is connected to the plunger rod through a radial opening or a proximal opening in the plunger rod such that the screw connection aspect sits within a proximal pocket in the plunger rod. Additionally or alternatively, this connection may be a snap-fit connection, an interference-fit connection, or a number of other connection methods known in the industry. Preferably, the connection between the screw and the plunger seal, or between the screw and plunger rod when a plunger rod is employed, is such that the screw is permitted to axially rotate while the plunger rod and/or the plunger seal remain rotationally fixed. 
     One preferred method of manufacturing a syringe having a dose control mechanism, according to one embodiment of the present invention, is described herein with reference to  FIGS. 9A-9D .  FIG. 9A  shows a pre-filled syringe, such as that described with reference to  FIGS. 7A-7B  above, except that the adapter is a two-component adapter having a proximal adapter portion  418 P and a distal adapter portion  418 D. An automation housing  495  may be formed with or secured to the distal adapter portion  418 D, as illustrated. Alternately, such an automation housing  495  may extend distally from the proximal adapter portion  418 P and ultimately be assembled around the distal adapter portion  418 D (not illustrated). Proximal adapter portion  418 P has one or more connection ports  418 E and distal adapter portion  418 D has corresponding connection prongs  418 F. When forced together, connection prongs  418 F and corresponding connection ports  418 E merge, mate, or otherwise connect to unite the two portions of the adapter  418 P,  418 D. 
     Initially, a cap  460  may be connected to the distal end of barrel  440  of syringe  400 . The distal adapter portion  418 D may be slidably mounted to the exterior of the barrel  440 . The interior of the barrel  440 , i.e. the drug chamber  438 , may be filled with a drug fluid or substance through the open proximal end of the barrel. The plunger seal  436  may be mounted into the barrel through the proximal end such that is in contact with the fluid. The optional plunger rod  434  may be connected to the plunger seal  436  prior to, or after, insertion of the plunger seal  436  into the barrel  440 . These steps may be performed in a sterile environment to maintain the container integrity and sterility of the drug treatment. 
     The remainder of the syringe may then be assembled in a non-sterile or sterile environment. The screw  132 , as a component of the control mechanism  100 , may then be connected to the plunger seal  436  or to the plunger rod  434  when a plunger rod  434  is employed. The distal adapter portion  418 D may then be slid in the proximal direction along the exterior of the barrel to connect to the proximal adapter portion  418 P as described above. The locking pin  192  may be slid through an aperture in the distal adapter portion  418 D, and brought into contact with the locking arm  200 . The connection between the distal adapter portion  418 D and the proximal adapter portion  418 P may capture a barrel flange  440 A aspect of the barrel  440  in order to retain the control mechanism  100  at the proximal end of the barrel  440 . 
     Various glues or adhesives may be utilized to ensure that such components and connections are retained in position during assembly, filling, manufacturing, transportation, storage, and operation of the novel devices of the present invention. The final assembly of the syringe, such as in the pre-filled syringe  400 , may appear as shown in  FIG. 9B , and with the automatic administration assembly  124  assembled thereto as illustrated in  FIG. 9C . This type of pre-filled syringe may be utilized when, for example, a syringe is to be filled with a standard amount of drug fluid by a pharmaceutical company or contract drug filler, when the drug dose is variably selectable by the user, when the needle length is variably selectable by the user, or in a number of other situations.  FIG. 9C  also shows the pre-filled syringe with a selectable needle that is attached via a luer lock connection, as described above. In such a scenario, the syringe may be held such that the distal end of the syringe is pointed upwards. The cap  460  (shown in  FIG. 9B ) may be removed and replaced by a barrel adapter assembly  450 . The barrel adapter assembly  450  includes a barrel tip  453  and needle  454  which may be selected by the user and attached to the pre-filled syringe just prior to use. The drug dose may be identified and selected by the user, as described above. Comparison of the pre-filled syringe  400  in  FIGS. 9C and 9D  clarifies the differences in the pre-filled syringe just prior to, and after, injection and delivery of the drug dose to the patient. Because of the pitch ratio between the plunger  126  and the screw  132 , screw  132  is caused to axially translated in the distal direction only incrementally or to a lesser distance when plunger  126  is depressed or axially translated in the distal direction (i.e., in the direction of solid arrow in  FIGS. 9C and 9D ). This difference in axial translation distance between plunger  126  and screw  132  is visible by comparing distances D 3  and D 4  in  FIGS. 9C and 9D . D 3  is the distance that plunger  126  axially translates while D 4  is the fractional distance that screw  132  axially translates. 
     Accordingly, the novel embodiments of the present invention provide dose control mechanisms, which allow for the accurate dosing and delivery of drug treatments, and drug delivery syringes which incorporate such control mechanisms. Such novel devices permit the identification and control of the dosage amount, permit the syringe to be “primed” (i.e., evacuated of air bubbles) prior to drug delivery, and ensure the accurate delivery of microliter volume dosages, all within a device size that is similar to commonly used conventional syringes available in the marketplace. Such novel devices are safe and easy to use, and are aesthetically and ergonomically appealing for clinical practitioners. The novel devices of the present invention provide these desirable features without any of the problems associated with known prior art devices. 
     A number of known filling processes and equipment may be utilized to achieve the filling steps of the syringe manufacturing process. The barrel assembly, needle, plunger seal, plunger rod, and other components described in these manufacturing and assembly processes may be as described above or may be a number of similar components which achieve the same functionality as these components. Throughout the specification, the aim has been to describe the preferred embodiments of the invention without limiting the invention to any one embodiment or specific collection of features. Various changes and modifications may be made to the embodiments described and illustrated without departing from the present invention. The disclosure of each patent and scientific document, computer program and algorithm referred to in this specification is incorporated by reference in its entirety. 
     In an alternative preferred embodiment, as shown in  FIG. 10 , the administration mechanism may include one or more electrical, mechanical, or electromechanical components  502  that, for example, act on the plunger, causing it to axially translate and axially rotate, as described further herein. As with the embodiments described above, torque may be transferred from the plunger to the fine pitch screw by way of the keyed interface, and from the fine pitch screw rotating as a result of engagement with the fine pitch nut to provide translational movement to the plunger seal, by way of a plunger  10  rod, if provided. The plunger rod preferably only axially translates, i.e. the plunger rod does not axially rotate, due to the slip fit with the screw. The plunger seal is caused to translate as it is connected or adjacent to the plunger rod, thereby delivering a drug or therapy to a user through a needle or cannula. 
     When an electrical, mechanical, or electromechanical arrangement  502  is utilized as the administration mechanism, the torque of such component is utilized to translate the plunger seal for drug delivery. In a particular embodiment, an electromechanical biasing member, such as a motor  504 , is employed to cause axial translation and axial rotation of the plunger. In such an embodiment, the administration mechanism may be coupled with the locking mechanism. That is, lack of actuation of a motor necessarily provides a locking mechanism, maintaining the plunger in a given position. The motor, such as a stepper motor, may be controlled by a myriad of actuators  506 , mechanisms or methodologies. For example, the motor, biasing member, and/or plunger may be controlled by a foot-operated actuator, a voice-activated actuator, or other such control or actuation mechanism. In at least one particular embodiment, the biasing member is controlled by a foot-operated actuation mechanism. In another particular embodiment, the biasing member is controlled by a voice-activated actuation mechanism. For example, the biasing member may be configured to deliver a predetermined volume of dose each time a user issues a command such as the word “dose.” In a preferred embodiment, these components may be configured to operate with the dose control mechanisms as described in International Publication WO2013/086167, although without limitation thereto. 
     In summary, in accordance with the invention, various embodiments of syringes include control mechanisms that include an automatic administration assembly having keyed members having respective thread pitches with a pitch ratio that determines the relative translational movement of a plunger seal, and an automatic administration assembly including an administration mechanism, a locking mechanism, and an activator. The administration mechanism may be, for example, a biasing member such as a spring, for example, a compression spring and/or a torsional spring. The administration mechanism, locking mechanism, and activator are configured such that actuation of the activator by the user manipulates the locking mechanism to permit the administration mechanism, such as a biasing member, to move from an initial energized state to a lower energy or deenergized state. In the case of an administration mechanism such as a motor, the activator permits movement of the administration mechanism from a locked state to administer the drug. In one embodiment, when the activation button is depressed, a locking pin of the locking mechanism is manipulated to release the plunger of the syringe. The biasing member is then permitted to act on the plunger, causing it to axially translate and axially rotate. Torque may be transferred from the plunger to the coarse pitch screw by way of a keyed interface, and from the fine pitch screw to the plunger seal as a result of the engagement of the fine pitch screw with the fine pitch nut, optionally by transferring force to the plunger seal by way of a plunger rod. The plunger rod preferably only axially translates, i.e. the plunger rod does not axially rotate, due to the slip fit with the screw. The plunger seal is caused to translate as it is connected or adjacent to the plunger rod, thereby delivering a drug or therapy to a user through a needle or cannula. When a torsional spring, or a torsional compression spring, is utilized as the biasing member, the torque of the spring is thus utilized to translate the plunger seal for drug delivery. These components may be configured to operate with the dose control mechanisms of essentially any design, either as an add-on or by being integrally formed with the syringe. 
     It will be appreciated that the foregoing description provides examples of the disclosed system and technique. However, it is contemplated that other implementations of the disclosure may differ in detail from the foregoing examples. All references to the disclosure or examples thereof are intended to reference the particular example being discussed at that point and are not intended to imply any limitation as to the scope of the disclosure more generally. All language of distinction and disparagement with respect to certain features is intended to indicate a lack of preference for those features, but not to exclude such from the scope of the disclosure entirely unless otherwise indicated. 
     The use of the terms “a” and “an” and “the” and “at least one” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The use of the term “at least one” followed by a list of one or more items (for example, “at least one of A and B”) is to be construed to mean one item selected from the listed items (A or B) or any combination of two or more of the listed items (A and B), unless otherwise indicated herein or clearly contradicted by context. 
     Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. 
     Accordingly, this disclosure includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the disclosure unless otherwise indicated herein or otherwise clearly contradicted by context.