Patent Description:
Many chemical and biological products (such as cell and gene therapies, pharmaceutical products, etc.) are manufactured in a "batch" method, meaning that a predetermined volume or "batch" is manufactured at a time. To ensure quality and efficacy of the product, each batch may undergo its own quality control (QC) testing to verify purity, potency, and sterility. Batch processing, however, inherently has limitations on batch size or batch volume and uses significantly more resources when compared to a continuous manufacturing method. Some processes, however, are not ideal candidates for continuous manufacturing.

For example, many of the fluids or products used in the manufacturing of cell and gene therapies are limited to batch manufacturing because they often require complex incubations as part of their workflows. Essentially, during the production process, some ingredients need to mix and then "incubate" for a specified period of time before the next ingredient(s) may be added. In some cases, multiple incubations may be required. In a batch manufacturing environment, this is easily achieved.

An alternative to batch processing is "continuous" processing, meaning that a manufacturing system outputs a product on a consistent basis. Continuous processing removes some of the costs and time constraints found in batch processing. It is also scalable to theoretically achieve any desired throughput. In contrast to batch processing, which may require each batch to undergo strict quality control testing, continuous processing is less resource dependent because quality tests and assays may be performed on a schedule.

In the bioprocessing industry, a standard method of continuous processing involves pumping fluid through sterile tube sets, also known as consumable sets. Peristaltic pumps are often used to transfer the fluid within these sterile tube sets. The benefit of peristaltic pumps is that they apply pressure external to the tubing to transfer fluid within it, effectively maintaining the sterility of the functionally-closed system. This design may be effective at transferring fluids within tubing, such as silicone, PVC or TPE.

However, it can be difficult to achieve proper manufacturing of certain products using continuous flow processing. In particular, it may difficult to achieve proper incubation of fluids when operating in a continuous flow fashion.

<CIT> describes a hose pump compris a housing with a circularly curving wall surface and a rotatable support means carrying a plurality of rollers. The support means is adapted to press said rollers against the circular wall surface and to cause the rollers to propel a fluid through a hose, a length of the hose being arranged between the wall surface and the rollers. The support means of the rollers is connected to the rollers by means of a displacing mechanism adapted to move the rollers into a squeezing engagement with the hose length in question when the support means is turned in the fluid propelling direction and to pull said rollers out of said engagement when said support means is turned in the opposite direction.

<CIT> describes a fluid pump of the compressible tube type, the pump comprising means for closing the tube progressively along its length at two points spaced apart longitudinally of the tube and means for automatically decreasing the distance between said two points during at least part of the pumping operation. During operation of a tube compressing mechanism the tubes are compressed successively by rollers. During compression of the tubes a pair of rails engage the ends of the rollers and rotate them on pivot pins inwardly towards a shaft against the force of springs. Thereby, a roller moves along the tubes towards an adjacent leading roller to shorten the portions of the lengths of the tubes engaged between the pair of rollers, thus causing an increase in pressure of the fluid in said portions.

<CIT> describes a pumping tube that may be lodged within a more resilient outer tube that may be mounted helically on a cylindrical drum and compressed by one or two planetary rollers. An aperture <NUM> may be provided at the upstream end of the pumping tube to allow working fluid e.g. blood, to enter an interspace <NUM>. The outer tube may alternatively have a bellows-like construction. Instead of roller, the tubes may be compressed by a gyrating outer drum.

<CIT> describes a peristaltic pumphead comprising a pumphead housing accommodating a pumping tube. A rotor extends along a pumphead axis through an end cap, an end wall, and a pumping chamber. The rotor is supported by bearings within the pumphead. The portion of the rotor projects from the pumphead and can be connected to a drive unit for driving the rotor. Regions of the end cap and the end wall through which the rotor extends are profiled such that they abut each other at the pumphead axis. A pressing element is arranged within the pumping chamber, and is coupled for rotation with the rotor. The pressing element has lobes which are arranged to press a tube, disposed about the pressing element, against an inner wall. The inner wall provides a pressing surface against which the tube is pressed.

The invention is defined in the annexed claims. Embodiments result from the dependent claims and the below description.

Disclosed is a fluid isolating pump for isolating volumes of liquid to allow the volumes of liquid to incubate for a predetermined amount of time. The fluid isolating pump mechanically and fluidically isolates small volumes of the fluid being incubated to allow for proper incubation of the resulting product.

The fluid isolating pump includes a rotating cage, one or more roller assemblies mounted on the rotating cage, a cam plate, and a non-rotating central shaft. The cage includes a front plate and a back plate connected by multiple connecting rods. Each roller assembly is rotatably attached to a corresponding connecting rod of the cage. Each roller assembly includes one or more arms rotatably attached to the connecting rod, a connecting bar coupled to the one or more arms, one or more levers rotatably attached to the connecting rod, one or more suspensions, and a roller. Each suspension is coupled to at least one arm and to at least one lever. The roller is coupled to the one or more levers. The cam plate includes multiple openings having a first end and a second end. The connecting rod of each roller assembly is configured to slide from the first end of the opening to the second end of a corresponding opening.

In some embodiments, the fluid isolating pump additionally includes a central gear mounted on the non-rotating central shaft. In addition, the fluid isolating pump may include multiple peripheral gears. Each peripheral gear may be mounted to a corresponding connecting rod of the cage. Moreover, the peripheral gears may be engaged to the central gear.

In some embodiments, the roller assembly further includes a roller gear coupled to the roller of the roller assembly. The roller gear may be engaged with a corresponding peripheral gear.

In some embodiments, the peripheral gears are configured to rotate around the central gear as the cage rotates around the non-rotating central shaft.

In some embodiments, the roller gear of a roller assembly is configured to rotate the roller based on the rotation of the corresponding peripheral gear.

In some embodiments, a roller assembly is in a disengaged position when the connecting bar of the roller assembly is in the first end of the corresponding opening, and wherein the rollers assembly is in an engaged position when the connecting bar of the roller assembly is in the second end of the corresponding opening.

In some embodiments, the roller of the roller assembly is compressing a tubing of the consumable when the roller assembly is in the engaged position. In some embodiments, when the roller assembly is in the engaged position, the cam plate applies a pressure to the connecting bar of the roller assembly, compressing the one or more suspensions.

In some embodiments, the non-rotating central shaft has a non-circular cross section.

In some embodiments, the fluid isolating pump additionally includes a motor coupled to the cage. The motor axially is aligned with the non-rotating central shaft. The motor is configured to rotate the cage around the non-rotating central shaft.

Additionally, disclosed is a roller assembly to be used in a fluid isolating pump for isolating volumes of liquid to allow the volumes of liquid to incubate for a predetermined amount of time. The roller assembly is configured to be mounted on an axle. The roller assembly includes one or more arms configured to be rotatably attached to the axle, a connecting bar coupled to the one or more arms, one or more levers configured to be rotatably attached to the axle, one or more suspensions, each suspension coupled to at least one arm and to at least one lever, and a roller coupled to the one or more levers.

In some embodiments, the roller assembly further includes a roller gear coupled to the roller of the roller assembly. The roller gear is configured to control a rotation of the roller. Moreover, in some embodiments, the roller assembly further includes a peripheral gear configured to be rotatably attached to the axel. The peripheral gear is configured to be coupled to a central gear. The peripheral gear is additionally configured to control a rotation of the roller gear.

In some embodiments, the roller assembly further includes an auxiliary gear between the roller gear and the peripheral gear. The auxiliary gear is configured to reverse a direction or rotation of the roller gear.

In some embodiments, in an engaged position, the connecting bar of the roller assembly is configured to receive a force compressing the one or more suspensions. In some embodiments, the one or more suspensions are configured to apply a compressive force to the roller to press the rollers against a consumable. In some embodiments, the one or more suspensions may be a spring suspension, a hydraulic suspension, or a pneumatic suspension.

Additionally, disclosed is a consumable to be used in a fluid isolating pump for isolating volumes of liquid to allow the volumes of liquid to incubate for a predetermined amount of time. The consumable includes a rigid tube and a tubing wrapped around the rigid tube. In some embodiments, the rigid tube has a substantially cylindrical shape. Moreover, in some embodiments, the rigid tube has a hollow center.

In some embodiments, the rigid tube has an inlet hole and an outlet hole. The inlet hole and the outlet hole may match an outer diameter of the tubing.

In some embodiments, the consumable additionally includes a back endcap coupled to a first end of the rigid tube and a front endcap coupled to a second end of the rigid tube. The back endcap includes a mounting hole to mount the consumable on an axle. The front endcap includes one or more openings to allow the tubing from entering or exiting the hollow center of the rigid tube.

In some embodiments, the tubing is made of an elastic material.

In some embodiments, the consumable additionally includes electrical connections for transmitting electrical signals to the fluid isolating pump and to receive electrical signals from the fluid isolating pump.

In some embodiments, the consumable additionally includes sensors for determining a property of a liquid flowing through the tubing. For example, a sensor may be a bubble sensor.

In some embodiments, the consumable additionally includes pumps for controlling an intake of fluid into the tubing of the consumable.

In some embodiments, the consumable additionally includes a thermal element (such as a heating element, a cooling element, or a combination thereof) to control a temperature of a fluid disposed inside the tubing. In some embodiments, the consumable additionally includes a temperature sensor to track the temperature of the fluid disposed inside the tubing.

The teachings of the embodiments can be readily understood by considering the following detailed description in conjunction with the accompanying drawings.

The figures (FIG. ) and the following description relate to preferred embodiments by way of illustration only. It should be noted that from the following discussion, alternative embodiments of the structures and methods disclosed herein will be readily recognized as viable alternatives that may be employed without departing from the principles of the embodiments.

It is noted that wherever practicable, similar or like reference numbers may be used in the figures and may indicate similar or like functionality. The figures depict embodiments for purposes of illustration only.

To facilitate understanding of the invention, a number of terms and abbreviations as used herein are defined below as follows:.

As used herein, the term "fluid" refers to a substance that flows continuously under an applied shear stress, wherein the substance is in liquid, gas, or plasma phases. As stated above, materials used for cell and gene therapies are examples of fluids that may include biological and non-biological components.

Batch production. As used herein, the term "batch production" refers to a method of manufacturing which can go through a series of steps to make the target product across a number of sets or batches, and steps which often vary across the sets or batches.

Continuous production. As used herein, the term "continuous production" refers to a method of manufacturing that occurs without interruption over a manufacturing time period.

Large molecule: As used herein, the term "large molecule" refers to a protein, synthetic polymer, antibody, lipid, carbohydrate, nucleic acid, or other entities which exceed <NUM> atoms.

Small molecule. As used herein, the term "small molecule" refers to an organic and inorganic molecule which does not exceed <NUM> atoms.

<FIG> shows a block diagram of a system for continuous in-line incubation, according to one embodiment. As shown in <FIG>, fluid from two vessels may be pumped into a common tube in an effort to incubate the two fluids for a period of time before ultimately entering an output vessel. Peristaltic pump <NUM> can rotate clockwise to transfer fluid from vessel <NUM> through tube <NUM> and into tube <NUM>. Concurrently, peristaltic pump <NUM> can rotate counterclockwise to transfer fluid from vessel <NUM> through tube <NUM> into tube <NUM>. Additionally, the length of tube <NUM> can be designed to be sufficient to contain fluids from vessels <NUM> and <NUM> for the duration of the desired incubation. After the incubation time is complete, the two fluids enter output vessel <NUM>.

In some embodiments, at the end of tube <NUM>, a third reagent may be mixed with the incubated fluid. For example, tube <NUM> may be connected to T-fitting that connects the tube <NUM> with a third pump that dispenses the third reagent.

The system shown in <FIG> is more effective when the friction of the inner surface of the tube <NUM> is low or when the effect of the friction is negligible (e.g., for short incubation times over a relatively short length of tube, or when only a small amount of reagents are being processed). As shown in <FIG>, without friction between the tubing and the fluid, the velocity of fluid near the tubing wall would be the same as at the center of the tubing. The length of each arrow represents its relative velocity. However, when the effect of the friction is more pronounced, this friction results in adhesive forces between the fluid and the inner walls of tube <NUM>. As shown in <FIG>, the relative velocity profile within tube <NUM> is parabolic. Fluid at the fluid-tube boundary has zero velocity or near zero velocity, while fluid at the center of the tube has the highest relative velocity.

This property of fluid-dynamics may prevent adequate incubation within tubing (e.g., tube <NUM>) because, even with the pump speeds of pump <NUM> and <NUM> remaining constant, the fluids from vessels <NUM> and <NUM> are not maintained at the correct ratios for the duration of the incubation. If collected and analyzed over a period of time, the incubated fluid entering output vessel <NUM> will contain inconsistent amounts of each ingredient and the fluid entering output vessel <NUM> will contain molecules that have experienced different incubation times, some more and some less than the desired time.

If the friction of the inner surface of the tube <NUM> is significant, a fluid isolating pump may be used in conjunction with the tube <NUM> to mechanically and fluidically isolate small volumes of the fluid being incubated, and to help each small volume of fluid to move in tandem as they travel through the tube <NUM>.

In a continuous in-line incubation process using a fluid isolating pump, two or more fluids are combined and mixed prior to entering a long tube. Upon entering the long tube, the fluid is segmented into small volumes by means of mechanical rollers external to the tubing and then progressed down the length of the tube. Each small volume of fluid remains mechanically and fluidically isolated as the volume of fluid travels along a length of a tubing. Each fluid segment will move from a first end to a second end of the tubing in an amount of time equal to, or approximately equal to, the desired incubation time. As incubated fluid continuously exits at the second end, new non-incubated fluid is continuously drawn into the first end of the tubing.

Since each volume of fluid is isolated as it travels through the tubing, and therefore cannot communicate or interact with adjacent isolated segments of fluid, the system can ensure adequate incubation of the fluid while maintaining a continuous manufacturing method. As such, a continuous in-line incubation process using a fluid isolating peristaltic pump mitigates many of the limitations and problems that are associated with batch manufacturing. Example processes that may utilize continuous in-line incubation include the manufacturing of thioamide and the manufacturing of recombinant proteins. Some example processes that may benefit from a continuous in-line incubation process are explained in more detail hereinbelow.

<FIG> and <FIG> show block diagrams of different configurations of a system for continuous in-line incubation, according to other embodiments. <FIG> and <FIG> show perspective views of some of the components of the system shown in <FIG>, according to one embodiment. In the example of <FIG> and <FIG>, a bulk reagent (liquid A) (e.g., acetophenone in the manufacturing of thioamide) is to be mixed with other reagents (liquids B and C) (e.g., morphine and S<NUM> in the manufacturing of thioamide). The bulk reagent is typically the reagent with the highest relative volume. The bulk reagent may be stored in a bag <NUM>, while other reagents may be stored in syringes <NUM>. The syringes are installed on a syringe pump <NUM> which is capable of accurately and independently dispensing the contents of both syringes. In some embodiments, as shown in the configuration of <FIG>, the bag <NUM> is connected to a pump <NUM> (e.g., a peristaltic pump or a gear pump) to control the dispensing of the bulk reagent. In other embodiments, as shown in the configuration of <FIG>, the fluid isolating pump <NUM> is used to control the dispensing of the bulk reagent. As such, in this embodiment, pump <NUM> may be omitted because the fluid isolating pump will draw or pull the bulk reagent during operation.

Fluidic junction <NUM> is a junction where liquids A, B, and C intersect. The fluidic junction <NUM> is coupled to a mixer <NUM> where liquids A, B, and C mix. For example, in the configuration shown in <FIG>, the mixer <NUM> may be an active mixer. Here, the pump <NUM> draws liquid A from bag <NUM> into the active mixer while syringe pump <NUM> doses contents from syringes <NUM> into the active mixer. The active mixer may include a sterile container having blades coupled to a motor. As the blades rotate, the blades provide agitation that causes the liquids held inside the sterile container become homogenous. In some embodiments, the liquid to be mixed is provided and mixed in batches. For example, the pumps <NUM> and <NUM> are configured to pump liquids A, B, and C into the active mixer when the fluid level inside the mixer reaches a lower threshold, and stops dispensing the liquids into the active mixer when the fluid level inside the mixer reaches an upper threshold. In another example, in the configuration shown in <FIG>, the mixer <NUM> may be a static mixer. The output of the mixer <NUM> is then coupled to a fluid isolating pump <NUM> to allow the mixed fluid to incubate or react for a specified amount of time.

In some embodiments, the fluid isolating pump is then coupled to a fluidic junction <NUM> where the output of the fluid isolating pump is intersected with an additional reagent (liquid D) (e.g., nickel (II) chloride solution in the manufacturing of thioamide). Liquid D may be stored in a reservoir <NUM>. In some embodiments, the additional reagent is pumped to the fluidic junction <NUM> by means of a peristaltic pump <NUM>. The final product is then collected or distributed to a collection reservoir <NUM>.

Fluid isolating pump <NUM> supports the continuous production or manufacturing of various fluidic chemistries historically restricted to batch processing. The fluid isolating pump <NUM> allows for the continuous production of liquid products by providing the capability of performing complex incubations in a continuous flow environment within a functionally-closed (sterile) system.

Using peristalsis, the fluid isolating pump <NUM> is capable of isolating predetermined volumes of fluid (e.g., liquid) within a continuous flow environment (e.g., a tube) to facilitate incubation or biological/chemical reaction(s). The system achieves fluid isolation by compressing portions of a tubing using multiple rollers that traverse the length of the tubing. As the rollers move from one end of the tubing to an opposite end of the tubing, the fluid that is confined within the space between two rollers is isolated from the rest of the fluid. Moreover, as the rollers traverse the length of the tubing, the compression of the tubing forces the fluid to also move across the length of the tubing.

<FIG> shows a cross-sectional view of a tubing in an uncompressed state. The tubing <NUM> is disposed over a rigid surface <NUM>. In an uncompressed state, center of the tubing <NUM> is open and may enclose a fluid that can travel through/along the tubing.

<FIG> shows a cross-sectional view of a tubing in a compressed state. In the compressed state, roller <NUM> applies a compressive force to the tubing <NUM>. As the gap between the roller <NUM> and the rigid surface <NUM> decreases, the opening at the center of the tubing <NUM> collapses, isolating a fluid on one side of the collapsed region from the fluid at the opposite side of the collapsed region. That is, fluid is prevented from traveling across the compressed portion of the tubing.

<FIG> shows a perspective view of a tubing for use in a fluid isolating pump, according to one embodiment. In the embodiment of <FIG>, the tubing is configured to have a helical structure. The tubing <NUM> may be wound into a helix while maintaining an input port <NUM> and an output port <NUM>. The geometry of a helical tubing <NUM> allows for a significantly larger fluid volume in a smaller footprint when compared to a linear embodiment. This results in a higher throughput from a smaller device. Elongated rollers, which apply pressure across the length of the helix are able to provide mechanical and fluidic isolation. In some embodiments, the tubing may be configured in structures other than a helix. For example, the tubing may be configured having a linear structure, a zigzag pattern, and the like. Various configurations of the tubing are described below.

There are two proposed configurations herein for implementing a fluid isolating pump using a helical tubing. In the first configuration, a force or pressure is applied from the outside of the helical tubing. This configuration is referred to as an "external roller pump. " In the second configuration, a force or pressure is applied from the inside of the helical tubing. This configuration is referred to as an "internal roller pump.

The helical tubing may be multiple individual tubes or a single tube with multiple coils around a cylindrical rigid tube. The chambers in each loop of the helical tubing are individually isolated for incubation, reaction, or other operations.

<FIG> shows a perspective view of an "external roller pump," according to one embodiment. <FIG> shows a perspective view of the external roller pump with a consumable inserted, according to one embodiment. <FIG> shows a perspective view of an external roller pump inside an external enclosure, according to one embodiment. <FIG> show perspective views of an external roller pump with a graphical user interface and peripheral components, according to one embodiment.

The external roller pump is a fluid isolating pump <NUM> configured to have rollers positioned radially outward from the tubing or consumable. The fluid isolating pump <NUM> shown in <FIG> has a roller pump assembly <NUM> and a consumable assembly <NUM>. In some embodiments, other components of the continuous in-line incubation system <NUM>, such as pump <NUM>, syringe pumps <NUM>, fluidic junction <NUM>, or mixer <NUM>, may be attached to the roller pump assembly <NUM>.

The roller pump assembly <NUM> includes a rigid base <NUM>, a motor <NUM>, a cage <NUM>, one or more roller assemblies <NUM>, one or more cam plates <NUM>, a cam brake <NUM>, a non-rotating central shaft <NUM>, a central gear <NUM>, and control electronics <NUM>. In some embodiments, the roller pump assembly <NUM> additionally includes an external enclosure <NUM> to protect the components, to assist with thermal insulation, to prevent a user from improperly operating the components of roller pump assembly <NUM>, and to improve safety in the operation of the roller pump assembly <NUM>.

The rigid base <NUM> provides a structure to support the various components of the roller pump assembly <NUM>. In some embodiments the rigid base <NUM> is made of a sturdy material such as a metal. In some embodiments, the base includes mounting holes to secure the roller pump assembly <NUM> to an external surface, such as to a table or workbench, to reduce the vibrations resulting from the operation of the fluid isolating pump. In the embodiment shown in <FIG>, the rigid base further includes a vertical mounting structure. The vertical mounting structure provides surfaces for mounting some of the components of the roller pump assembly <NUM>.

The non-rotating central shaft <NUM> is mounted to the vertical mounting structure of the rigid base <NUM>. The non-rotating central shaft <NUM> provides an interface to attach to the consumable <NUM>. For example, the non-rotating central shaft <NUM> has a cross-section (e.g. a hexagonal cross section) that matches a shape of central hole of the consumable <NUM>.

In some embodiments, if the consumable includes thermal control and measurement devices, then heat is evenly distributed to the fluid within the tubing based on the secured position of the non-rotating central shaft <NUM>. Heat can be continuously sent to other regions from the secured position. This can reduce variability during production runs as a consistent heat profile is maintained. Large scale biopolymer synthesis and protein functionalization are often difficult to reproduce due to conformational dynamics and inherent distribution of varied molecular weights. Thermal runways which can impact polydispersity and induce variability in polymeric structures can be minimized or eliminated by securing the position of the thermal control and measurement devices.

The central gear <NUM> is configured to be mounted on the non-rotating central shaft <NUM>. In some embodiments, the central gear <NUM> has a central opening that matches the cross-section of the non-rotating central shaft <NUM>. As such, similar to the non-rotating central shaft <NUM>, the central gear <NUM> is also configured to be non-rotating.

Motor <NUM> is mounted to the rigid base <NUM>. In some embodiments, the motor <NUM> is mounted on the vertical mounting structure of the rigid base <NUM>. In some embodiments, the motor <NUM> is a hollow rotary actuator. A hollow rotary actuator is a motor that includes a rotating disc (also referred to as a rotating table) that has a hollow center. The hollow rotary actuator is positioned such that the center of the rotating disc is axially aligned with the non-rotating central shaft <NUM>. As such, the hollow rotary actuator allows the central shaft <NUM> and the consumable <NUM> to remain stationary while other components, such as the cage <NUM> and the roller assemblies <NUM> rotate about the non-rotating central shaft <NUM>.

The cage <NUM> is mounted to the motor <NUM> and provides an interface to mount the roller assemblies <NUM>. The cage <NUM> is described in more detail hereinbelow in conjunction with <FIG> and <FIG>.

The roller assemblies <NUM> are attached to the cage <NUM> and are configured to press a tubing of the consumable <NUM>. In some embodiments, the roller pump assembly <NUM> includes six roller assemblies. In other embodiments, the roller pump assembly <NUM> includes more or less roller assemblies depending on the size of the fluid isolating pump and the parameters of the process being run. The roller assemblies <NUM> are described in more detail hereinbelow in conjunction with <FIG> and <FIG>.

The cam plate <NUM> interfaces with the roller assemblies <NUM> to position the roller assemblies <NUM> in an engaged or a disengaged position. In the disengaged position, the rollers assemblies <NUM> are positioned such that pressure is not applied to the consumable <NUM>. This position allows for the installation or removal of the consumable <NUM>. In the engaged position, the roller assemblies <NUM> are positioned such that pressure is applied to the consumable <NUM>. This is the position of the roller assemblies <NUM> during normal operation of the fluid isolation pump. The pressure applied by the roller assemblies <NUM> allows for the mechanical isolation of the fluid as the fluid traverses the consumable <NUM>. The cam plate <NUM> is described in more detail hereinbelow in conjunction with <FIG>.

Cam brake <NUM> is mounted on the rigid base <NUM>. The cam brake <NUM> may be used to prevent or permit the rotation of cam plate <NUM>. When engaged, cam plate <NUM> is prevented from rotating. Since each roller assembly <NUM> is connected to the cam plate <NUM>, the roller assemblies <NUM> drive radially inward or radially outward depending on the direction of motor <NUM>. Cam brake <NUM> may be engaged by a pin, by a pneumatic or hydraulic brake caliper, or by other mechanisms for achieving the same outcome.

<FIG> shows a perspective view of the front of the rigid base <NUM>, according to one embodiment. <FIG> shows a perspective view of the back of the rigid base <NUM>, according to one embodiment. <FIG> shows a front view of the rigid base <NUM>, according to one embodiment.

The rigid base <NUM> provides a rigid body to mount the various components of the roller pump assembly <NUM>. The rigid base <NUM> may be constructed of metal, or any suitable rigid material. The rigid base <NUM> includes a vertical mounting structure <NUM>. In the embodiment of <FIG>, the vertical mounting structure has two vertical supports and a mounting plate attached to the vertical supports.

The motor <NUM> is attached to the mounting plate of the vertical mounting structure <NUM>. Similarly, the non-rotating central shaft <NUM> is also attached to the mounting plate of the vertical mounting structure <NUM>. As such, both the motor <NUM> and the non-rotating central shaft <NUM> are secured to the rigid base <NUM> and are prevented from moving relative to the rigid base <NUM>. Moreover, the components that are directly attached to the non-rotating central shaft <NUM> are also prevented from rotating relative to the rigid base <NUM>. However, the components that are attached to the output table or output shaft of the motor <NUM> are allowed to rotate relative to the rigid base <NUM>.

In some embodiments, the rigid base <NUM> includes rollers <NUM>. Rollers <NUM> provide support and aid in maintaining axial alignment for one or more rotating components of the roller pump assembly <NUM>. For example, the rollers <NUM> shown in <FIG> provide support for the cam plate <NUM>. However, the rigid base <NUM> may also include rollers for providing support to the cage <NUM>.

In some embodiments, the rigid base <NUM> provides a mounting surface for additional components such as auxiliary pumps (e.g., one or more peristaltic pumps, and one or more syringe pumps), static mixers, dynamic mixers, fluidic junctions, and the like. Moreover, the rigid base <NUM> provides a mounting surface for electronics <NUM> to control the motor <NUM>, cam brake <NUM>, and auxiliary pumps. The electronics <NUM> may include a digital interface (e.g., a Universal Serial Bus (USB) interface), a motor driver, and an alternating current (AC) to direct current (DC) converter. The electronics <NUM> may further include a user interface <NUM> such as one or more buttons or a touch screen to control set operating parameters of the fluid isolating pump. The electronics <NUM> may further include a system controller that reads data from various internal and/or external sensors, and controls the motor drivers. The system controller may be a single board computer, an application specific integrated circuit (ASIC), a system-on-a-chip (SoC), or the like.

<FIG> shows a perspective view of the cage <NUM>, according to one embodiment. <FIG> shows a perspective view of the cage <NUM> having peripheral gears, according to one embodiment. The cage <NUM> is mounted to the motor <NUM> and provides an interface to mount the roller assemblies <NUM>. The cage <NUM> is configured to rotate during operation. In some embodiments, the cage <NUM> is directly mounted to the motor <NUM>. For example, the cage <NUM> is secured to a rotating table of a hollow rotary actuator. In other embodiments, the cage <NUM> is coupled to the motor via one or more gears or belts.

The cage <NUM> includes a front plate <NUM>, a back plate <NUM>, and one or more connecting rods <NUM>. In some embodiments, the cage <NUM> further includes peripheral gears <NUM> that are configured to be linked to the central gear <NUM>. In some embodiments, the front plate <NUM> and the back plate <NUM> are metal plates, however, other suitable materials are also possible. Moreover, in some embodiments, the connecting rods <NUM> are metal rods however, other suitable materials are also possible.

The connecting rods <NUM> have a front end and a rear end. The front end of each connecting rod <NUM> is attached to the front plate <NUM>. The rear end of each connecting rod <NUM> is attached to the back plate <NUM>. In some embodiments, the connecting rods <NUM> are attached to the front and back plates with screws. In other embodiments, the connecting rods <NUM> are welded to the front and back plates. In yet other embodiments, other suitable methods for attaching the connecting rods <NUM> to the front plate <NUM> and the back plate <NUM> may be used.

The connecting rods <NUM> are constructed of a metal, such as steel, or any other suitable material. In addition to connecting the front plate <NUM> and the back plate <NUM>, the connecting rods provide an attaching point to other components of the roller pump assembly <NUM>. For instance, the connecting rods <NUM> provide an attaching point for the roller assemblies <NUM>. Moreover, the connecting rods <NUM> may have a circular cross-section to allow for relative rotation of components installed. For example, the connecting rods <NUM> serve as pivots for the roller assemblies <NUM>. In the example of <FIG>, there are six roller assemblies, and thus there are six units of connecting rods <NUM>, however, other number of rods may be used depending on the application.

The front plate <NUM> adds rigidity and strength to the cage <NUM>. Moreover, the front plate <NUM> provides a connecting point to the connecting rods <NUM> to increase the parallelism of the connecting rods <NUM>. The front plate <NUM> may have a circular shape, however, other shapes are also possible. Moreover, the front plate <NUM> may be constructed of a metal, however, any other suitable material may also be used. The front plate <NUM> has an opening <NUM>. In some embodiments, the front opening <NUM> has a circular shape. The front opening <NUM> allows the consumable <NUM> to be inserted inside the cage <NUM>. Thus, the size of the front opening <NUM> is larger than the diameter of the consumable <NUM>. In some embodiments, the front opening <NUM> is axially aligned with the center of rotation of the cage <NUM>. Moreover, in some embodiments, the front opening <NUM> is aligned with the center of the front plate <NUM>.

The back plate <NUM> may have a circular shape, however, other shapes are also possible. The back plate <NUM> has an opening <NUM>. In some embodiments, the back opening <NUM> has a circular shape. In some embodiments, the back opening <NUM> is aligned with the center of rotation of the cage <NUM>. Moreover, in some embodiments, the back opening <NUM> may be aligned with the center of the back plate <NUM>. The back opening <NUM> is configured to allow the non-rotating central shaft <NUM> to go through the back opening <NUM>. Thus, the size of the back opening <NUM> is larger than the cross-section of the non-rotating central shaft <NUM>.

In some embodiments, the back plate <NUM> further includes one or more peripheral openings <NUM>. The peripheral openings <NUM> allow a portion of the roller assemblies <NUM> to penetrate. For example, the peripheral openings <NUM> allow gears of the roller assemblies <NUM> to move radially inward and outward as the roller assemblies are moved back and forth between an engaged and a disengaged position.

In some embodiments, the cage <NUM> further includes peripheral gears <NUM>. The central gear <NUM> and the peripheral gears <NUM> may form a planetary gear system, wherein the central gear <NUM> is the sun gear and the peripheral gears <NUM> are the planet gears. The central gear <NUM> is aligned with the center of rotation of the cage <NUM>. Moreover, each peripheral gear <NUM> is axially aligned with a connecting rod <NUM>. In some embodiments, each peripheral gear <NUM> is mounted on a corresponding connecting rod <NUM>. In this embodiment, the peripheral gears <NUM> are configured to be able to rotate about the corresponding connecting rod <NUM>. The peripheral gears <NUM> are configured to be linked to a gear of a corresponding roller assembly <NUM>. The central gear <NUM> and the peripheral gears <NUM> allow the rollers of the roller assemblies <NUM> to rotate with a rotational velocity that is proportional to the rotational velocity of the cage <NUM>.

<FIG> and <FIG> show perspective views of a roller assembly <NUM>, according to one embodiment. The roller assemblies <NUM> are attached to the cage <NUM> and are configured to compress a tubing of the consumable <NUM>. Although the embodiments below are described using rollers, other embodiments may use structures that do not roll (e.g., structures that slide along the tubing instead of rolling).

The roller assembly <NUM> includes a front arm 910A, a back arm 910B, a front lever 915A, a back lever 915B, a front suspension 920A, a back suspension 920B, a connecting bar <NUM>, a roller <NUM>, and one or more gears <NUM>. In some embodiments, the roller assembly <NUM> further includes one or more bearings or bushings <NUM> to allow the front and back arms <NUM>, and the front and back levers <NUM> to rotate. Moreover, in some embodiments, the roller assembly <NUM> further includes one or more bearings or bushings <NUM> mounted on the connecting bar <NUM> to reduce friction between the connecting bar <NUM> and the cam plate <NUM>.

The front arm 910A and the back arm 910B are configured to pivot about the connecting bar <NUM> of the cage <NUM>. The front arm 910A and the back arm 910B transfer forces from the cam plate <NUM> into the suspensions <NUM> to press the roller <NUM> onto the consumable <NUM>.

The front arm 910A is connected to the back arm 910B by the connecting bar <NUM>. In some embodiments, the connecting bar has a bushing <NUM> that is configured to interface with the cam plate <NUM>. In some embodiments, the bushing <NUM> includes shaft collars <NUM> on either side that are configured to align the cam plate <NUM> perpendicular to the axis of rotation and prevent the cam plate <NUM> from moving axially along the connecting bar <NUM>. That is, the shaft collars <NUM> prevent the cam plate <NUM> from sliding to the back or the front of the roller assembly <NUM>. In some embodiments, the shaft collar <NUM> includes a shaft clamp, such as an e-ring.

In some embodiments, the front arm 910A has a bearing or bushing 960A. Similarly, the back arm 910B has a bearing or bushing 960B. The bearings <NUM> are configured to have a size corresponding to the connecting rods <NUM> of the cage <NUM>. As such, the connecting rods <NUM> of the cage <NUM> are configured to go through the bearings <NUM> of a corresponding roller assembly <NUM>, thus, attaching the roller assembly <NUM> to the cage <NUM>.

The front lever 915A and the back lever 915B are configured to pivot about a connecting rod <NUM> of the cage <NUM>. The front lever 915A and the back lever 915B transfer forces from the suspensions <NUM> into the roller <NUM>.

The front lever 915A is connected to the front arm 910A through the front suspension 920A. The back lever 915B is connected to the back arm 910B through the back suspension 920B. The front suspension 920A and the back suspension 920B transfer force from the cam plate <NUM> to push the roller <NUM> onto the consumable <NUM>. In some embodiments, the front and back suspensions <NUM> are spring suspensions. In other embodiments, the front and back suspensions <NUM> are hydraulic suspensions. In yet other embodiments, the front and back suspensions <NUM> are pneumatic suspensions. In yet other embodiments, any other suitable type of suspension may be used. In some embodiments, the front and back suspensions <NUM> have an adjustable preload. As such, the force applied to the roller <NUM> may be controlled based on the application.

The front and back suspensions <NUM> provide adjustability in the force applied by the rollers <NUM>. That is, the front and back suspensions <NUM> allow for the fluid isolation pump to correct for a variation in the thickness of the consumable <NUM> used. For example, when a thicker tubing is used in the consumable <NUM>, a larger force may be used to provide sufficient fluid isolation. Since a thicker tubing would provide a larger amount of compression of the front and back suspensions <NUM>, the front and back suspensions <NUM> would provide a larger amount of force to the rollers <NUM>. Moreover, the front and back suspensions <NUM> allow for the fluid isolation pump to account for variability in the manufacturing of the various components used and misalignment of the various components in the assembled system.

In some embodiments, the front lever 915A is further connected to the front arm 910A through bearing or bushing 960A. In other embodiments, the front lever 915A has a separate bearing or bushing <NUM> that is configured to be coupled to a corresponding connecting rod <NUM> of the cage <NUM>. In some embodiments, the bearing or bushing 960A of the front arm 910A and the bearing or bushing <NUM> of the front lever 915A are coupled to the same connecting rod <NUM>. Similarly, the back lever 915B is further connected to the back arm 910B through bearing or bushing 960B. In other embodiments, the back lever 915B has a separate bearing or bushing <NUM> that is configured to be coupled to a corresponding connecting rod <NUM> of the cage <NUM>. In some embodiments, the bearing or bushing 960B of the back arm 910B and the bearing or bushing <NUM> of the back lever 915B are coupled to the same connecting rod <NUM>.

The roller <NUM> is configured to provide pressure to the consumable to compress a tubing to isolate a volume of fluid traveling through the tubing of the consumable. In some embodiments, the roller <NUM> is constructed from metals, such as stainless steel, or plastics, such as polycarbonate. The roller may be solid or hollow. In some embodiments, the roller has a diameter sufficient to prevent the roller from bending during operation. For example, the roller may have a diameter between <NUM> inches and <NUM> inches.

The roller <NUM> is attached at a first end to the front lever 915A, and at a second end to the back lever 915B. In one embodiment, the roller <NUM> is attached to the front and back levers <NUM> by bearings or bushings. As such, the roller <NUM> is allowed to rotate with respect to the front and back levers <NUM>. The roller <NUM> is attached to a gear <NUM>. The gear <NUM> is then coupled to a corresponding peripheral gear <NUM> of the cage <NUM>. As such, the angular velocity of the roller <NUM> is a function of the angular velocity of the peripheral gear <NUM> of the cage <NUM>. The gear <NUM> causes the roller <NUM> to rotate as the roller travels round the consumable, reducing the wear and stress of the tubing, increasing longevity of the consumable. In some embodiments, the rotation of the roller <NUM> increases consistency of the flow-rate of the fluid isolating pump by reducing tube walking and stretching. In some embodiments, the gear <NUM> is coupled to the peripheral gear <NUM> through additional gears. The additional gears may be selected to control the proportionality between the angular velocity of the roller <NUM> and the peripheral gear <NUM> of the cage <NUM>. Moreover, the additional gears may reverse the direction of rotation of the gear <NUM>. The additional gears may be attached to the back lever 915B.

The connected combination of components in the roller assembly may reduce the amount of energy used by the fluid isolation pump system. The components used in the roller assembly may significantly reduce the force required to compress the tubing due to mechanical leverage and thus reduce the torque requirements of motor <NUM>.

In some embodiments, an alignment mechanism, such as an alignment spring is used to bias the roller assemblies <NUM> to one side of the connecting rods <NUM>. The alignment mechanism may provide a force that presses the roller assembly onto the back plate <NUM> of the cage <NUM>. The alignment mechanism may improve the coupling between the various gears used. That is, the alignment mechanism improves the coupling between the central gear <NUM> and the peripheral gear <NUM>, and the coupling between the peripheral gear <NUM> and the one or more gears <NUM> of the roller assembly.

In some embodiments, the peripheral gears <NUM> are part of the roller assemblies <NUM> instead of the cage <NUM>. That is, each peripheral gear <NUM> is attached to the back lever 915B of a roller assembly <NUM>. In some embodiments, the peripheral gears <NUM> are attached to a bearing or bushing <NUM> of a roller assembly <NUM>.

<FIG> shows a front view of the cam plate <NUM>, according to one embodiment. <FIG> shows a perspective view of the cam plate <NUM>, according to one embodiment. <FIG> shows a zoomed in version of the front view of the cam plate <NUM> illustrating a single opening <NUM>, according to one embodiment. The cam plate <NUM> interfaces with the roller assemblies <NUM> to position the roller assemblies <NUM> in an engaged or a disengaged position. In the disengaged position, the rollers assemblies <NUM> are positioned such that pressure is not applied to the consumable <NUM>. This position allows for the installation or removal of the consumable <NUM>. In the engaged position, the roller assemblies <NUM> are positioned such that pressure is being applied to the consumable <NUM>.

In some embodiments, the cam plate <NUM> is a rigid disk with a hollow center <NUM>. The cage <NUM> is then configured to fit in the hollow center of the cam plate <NUM>. The cam plate <NUM> includes one or more openings <NUM> and one or more notches <NUM>. In some embodiments, a cam brake <NUM> is used instead of the one or more notches <NUM>. Each cam opening <NUM> has a first side <NUM> and a second side <NUM>. The bushing <NUM> of each roller assembly <NUM> is configured to mate with a corresponding cam opening <NUM>.

The first side <NUM> of the cam opening <NUM> and the second side <NUM> of the cam opening <NUM> are stable positions for the bushing <NUM>. When the bushing <NUM> is in one of those two positions, the bushing <NUM> is configured to stay in that position until a threshold amount of force is applied to move the bushing <NUM> from the stable position. In some embodiments, if the bushing <NUM> is not in one of the stable positions, if a force lower than the threshold amount of force is applied, the bushing <NUM> slides to one of the two stable positions. In some embodiments, the bushing <NUM> slides to the first side <NUM> of the cam opening <NUM> if the bushing <NUM> is within the first opening region <NUM> and a force less than the threshold amount is being applied. That is, when the bushing <NUM> is in the first side <NUM> of the cam opening <NUM> (in the disengaged position), the bushing <NUM> is prevented from moving to the engaged position unless a threshold amount of force is applied. Once the threshold amount of force is applied and the bushing <NUM> moves from the first side <NUM> to second opening region <NUM>, the bushing <NUM> would slide over to the second side <NUM> of the cam opening transitioning to the engaged configuration. Similarly, the bushing <NUM> slides to the second side <NUM> of the cam opening <NUM> if the bushing <NUM> is within the second opening region <NUM> and a force less than the threshold amount is being applied. That is, when the bushing <NUM> is in the second side <NUM> of the cam opening <NUM> (in the engaged position), the bushing <NUM> is prevented from moving to the disengaged position unless a threshold amount of force is applied. Once the threshold amount of force is applied and the bushing <NUM> moves from the second side <NUM> to first opening region <NUM>, the bushing <NUM> would slide over to the first side <NUM> of the cam opening transitioning to the disengaged configuration.

<FIG> show the operation of the cam plate <NUM>. <FIG> shows a front and rear view of the cam plate <NUM> with roller assemblies <NUM> in the disengaged position, according to one embodiment. <FIG> shows a perspective view of the cam plate <NUM> with roller assemblies <NUM> in the disengaged position, according to one embodiment.

In the configuration of <FIG> and <FIG>, the bushing <NUM> of each of the roller assemblies <NUM> are positioned radially within the first side <NUM> of the openings <NUM>. When a bushing <NUM> of a roller assembly <NUM> is positioned within the first side <NUM> of a corresponding opening <NUM> of the cam plate <NUM>, the connecting bar <NUM> of the roller assembly <NUM> lifts one end of the front arm 910A and back arm 910B of the roller assembly <NUM>. Since the front and back arms <NUM> of the roller assembly <NUM> are held by a connecting rod <NUM> of the cage <NUM>, the front and back arms <NUM> of the roller assembly <NUM> pivot or rotate about the connecting rod <NUM>. As the bushing <NUM> of the roller assembly <NUM> is moved towards the first side <NUM> of the corresponding opening <NUM> of the cam plate <NUM>, the front and back arms <NUM> move radially outwards to disengage the rollers <NUM>.

At this position, the gap between the location on the front and back arms <NUM> where the suspensions <NUM> are attached and the consumable is larger than the height of the suspensions <NUM>. As such, the suspensions <NUM> raise the front and back levers <NUM>, raising the roller <NUM>. As a result, the roller <NUM> is prevented from applying pressure to the consumable <NUM>.

<FIG> shows a front and rear view of the cam plate <NUM> with roller assemblies <NUM> in the engaged position, according to one embodiment. <FIG> shows a perspective view of the cam plate <NUM> with roller assemblies <NUM> in the engaged position, according to one embodiment. In the figures, some of the components have been made translucent to better demonstrate the mechanisms.

In the configuration of <FIG> and <FIG>, the bushings <NUM> of each of the roller assemblies <NUM> are positioned within the second side <NUM> of the openings <NUM>. When a bushing <NUM> of a roller assembly <NUM> is positioned within the second side <NUM> of a corresponding opening <NUM> of the cam plate <NUM>, the connecting bar <NUM> of the roller assembly <NUM> lowers one end of the front arm 910A and back arm 910B of the roller assembly <NUM>. Since the front and back arms <NUM> of the roller assembly <NUM> is held by a connecting rod <NUM> of the cage <NUM>, the front and back arms <NUM> of the roller assembly <NUM> pivot or rotate about the connecting rod <NUM>. As the bushing <NUM> of the roller assembly <NUM> is moved towards the second side <NUM> of the corresponding opening <NUM> of the cam plate <NUM>, the front and back arms <NUM> move radially inwards to engage the rollers <NUM>.

At this position, the gap between the location on the front and back arms <NUM> where the suspensions <NUM> are attached and the consumable is smaller than the resting height of the suspensions <NUM>. As such, the suspensions <NUM> are compressed, thus applying pressure to the front and back levers <NUM>. As a result, the roller <NUM> is pressed against the consumable <NUM>.

Moreover, since the front and back levers <NUM> of the roller assembly <NUM> are attached to a corresponding connecting rod <NUM> of the cage <NUM>, as the front and back levers <NUM> move from the disengaged position to the engaged position, and from the engaged position to the disengaged position, the gears <NUM> of the roller assembly <NUM> stay engaged to the peripheral gears <NUM>. That is, as the front and back levers <NUM> rotate about the connecting rods <NUM>, since the gears <NUM> of the roller assembly <NUM> are also fixed to the front or back levers <NUM>, the gears <NUM> of the roller assembly <NUM> rotate together with front and back levers <NUM>. As the peripheral gears <NUM> are centered with the connecting rods <NUM>, the distance between the peripheral gear <NUM> and the gears <NUM> of the roller assembly <NUM> stay constant.

Notches <NUM> are locations where cam plate <NUM> may be pinned, or captured, to prevent rotation. For example, a pin may be mounted to the rigid base <NUM> such that the pin would align with one of the notches <NUM>. When the pin is engaged, the pin locks the cam plate <NUM> in a specific position. In some embodiments, the cam brake <NUM> is used instead or in conjunction with the notches <NUM> to prevent the cam plate <NUM> from rotating. When the cam plate <NUM> is locked and prevented from rotating, if the cage <NUM> is rotated (e.g., by the motor <NUM>), the rotation of the cage <NUM> results in the movement of the roller assemblies <NUM>, resulting in the bushing <NUM> of each of the roller assemblies <NUM> sliding from one position to a second position of the openings <NUM> of the cam plate <NUM>. For example, if the bushing <NUM> of each of the roller assemblies <NUM> are in the first side <NUM>, and the cage <NUM> is rotated counterclockwise, the bushings <NUM> of each of the roller assemblies <NUM> are forced to slide from the first side <NUM> of the opening <NUM> to the second side <NUM> of the opening <NUM> of the cam plate <NUM>. Similarly, if the bushings <NUM> of each of the roller assemblies <NUM> are in the second side <NUM>, and the cage <NUM> is rotated clockwise, the bushings <NUM> of each of the roller assemblies <NUM> are forced to slide from the second side <NUM> of the opening <NUM> to the first side <NUM> of the opening <NUM> of the cam plate <NUM>.

In some embodiments, the torque of motor <NUM> is restricted or limited to prevent damage of the cam plate <NUM> or the roller assemblies <NUM>. For example, if the bushings <NUM> of each of the roller assemblies <NUM> are in the first side <NUM>, and the cage <NUM> is rotated clockwise, the bushings <NUM> of each of the roller assemblies <NUM> are forced against the cam plate <NUM> while the cam plate <NUM> is prevented to rotate. Similarly, if the bushings <NUM> of each of the roller assemblies <NUM> are in the second side <NUM>, and the cage <NUM> is rotated counter-clockwise, the bushings <NUM> of each of the roller assemblies <NUM> are forced against the cam plate <NUM> while the cam plate <NUM> is prevented to rotate. If excessive torque is applied, this force could cause damage in the cam plate <NUM> or the roller assemblies <NUM>. That is, in this configuration, the motor <NUM> (though the cage <NUM>) is applying a torque to the roller assembly in one direction, while the cam plate <NUM> is applying a torque in the opposite direction. To prevent damaging the cam plate <NUM> or the roller assemblies <NUM>, the motor may be controlled to stop providing a torque after a threshold amount of resistance is sensed.

<FIG> shows a perspective view of the central gear <NUM>, according to one embodiment. The central gear <NUM> is configured to be mounted on the non-rotating central shaft <NUM>. In some embodiments, the central gear <NUM> is press-fit onto the non-rotating central shaft <NUM>. The central gear <NUM> has a central opening <NUM> that matches the cross-section of the non-rotating central shaft <NUM>. In some embodiments, the central opening <NUM> is part of an anchor block <NUM> that is attached to the center of the central gear <NUM>. The central opening <NUM> and the anchor block <NUM> prevent the central gear <NUM> from sliding axially and rotating about the non-rotating central shaft <NUM>.

In some embodiments, the central gear <NUM> further includes a locating boss feature <NUM>. The locating boss feature is axially aligned with the back plate <NUM> of the cage <NUM>. In some embodiments, the back opening <NUM> of the back plate <NUM> closely matches the size of the locating boss feature <NUM>. In some embodiments, the locating boss feature <NUM> fits inside the back opening <NUM> of the back plate <NUM>. The locating boss feature may act as a bushing and allows the cage <NUM> to rotate with respect to the central gear <NUM>.

In some embodiments, the pitch diameter of the central gear <NUM> matches the diameter of the consumable <NUM>. In some embodiments, the pitch diameter of the central gear <NUM> matches the diameter of the consumable <NUM> when the tubing of the consumable <NUM> is in a compressed state.

In some embodiments, the central gear <NUM> further includes magnet counterbores <NUM>. Magnets may then be mounted in the magnet counterbores <NUM>. The magnets are not shown for simplicity. The magnets may align with magnets in the consumable <NUM> and provide an attractive force to hold the consumable <NUM> in place.

<FIG> and <FIG> show perspective views of the consumable <NUM>, according to one embodiment. <FIG> shows an exploded view of the consumable <NUM>, according to one embodiment. The consumable <NUM> is configured to be inserted and removed from the roller pump assembly <NUM>. The consumable <NUM> provides the space to isolate volumes of fluid for a predetermined amount of time. The consumable <NUM> includes a consumable cartridge <NUM> and a tubing <NUM>. Moreover, the consumable cartridge <NUM> includes a rigid tube <NUM>, a front endcap 1220A, a back endcap 1220B, and support bars <NUM> connecting the back endcap 1220B and the front endcap 1220A together, according to one embodiment. <FIG> shows a perspective view of the tubing <NUM>, according to one embodiment. <FIG> shows a perspective view of the consumable cartridge <NUM>, according to one embodiment.

The tubing <NUM> provides the space to isolate the volume of fluid. The tubing <NUM> wraps around the rigid tube <NUM>. For instance, the tubing <NUM> wraps around the rigid tube <NUM> in a helical pattern. The tubing <NUM> may be made from PVC, TPE, Tygon, C-Flex, silicone, or other common tubing material that is compatible with peristaltic pumps. The tubing <NUM> may have different dimensions depending on the application. In some embodiments, the tubing <NUM> may have an inner diameter between <NUM>/<NUM> of an inch and <NUM> inch, and a wall thickness between <NUM>/<NUM> of an inch and <NUM>/<NUM> of an inch. Moreover, the length of the tubing may vary depending on the desired isolation/incubation time and flow rate of the fluid isolating pump. In some embodiments, the length of the tubing <NUM> is increased to increase a flow rate of the fluid isolating pump. In one embodiment, the tubing has a length between <NUM> ft. and <NUM> ft.

The tubing <NUM> is not parallel to the direction of travel of each roller <NUM>. This is due to the multiple loops used to make a helical structure and the resulting pitch of each loop. Since each loop of the helical tubing <NUM> is not parallel to the travel direction of each roller <NUM>, resulting forces are applied to the tubing <NUM> which forces tubing <NUM> back and forth in the direction of each roller's axis. This is known as tube "walking" or "travel.

As shown in <FIG>, the tubing <NUM> is may be connected to fluidic junction <NUM>. The fluidic junction allows multiple fluid sources to be combined before entering the tubing <NUM>. As shown in the diagram of <FIG>, the fluidic junction <NUM> may connect a bulk reagent with other lower volume reagents. In some embodiments, the fluidic junction allows the coupling of tubing of different internal diameters. For example, the fluidic junction may connect a first tubing with a first inner diameter for supplying the bulk reagent, and a second tubing with a second inner diameter (e.g., smaller than the first inner diameter) for supplying low volume reagents. In the embodiment of <FIG>, a barbed T-fitting reducer is used as the fluidic junction <NUM>, however, other suitable fluidic junctions may be used instead, including but not limited to Luer-style fittings.

In some embodiments, the inlets and outlets of the tubing are sealed or connected to a Luer lock or other type of aseptic connector when the consumable is not in use. Moreover, the inlet and outlets of the tubing may be weldable for use with a sterile tube welder.

Tubing <NUM> may be installed onto the cartridge <NUM> by means of a coil winding machine to maintain consistency in tube tension and pitch. Tubing <NUM> may be sterilized by means of ethylene oxide, gamma irradiation, autoclave or other suitable means.

<FIG> shows a perspective view of the rigid tube <NUM>, according to one embodiment. Rigid tube <NUM> provides a minimally-compliable surface for tubing <NUM> to be wrapped around. Rigid tube <NUM> has sufficient strength to counter the compressive forces of the rollers <NUM>. The rigid tube <NUM> is constructed of metals (such as stainless steel), plastics (such as acetal or polycarbonate), ceramics, or any other suitable material. The rigid tube <NUM> includes an inlet hole 1215A and an outlet hole 1215B. The inlet and outlet holes <NUM> allow the tubing <NUM> to pass through them. In some embodiments, the diameter of the inlet and outlet holes <NUM> matches the outer diameter of the tubing <NUM>. The inlet and outlet holes <NUM> may additionally aid in preventing the tubing <NUM> from sliding due to forces applied to the tubing by the rollers <NUM> of the roller assemblies <NUM>. In some embodiments, the rigid tube <NUM> includes notches to align to the front and back endcaps <NUM>. The notches prevent the rigid tube <NUM> from rotating relative to the endcaps <NUM>.

In some embodiments, the rigid tube <NUM> is made from a single piece. In other embodiments, the rigid tube <NUM> is made from multiple pieces that may rotate independently of each other. The multiple pieces may be used to aid in the tensioning of the tubing <NUM>. A consumable <NUM> having a rigid tube <NUM> made from multiple sections is described hereinbelow in conjunction with <FIG>.

In some embodiments, the rigid tube <NUM> allows the transfer of heat to or from the liquid contained inside the tubing <NUM>. That is, the rigid tube <NUM> may be a heat exchanger having a controllable temperature. The temperature of the rigid tube <NUM> may be controlled using a thermal element that is activated based on signals received from the fluid isolating pump <NUM>. In some embodiments, the thermal element includes a heating element. For instance, the rigid tube <NUM> may include resistive filaments or Peltier devices that are able to heat up when electrical current is applied. Moreover, the temperature of the rigid tube <NUM> may additionally be controller by a cooling element that is activated based on signals received from the fluid isolating pump <NUM>. In some embodiments, the rigid tube <NUM> further includes sensors to control the temperature of the rigid tube <NUM> or the fluid contained within the tubing <NUM>.

The front and back endcaps <NUM> fit into respective ends of the rigid tube <NUM>. The endcaps <NUM> provide additional rigidity to the consumable <NUM>. In some embodiments, the front endcap 1220A includes a handle <NUM> to ease the installation and removal of the consumable <NUM>. The end caps <NUM> may be constructed of metals (such as stainless steel), plastics (such as acetal or polycarbonate), or any other suitable material.

The endcaps <NUM> may have a central mounting hole <NUM> that matches the cross-section of the non-rotating central shaft <NUM>. As such, the endcaps allow the consumable <NUM> to be mounted onto the non-rotating central shaft <NUM>, while preventing the consumable <NUM> from rotating about the non-rotating central shaft <NUM>.

<FIG> shows a perspective view of the back endcap 1220B, according to one embodiment. The back endcap 1220B may include magnet counterbores <NUM>. The position of the magnet counterbores <NUM> of the consumable <NUM> match the position of the magnet counterbores <NUM> of the central gear <NUM>. Magnets <NUM> may then be mounted in the magnet counterbores <NUM>.

<FIG> shows a front view of the front endcap 1220A, according to one embodiment. The front endcap 1220A may include openings <NUM> to allow the tubing <NUM> from entering and exiting. That is, the openings <NUM> of the front endcap 1220A allows the tubing to penetrate the front endcap 1220A. As such, the tubing <NUM> may be attached to other components of a system, such as fluid sources or reservoirs, through the front side. In some embodiments, the front endcap may include fittings to attach to the tubing <NUM> and external tubing. The fittings allow for fluidic coupling between the external tubing and the tubing <NUM>.

In some embodiments, the front endcap 1220A additionally includes a vibrating tube holder <NUM>. The vibrating tube holder <NUM> holds a section of the tubing <NUM>. The vibrating tube holder <NUM> includes a vibrating motor that causes bubbles trapped in the tubing to progress through the tubing. In some embodiments, the portion of the tubing <NUM> that is attached to the vibrating tube holder <NUM> is equipped with a static mixer. In this embodiment, the vibrating tube holder <NUM> causes bubbles trapped within the tubing <NUM> to move through the static mixer to ensure consistent mixing performance of the static mixer.

In some embodiments, the front endcap 1220A additionally includes bubble sensors <NUM>. For example, in <FIG>, the front endcap 1220A includes a first bubble sensor 1255A for detecting bubbles in the inlet tubing that receives the bulk reagent, and a second bubble sensor 1255B for detecting bubbles in the inlet tubing that receives the lower volume reagent. The bubble sensors <NUM> detect the presence of liquid in the inlet tubing and is used for priming the tubing. Moreover, the bubble sensors <NUM> may be used to detect when a reagent has been depleted.

In some embodiments, the front endcap 1220A includes electrical connectors <NUM> for connecting the consumable <NUM> to external electronic components. Additionally, in some embodiments, the front endcap 1220A includes electrical connectors for connecting the consumable <NUM> to internal electronics. For example, the electrical connectors may allow internal electronics to receive a signal from a bubble sensor or to provide a signal to a vibrating motor attached to the consumable <NUM>. In another example, the electrical connector may facilitate thermal control to the heating of the isolated fluid as the isolated fluid travels through the tubing <NUM>.

In some embodiments, the consumable <NUM> includes a static mixer <NUM>. <FIG> illustrates a perspective view of the static mixer <NUM>, according to one embodiment. The static mixer is installed within tubing <NUM> after the fluidic junction <NUM>. The static mixer aids in mixing the various reagents being provided to the fluid isolating pump.

In some embodiments, the endcaps <NUM> may have features for guiding the tubing <NUM> and holding the tubing <NUM> in place. In addition, the features for guiding the tubing <NUM> may introduce slight tension to the tubing <NUM> to keep the tubing <NUM> from getting loose over time.

In some embodiments, instead of having a replaceable consumable as depicted in <FIG>, the fluid isolating pump is configured to receive the tubing <NUM> and the fluid isolating pump wraps the tubing <NUM> around the rigid tube <NUM>. As such, the rigid tube, as well as the endcaps <NUM> and the components mounted on the end endcaps do not need to be replaced each time the tubing <NUM> is to be replaced. Instead, the old tubing <NUM> maybe unwrapped from the rigid tube <NUM> and the fluid isolating pump <NUM> is able to load the new tubing <NUM> with a predetermined amount of tension.

In some embodiments, to wrap the new tubing <NUM> around the rigid tube <NUM>, the fluid isolating pump <NUM> rotates the rigid tube at a predetermined angular velocity while the roller assemblies <NUM> are in the disengaged position. In some embodiments, the rigid tube <NUM> extends outwards from the cage <NUM>, protruding towards a user, during the installation of a new tubing <NUM>. While the rigid tube <NUM> is outside of the cage <NUM>, the user is able to install the new tubing <NUM> around the rigid tube <NUM>. Once the new tubing <NUM> is installed, the rigid tube <NUM> retracts back into the cage <NUM>. Moreover, while the rigid tube <NUM> is rotating, one end of the tubing <NUM> is kept secured to the rigid tube to provide tension to the tubing to enable the tubing <NUM> to be fed into the fluid isolating pump <NUM> and to be wrapped around the rigid tube <NUM>. In some embodiments, after the new tubing <NUM> has been loaded onto the rigid tube <NUM>, the ends of the new tubing <NUM> are connected to fittings (e.g., a T-fitting) to fluidically couple the new tubing <NUM> to other components of the system.

<FIG> shows a flow diagram of a process for operating the fluid isolating pump.

The consumable <NUM> is inserted <NUM> into the roller pump assembly <NUM>. The consumable <NUM> is mounted on the non-rotating central shaft <NUM> inside the cage <NUM>. In some embodiments, the consumable <NUM> is inserted in an orientation such that magnets embedded in the consumable <NUM> align to magnets embedded in the central gear <NUM>. Moreover, the consumable <NUM> is inserted in an orientation such that electrical contacts embedded in the consumable <NUM> align with electrical contacts embedded in the central gear <NUM>. The electrical contacts may provide an interface to operate and communicate with sensors and other electronics embedded in the consumable <NUM>.

Additionally, the consumable <NUM> is fluidically connected to the input reagents and a collection reservoir. In some embodiments the consumable is connected to external pumps, such as external peristaltic pumps, or to a mixer, such as a static mixer or a dynamic mixer. In other embodiments, the consumable <NUM> is equipped with onboard peripheral pumps (e.g., syringe pumps, gear pumps, peristaltic pumps, piezo pumps, diaphragm pumps, and the like). In yet other embodiments, the peripheral pumps are installed on the roller pump assembly <NUM>, and the consumable <NUM> is fluidically coupled to the peripheral pumps when the consumable <NUM> is installed in the roller pump assembly <NUM>.

In some embodiments, the roller pump assembly <NUM> communicates with the consumable <NUM> to identify the properties of the consumable. For example, the consumable <NUM> may transmit data indicating the tubing thickness, tubing length, tube flow rates, calibration data, manufacturing lot number, expiration date, material data, consumable identification number, and the like. The roller pump assembly <NUM> may log this information and may modify operating parameters of the system.

The roller assemblies <NUM> are engaged <NUM>. To engage the roller assemblies, cam brake <NUM> is engaged such that the cam plate <NUM> is prevented from rotating and the motor <NUM> is rotated until the bushings <NUM> of the roller assemblies <NUM> translate from the first side <NUM> of the openings <NUM> of the cam plate <NUM> to the second side <NUM> of the openings <NUM> of the cam plate <NUM>. As the bushings <NUM> translate to the engaged position, the arms <NUM> of the roller assemblies <NUM> are lowered compressing the suspensions <NUM>, thus pressing the rollers <NUM> onto the tubing <NUM> of the consumable <NUM>.

The fluid isolating pump is primed <NUM>. In some embodiments, the fluid isolating pump is primed with the bulk reagent. For example, pump <NUM> is operated to pump the bulk reagent into the tubing <NUM> of the consumable <NUM>. In some embodiments, the roller pump assembly <NUM> may be operated at a reduced speed during the priming process. For instance, the motor <NUM> may be driven at a priming speed to aid the bulk reagent to flow through the tubing <NUM> of the consumable <NUM>.

After the fluid isolating pump has been primed with the bulk reagent, the other reagents may also be primed. For instance, the syringe pump <NUM> may be operated to prime the other reagents used in the process.

In some embodiments, sensors attached to the consumable <NUM> or the roller pump assembly <NUM> are used to determine if the priming process has been completed. For example, the consumable may include one or more sensors <NUM> that detect the presence of bubbles inside the tubing <NUM>. When the sensors <NUM> determine that the priming process has been completed, the consumable <NUM> may send a signal to the roller pump assembly <NUM> to end the priming process. In some embodiments, the signals are sent from the consumable <NUM> to the roller pump assembly <NUM> via contacts terminal embedded in the consumable <NUM> and the central gear <NUM>. In other embodiments, the consumable sends the signals wirelessly (e.g., though a Wi-Fi or Bluetooth signal).

Once the system has been primed, the fluid isolating pump is operated by rotating <NUM> the cage <NUM> at a predetermined speed. The angular velocity of the cage <NUM> and the length of the tubing <NUM> determine the length of time each volume of fluid will be isolated. In some embodiment, sensors such as a mass flow controller (liquid flow sensor), coupled to the consumable <NUM>, or load cells measuring the weight of the bag <NUM> containing the bulk reagent, are used to determine an amount of reagent being processed. This information may be used by the fluid isolating pump to balance flow rates.

After the processing has been completed, the roller assemblies <NUM> are disengaged to allow the removal of the consumable <NUM> from the roller pump assembly <NUM>. To disengage the roller assemblies <NUM>, the cam brake <NUM> is engaged such that the cam plate <NUM> is prevented from rotating and the motor <NUM> is rotated in a reverse direction until the bushings <NUM> of the roller assemblies <NUM> translate from the second side <NUM> of the openings <NUM> of the cam plate <NUM> to the first side <NUM> of the openings <NUM> of the cam plate <NUM>. As the bushings <NUM> translate to the disengaged position, the arms <NUM> of the roller assemblies <NUM> are lifted releasing the compression of the suspensions <NUM>, thus, lifting the rollers <NUM>.

Four methods herein may eliminate or mitigate tube walking to the maximum extent practical for continuous and long-term pump use.

The first method to mitigate tube walking involves the installation of tube tensioning mechanisms within the hollow center of the consumable's rigid tube <NUM>. These tensioning mechanisms may apply tension to the helical tubing <NUM> as the tube enters the center of rigid tube <NUM> at holes <NUM>. If tension is applied to both ends of the helical tubing, the forces exerted by the rollers are less likely to cause tube walking.

These tube tensioning mechanisms may be in the form of cams, springs, pneumatics, actuators, or any combination thereof.

Tensioning mechanisms may be pre-loaded during the assembly of each consumable or engaged prior to pump operation.

The second method to mitigate tube walking involves the modification of the geometry of the rigid tube such that the helical tubing (e.g., helical tubing <NUM>) is reoriented. When reoriented, the majority of the helical tubing remains parallel to the travel direction of each roller. This method ensures that the rollers only apply significant compressive forces to the helical tubing when the helical tubing is parallel to the travel direction of each roller. In this case, the forces applied to the helical tubing are perpendicular to the rollers and result in significantly less tube walking.

To achieve this, a series of holes may be added to one side of the rigid tube as shown in <FIG>. Two rows of holes <NUM> are required as shown in <FIG>. These holes are used to briefly divert the helical tubing into the center of the rigid tube <NUM>. Once in the center of the rigid tube, the helical tubing 'jogs' to the next row of holes before exiting rigid tube <NUM>. This is repeated until the tubing is installed.

This tube routing method allows the tubing to depart from the geometry of a traditional helix and instead have several sections of tubing parallel to each roller's direction of travel, as shown in <FIG>. As shown in <FIG>, tubing coil <NUM> remains parallel to the direction of travel of each roller on all sections of tubing external to rigid tube <NUM>. Thereby, the sections of tubing within the rigid tube <NUM> are not subjected to compressive forces from the rollers.

In <FIG>, items <NUM> and <NUM> represent the inlet and outlet of the helical tubing. Fluidic chemical and/or biological entities are: (i) loaded into tubing via the inlet; (ii) passed through the tubing for transformative processing (e.g., incubations or pulverization); and (iii) move out of the tubing via the outlet. Note that both the inlet and the outlet are diverted towards the same side of the consumable. This makes loading the fluidic connections easier for the end user.

<FIG> is a front-end view of <FIG>. <FIG> is an isometric view of <FIG> for further clarification.

The third method to mitigate tube walking involves the usage of slots instead of holes in the rigid tube. <FIG> shows a top view of a rigid tube <NUM> with six (<NUM>) slots <NUM>. In other embodiments, a different number of slots may be used. Each slot <NUM> is angled from the axis of the rigid tube <NUM> by theta degrees. As shown, theta or item <NUM> is less than <NUM> degrees.

A side view of <FIG> may be seen in <FIG>. An isometric view of <FIG> may be seen in <FIG>.

A benefit of this slotted method over the previously discussed method where holes were employed, is that the tubing can be easily assembled by laying the tubing into the slots as opposed to weaving or lacing the tubing through holes.

An assembly view is shown in <FIG>. Item <NUM> represents the rigid tube. Item <NUM> represents the tubing coil. By adding the slots in the rigid tube <NUM>, the material that opposes the compressive force of the rollers is removed in these areas. Therefore, not only is the tubing slightly recessed, but the rollers are incapable of applying significant forces to the tubing in these areas. This results in the rollers only applying compressive forces to sections of tubing which are parallel to the direction of each roller's travel.

<FIG> is a front-end view of the consumable assembly of <FIG> with rollers in the engaged position. Item <NUM> represents the rigid tube. Item <NUM> represents the tubing. Items <NUM> represent engaged rollers at a diameter of <NUM>. As shown in <FIG>, the top roller <NUM> is not making contact with tubing <NUM>, which thus does not apply significant forces to the tubing in the areas where the slots exist.

The fourth method to mitigate tube walking involves the construction of the rigid tube <NUM> in <FIG> out of several sections, which may rotate independent of each other as seen in the assembly view in <FIG>. Note that the helical tubing is not shown in <FIG> to better demonstrate the concept. An exploded assembly view can be seen <FIG>. Item <NUM> represents the helical tubing; item <NUM> is an end cap; item <NUM> is the first section of the rigid tube; items <NUM> are center sections of the rigid tube; item <NUM> is the last section of the rigid tube; item <NUM> is an end cap.

Note that sections <NUM>, <NUM>, and <NUM> operationally mate with each other such that sections <NUM>, <NUM>, and <NUM> become axially aligned when joined. The resulting fit allows for relative rotation. Item <NUM> and item <NUM> are fixed as to rotate together. Item <NUM> and item <NUM> are fixed as to rotate together. Sections <NUM> and <NUM> have holes <NUM> and <NUM> where the tubing may enter the center of the consumable. A cross-sectional view of the complete assembly may be seen in <FIG>.

This concept works by means of tensioning the helical tubing such that tension is evenly distributed across the tubing. To use this design, a helical tubing <NUM> will exit the consumable through hole <NUM> in section <NUM>, wrap around the center sections <NUM> and then enter the consumable through hole <NUM> in section <NUM>. The ends of the helical tubing will then be secured to section <NUM> and <NUM>.

Once the tubing is secured, the user may hold item <NUM> rigid and rotate section <NUM> clockwise as shown by direction <NUM>. This rotation causes the helical tubing <NUM> to tighten evenly across all sections of the rigid tube.

Note that item <NUM> has a hexagon cutout in its center and <NUM> has a round cutout. This is to allow the consumable to be installed on the non-rotating central shaft <NUM> once the consumable is tensioned.

A tool such as a torque wrench may be utilized to apply consistent tension during manufacturing or use. Internal mechanisms (not shown) may be used to maintain the applied tension, such as but not limited to ratchet and pawl, friction clutch, or dowels.

The second pump system is referred to as an 'internal roller" pump in this document. As the name suggests, the rollers are positioned radially inward from the tubing and/or consumable. Depicted in <FIG> is an example of an internal roller pump assembly with its consumable set aligned but not installed, according to one embodiment. <FIG> is an assembly view of an internal roller pump with its consumable installed, according to one embodiment. The internal roller pump assembly includes a motor <NUM>, a rigid base <NUM>, a rigid cage <NUM>, roller assemblies <NUM>, anti-rotation features <NUM>, motor controller and electronics enclosure <NUM>, and consumable assembly <NUM>.

Rigid cage <NUM> is mounted to motor <NUM> and rotates with the motor's rotor. Roller assemblies <NUM> are connected to rigid cage <NUM> for compressing the helical tubing. Anti-rotation features <NUM> prevent the consumable <NUM> from rotating during use.

<FIG> shows a perspective view of the rigid cage with a set of roller assemblies, according to one embodiment. The rigid cage <NUM> includes a central hub <NUM> that the roller assemblies <NUM> connected to. When central hub <NUM> is rotated counter-clockwise, the rollers of the roller assemblies <NUM> are extended outward. The mechanism example shown in <FIG> is an over-center mechanism. In the over-center mechanism, the rollers can lock into an engaged position even after a counter-clockwise torque is removed.

<FIG> is a front view of the roller engagement mechanism in a disengaged or retracted position. <FIG> is a front view of the roller engagement mechanism in an engaged or extended position.

<FIG> is an isometric view of consumable assembly <NUM>. The consumable assembly includes a rigid tube <NUM>; helical tubing <NUM>; and an anti-clocking mechanism <NUM>.

Rigid tube <NUM> may be composed of plastic, metal, or any rigid material. Rigid tube <NUM> provides a rigid surface to oppose the compressive forces exerted on the tubing by the rollers.

<FIG> is a front view of the installed consumable. The rigid tube is shown as item <NUM>. The helical tubing is shown as item <NUM>. Note that rollers <NUM> are not contacting tubing <NUM> in this disengaged or retracted position. This allows the consumable to be installed or removed.

<FIG> is a front view of the installed consumable. The rigid tube is shown as item <NUM>. The helical tubing is shown as item <NUM>. Note that rollers <NUM> are contacting the tubing <NUM> in this engaged or extended position. In this configuration the helical tubing is compressed.

An alternate method is to create a linear peristaltic pump that operates in a method similar to the tracks of a military tank. The fluid isolating pump <NUM> may be designed to allow the rollers to rotate about multiple axis of rotation. As such, the rollers of the fluid isolating pump <NUM> are able to translate in a linear fashion. A high-level schematic of this design is shown in <FIG>. A zoomed in view of <FIG> is shown in <FIG>.

<FIG> is a cross-sectional view of a linear roller pump, according to one embodiment. As shown in <FIG>, the linear roller pump includes sprockets <NUM>, a belt or track <NUM>, rollers <NUM>, tubing <NUM>, a rigid frame <NUM>, roller supports <NUM>, hard movable surface <NUM>, and a rigid base (not shown). In some embodiments, sprockets 2310A and 2310B may be driven by a motor (not shown). In other embodiments, one sprocket 2310A may be motor-driven and therefore active, while the other sprocket 2310B may be passive. The belt or track <NUM> acts as a conveyer around sprockets 2310A and 2310B. The belt or track <NUM> can carry or transport the rollers <NUM>. The rollers <NUM> are used to compress the tubing <NUM> and transfer fluid as the rollers <NUM> progress down the tubing <NUM>. Tubing <NUM> may be any type of hollow tubing used in the medical or bioprocessing industry, such as TPE, silicone, or PVC tubing. The rigid frame <NUM> supports both sprockets 2310A and 2310B. Rigid frame <NUM> can also provide a rigid surface for the rollers to transfer the reactive forces from the tubing <NUM>. The roller supports <NUM> may be spring loaded to compensate for any system misalignments. Hard surface <NUM> is movable between at least two positions. If hard surface <NUM> moves in the -y direction, a gap is opened between hard surface <NUM> and the rollers <NUM> to allow tubing to be installed between the rollers <NUM> and the hard surface <NUM>. When hard surface <NUM> moves in the +y direction to a "clamped" position, the tubing <NUM> may be installed in the linear roller pump and ready for fluid transfer. Rigid frame <NUM> and hard surface <NUM> can both be secured to a common rigid base (not shown) to maintain relative positions.

In some embodiments, the distance between two rollers <NUM> is application-dependent and may be adjusted. The fluid volume isolated between two rollers is proportional to the distance between the rollers. To operate the linear roller pump in <FIG>, either sprocket 2310A or sprocket 2310B may be driven by a motor either clockwise or counterclockwise to transfer fluid.

<FIG> is a detailed view of two isolated fluid volumes depicted in <FIG>, according to one embodiment. <FIG> shows how the tubing <NUM> is compressed by the rollers <NUM> and how the compression isolates and transfers the fluid in a linear roller pump. As shown in <FIG>, three rollers <NUM> are be pressed against tubing <NUM> effectively isolating the fluid in each chamber <NUM>. A first fluid in chamber 2390A is mechanically isolated from the fluid in a second chamber 2390B and so on. This isolation can allow for the fluid in each chamber to incubate as the fluid progresses through the linear peristaltic pump. The rollers <NUM> travel in the x direction and rotate about their own individual axes in the z direction. If the rollers travel in the +x direction, fluid in the chambers are transferred right and vice-versa. The rollers <NUM> exert a force in the -y direction. Rigid bodies <NUM> and <NUM> can resist the forces in the y direction and thus tubing <NUM> may be compressed.

<FIG> is a cross-sectional view of a linear roller pump, according to another embodiment. The linear roller pump <NUM> of <FIG> includes sprockets <NUM>, a belt or track <NUM>, roller assemblies <NUM>, tubing <NUM>, a rigid frame <NUM>, and a rigid body <NUM>.

The sprockets <NUM> are linked to the belt or track <NUM> and rotate to drive the belt or track <NUM> in a predetermined direction. Similar to the linear roller pump of <FIG>, the sprockets may be driven by one or more motor (not shown). Additionally, depending on the configuration of the linear roller pump, only one or both sprockets may be driven by a motor.

The roller assemblies <NUM> are attached to the belt or track <NUM> and move around the rigid frame <NUM> following the movement of the belt or track <NUM>. The roller assemblies <NUM> include multiple gears <NUM> for causing the rollers <NUM> to rotate as the rollers move around the rigid frame <NUM>. In some embodiments, the gears <NUM> are configured to cause the rollers <NUM> to roll over the surface of tubing <NUM> to prevent friction between the rollers <NUM> and the tubing <NUM> from causing the tubing <NUM> to stretch or move.

The gears <NUM> of the roller assemblies <NUM> are engaged with teeth <NUM> on a surface of the rigid frame <NUM>. Unlike the gears <NUM>, the teeth <NUM> of the rigid frame <NUM> are configured to remain stationary. Thus, as the roller assemblies <NUM> move, the teeth <NUM> of the rigid frame <NUM> cause the gears <NUM> to rotate. In some embodiments, each roller assembly <NUM> includes multiple gears to adjust the direction and velocity of the rotation of the roller <NUM>.

The rigid body <NUM> includes a compliant member <NUM> that allows the rigid body to move up or down (i.e., closer to the rollers or away from the rollers). For example, the compliance members <NUM> may be suspensions, springs, pneumatics, or hydraulics. The compliance member <NUM> provides a force to push the tubing <NUM> against the rollers <NUM> of the roller assemblies <NUM>. Moreover, the compliance member <NUM> allows for the linear roller pump <NUM> to adjust for varying thicknesses of tubing and for allowing greater manufacturing tolerances and misalignments in the system. Furthermore, the compliance member <NUM> allows for easy installation and removal of tubing <NUM>. That is, the rigid body <NUM> can be lowered by compressing the compliance members <NUM> to install or remove the tubing <NUM>.

Aspects of the present teachings may be further understood in light of the following examples, which should not be construed as limiting the scope of the present teachings in any way.

The systems and methods herein have the ability to: (i) apply thermal control to the tubing, heating or cooling by convection or conduction to meet thermal incubation requirements; (ii) install in-line static mixer upstream or downstream of pump; (iii) increase or decrease number of rollers, length of pump, speed of pump, inner diameter (ID) and outer diameter (OD) of tubing, material of tubing; (iv) monitor the position of the pump by a motor encoder, stepper motor, or PID loop; (v) orient the pump in any position while also achieving (i)-(iv); (vi) achieve complex workflows with multiple incubations using multiple linear peristaltic pumps; (vii) place multiple helical tubes to increase production; and (viii) using both sides of a peristaltic pump, where a second consumable set is installed in the opposite orientation.

While in Examples <NUM> and <NUM>, the target products are small molecule chemical compounds, large biological molecules, antibodies, and other chemical and/or biological entities may be generated and isolated via continuous flow using the systems and methods herein. While Example <NUM> is directed to recombinant proteins, the systems and methods herein are compatible with CRISPR, zinc finger nuclease, homologous recombination, and other techniques in the biotechnology arts.

A manufacturer produces chemical compound ABC. Chemical compound ABC consists of three types of chemicals, A, B and C. During the manufacturing of chemical compound ABC, chemicals A-C cannot be mixed concurrently. This is because chemicals A and B must be mixed and allowed to react or incubate for at least a threshold amount of time (e.g., <NUM> minutes) before chemical C is added. Typically, chemical compound ABC has been made in batches due to the complex incubation requirements. To reduce the cost and inconsistencies of batch manufacturing, a fluid isolating pump that achieves continuous processing can used to manufacture of chemical compound ABC. In this example, the operational steps involve: (<NUM>) mixing A and B; (<NUM>) isolating and incubating the mixed fluid volume via one or more fluid isolating pumps (i.e., fluid isolating pump <NUM>); (<NUM>) mixing C with intermediate, A+B mixture; and (<NUM>) generating chemical ABC as an output.

Operational Step (<NUM>): To manufacture chemical compound ABC, chemicals A and B are dispensed and mixed. For example, chemicals A and B may be dispensed by actuating a peristaltic pump, a gear pump, or a syringe pump. In other examples, at least one of chemical A or B is dispensed by operating the fluid isolating pump <NUM>. That is, the fluid isolating pump <NUM> may act as a peristaltic pump for one or both chemicals A and B.

Operation Step (<NUM>): The mixture of chemicals A and B is supplied to the fluid isolating pump <NUM> to allow the mixture of chemical A and B to incubate for a predetermined amount of time. For example, the fluid isolating pump <NUM> is configured to isolate fluid volumes between rollers for <NUM> minutes. Therefore, when the system herein has been operating, the fluid at one end of the fluid isolating pump <NUM> is beginning incubation while the fluid at the opposite end of the fluid isolating pump <NUM> has completed its <NUM>-minute incubation. The fluid isolating pump <NUM> can also be configured for, but not limited to: cooling, degassing, filtering, and coating functions for continuous flow methods.

Operational Step (<NUM>): The fluid that exits the fluid isolating pump is now ready to receive chemical C. As such, chemical C is dispensed (e.g., by actuating peristaltic pump <NUM>) to transfer chemical C into the fully incubated intermediate (i.e., A+B mixture).

Operational Step (<NUM>): Chemical compound ABC then enters the collection reservoir <NUM>.

A manufacturer produces a thioamide as a chemical compound ABC. The methods and systems herein are performing a Willgerodt-Kindler Reaction to yield thioamide (C<NUM>H<NUM>)-CH<NUM>-C(=S)-(N(CH<NUM>CH<NUM>)<NUM>O). Chemical A is acetophenone ((C<NUM>H<NUM>)-C(=O) -CH<NUM>), chemical B is morpholine (HN(CH<NUM>CH<NUM>)<NUM>O), and chemical C is S<NUM>. Chemicals A-C are dissolved in organic solvent to yield a fluid state. In a setup similar to Example <NUM> where acetophenone is stored in bag <NUM>, morpholine is stored in syringe 320A and a slurry of S8 is stored in syringe 320B. When morpholine and acetophenone mix and react, an enamine and water are fully formed at static mixer <NUM>. Water can react with enamine to revert back to the starting morpholine and acetophenone. Thermal control in the fluid isolating pump <NUM> remove the water, such that enamine is formed and selectively persists as isolated fluid volumes. The enamine is an intermediate, mixture A+B, which subsequently reacts with S8. In turn, thioamide (C<NUM>H<NUM>)-CH<NUM>-C(=S)-(N(CH<NUM>CH<NUM>)<NUM>O) is generated and transported to intersection <NUM>. Nickel (II) chloride solution in reservoir <NUM> is pumped to intersection <NUM> via peristaltic pump <NUM>. The thioamide in intersection <NUM> reacts with nickel(ii) chloride to yield a thioamide-nickel complex, which is transported to collection reservoir <NUM>.

While a linear sequence of chemical reactions is employed in this example, parallel or complex scheme of chemical reactions may be employed with an arrangement of multiple linear peristaltic pumps in combination with multiple traditional peristaltic pumps.

Batch production is often not amenable for efficient and uniform production of large molecule biologics. By using the systems and methods herein, the fluid isolating pump <NUM> generates a durable and perpetual production environment useful for the efficient and uniform production of biologics.

A manufacturer produces large molecule biologics. In this example, the large molecule biologics are recombinant proteins. In other examples, the large molecule biologics may be enzymes, cytokines, growth factors, hormones, receptors, transcription factors, antibodies, antibody fragments, and so forth. Agar in vessel <NUM> and extracellular fluids in syringes 320A and 320B are sent to junction <NUM> and static mixer <NUM>. Within a <NUM>-hour time period, the mixture of agar and extracellular fluid begins incubation in fluid isolating pump <NUM>. If this incubation profile is not met, then an intractable mixture results without an enriched amount of recombinant DNA. The incubated mixture of agar and extracellular fluid contain an enriched amount of recombinant DNA, which is a gene for encoding the recombinant proteins. The incubated mixture of agar and extracellular fluid is sent to a first output chamber. The first output chamber is connected to peristaltic pump <NUM>, wherein peristaltic pump <NUM> contains cloning vectors in a fluid to increase the output of the genes for encoding the recombinant proteins. The genes for encoding recombinant proteins are sent to a second output chamber. The second output chamber is connected to another peristaltic pump, wherein the other peristaltic pump contains expression vectors in a fluid, such as the promoters, translation initiation sequence, a termination codon, and transcription termination sequence. The promoter and translation initiation sequence dependent steps take place in fluidic junction <NUM>. The termination codon and transcription termination sequence steps take place in collection reservoir <NUM>. In turn, recombinant proteins are formed and sent to another output chamber. A peristaltic pump is connected to the other output chamber, which contains an absorbent which can remove impurities from recombinant proteins without compromising the structure or properties of the recombinant proteins. In turn, purified forms of the recombinant proteins are generated and isolable via continuous manufacturing supported by the systems and methods herein.

Batch production is often not amenable for efficient and uniform production of target products (small molecule or large molecules) that are contained within a sludge. The target product is extracted from the sludge, which also contains heterogeneous components. This further complicates the extraction process for obtaining the desired target product. By using the systems and methods herein, a helical peristaltic pump assembly generates a durable and perpetual production environment needed to for the efficient and uniform isolation of target product from a seemingly intractable mixture, such as the sludge.

A manufacturer produces dye molecules on the kilogram scale. For example, the dye molecule has a tendency to create a gel barrier during the synthesis. Other impurities in the sludge render traditional washes and pulverizations ineffective at extracting the dye molecule. Also, the amount of material needed when using traditional washes makes the batch production inefficient and impractical. A fluidized sludge and acidic methanol are dispensed and mixed. Within a <NUM> hour time period, the mixture of the sludge and acidic fluid is incubated using a fluid isolating pump (e.g., a helical fluid isolating pump or a linear fluid isolating pump). The fluid isolating pump assembly is able to accommodate a larger amount of sludge while also supporting purification steps that must meet a strict incubation profile. When the roller assembly rotates, the mixture of fluid enters the tubing of the fluid isolating pump. To maintain the structural integrity of the dye and ensure homogeneity of the mixture, incubation is performed for <NUM> minutes. The initially added amount of acidic methanol is a maximum amount that can be used to extract the target dye molecule. If additional acidic methanol is used, then the target dye molecule decomposes. After the <NUM>-minute incubation, the mixture of fluid that exits the fluid isolating pump is fully homogenized, transferred to a beaker, and treated with water. In turn, the target dye molecule precipitates out in purified form. A coarse frit-aided vacuum filtration is used to isolate the purified form of the target dye molecule. In turn, purified form of the target dye molecule is isolable via continuous manufacturing supported by the systems and methods herein.

In addition, use of the "a" or "an" are employed to describe elements and components of the embodiments herein. This is done merely for convenience and to give a general sense of the invention. This description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise.

Claim 1:
A fluid isolating pump (<NUM>), comprising:
a cage (<NUM>) comprising:
a front plate (<NUM>) having a front opening (<NUM>),
a back plate (<NUM>) having a back opening (<NUM>), and
a plurality of connecting rods (<NUM>), each connecting rod (<NUM>) having a front end attached to the front plate (<NUM>) and a back end attached to the back plate (<NUM>);
a plurality of roller assemblies (<NUM>), each roller assembly (<NUM>) coupled to a corresponding connecting rod (<NUM>) of the cage (<NUM>), each roller assembly (<NUM>) comprising:
one or more arms (910A, 910B) rotatably attached to the corresponding connecting rod (<NUM>),
a connecting bar (<NUM>) coupled to the one or more arms (910A, 910B),
one or more levers (915A, 915B) rotatably attached to the corresponding connecting rod (<NUM>),
one or more suspensions (920A, 920B), each suspension (920A, 920B) coupled to at least one arm (910A, 910B) and to at least one lever (915A, 915B), and
a roller (<NUM>) coupled to the one or more levers (915A, 915B);
a cam plate (<NUM>) coupled to the connecting bar (<NUM>) of each roller assembly (<NUM>) of the plurality of roller assemblies (<NUM>), the cam plate (<NUM>) comprising:
a plurality of openings (<NUM>), the openings (<NUM>) having a first end (<NUM>) and a second end (<NUM>), wherein the connecting rod (<NUM>) of each roller assembly (<NUM>) is configured to slide from the first end (<NUM>) of the opening (<NUM>) to the second end (<NUM>) of a corresponding opening (<NUM>), and
a non-rotating central shaft (<NUM>), the non-rotating central shaft (<NUM>) axially aligned with the cage (<NUM>), the non-rotating central shaft (<NUM>) for supporting a consumable (<NUM>).