Patent Publication Number: US-2020282393-A1

Title: Modular and expandable low flow pumping assemblies

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     The present application claims the benefit U.S. Provisional Application No. 62/815,691, filed Mar. 8, 2019, the entirety of which is hereby incorporated by reference. 
    
    
     TECHNICAL FIELD 
     The present specification generally relates to modular and expandable low flow pumping assemblies and, more specifically, modular and expandable low flow pumping solutions for discrete flow control and integration into multichannel perfusion networks. 
     BACKGROUND 
     Well-plates may be flat plates with multiple separate wells formed therein. The individual wells may be used in a variety of capacities. For example, each well may be used as a Petri Dish for growing and/or printing biologic structures. Oftentimes fluid is added and/or removed from the various wells of the well-plate. For example, in some cases it may be advantageous to perfuse a structure within a well of a well-plate with a fluid. Traditionally fluid may be added to a well-plate using a pipettes, syringes, or similar structures. However, because well-plates may define arrays of wells larger than  96  wells, such perfusion of individual wells may prove to be tedious. Moreover, it may be desirable to have the ability to generate independent flow control to each discrete well or to separate groups of wells within the well-plate. 
     Accordingly, a need exists for alternative modular and expandable low flow pumping solutions for discrete flow control and integration into multichannel perfusion networks. 
     SUMMARY 
     In one embodiment, a modular pump assembly includes a plurality of mounting frames configured to be stackable with one another in a modular configuration, and an array of pumps mounted to each of the plurality mounting frames, the array of pumps comprising an array of inlet pumps configured to be fluidically coupled a plurality of fluid inlet paths of a well-plate manifold or an array of fluid outlet pumps configured to be fluidically coupled to a plurality of fluid outlet paths of the well-plate manifold, or any combination thereof. 
     In another embodiment, a perfusion assembly includes a well-plate assembly, a modular pump assembly, a fluid inlet line, and a fluid outlet line. The well-plate assembly includes a well-plate defining a plurality of well-groups each comprising one or more wells, and a well-plate manifold including a plurality of fluid inlet paths and fluid outlet paths corresponding to each well-group. The modular pump assembly includes a plurality of mounting frames configured to be stackable with one another in a modular configuration, and an array of pumps mounted to each of the plurality mounting frames. The array of pumps comprising an array of inlet pumps fluidically coupled to the plurality of fluid inlet paths, an array of outlet pumps fluidically coupled to plurality of fluid outlet paths, or any combination thereof. 
     In yet another embodiment, a method of delivering fluid to a well-plate assembly includes fluidically coupling the well-plate assembly to a modular pump assembly. The well-plate assembly includes a well-plate defining a plurality of well-groups each comprising one or more wells, and a well-plate manifold including a plurality of fluid inlet paths and fluid outlet paths corresponding to each well-group. The modular pump assembly includes one or more mounting frames, and an array of pumps mounted to the one or more mounting frames, the array of pumps comprising an array of inlet pumps fluidically coupled to the plurality of fluid inlet paths, an array of outlet pumps fluidically coupled to plurality of fluid outlet paths, or any combination thereof. The method further includes fluidically coupling the modular pump assembly to one or more fluid reservoirs, and controlling fluid flow into and/or out of one or more of the well-groups by selectively activating, with one or more processors, a pump of the array of pumps associated with each of well-groups. 
     These and additional features provided by the embodiments described herein will be more fully understood in view of the following detailed description, in conjunction with the drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The embodiments set forth in the drawings are illustrative and exemplary in nature and not intended to limit the subject matter defined by the claims. The following detailed description of the illustrative embodiments can be understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which: 
         FIG. 1  schematically illustrates a perfusion assembly, according to one or more embodiments shown and described herein; 
         FIG. 2  schematically illustrates an alternative perfusion assembly, according to one or more embodiments shown and described herein; 
         FIG. 3  schematically illustrates a control system for controlling flow with a modular pump assembly, according to one or more embodiments shown and described herein; 
         FIG. 4  depicts a flow chart depicting a method of delivering fluid to a well-plate assembly, according to one or more embodiments shown and described herein; 
         FIG. 5  depicts a modular pump assembly, according to one or more embodiments shown and described herein; 
         FIG. 6A  depicts an expanded modular pump assembly, according to one or more embodiments shown and described herein; 
         FIG. 6B  depicts another expanded modular pump assembly, according to one or more embodiments shown and described herein; 
         FIG. 7  depicts another modular pump assembly, according to one or more embodiments shown and described herein; 
         FIG. 8A  depicts a front perspective view of an array of pump pairs of the modular pump assembly of  FIG. 7 , according to one or more embodiments shown and described herein; 
         FIG. 8B  schematically depicts a rear perspective view of the array of pump pairs of  FIG. 8A , according to one or more embodiments shown and described herein; 
         FIG. 9  depicts an exploded view of the array of pump pairs  FIG. 8A , according to one or more embodiments shown and described herein; 
         FIG. 10  depicts an exploded view of a cartridge of the array of pump pairs of  FIG. 8A , according to one or more embodiments shown and described herein; 
         FIG. 11A  depicts a front perspective view of the modular pump assembly of  FIG. 7 , according to one or more embodiments shown and described herein; 
         FIG. 11B  depicts a rear perspective view of the modular pump assembly of  FIG. 11A , according to one or more embodiments as shown and described herein; and 
         FIG. 11C  depicts an exploded view of the modular pump assembly of  FIG. 11A , according to one or more embodiments shown and described herein. 
     
    
    
     DETAILED DESCRIPTION 
     The present disclosure is directed to a modular and expandable low flow pumping solution for discrete flow control and integration into multichannel perfusion networks. Such multi-channel perfusion networks (e.g., well-plate and fluid manifold assemblies) are described in greater detail in U.S. patent application Ser. No. 16/135,299, entitled “Well-Plate and Fluidic Manifold Assemblies and Methods,” filed Sep. 19, 2018, hereby incorporated by reference in its entirety. Pumping solutions/assemblies as described herein have the ability to generate independent flow control to each discrete well within the well-plate/manifold assembly to distribute a fluid, such as but not limited to cell culture media, water, blood, blood serum, etc., to biological structures printed or lab grown within well-plates of varying capacity (i.e. 6, 12, 24, 48, 96 wells, etc.). While fluid distribution to biological structures printed or lab grown within well-plates are one contemplated application of the present disclosure, other applications of the present pumping solutions/assembly are contemplated and possible. 
     Pumping solutions and assemblies may incorporate, but are not limited to, an array of pumps, valves, flow sensors, and/or pressure sensors to supply discrete flow to each well or to predetermined groups of wells of a well-plate. The unit may be devised to be modular so that it can be expandable to larger array of hardware to accommodate each well-plate capacity (e.g., 6, 12, 24, 48, 96 wells, etc.). For example,  FIG. 1  schematically illustrates perfusion assembly for the delivery of fluid to the various wells of a well-plate. For example, the well-plate may define a plurality of well-groups each having one or more wells. A well-plate manifold includes a plurality of fluid inlet and/or outlet paths corresponding to a well-group for the delivery of fluid into and/or out of each well-group. A modular pump assembly may include an array of pumps. The array of pumps may include an array of inlet pumps configured to push fluid through the well-groups of a well-plate, an array of outlet pumps configured to pull fluid through the well-groups of the well-plate, and/or any combination thereof. For example, in some embodiments the array of pumps including one or more pump pairs each including an inlet pump and an outlet pump. Each pair corresponds to a well-group of the well-plate. A fluid inlet line couples the inlet pump to a fluid inlet path of the well-plate manifold. In some embodiments, a fluid outlet line couples the outlet pump to a fluid outlet path of the well-plate manifold. In this way, flow to each group may be independently controlled. Accordingly, in some embodiments, fluid delivery into a well of a well-plate and/or extraction of fluid from the well of the well-plate may be independently controlled. This may allow operators to apply various conditions or parameters to different wells within the same well-plate. These and additional embodiments will be described in greater detail herein. 
     Referring now to  FIG. 1 , a perfusion assembly  10  may include a well-plate assembly  30  and a modular pump assembly  15  that is configured to fluidically couple the well-plate assembly  30  to one or more fluid reservoirs  12 . 
     Well-plate assemblies are described in greater detail in U.S. patent application Ser. No. 16/135,299, entitled “Well-plate and Fluidic Manifold Assemblies and Methods,” filed Sep. 19, 2018, hereby incorporated by reference in its entirety. In particular, a well-plate assembly  30  includes a well-plate  31  defining a plurality of well-groups  32 . Each well-group  32  may include one or more wells. It is noted that well-plates according to the present disclosure may have 6 or more wells, 12 or more wells, 24 or more wells, 48 or more wells, 96 or more wells, etc. As will be described in greater detail herein, the modular pump assembly  15  may be expanded to provide individualized flow control to any number of wells or well-groups  32  within a well-plate  31 . 
     In some use cases, wells may be used for growing and/or printing biological constructs. However, other uses are contemplated and possible. Printed biological constructs and methods of fabrication are further described in U.S. patent application Ser. No. 15/202,675, filed Jul. 6, 2016, entitled “Vascularized In Vitro Perfusion Devices, Methods of Fabricating, and Applications Thereof,” hereby incorporated by reference in its entirety. Such printed biological constructs may be formed directly within a well of a well-plate 31. For example, a 3-D printer (e.g., bioassemblybot® 3-D printing and robotics systems such as described in U.S. patent application Ser. No. 15/726,617, filed Oct. 6, 2017, entitled “System and Method for a Quick-Change Material Turret in a Robotic Fabrication and Assembly Platform,” hereby incorporated by reference in its entirety and as available from Advanced Solutions Life Sciences, LLC of Louisville, Ky.) may be used to fabricate biological constructs within each of the wells of the well-plate  31  with channel structures formed therein. The channel structures may be perfused with culture media solution or other fluid by the modular pump assembly  15 . It may be desirable to provide various flow conditions to individual constructs within a well-plate  31 . Accordingly, the modular pump assembly  15  is configured to provide independent flow control to separate groupings of wells and/or each individual well such that flow parameters to each well or well-group  32  within a single well-plate  31  may be varied from one another. 
     A well-plate manifold  50  may be positioned over the well-plate  31  and provide fluid flow paths into and out of each of the wells of the well-plate  31 . For example, the well-plate manifold  50  may provide a plurality of fluid inlet paths  54  and a plurality of fluid outlet paths  56 . The plurality of fluid inlet paths  54  may provide an inlet into the wells of each well-group  32  and the plurality of fluid outlet paths  56  may provide an outlet for fluid to be removed from each well-group  32  to a receptacle  11  or other location. It is noted that in illustrated embodiment, there are three wells in each group, however, a greater or fewer number of wells may be in each group without departing from the scope of the present disclosure. For example, each individual well may be a well-group  32  and may have a dedicated fluid inlet and outlet path, such that flow to each individual well may be separated controlled. 
     The inlet pumps  18  fluidically couple each well-group  32  to one or more fluid reservoirs  12 . Each inlet pump  18  may be fluidically coupled to the same fluid reservoir  12  as illustrated in  FIG. 1 . However, it is contemplated that the inlet pumps  18  may be fluidically coupled to different fluid reservoirs  12 . For example,  FIG. 2  illustrates a first portion of the fluid inlet pumps  18  fluidically coupled to a first fluid reservoir  12   a  and a second portion of the fluid inlet pumps  18  fluidically coupled to a second fluid reservoir  12   b.  Accordingly, different fluid reservoirs may be used for supplying fluid to different well-groups  32 . In some embodiments, each well  32  of the well-plate  31  may be supplied with fluid from a different fluid reservoir  12 . 
     Referring again to  FIG. 1 , in some embodiments, fluid from the fluid reservoir  12  may first be drawn by one or more inlet pumps  18  into a fluid manifold  14 , which may separate the fluid from the fluid reservoir  12  onto the fluid inlet lines  16 . That is a single first fluid inlet line  13  may fluidically couple the fluid reservoir  12  to the fluid manifold  14 , which is then separated to the various fluid inlet lines  16 . With reference again to  FIG. 2 , each fluid reservoir  12   a,    12   b  may be fluidically coupled by a first fluid inlet line  13   a,    13   b  to separate fluid manifolds  14   a,    14   b,  which separates the fluid to the various fluid inlet lines  16  to which the fluid is to be delivered. However, and with reference to both  FIGS. 1 and 2 , in some embodiments, there may be no fluid manifold upstream of the inlet pumps  18  and, instead, the inlet pumps  18  may pull fluid directly from the fluid reservoir (e.g.,  12 ,  12   a,  and/or  12   b ). 
     Fluid flow through the well-plate manifold  50  may be controlled with the modular pump assembly  15 . The modular pump assembly  15  may comprise an array of pumps. The array of pumps may include an array of inlet pumps  18  configured to push fluid through the well-groups of a well-plate, an array of outlet pumps  19  configured to pull fluid through the well-groups  32  of the well-plate  31 , and/or any combination thereof. For example, in some embodiments the array of pumps includes an array of pump pairs. Each pump pair may include an inlet pump  18  and an outlet pump  19 . A fluid inlet line  16  may fluidically couple the inlet pump  18  to a fluid inlet path  54  of the well-plate manifold  50  and a fluid outlet line  17  may fluidically couple the outlet pump  19  to the fluid outlet path  56  of the well-plate manifold  50 . The fluid inlet and outlet lines  16 ,  17  may be any type of tubing, pipes, etc. for containing fluid flow. The inlet pumps  18  and/or outlet pumps  19  may be any types of pumps including, but not limited to micropumps (e.g., ttpventus BL Series pumps, ttpventus XP Series pumps, ttpventus LT Series pumps, ttpventus HP series pumps, Bartels Mikrotechnik GmbH mp6 micropumps). The inlet pumps  18  and the outlet pumps  19  may be capable of functioning in a small form factor. For example, pumps according to the present disclosure may support low flow rates of 1-2 μl/min. However, greater or smaller flow rates are contemplated and possible. 
     For controlling the flow of fluid through the well-plate assembly  30 , each fluid inlet line  16  may include a flow control valve  20 , a flow sensor  22 , and/or a pressure sensor  24 .  FIG. 3  schematically illustrates communication between various components of the modular pump assembly  15 . For control of fluid flow through the perfusion assembly  10 , the modular pump assembly  15  may include a communication path  60 , one or more processors  62 , one or more memory modules  64 , one or more user interface devices  66 , each of the inlet pumps  18  and/or each of the outlet pumps  19 , the flow control valves  20 , the flow sensors  22 , and the pressure sensors  24 . It is noted that a greater or fewer number of modules may be including without departing from the scope of the present disclosure. It is also noted that not every inlet line  16  may include the same sensors. Additionally, in some embodiments, additional flow sensors, pressure sensors, or the like may measure characteristics of flow through the fluid outlet lines  17 . 
     The communication path  60  provides data interconnectivity between various modules disposed within the modular pump assembly  15 . Specifically, each of the modules can operate as a node that may send and/or receive data. In some embodiments, the communication path  60  includes a conductive material that permits the transmission of electrical data signals to processors, memories, sensors, valves, and pumps throughout the modular pump assembly  15 . In another embodiment, the communication path  60  can be a bus. In further embodiments, the communication path  60  may be wireless and/or an optical waveguide. Components that are communicatively coupled may include components capable of exchanging data signals with one another such as, for example, electrical signals via conductive medium, electromagnetic signals via air, optical signals via optical waveguides, and the like. 
     The one or more processors  62  may include any device capable of executing machine-readable instructions (logic) stored on a non-transitory computer-readable medium. Accordingly, each processor may include a controller, an integrated circuit, a microchip, a computer, and/or any other computing device, or any combination thereof. 
     The one or more memory modules  64  are communicatively coupled to the one or more processors  62  over the communication path  60 . The one or more memory modules  64  may be configured as volatile and/or nonvolatile memory and, as such, may include random access memory (including SRAM, DRAM, and/or other types of RAM), flash memory, secure digital (SD) memory, registers, compact discs (CD), digital versatile discs (DVD), and/or other types of non-transitory computer-readable mediums. The one or more memory modules  64  may be configured to store one or more pieces of logic, as described in more detail below for controlling flow through the perfusion assembly  10 . For example, the one or more pieces of logic may include instructions for operating the inlet pumps  18  and/or the outlet pumps  19 , in response to a perfusion criteria stored on the one or more memory modules  64  or otherwise received over the one or more user interface devices  66 . 
     The one or more user interface devices  66  may be communicatively coupled to the one or more processors  62  over the communication path  60 . The one or more user interface devices  66  may include any devices that allow a user to interact with the perfusion assembly  10 , and more specifically, the modular pump assembly  15 . For example, the one or more user interface devices  66  may include any number of displays and/or input devices (e.g., buttons, toggles, knobs, keyboards, microphones, touchscreens, etc.) which allow interaction and exchange of information between the user and the modular pump assembly  15 . For example, a user may observe flow parameters (e.g., flow rates, pressures, etc.) through the various inlet and outlet lines  16 ,  17  and/or input flow parameters (e.g., flow rates, pressures, etc.) to control the inlet pumps  18 , outlet pumps  19 , and/or flow control valves  20  to adjust the fluid flow parameters through individual inlet and/or outlet lines  16 ,  17 . 
     The flow control valves  20  may be fluidically coupled to the inlet pumps  18  over the fluid inlet line  16  and communicatively coupled to the one or more processors  62  over the communication path  60 . The flow control valves  20  may regulate the fluid flow or pressure of a fluid through the fluid inlet line  16  in response to detected pressure and/or flow rates. For example, the flow control valves  20  may include, but are not limited to, hydraulic valves, pneumatic valves, electronic valves, solenoid valves, etc. One or more of the flow control valves  20  may be actuated, by the one or more processors executing logic stored on the one or more memory modules  64 , in response to input received from the one or more user interface devices  66  or feedback from the pressure sensors  24  and/or the flow sensors  22  to adjust flow through the fluid inlet line  16 . Flow control valves may be similarly incorporated into the fluid outlet lines  17 , if desired. 
     The fluid flow sensors  22  (e.g., a flow meter) may include any sensor configured to output a flow signal indicative of a fluid flow rate through the fluid inlet line  16 . Each fluid inlet line  16  may include one or more fluid flow sensors  22  communicatively coupled to the one or more processors  62  over the communication path  60 . The fluid flow sensors  22  may be positioned downstream (e.g., along the fluid inlet line  16 ) of the inlet pumps  18  and/or the control valves. The one or more processors  62  may execute logic, stored on the one or more memory modules  64 , to actuate the flow control valve  20 , the inlet pump  18 , and/or the outlet pump  136  in response to the flow signal received from the flow sensor  22  to ensure desired flow rates through the perfusion assembly  10  and through the well-group  32 . Each fluid inlet line  16  may include a fluid flow sensor  22  such that flow can be independently monitored to each well-group  32  (and/or to each individual well  32 ). In some embodiments, it is contemplated the fluid flow sensors  22  may be incorporated into the fluid outlet lines  17 , if desired, to measure fluid flow rates out of the well-groups  32  and/or each individual well. 
     The pressure sensors  24  may include any sensor configured to output a pressure signal indicative of pressure within the fluid inlet line  16 . Each fluid inlet line  16  may include one or more pressure sensors  24  communicatively coupled to the one or more processors  62  over the communication path  60 . The pressure sensors  24  may be positioned downstream (e.g., along the fluid inlet line  16 ) of the inlet pumps  18  and/or the control valves. The one or more processors  62  may execute logic, stored on the one or more memory modules  64 , to actuate the flow control valve  20 , the inlet pump  18 , and/or the outlet pump  19  in response to the pressure signal received from the pressure sensor  24  to ensure desired flow through the perfusion assembly  10  and through the well-group  32 . Each fluid inlet line  16  may include a pressure sensor such that pressure can be independently monitored to each well-group  32  (and/or to each individual well  32 ). In some embodiments, it is contemplated the pressure sensors  24  may be incorporated into the fluid outlet lines  17 , if desired, to measure fluid pressure within the fluid outlet lines  17 . 
       FIG. 4  depicts a flow chart illustrating as method  200  of delivering fluid to a well-plate assembly  30  such as described above, according to one or more embodiments. It is noted that though only three steps (e.g., steps  202 ,  204 , and  206 ) are depicted, a greater or fewer number of steps, in any order, may be included without departing from the scope of the present disclosure. 
     At step  202 , the method  200  includes fluidically coupling the well-plate assembly  30  to the modular pump assembly  15 . Such may include attaching the fluid inlet lines  16  to fluid inlet paths  54  of the well-plate manifold  50  to fluidically couple the fluid inlet paths  54  of the well-plate manifold  50  to the inlet pumps  18 . At step  204 , the method  200  further includes fluidically coupling the modular pump assembly  15  to one or more fluid reservoirs  12 . As noted above, each inlet pump  18  of the modular pump assembly  15  may be fluidically coupled to separate fluid reservoirs  12  or the same fluid reservoir  12 . In some embodiments, a portion of the inlet pumps  18  may be fluidically coupled to a first fluid reservoir  12   a  and a second portion of the inlet pumps  18  may be fluidically coupled to a second fluid reservoir  12   b  that is different from the first fluid reservoir  12   a,  such as illustrated in  FIG. 2 . In some embodiments, one or more fluid manifolds  14  fluidically couple the one or more fluid reservoirs  12  to the inlet pumps  18  of the modular pump assembly  15 . 
     Step  206  includes controlling fluid flow into/out of the well-plate assembly  30 . That is, the inlet/outlet pumps  19  may be primed with the desired media/solution for an experimental procedure, for example. Accordingly, the outlet pumps  19  may be fluidically coupled to the outlet pumps  19  of the modular pump assembly  15  through fluid outlet line  17 . The outlet pumps  19  may deliver fluid into a receptacle  11  (e.g., a waste receptacle) or other location for further processing. For example, the one or more processors  62  may execute instructions received over the one or more user interface devices  66  and/or by executing logic stored on the one or more memory modules  64 , to selectively activate a pump (e.g., the inlet pump  18  and/or the outlet pump  19 ) of a pump pair associated of the one or more well-groups  32  to cause fluid to flow through one or more of the well-groups  32 . In some embodiments, controlling fluid flow further includes detecting fluid flow parameters (e.g., flow rate with the fluid flow sensors  22  and/or pressure with the fluid pressure sensors  24 ) within the fluid inlet lines  16  fluidically coupling the inlet pumps  18  to the fluid inlet path  54  of the well-plate manifold  50  and adjusting (e.g., automatically) fluid flow parameters (e.g., with the inlet pump  18 , outlet pump  19 , and/or control valve  20 ) to the fluid inlet path  54  in response to the detected fluid flow parameters. That is, fluid flow rates and/or pressures may be adjusted to stay within predetermined limits. For example, fluid flow rates may be controlled to be less than about 6 ml/min or between about 1 nl/min to about 1000 μl/m. In particular, fluid flow rates may be controlled to be similar to fluid flowrates within a physiological vasculature. For example, in some embodiments flow rates may be controlled to be between about 150 to about 300 μl/min. However, other flow rates are contemplated and possible. Similarly, pressure parameters may similarly be controlled to be aligned with physiological blood pressures (e.g., 180/120, 110/70, etc). In some embodiments, pressure parameters may be similar to physiological capillary blood pressures (e.g., 0.5 to 22.5 mmHg). However, other pressure parameters are contemplated and possible. 
     For example, the method  200  may include detecting a fluid pressure within a fluid inlet line  16  fluidically coupling the inlet pump  18  to a fluid inlet path  54  of the well-plate manifold  50  and adjusting a flow control valve  20  positioned along the fluid inlet line  16  to adjust the fluid pressure within the fluid inlet line  16  in response to the detected fluid pressure. As another example, the method  200  may include detecting a fluid flow rate within a fluid inlet line  16  fluidically coupling the inlet pump  18  to a fluid inlet path  54  of the well-plate manifold  50 , and adjusting a flow control valve  20  positioned along the fluid inlet line  16  to adjust the fluid flow rate within the fluid inlet line  16  in response to the fluid flow rate. 
       FIG. 5  schematically illustrates an embodiment of a modular pump assembly  15  fluidically coupling a fluid reservoir  12  to a well-plate manifold  50 . In this particular embodiment, the modular pump assembly  15  includes a mounting frame  70  to which an array of pump pairs  102  is mounted. Each of the pump pairs includes an inlet pump  18  and an outlet pump  19 . The frame  70  may be a printed circuit board onto which the array of pump pairs may be physically and electronically mounted. Is noted that while the modular pump assembly  15  illustrates the inlet pumps  18  along a first side of the frame  70  and the outlet pumps  19  arranged along a second side of the frame  70 , in some embodiment, the inlet pumps  18  may be arranged along a top surface of the frame  70  while the outlet pumps  19  are arranged along a bottom surface of the frame  70  opposite the inlet pumps  18 . It is noted that the frame  70  may be sized to house any number of pump pairs (e.g., 6 pumps pair, 8 pump pairs, 12 pumps pairs, etc.). In some embodiments, the inlet and outlet pumps  18 ,  19  may be pluggable and unpluggable onto the frame  70  to allow for customization of the number of pump pairs  102  arranged on the frame  70 . 
     As illustrated in  FIGS. 6A and 6B  additional frames (e.g.,  70   a,    70   b,    70   c,  and  70   d ) may be stackable with one another in a modular configuration such that any desired number of frames may be stacked together to provide an adjustable form factor. For example,  FIG. 6A  illustrates a first frame  70   a  stacked with a second frame  70   b.    FIG. 6B  illustrates a first frame  70   a,  a second frame  70   b,  a third frame  70   c,  and a fourth frame  70   d  vertically stacked on top of one another. Accordingly, any number of pumps may be provided in a compact structure for perfusion of a well-plate assembly  30 . For example, frames with twelve pump pairs may be stacked to provide capacity to individually control perfusion into 12 wells, 24 wells, 48 wells, 96 wells, etc. 
       FIG. 7  illustrates an alternative modular pump assembly  100  for fluidically coupling the fluid reservoir  12  to the well-plate manifold  50 . Unless otherwise noted, the above description in regards to  FIGS. 1-4  is applicable to the present embodiment unless otherwise specifically noted or apparent from the description and/or figures. 
     In particular, the modular pump assembly  100  includes housing  110 , an array of pump pairs  102   a  and/or  102   b,  wherein each pump pair is arranged within an enclosure that is pluggable into a mounting frame  112   a,    112   b.    
       FIGS. 8A and 8B  illustrate a more detailed view of an array of pump pairs  102  mounted to a mounting frame  112 . The arrays of pump pairs  102  may include a plurality of cartridges  130  that house each pump pair therein. The frame  112  may be a printed circuit board  132  that couples the plurality of cartridges  130  to micropump drive boards  118 , which may form part of the one or more processors  62  and/or memory modules  64  described above. The frame  112  includes a plurality of fluid couplings  116  (e.g., nozzles, quick-connect ports, or the like) for fluidically coupling the cartridges  130  to fluid inlet and outlet lines  16 ,  17  (not shown), described above.  FIG. 9  illustrates an exploded view of the plurality of cartridges  130  from the mounting frame  112 . In the illustrated embodiment, the frame  112  includes a fluid distribution board  114  that fluidly couples inlet and outlet openings  144  and/or flow connectors  138  (illustrated in  FIG. 10 ) of the cartridges  130  to the plurality of fluid couplings  116  shown in  FIG. 8B . 
     Referring now to  FIG. 10  a cartridge  130  of the plurality of cartridges  130  is illustrated in an exploded view. In this view, the cartridge  130  includes an enclosure  131 , an inlet pump  134 , an outlet pump  136 , and a printed circuit board  132 . It is noted that tubing has been removed for simplicity of illustration. 
     The enclosure  131  may be separable into a first side wall  140   a  and a second side wall  140   b.  The housing  131  further includes a fluid communication end wall  142 . Together the first side wall  140   a,  the second side wall  140   b,  and the fluid communication end wall  142  form the enclosure  131  around the inlet pump  134 , the outlet pump  136 , and the printed circuit board  132 . The fluid communication end wall  142  may include a plurality of opening  144  through which the inlet and outlet lines may be attached. For example, the inlet pump  134  may draw fluid from the fluid reservoir  12  over the first fluid inlet line  13  (or a line from the fluid manifold  14  illustrated in  FIG. 1 ) and pump fluid into the fluid inlet line  16  and into the well-plate manifold  50  described above. The outlet pump  136  may draw fluid from the well-plate manifold  50  into the outlet line, which may then dump the fluid into a receptacle  11 . To accomplish this, the plurality of openings  144  of the fluid communication end wall may have flow connectors  138  positioned therein that are fluidically coupled to inlet and outlets of the pumps  134 ,  136  with tubing, not shown for simplicity. The flow connectors  138  may plug into the fluid distribution board  114  of the frame  112 , shown in  FIG. 9 . 
     Referring now to  FIG. 11A-11C , the arrays of pump pairs  102   a,    102   b  may be mounted to the housing  110  through a plurality of standoff pins  108 . The standoff pins may form a space between the housing  110  and the mounting frames  112   a  to allow room for tubing to be run to the various cartridges  130 . 
     Referring to  FIG. 11C , the housing  110  includes a top flange  111 , a first and second side flanges  115   a,    115   b,  a base flange  113 , and a back wall  117 . It is noted that multiple housings  110  may be bonded or stacked together in any direction to provide support to additional arrays of pump pairs. For example, additional housings may be coupled to on another along the top flange  111 , the first and/or second side flanges  115   a,    115   b,  and/or the base flange  113 . In some embodiments, additional housings  110  may simply be stacked on another such that the arrays of pump pairs  102   a,    102   b  support subsequent layers of modular pump assemblies  100 . In some embodiments, the top flange  111  may provide a support surface for supporting one or more processors  62  and/or one or more memory modules  64  as described herein. 
     As noted above, the arrays of pump pairs  102   a,    102   b  may be mounted to the housing  110 . In particular, the array of pump pairs  102   a,    102   b  may be bounded to the back wall  117  by the plurality standoff pins  108  such that the mounting frames  112   a,    112   b  of the array of pump pairs  102 ,  102   b  are spaced from the back wall  117 . 
     In some embodiments mounted to the opposite side of the back wall  117 , opposite the arrays of pump pairs  102   a,    102   b,  may be one or more fluid manifolds  146   a,    146   b . These fluid manifolds  146   a,    146   b  may be similar to those described in regards to  FIG. 1 or 2 , wherein a first fluid inlet line  13  delivers fluid to the fluid manifolds  146   a,    146   b,  which is then split to the individual inlet pumps. 
     It is noted that any embodiments as provided herein may be integrated into an automated assembly (e.g., BioAssemblyBot® 3-D Printing and Robotics Systems such as described in U.S. patent application Ser. No. 15/726,617, filed Oct. 6, 2017, entitled “System and Method for a Quick-Change Material Turret in a Robotic Fabrication and Assembly Platform,” hereby incorporated by reference in its entirety and as available from Advanced Solutions Life Sciences, LLC of Louisville, Ky., and/or automated storage assemblies such as described in U.S. Patent Application No. 16/502,795, entitled “Modular Storage Units for Perfusion and/or Incubation of One or More Specimens and Storage Assemblies,” filed Jul. 3, 2019, hereby incorporated by reference in its entirety). However, the assemblies as described herein may also be used in manual benchtop applications. 
     It is noted that in the various embodiments described herein the various parts, for example, the pumps, frames, tubes, sensors, valves, etc., may be sterilizable for repeated use and/or use in different experiments. 
     Additionally embodiments of the present disclosure may have a small overall size such that an entire modular pump assembly  100  may sit on or below a well-plate assembly  30  or within another limited storage area. However, it is noted that larger assemblies are contemplated and possible. 
     Embodiments can be described with reference to the following numbered clauses, with preferred features laid out in the dependent clauses: 
     1. A modular pump assembly comprising: a plurality of mounting frames configured to be stackable with one another in a modular configuration; and an array of pump mounted to each of the plurality mounting frames, the array of pumps comprising an array of inlet pumps configured to be fluidically coupled a plurality of fluid inlet paths of a well-plate manifold or an array of fluid outlet pumps configured to be fluidically coupled to a plurality of fluid outlet paths of the well-plate manifold, or any combination thereof 
     2. The modular pump assembly of clause 1, wherein the array of pumps comprises an array of pump pairs, each pump pair comprising an inlet pump and an outlet pump. 
     3. The modular pump assembly of any preceding clause, further comprising one or more processors communicatively coupled to the inlet pump and the outlet pump; and one or more memory modules that store logic that when executed by the one or more processors cause the one or more processors to: control the inlet pump to deliver fluid from a fluid reservoir to a well of a well-plate; and control the outlet pump to remove the fluid from the fluid reservoir of the well of the well-plate. 
     4. The modular pump assembly of clause 3, further comprising: a flow control valve fluidically coupled to the inlet pump and communicatively coupled to the one or more processors, wherein the one or more processors execute logic to actuate the flow control valve to control a flow of fluid from the inlet pump to the well of the well-plate. 
     5. The modular pump assembly of clause 4, further comprising: a flow sensor configured to output a flow signal indicative of a flow rate of fluid between the inlet pump and the well of the well-plate, wherein the one or more processors execute logic to actuate the flow control valve in response to the flow signal received from the flow sensor. 
     6. The modular pump assembly of any of clauses 3-5, further comprising: a pressure sensor configured to output a pressure signal indicative of pressure within a fluid inlet line extending from the inlet pump to a well of the well-plate, wherein the one or more processors execute logic to actuate the flow control valve in response to the pressure signal received from the pressure sensor. 
     7. The modular pump assembly of any of clauses 2-6, further comprising an enclosure housing each pump pair. 
     8. A perfusion assembly, comprising: a well-plate assembly comprising: a well-plate defining a plurality of well-groups each comprising one or more wells; and a well-plate manifold comprising a plurality of fluid inlet paths and fluid outlet paths corresponding to each well-group; a modular pump assembly comprising: a plurality of mounting frames configured to be stackable with one another in a modular configuration; an array of pumps mounted to each of the plurality mounting frames, the array of pumps comprising an array of inlet pumps fluidically coupled to the plurality of fluid inlet paths, an array of outlet pumps fluidically coupled to plurality of fluid outlet paths, or any combination thereof. 
     9. The perfusion assembly of clause 8, wherein the array of pumps comprises an array of pump pairs, each pump pair comprising an inlet pump and an outlet pump. 
     10. The perfusion assembly of clause 8 or 9, further comprising: one or more processors communicatively coupled to the inlet pump and the outlet pump; and one or more memory modules that store logic that when executed by the one or more processors cause the one or more processors to: control the inlet pump to deliver fluid from a fluid reservoir to a well-group of the well-plate; and control the outlet pump to remove the fluid from the well-group of the well-plate. 
     11. The perfusion assembly of clause 10, wherein the modular pump assembly further comprises: a flow control valve fluidically coupled to the inlet pump by a fluid inlet line and communicatively coupled to the one or more processors, wherein the one or more processors execute logic to actuate the flow control valve to control a flow of fluid from the inlet pump to the well-group of the well-plate. 
     12. The perfusion assembly of clause 10 or 11, wherein the modular pump assembly further comprises: a flow sensor configured to output a flow signal indicative of a flow rate of fluid within the fluid inlet line, wherein the one or more processors execute logic to actuate the flow control valve in response to the flow signal received from the flow sensor. 
     13. The perfusion assembly of any of clauses 10-12, wherein the modular pump assembly further comprises: a pressure sensor configured to output a pressure signal indicative of pressure within the fluid inlet line extending from the inlet pump to the well of the well-plate, wherein the one or more processors execute logic to actuate the flow control valve in response to the pressure signal received from the pressure sensor. 
     14. The perfusion assembly of any of clauses 9-12, wherein each pump pair is arranged within an enclosure. 
     15. A method of delivering fluid to a well-plate assembly, the method comprising: fluidically coupling the well-plate assembly to a modular pump assembly, wherein: the well-plate assembly comprises a well-plate defining a plurality of well-groups each comprising one or more wells; and a well-plate manifold comprising a plurality of fluid inlet paths and fluid outlet paths corresponding to each well-group; and the modular pump assembly comprises: one or more mounting frames; and an array of pumps mounted to the one or more mounting frames, the array of pumps comprising an array of inlet pumps fluidically coupled to the plurality of fluid inlet paths, an array of outlet pumps fluidically coupled to plurality of fluid outlet paths, or any combination thereof; fluidically coupling the modular pump assembly to one or more fluid reservoirs; and controlling fluid flow into and/or out of one or more of the well-groups by selectively activating, with one or more processors, a pump of the array of pumps associated with each of the well-groups. 
     16. The method of clause 15, further comprising: detecting fluid flow parameters within a fluid inlet line fluidically coupling a fluid reservoir to the well-plate manifold; and adjusting fluid flow parameters to a fluid inlet path in response to detected fluid flow parameters. 
     17. The method of clause 15 or 16, further comprising: detecting a fluid pressure within a fluid inlet line fluidically coupling the one or more fluid reservoirs to the well-plate manifold; and adjusting a control valve positioned along the fluid inlet line to adjust the fluid pressure within the fluid inlet line in response to the fluid pressure. 
     18. The method of any of clauses 15-17, further comprising: detecting a fluid flow rate within a fluid inlet line fluidically coupling the one or more fluid reservoirs to the well-plate manifold; and adjusting a control valve positioned along the fluid inlet line to adjust the fluid flow rate within the fluid inlet line in response to the fluid flow rate. 
     19. The method of any of clauses 15-18, further comprising fluidically coupling a fluid reservoir to each of the one or more of the inlet pumps. 
     20. The method of any of clauses 15-19, further comprising fluidically coupling a portion of the inlet pumps to a first fluid reservoir; and fluidically coupling a second portion of the inlet pumps to a second fluid reservoir that is different from the first fluid reservoir. 
     It should now be understood that embodiments as described herein are directed to a modular and expandable low flow pumping solution for discrete flow control and integration into multichannel perfusion networks. Pumping solutions and assemblies may incorporate, but are not limited to, an array of pumps, valves, flow sensors, and/or pressure sensors to supply discrete flow to each well of a well-plate or discrete groups of wells in a well-plate. The unit may be devised to be a modular construct so that it can be expandable to larger array of hardware to accommodate each well-plate capacity. Accordingly, individualized perfusion control of any number of wells in a well-plate may be realized. 
     While particular embodiments have been illustrated and described herein, it should be understood that various other changes and modifications may be made without departing from the spirit and scope of the claimed subject matter. Moreover, although various aspects of the claimed subject matter have been described herein, such aspects need not be utilized in combination. It is therefore intended that the appended claims cover all such changes and modifications that are within the scope of the claimed subject matter.