Liquid-operated pump, pump unit, and method for pumping process fluid.

Abstract

This disclosure relates to liquid-operated pumps 100, 200, 300, and 400 for bioprocessing systems, each pump 100, 200, 300, and 400 comprising pump chambers 130, 230, and 330, a flexible diaphragm 132 configured to form a barrier between the control fluid portion 136 of the pump chambers 130, 230, and 330 and the process fluid portion 134 of the pump chambers 130, 230, and 330, process fluid passages 110, 210, and 310 including the process fluid portion 134 of the pump chambers 130, 230, and 330, and control fluid passages 120, and control fluid passage 120 The 220 comprises an inlet 122 to the pumps 100, 200, 300, and 400, an outlet 124 from the pumps 100, 200, 300, and 400, and a control fluid section 136 of the pump chambers 130, 230, and 330, wherein the control fluid passages 120 and 220 are configured to contain at least a portion of the volume of the captured control fluid, and the displacement of the volume of the captured control fluid causes deformation of a flexible diaphragm 132, which in turn causes movement of process fluid in the process fluid passages 110, 210, and 310, relating to the liquid-operated pumps 100, 200, 300, and 400.

Description

Technical Field

[0001] The present disclosure relates to a liquid-operated pump for a bioprocessing system, a pump unit for a bioprocessing system, and a method of operating a liquid-operated pump.

Background Art

[0002] Bioprocessing systems typically require effective liquid handling to perform processes under controlled and contained conditions. This can involve aseptic handling in a closed liquid handling system and the use of pre-sterilized components.

[0003] In recent years, modular bioprocessing systems based on single-use flow paths have been developed. Single-use components are implemented as modular or integrated consumables, which are intended to be discarded after process execution. Single-use flow path components eliminate the time-consuming and labor-intensive pre-cleaning and post-cleaning of wetted flow paths. This improves overall process efficiency and reduces costs. Also, the elimination of equipment cleaning and any associated cleaning validation processes greatly reduces the risk of cross-contamination between different batches processed using the bioprocessing system.

[0004] Single-use components are, by their nature, discarded after use. Therefore, it is beneficial to minimize the cost, complexity, and material usage of such single-use components while maximizing ease of production. Furthermore, it is beneficial to provide configurable single-use components for various liquid handling processes in order to minimize the number of single-use component types required for a particular liquid handling operation. Additionally, it is beneficial to provide flexible and scalable single-use components to accommodate different processing capabilities or needs. For example, pumps or valves may need to be supplied in different sizes to handle various liquids that will be handled at different volumes and / or flow rates.

[0005] An example of a single-use component including a pneumatically or hydraulically actuated diaphragm valve is described in U.S. Patent No. 10,451,591. This document describes a valve system in which a pneumatic or hydraulic control system controls the application of pneumatic or hydraulic pressure to actuate a diaphragm valve in a valve block that forms part of a single-use flow path. The diaphragm valve is used to control the flow of liquid in the single-use flow path. Prior to the actuation of the diaphragm valve, the valve block is connected to a connector unit that allows connection and disconnection of conduits in the pneumatic or hydraulic control system to conduits in the valve block.

[0006] Bioprocessing involves a variety of different liquid handling operations. Requirements for liquid handling equipment (e.g., pumps and valves) can vary depending on the type of processing operation (usually called a unit operation (UOp)). Various critical separation and purification unit operations (e.g., tangential flow filtration (TFF) and chromatography) require pumps that deliver continuous, pulsation-free liquids to achieve the efficiency and reproducibility required in biopharmaceutical processing.

[0007] In TFF, a continuous and virtually pulsation-free liquid flow allows for stable conditions in the filtration device in terms of flow and pressure, resulting in high separation efficiency and performance and avoiding fouling of the filter device. In chromatography, a continuous and precise liquid flow is a prerequisite for good control and reproducibility of operation, enabling the precise separation of different effluent fractions and the collection of the drug substance of interest at the desired purity and yield. There are other unit operations in bioprocessing where a continuous, stable, and pulsation-free flow is required or advantageous, such as in single-pass TFF operation, conventional flow filtration, plug-flow reactions, and mixing operations.

[0008] Current pump technology for bioprocessing systems is typically based on pump design solutions that directly engage the internal liquid displacement parts of the pump (e.g., pistons, diaphragms, lobe rotors, centrifugal rotors, or peristaltic tubes) by using a motor or electric drive unit attached to the pump. Particularly with regard to single-use technology, the need to directly combine and connect a reusable drive unit with a single-use, disposable pump unit imposes significant limitations in several aspects, such as efficient use of space, flexibility in positioning, integrating, and miniaturizing liquid handling components, and ease of use when installing, removing, and replacing single-use processing liquid handling units as consumable devices.

[0009] For example, current technologies are not well-suited to facilitating the physical miniaturization required to provide single-use consumables with small physical size and low liquid hold-up volume (which is necessary to achieve high separation efficiency and to enable cost-effective solutions that are easy to use and safe to use), particularly when reducing the scale and workload for single-use bioprocessing, as is required for the production of drug substances for individualized therapies. [Prior art documents] [Patent Documents]

[0010] [Patent Document 1] U.S. Patent No. 10,451,591 [Overview of the Initiative] [Problems that the invention aims to solve]

[0011] Therefore, there is a need to provide single-use systems and components that achieve high efficiency, precision, and scalability for small-volume processing. In particular, there is a need to provide pump solutions that provide a continuous and virtually pulsation-free flow for small-scale single-use isolation, minimizing the cost and complexity of such single-use components. [Means for solving the problem]

[0012] This summary introduces concepts that are explained in more detail in the detailed description. It should not be used to identify essential features of the claimed subject matter, nor should it be used to limit the scope of the claimed subject matter.

[0013] A first aspect of the present disclosure provides a liquid-operated pump for a bioprocessing system, the pump comprising a pump chamber, a flexible diaphragm configured to form a barrier between a control fluid portion of the pump chamber and a process fluid portion of the pump chamber, a process fluid passage containing the process fluid portion of the pump chamber, and a control fluid passage comprising an inlet to the pump, an outlet from the pump, and the control fluid portion of the pump chamber, the control fluid passage being configured to contain at least a portion of a captured volume of control fluid, wherein displacement of the captured volume of control fluid causes deformation of the flexible diaphragm, and deformation of the flexible diaphragm causes movement of a process fluid (e.g., process fluid) in the process fluid passage.

[0014] Therefore, the liquid-operated pump of the first embodiment allows process fluids to be driven using a liquid-operated pump with a small number of components. The small number of components of the liquid-operated pump allows the liquid-operated pump to be supplied as a low-cost consumable (e.g., a single-use consumable), to be small in size, to be manufactured using small amounts of material (to reduce environmental impact), and to be easy to use. Furthermore, the use of a flexible diaphragm for pumping action ensures complete closure and integrity of the process flow path, eliminating the risk of contamination of the process fluid or leakage from the process side to the environment and / or control fluid. When the process fluid is considered to be a process fluid and therefore incompressible, the amount of captured volume control fluid displaced into the pump chamber is equal to the amount of process fluid displaced from the pump chamber. Thus, there is a one-to-one relationship between the displacement of the captured volume control fluid and the displacement of the process fluid in the liquid-operated pump. This enables high precision of the pump because precise volumes of process fluid can be displaced from the liquid-operated pump according to the present invention. Furthermore, the liquid-operated pump of the first embodiment is suitable for integration into a pumping system having two pumps and two parallel-connected pump chambers (alternatively, three or more pumps and two parallel-connected pump chambers), where one pump supplies positive pressure and displaces the process fluid from one pump chamber, while another pump supplies negative pressure and draws the process fluid into the other pump chamber (then the pumps operate in reverse). Such an arrangement allows for a substantially continuous and pulsation-free flow of the process fluid.

[0015] A second aspect of the present disclosure provides a pump unit for a bioprocessing system, the pump unit comprising: a pump unit outlet configured for connection to a control fluid inlet of a liquid-operated pump; a pump unit inlet configured for connection to a control fluid outlet of a liquid-operated pump, such that a control fluid flow path includes the pump unit outlet, a liquid-operated pump, and the pump unit inlet; a pump configured to drive the movement of a control fluid in the control fluid flow path; and one or more valves configured to cause a predetermined volume of control fluid to be trapped in a portion of the control fluid flow path including the pump and the liquid-operated pump, such that the movement of the pump causes the displacement of the trapped volume of fluid.

[0016] A third aspect of the present disclosure provides a method for pumping a process fluid in a bioprocessing system, the method comprising the steps of: providing a liquid-operated pump and a pump unit, the liquid-operated pump comprising a pump chamber and a flexible diaphragm configured to form a barrier between a control fluid portion of the pump chamber and a process fluid portion of the pump chamber; capturing a predetermined volume of control fluid in a portion of a control fluid flow path, the portion of the control fluid flow path comprising a pump of a pump unit and a control fluid portion of a pump chamber; and using the pump to displace the captured volume of control fluid, deform the flexible diaphragm, and cause movement of the process fluid in the process fluid flow path, including the process fluid portion of the pump chamber.

[0017] Specific embodiments are described below, merely as examples, with reference to the attached drawings. [Brief explanation of the drawing]

[0018] [Figure 1]Schematic diagram of a first pumping system including a liquid-operated pump and a pump unit according to the first example. [Figure 2] Cross-sectional view through a liquid-operated pump according to the first example. [Figure 3] Schematic diagram of a second pumping system including a liquid-operated pump according to the second example. [Figure 4] Schematic diagram of a third pumping system including a liquid-operated pump according to the third example. [Figure 5] Schematic diagram of a pumping system according to the fourth example. [Figure 6A] Diagram showing the valve state of the pumping system shown in FIG. 5 during priming of the pumping system. [Figure 6B] Diagram showing the valve state of the pumping system shown in FIG. 5 during priming of the pumping system. [Figure 7] Diagram showing the valve state of the pumping system shown in FIG. 5 when used to drive a liquid-operated pump. [Figure 8] Diagram showing the valve state of the pumping system shown in FIG. 5 during drain discharge of the pumping system. [Figure 9] Flowchart of a method of performing a pumping operation to pump a process fluid using a pumping system. [Figure 10] Flowchart of a method of priming a pumping system. [Figure 11] Flowchart of a method of operating a pumping system to pump a process fluid. [Figure 12] Flowchart of a method of draining a pumping system.

DETAILED DESCRIPTION OF THE INVENTION

[0019] Implementations of the present disclosure are described below with particular reference to bioprocessing systems. However, it will be recognized that the implementations described herein are also applicable to other liquid handling operations in which the fluid is pumped.

[0020] Figure 1 includes a schematic diagram of a pumping system 190, which includes a liquid-operated pump 100 connected to a pump unit 150, while Figure 2 is a cross-sectional view through the liquid-operated pump 100. The liquid-operated pump 100 can be a component of a bioprocessing system (for example, a tangential flow filtration (TFF) system or a chromatography system).

[0021] As shown in Figure 1, the liquid-operated pump 100 includes two flow paths (a process fluid flow path 110 and a control fluid flow path 120). The process fluid flow path 110 can provide fluid connections to columns, filters, reservoirs, conduits, and / or chambers (not shown) for handling the fluid being processed by the bioprocessing system (it can be, for example, a drug formulation, monoclonal antibodies (MABs), mRNA, etc., or may include them). As shown in Figure 1, the process fluid flow path 110 includes a process fluid inlet 112, a process fluid outlet 114, a first valve 116 disposed between the process fluid inlet 112 and the pump chamber 130 of the liquid-operated pump 100, and a second valve 118 disposed between the pump chamber 130 and the process fluid outlet 114.

[0022] If the liquid-operated pump 100 is a component of a TFF system, the process fluid inlet 112 can receive process fluid (e.g., liquid) from the TFF reservoir and / or diafiltration buffer reservoir, while the process fluid outlet 114 can supply liquid to the TFF filter. If the liquid-operated pump 100 is a component of a chromatography system, the process fluid inlet 112 can receive process fluid (e.g., liquid) from an inlet container (which can receive one or more liquids from an inlet manifold and associated valves), while the process fluid outlet 114 can supply liquid to a chromatography column. The process fluid inlet 112 and process fluid outlet 114 can also be seen in Figure 2.

[0023] In one example, each of the first valve 116 and the second valve 118 is a check valve (e.g., a ball valve, membrane valve, or umbrella valve). Implementing the first valve 116 and the second valve 118 as check valves allows for the implementation of passive valves, thereby eliminating the need for active valves and further simplifying the operation of the fluid-operated pump 100. Alternatively, as shown in Figure 2, each of the first valve 116 and the second valve 118 can be an active valve, such as a fluid-operated (e.g., air-operated) membrane valve. In particular, if the flexible layer forming the diaphragm of the pump chamber 130 (described further below) is also used to provide the membrane of a fluid-operated membrane valve (as shown in Figure 2), the active valve, such as a fluid-operated membrane valve, can be incorporated using fewer components (thus reducing the complexity of the fluid-operated pump 100).

[0024] The control fluid passage 120 includes a conduit for applying pressure to the diaphragm 132 of the pump chamber 130 using the control fluid. As shown in Figure 1, the control fluid passage 120 includes a control fluid inlet 122 located upstream of the pump chamber 130 and a control fluid outlet 124 located downstream of the pump chamber 130.

[0025] The diaphragm 132 of the pump chamber 130 divides the pump chamber 130 into two parts: a process fluid portion 134 of the pump chamber 130 and a control fluid portion 136 of the pump chamber 130. The process fluid passage 110 includes the process fluid portion 134 of the pump chamber 130, while the control fluid passage 120 includes the control fluid portion 136 of the pump chamber 130. The diaphragm 132 forms an impermeable barrier between the process fluid portion 134 and the control fluid portion 136, preventing fluid leakage between the two portions 134 and 136. The impermeability of the diaphragm 132 to liquids allows the diaphragm 132 to be displaced by applying pressure to the diaphragm 132 using the control fluid.

[0026] As shown in more detail in Figure 2, the diaphragm 132 can be sandwiched between two parts of the liquid-actuated pump 100. A single unitary diaphragm 132 (for example, provided as a sheet of thermoplastic elastomer (TPE)) can be used to provide pumping action within multiple cavities, for example, within the control fluid portion of the pump chamber, the pump chamber, and / or the process fluid portion of the pump chamber. Such a single unitary diaphragm 132 can also form a structural joint part of a sandwiched structure in which the liquid-actuated pump is housed (for example, within a single-use unitary cassette designed for small-volume sample bioprocessing applications). The first part 102 may include a process fluid channel 110, while the second part 104 may include a control fluid channel 120. The diaphragm 132 can be formed from a flexible material (e.g., a polymer) that is flexible enough to allow deflection when pressure is applied using a control fluid. Such flexible pressure-responsive materials can be, for example, fluoropolymers or elastomers. In one particular example, the diaphragm 132 is formed from a perfluoroalkoxy copolymer resin thermoplastic material. Materials such as silicone rubber, EPDM rubber, and thermoplastic elastomers (TPEs) can also be used as alternatives. TPEs are particularly suitable for bonding to the first part 102 and / or second part 104 of the liquid-operated pump 100, while on the one hand providing high flexibility (e.g., 700% elongation before rupture). One example of a TPE particularly suitable for the diaphragm 132 is Mediprene (RTM) TPE from Heexpol AB in Malmö, Sweden.

[0027] Suitable materials for the first part 102 and the second part 104 include, for example, polypropylene, polymethylpentene (also known as TPX(RTM)), and cyclic olefin copolymers (COC). One example of a material particularly suitable for the first part 102 and the second part 104 is a COC having a low glass transition temperature (e.g., Tg between 60°C and 100°C, preferably between 70°C and 85°C) to address bonding with TPEs such as Mediprene(RTM). It will be recognized that other glass transition temperature ranges will be applicable to alternative polymers to address bonding with the diaphragm 132. However, in examples where the diaphragm 132 is clamped or screwed to the first part 102 and / or second part 104 (instead of being bonded), materials such as stainless steel can be used for the first part 102 and / or second part 104, along with elastomer diaphragm materials (for example, Kalrez(RTM) elastomer from DuPont, Wilmington, Delaware, USA).

[0028] In various preferred embodiments, the diaphragm 132 comprises a TPE (having at least one thermoplastic component and at least one elastomer component) and is bonded to a first part 102 and / or second part 104 comprising a cyclic olefin copolymer (COC). Bonding between such components can be provided, for example, by temperature-induced thermal bonding / diffusion bonding.

[0029] The elastomer component may contain a SEBS (styrene-ethylene-butadiene-styrene) matrix, which can provide several glass transition temperatures and elastomer components with different properties. For example, it may contain both soft segments (e.g., polyethylene and polybutadiene) and hard segments (e.g., polystyrene).

[0030] Furthermore, the TPE-based diaphragm 132 includes at least one material component having a glass transition temperature (Tg) that matches the glass transition temperature (Tg) of the COC. This material component can be, for example, a thermoplastic resin used to replace polypropylene, which is otherwise used in conventional TPE-based membranes.

[0031] For example, COC8007 having a Tg of 65-95°C can be used. One or more thermoplastic components (having a lower Tg or melting point than polypropylene) added to a TPE-based membrane can then be used to provide a substantially matched Tg.

[0032] Matching the Tg properties in this way allows for improved diffusion bonding through molecular transfer between components, providing a strong bond between them. Therefore, the TPE-based diaphragm 132 can be used to provide additional structural support for fixing the first part 102 and the second part 104 together, or alternatively, it can be used solely to provide such support between them.

[0033] Generally, materials used to construct single-use bioprocessing components should be compatible with typical sterilization methods (e.g., gamma irradiation or X-ray irradiation and / or ethylene oxide sterilization). Furthermore, materials used for components in contact with process fluids (so-called "wetted parts") should comply with regulatory requirements as well as material requirements that meet current best practices and standards in cGMP processing (e.g., no animal-derived components, compliance with USP (Class 6) requirements).

[0034] Returning to Figure 1, it can be seen that the pump unit 150 includes a pump unit inlet 152 and a pump unit outlet 154 (which are also schematically shown in Figure 2). The pump unit outlet 154 is in fluid communication with the control fluid inlet 122 of the liquid-operated pump 100, so that the control fluid inlet 122 receives the control fluid from the pump unit outlet 154. Similarly, the pump unit inlet 152 is in fluid communication with the control fluid outlet 124 of the liquid-operated pump, so that the pump unit inlet 152 receives the control fluid from the control fluid outlet 124. The fluid communication between the pump unit inlet 152 and the control fluid outlet 124, and between the pump unit outlet 154 and the control fluid inlet 122, can be direct connections between the respective outlets and inlets. Alternatively, the respective outlets and inlets can be connected via additional conduits (e.g., flexible tubing).

[0035] Furthermore, the pump unit 150 is in fluid communication with a reservoir 156, which stores the control fluid supplied to the control fluid passage 120 of the liquid-operated pump 100. The reservoir 156 can be supplied in the form of a Falcon tube or plastic bag containing the control fluid. In some examples, the reservoir 156 can be a component of the pump unit 150 itself. For example, the control fluid can be water, oil, glycerin, or a blend of water and alcohol (e.g., ethanol) (e.g., a blend with 20% alcohol). The control fluid is used to deform the diaphragm 132 of the pump chamber 130 and is therefore preferably a low-viscosity liquid. Using a blend of water and alcohol prevents the development of microorganisms in the pump unit 150. The control fluid can also contain other additives to prevent microbial growth. In one example, the control fluid is the same liquid (e.g., a water-alcohol blend) used by the pump unit 150 to rinse the bioprocessing equipment (e.g., to rinse the "back" of the piston of a piston pump). In this case, the same reservoir can be used for both the rinsing and pumping operations. Other control fluids and compositions can also be utilized. Furthermore, the control fluid can be pre-prepared (e.g., pre-filtered, pre-sterilized, pre-degassed, or otherwise pre-treated). Alternatively, the control fluid can be treated during use, for example, by a filter, a bioburden control regime (e.g., UV light treatment). The pumping system 190 and / or bioprocessing system can be configured to automatically manage the filling, treatment, and / or removal and disposal of the control fluid. It can also be configured to perform cleaning of the pump unit 150 and / or its hydraulic fluid circuit before or after processing.

[0036] The pump unit 150 further includes a pump 158 (for example, a piston pump), which drives the movement of control fluid in the control fluid passage 160 of the pumping system 190. The control fluid passage 160 of the pumping system 190 includes a reservoir 156, pump 158, a pump unit outlet 154, a control fluid passage 120 of the liquid-operated pump 100, and a pump unit inlet 152. Figure 1 shows an example where, for example, during priming of the pumping system 190, the control fluid received through the pump unit inlet 152 can be returned to the reservoir 156 via a valve 166 (described further below). In other words, the control fluid passage 160 is configured to return the control fluid to the reservoir 156. In addition, as shown in Figure 1, the control fluid received through the pump unit inlet 152 can be routed to the waste outlet 148 via the waste outlet valve 170 (which will be further described below) during, for example, the drain discharge of the pumping system 190.

[0037] The pump unit 150 also includes several valves. A first valve 162 is located upstream of both the pump 158 and the liquid-operated pump 100 in the control fluid flow path 160. A second valve 164 is located between the pump 158 and the liquid-operated pump 100 in the control fluid flow path 160. A third valve 166 is located downstream of both the pump 158 and the liquid-operated pump 100 in the control fluid flow path 160. In the example shown in Figure 1, the first valve 162 and the second valve 164 are located upstream of the pump unit outlet 154 in the control fluid flow path 160, while the third valve 166 is located downstream of the pump unit inlet 152 in the control fluid flow path 160.

[0038] In the example shown in Figure 1, the first valve 162 and the second valve 164 allow the pump 158 to be operated to drive the movement of control fluid through the control fluid passage 160. Specifically, when the pump 158 is drawing control fluid from the reservoir 156 (i.e., by providing negative pressure), the second valve 164 is closed and the first valve 162 is open. Closing the second valve 164 prevents the pump 158 from drawing control fluid from downstream components of the pump 158 (for example, from the control fluid passage 120 of the liquid-operated pump 100). Then, when the pump 158 is used to drive the forward movement of the control fluid along the control fluid passage 160, the first valve 162 is closed and the second valve 164 is open. Closing the first valve 162 prevents the pump 158 from driving the control fluid back to the reservoir 156.

[0039] Together with the first valve 162, the third valve 166 allows a predetermined volume of control fluid to be trapped in a portion of the control fluid passage 160, which includes the pump 158 and the liquid-operated pump 100. Specifically, when the portion of the control fluid passage 160 between the first valve 162 and the third valve 166 is filled with control fluid (preferably, without gas bubbles), the first valve 162 and the third valve 166 can be closed to trap a predetermined volume of control fluid in that portion of the control fluid passage 160.

[0040] In one example, the first valve 162, the second valve 164, and the third valve 166 are each active valves, such as active membrane valves. The first valve 162 and the third valve 166 are implemented as active valves because they need to be completely closed when the pump unit 150 is used to drive the movement of process fluid in the liquid-operated pump 100. The second valve 164 is implemented as an active valve because it needs to be completely open when the pump unit 150 is used to drive the movement of process fluid in the liquid-operated pump 100. In one example, the third valve 166 is a pressure control valve that allows the discharge of liquid to the reservoir 156 in the event of an excessive pressure rise in the control liquid passage 160.

[0041] As shown in Figure 1, the pump unit further includes a waste outlet valve 170 that allows the control fluid to be discharged to the waste outlet 148. The conduit connecting the control fluid passage 160 to the waste outlet valve 170 can branch off from the control fluid passage 160 at a point between the pump unit inlet 152 and a third valve 166. Thus, to return the control fluid to the reservoir 156, the third valve 166 is opened, while the waste outlet valve 170 is closed. Conversely, when routing the control fluid to the waste outlet 148, the third valve 166 is closed and the waste outlet valve 170 is opened. The waste outlet valve 170 can also be a pressure control valve that allows the discharge of fluid to the waste outlet 148 in the event of an excessive pressure rise in the control fluid passage 160.

[0042] During use, the liquid-operated pump 100 is first connected to the pump unit 150. In one example, to prevent accidental leakage of the control fluid from the pump unit outlet 154 or the pump unit inlet 152, the second valve 164 and the third valve 166 are closed while the liquid-operated pump 100 is connected to the pump unit 150.

[0043] Next, pump 158 is used to drive the movement of control fluid through the control fluid passage 160 of the pumping system 190 (which includes the control fluid passage 120 of the liquid-operated pump 100). This is achieved by first opening the first valve 162 while keeping the second valve 164 closed, and by applying negative pressure using pump 158 to draw the control fluid from reservoir 156 into pump 158. Then, positive pressure is applied using pump 158 with the first valve 162 closed, and with the second valve 164 and third valve 166 open, to drive the movement of control fluid along the control fluid passage 160. These steps are then repeated to draw an additional volume of control fluid from the reservoir 156 (i.e., with the second valve 164 closed and the first valve 162 open) and to drive the movement of an additional volume of control fluid along the control fluid flow path 160 (i.e., with the first valve 162 closed and the second valve 164 open).

[0044] When the portion of the control fluid passage 160 between the first valve 162 and the third valve 166, and including the pump 158, contains control fluid, the first valve 162 and the third valve 166 can be closed. This results in a predetermined volume of control fluid being trapped between the first valve 162 and the third valve 166. This trapped volume of control fluid is partially contained within the control fluid passage 120 of the liquid-operated pump 100 and also partially contained within the pump unit 150 (specifically, between the first valve 162 and the pump unit outlet 154, and between the pump unit inlet 152 and the third valve 166).

[0045] Following the closure of the first valve 162 and the third valve 166 to capture a predetermined volume of control fluid, the pump 158 is used to displace the captured volume of fluid. In the example shown in Figure 1, the pump 158 supplies positive pressure (i.e., by positive displacement of the piston) to push the control fluid out of the pump unit outlet 154. This means that the control fluid passage 120 of the liquid-operated pump 100 is forced to contain a larger volume of control fluid than the volume contained before the activation of the pump 158. It is possible to consider the control fluid to be an incompressible fluid under the operating conditions of the pump unit 150. Given the incompressibility of the control fluid, the increased volume of control fluid is contained in the control fluid passage 120 by the deformation of the diaphragm 132, which increases the volume of the control fluid portion 136 of the pump chamber 130. The deformation of the diaphragm 132 resulting from the displacement of the captured volume of control fluid consequently reduces the volume of the process fluid portion 134 of the pump chamber 130, thereby driving the movement of the process fluid in the process fluid passage 110.

[0046] In other words, by trapping a predetermined volume of control fluid between the first valve 162 and the third valve 166, the control fluid is trapped between the pump 158 and the diaphragm 132. This means that any movement of the pump 158 is transmitted to the diaphragm 132. In addition, there is no need to control or monitor the position of the diaphragm 132, because the position of the diaphragm 132 can be determined using the pump 158.

[0047] Since the control fluid can be considered incompressible under the operating pressure of the pump unit 150, the amount of control fluid displaced by the pump 158 is equal to the amount of control fluid contained in the control fluid portion 136 of the pump chamber 130. If the process fluid is a process fluid (and therefore considered incompressible), the amount of control fluid displaced by the pump 158 is equal to the amount of process fluid displaced from the process fluid portion 134 of the pump chamber 130. Thus, in the ideal scenario in which the first valve 162 and the third valve 166 can be closed instantaneously, there is a one-to-one relationship between the displacement of the control fluid (controlled by the pump unit 150) and the displacement of the process fluid in the liquid-actuated pump 100. This allows a precise volume of process fluid to be displaced from the liquid-actuated pump 100 under the control of the pump 158 in the pump unit 150. The accuracy of the process fluid displacement can be improved by reducing the operating time of the first valve 162 and the third valve 166.

[0048] As described above, each of the first valve 116 and the second valve 118 can be a check valve. In other words, each of the first valve 116 and the second valve 118 can allow the flow of process fluid along the process fluid passage 110 toward the process fluid outlet 114 and prevent the flow of process fluid in the reverse direction along the process fluid passage 110. Preferably, the check valve is a mechanical check valve that allows the forward flow of process fluid and prevents backflow of process fluid without requiring operation using a control system. When the trapped volume of liquid is displaced by the application of positive pressure from the pump 158 of the pump unit 150, the trapped volume of liquid acts positive pressure on the diaphragm 132, deforming the diaphragm 132 and reducing the volume of the process fluid portion 134 of the pump chamber 130, thereby pushing the process fluid out of the process fluid portion 134. In this case, the second valve 118 allows the process fluid to flow along the process fluid passage 110 toward the process fluid outlet 114, while the first valve 116 prevents the process fluid from flowing in the reverse direction.

[0049] Similarly, when the pump 158 is subsequently drawn back, the captured volume of liquid is displaced away from the process fluid portion 134 of the pump chamber 130 so that a negative pressure difference is provided between the pump 158 and the control fluid portion 136 of the pump chamber 130, and the negative pressure is exerted on the diaphragm 132, thereby increasing the volume of the process fluid portion 134. In this case, the first valve 116 allows the process fluid to be drawn into the process fluid portion 134 of the pump chamber 130 through the process fluid inlet 112, while the second valve 118 prevents the process fluid from being drawn into the process fluid portion 134 through the process fluid outlet 114. It will be recognized that the first valve 116 and the second valve 118 could also be implemented as check valves that allow the movement of the process fluid in the opposite direction to that described above (i.e., outward from the process fluid inlet 112). Furthermore, it will be recognized that such functionality of the first valve 116 and the second valve 118 can also be provided by using an active valve that opens or closes depending on whether positive or negative pressure is supplied by the pump 158.

[0050] Therefore, the process fluid can be driven using a liquid-actuated pump 100 having a small number of components. Specifically, the process fluid can be driven using a liquid-actuated pump 100, which includes a pump chamber 130 with a diaphragm 132 dividing the pump chamber 130 into a process fluid portion 134 and a control fluid portion 136; a process fluid flow path 110 including a process fluid inlet 112, a process fluid outlet 114, and the process fluid portion 134 of the pump chamber 130; and a control fluid flow path 120 including a control fluid inlet 122, a control fluid outlet 124, and the control fluid portion 136 of the pump chamber 130. The small number of components of the liquid-actuated pump 100 allows the liquid-actuated pump 100 to be offered as a low-cost consumable (e.g., a single-use consumable), to be small in size, and to be easy to use.

[0051] In addition, provided that there are no cracks or openings in the diaphragm 132 of the pump chamber 130, the control fluid cannot leak into the process fluid channel. Therefore, the process fluid can be driven without the risk of contamination by the control fluid.

[0052] Figure 3 is a schematic diagram of the second pumping system 290, which includes a second liquid-operated pump 200 and a second pump unit 250. In Figure 3, the liquid-operated pump 200 and the pump unit 250 are schematically shown in plan view.

[0053] The liquid-operated pump 200 includes all the components of the liquid-operated pump 100 shown in Figures 1 and 2. Specifically, the liquid-operated pump 200 includes a process fluid passage 210a, a control fluid passage 220a, and a pump chamber 230a, which include a process fluid inlet 212, a process fluid outlet 214, a first valve 216a, and a second valve 218a. Similarly, the pump unit 250 includes all the components of the pump unit 150 shown in Figure 1. Specifically, the pump unit 250 includes a connection to the reservoir 256, a pump 258a, a first valve 262a, a second valve 264a, and a third valve 266a.

[0054] In contrast to the liquid-operated pump 100 shown in Figures 1 and 2, the liquid-operated pump 200 shown in Figure 3 includes a first pump chamber 230a and a second pump chamber 230b, along with a third valve 216b and a fourth valve 218b. The two pump chambers 230 are connected in parallel on the process fluid side of the liquid-operated pump 200. That is, the process fluid received at the process fluid inlet 212 can flow through either the first process fluid passage 210a or the second process fluid passage 210b, the first process fluid passage 210a including the first valve 216a, the process fluid portion of the first pump chamber 230a, the second valve 218a, and the process fluid outlet 214, and the second process fluid passage 210b including the third valve 216b, the process fluid portion of the second pump chamber 230b, the fourth valve 218b, and the process fluid outlet 214.

[0055] In contrast to the pump unit 150 shown in Figure 1, the pump unit 250 shown in Figure 3 includes a first pump 258a and a second pump 258b, along with a fourth valve 262b, a fifth valve 264b, and a sixth valve 266b. Each pump 258 is part of a control fluid passage 260 that includes a reservoir 256. Specifically, the first control fluid passage 260a includes the reservoir 256, a first valve 262a, a first pump 258a, a second valve 264a, the control fluid portion of the first pump chamber 230a, and a third valve 266a, and returns to the reservoir 256 (or optionally, to a separate waste outlet (not shown in Figure 3 for simplicity)). Similarly, the second control fluid passage 260b includes the reservoir 256, the fourth valve 262b, the second pump 258b, the fifth valve 264b, the control fluid portion of the second pump chamber 230b, and the sixth valve 266b, which returns to the reservoir 256 (or a separate waste outlet).

[0056] Each control fluid channel 260 is configured to contain a trapped volume of liquid that can be displaced by the pump 258 in the same manner as described above with reference to Figure 1, in order to drive the movement of process fluid in its corresponding process fluid channel 210. Specifically, the first control fluid channel 260a is configured to contain a first trapped volume of liquid by closing the first valve 262a and the third valve 266a. This first trapped volume of liquid can be displaced by the first pump 258a, deforming the diaphragm of the first pump chamber 230a and driving the movement of process fluid in the first process fluid channel 210a. Similarly, the second control fluid channel 260b is configured to contain a second trapped volume of liquid by closing the fourth valve 262b and the sixth valve 266b. The second captured volume of liquid can be displaced by the second pump 258b, which deforms the diaphragm of the second pump chamber 230b and drives the movement of the process fluid in the second process fluid channel 210b.

[0057] By implementing the two pump chambers 230 in parallel, the first pump 258a can be used to dispense process fluid from the process fluid portion of the first pump chamber 230a, while the second pump 258b is used to draw process fluid into the process fluid portion of the second pump chamber 230b. Subsequently, the second pump 258b can be used to dispense process fluid from the second pump chamber 230b, while the first pump 258a is used to draw process fluid into the process fluid portion of the first pump chamber 230a. Thus, during the operation of the pumping system 290, one pump 258 is always used to dispense process fluid, while the other pump 258 is always used to draw process fluid into the pump chamber 230. Therefore, by implementing the two pump chambers 230 in parallel, the process fluid can be continuously dispensed from one of the pump chambers 230. This means that a substantially continuous and pulsation-free flow of process fluid can be provided to the process fluid outlet 214.

[0058] As an alternative to having two parallel pump chambers 230 sharing a common process fluid inlet 212 and a common process fluid outlet 214 (i.e., as shown in Figure 3), the liquid-operated pump can include distinctly different process fluid passages, each including its own process fluid inlet, its own process fluid outlet, and pump chamber. Such an arrangement can be used in conjunction with the pump unit 250 shown in Figure 3 to pump two process fluids separately. Alternatively, the two process fluid passages can have different process fluid inlets but share a common process fluid outlet, allowing the liquid-operated pump to be used to blend two different process fluids together.

[0059] As a further alternative (shown in Figure 4), a third pumping system 390 includes a liquid-operated pump 300 containing four pump chambers 330 and is used in conjunction with a pump unit 350 having four pumps 358. In this case, the liquid-operated pump 300 includes two sets of parallel-connected pump chambers 230, as shown in Figure 3. As shown in Figure 4, each set of parallel-connected pump chambers 330 has a different process fluid inlet 312. Specifically, a first process fluid inlet 312a is capable of receiving a first process fluid, which can be pumped along a first process fluid passage 310a using a first pump 358a of the pump unit 350, and can also be pumped along a second process fluid passage 310b using a second pump 358b of the pump unit 350. The second process fluid inlet 312b is capable of receiving the second process fluid 312b, which can be pumped along the third process fluid passage 310c using the third pump 358c of the pump unit 350, and can also be pumped along the fourth process fluid passage 310d using the fourth pump 358d of the pump unit 350. Thus, the pumping system 390 uses four captured volumes of control fluid to drive the movement of the process fluid in the liquid-operated pump 300.

[0060] Each set of parallel-connected pump chambers 330 operates in the same manner as the parallel-connected pump chambers 230 shown in Figure 3. This means that a substantially continuous and pulsation-free flow of the first process fluid can be provided at the first process fluid outlet 314a, while a substantially continuous and pulsation-free flow of the second process fluid can be provided at the second process fluid outlet 314b.

[0061] Providing a continuous, pulsation-free flow of two process fluids is desirable in bioprocessing operations such as TFF. Although the process fluid outlets 314 are clearly shown as separate in Figure 4, they can be connected together, allowing the liquid-operated pump 300 to blend the two different process fluids together.

[0062] Figure 5 is a schematic diagram of a pumping system 490 that may represent the pumping systems 190, 290, and 390 described with reference to Figures 1, 3, and 4. Figure 5 shows the control fluid flow path 460 through the pumping system 490, but does not show the process fluid flow path through the liquid-actuated pump 400. Various components of the pumping system 490 can be provided in the form of a pump unit to which the liquid-actuated pump 400 is connected.

[0063] The pumping system 490 includes a reservoir 456a configured to hold a control fluid, such as a water-ethanol blend. A degassing unit 480 is located downstream of the reservoir 456a and is configured to remove air from the control fluid from the reservoir 456a. For example, the degassing unit 480 may include a bubble trap configured to capture any air bubbles in the flow of the control fluid from the reservoir 456a. Removing air from the control fluid is preferable because any air in the captured volume of fluid used to deform the diaphragm of the pump chamber would provide a spring effect due to the compression of the air. Such a spring effect would reduce the deformation of the diaphragm with respect to a given displacement of the captured volume of fluid, thus reducing the amount of process fluid pumped and reducing the volumetric accuracy of the process fluid pumping.

[0064] The first valve 462 is located between the degassing device 480 and the piston pump 458 of the pumping system 490. In one example, the first valve 462 is an active membrane valve.

[0065] The liquid-operated pump 400 is located downstream of the piston pump 458 in the control fluid passage 460. Specifically, the control fluid passage 460 includes the control fluid inlet of the liquid-operated pump 400, the control fluid portion of the pump chamber of the liquid-operated pump 400, and the control fluid outlet of the liquid-operated pump 400. Consequently, the first valve 462 is located upstream of both the piston pump 458 and the liquid-operated pump 400.

[0066] A second valve 464 is positioned between the piston pump 458 and the liquid-actuated pump 400 in the control fluid passage 460. The second valve 464 is used to allow the piston pump 458 to draw control fluid from the reservoir 456a, which can then be driven through the control fluid passage 460.

[0067] The third valve 466 is located downstream of both the piston pump 458 and the liquid-actuated pump 400 in the control fluid passage 460. The third valve 466 is used to capture a predetermined volume of control fluid between the first valve 462 and the third valve 466 during the operation of the pumping system 490.

[0068] The fourth valve 468 is located between the degassing device 480 and the first valve 462. The fourth valve 468 can be closed to ensure that any air supplied to drain the control fluid passage 460 is pushed through the control fluid passage 460 in the correct direction.

[0069] The pumping system 490 also includes a gas supply unit (for example, an air supply unit 482), which is connected to the control fluid passage 460 between a fourth valve 468 and a first valve 462. An air supply valve 484 is positioned between the air supply unit 482 and the point of its connection to the control fluid passage 460. The air supply valve 484 controls whether air is supplied to the control fluid passage 460 to drain the control fluid passage 460 and prevents the control fluid from reaching the air supply unit 482. The first valve 462 isolates the piston pump 458 from any air that could be trapped in the conduit branching from the control fluid passage 460 to the air supply unit 482 (this could happen if a single valve were implemented in the place of the fourth valve 468 rather than implementing separate first valve 462 and fourth valve 468).

[0070] In addition, the pumping system 490 includes a pressure sensor 486, which is configured to monitor the pressure of a predetermined volume of control fluid trapped between a first valve 462 and a third valve 466. In the example shown in Figure 5, the pressure sensor 486 is located between a second valve 464 and a liquid-actuated pump 400. The pressure of the trapped volume of control fluid should be substantially equal to the pressure applied to the process fluid in the liquid-actuated pump (wherein the term “substantially” is used, acknowledging the slight pressure loss due to the diaphragm's characteristics). In one example, the pressure sensor 486 can be provided within the pump unit. Implementing the pressure sensor 486 in this way allows the pressure applied to the process fluid to be monitored without requiring the pressure sensor to be provided within the liquid-actuated pump 400, thereby simplifying the construction and operation of the liquid-actuated pump 400 and minimizing cost and complexity.

[0071] The pumping system 490 also includes a waste outlet valve 470 disposed between the liquid-actuated pump 400 and a second valve 464. The waste outlet valve 470 allows, for example, during drain discharge of the pumping system 490, control fluid and gas (e.g., air) to be discharged to a separate waste outlet (not shown in Figure 5). The waste outlet valve 470 may be a pressure relief valve, which releases control fluid above a certain pressure (e.g., 8 bar) in the event of a malfunction in the liquid-actuated pump 400 (e.g., incorrect diaphragm position), thus preventing a pressure increase in the liquid-actuated pump 400 from destroying it. In an alternative example, the second valve 464 may function as a safety valve and may be configured to release control fluid into a reservoir 456b if the pressure exceeds a predetermined value (e.g., 8 bar).

[0072] The pumping system 490 also includes a bubble detector 488 located downstream of the second valve 464. The bubble detector 488 is used during the priming of the pumping system 490 to verify whether air bubbles are present in the flow of the control fluid through the control fluid channel 460. Implementing the bubble detector 488 allows for confirmation of whether the priming of the pumping system 490 was successful (i.e., whether air bubbles are present in the flow of the control fluid over a period of time). In some examples, a second bubble detector may be implemented upstream of the pump 458 to ensure that the reservoir 456a supplies fluid to the pump 458.

[0073] Finally, the pumping system 490 includes a rinse reservoir 456c, which is connected to the piston pump 458 via a rinse reservoir valve 472. The rinse reservoir 456c supplies rinse fluid, which is used to rinse the "back" of the piston of the piston pump 458. It is recognized that the piston pump 458 includes a piston that moves inside a cylinder and has a dynamic seal between the piston and the cylinder. The area beyond the dynamic seal can potentially become contaminated over time and may be subject to bioburden problems. Thus, in this context, rinsing the "back" of the piston typically means rinsing beyond the dynamic seal between the piston and the cylinder using a bacteriostatic fluid. In one example, the rinse reservoir 456c is the same as or connected to reservoir 456a.

[0074] After passing through the bubble detector 488, the control fluid moves to reservoir 456b, which can be the same as reservoir 456a at the inlet to the degassing unit 480, or it can be a distinctly different reservoir 456b (which can be connected to reservoir 456a at the inlet to the degassing unit 480). Implementing reservoir 456b as a reservoir connected to reservoir 456a at the inlet may be preferable, among other things, during the priming of the pumping system 490 (described below). This is because the control fluid can be recirculated to reduce waste of the control fluid. Each of the reservoirs 456a, 456b may include a vent or filter to prevent the ingress of other fluids into the pumping system 490.

[0075] The typical operating pressure of the piston pump 458 during the operation of the pumping system 490 is between 0 bar and 4 bar. In this example, the third valve 466 is a pressure control valve that opens at pressures exceeding a predetermined maximum pressure (e.g., 6 bar) to prevent damage to the liquid-actuated pump 400 and / or high-pressure ejection of the control fluid from the pumping system 490. When the pressure supplied by the pump 458 exceeds the predetermined maximum pressure, the control fluid returns to the reservoir 456b via the third valve 466.

[0076] In some examples, an additional air inlet can be implemented downstream of the piston pump 458 (along with an additional valve). The additional air inlet can be used to displace the control fluid in the control fluid passage 460 to the waste outlet following the operation of the pumping system 490 (for example, as described below with reference to Figure 8). If an additional air inlet is present, an additional valve can be incorporated upstream of its connection to the control fluid passage 460 to prevent air from backflowing the control fluid towards the pump 458 and reservoir 456a. Incorporating the additional air inlet downstream of the pump 458 allows for the discharge-free disconnection of the liquid-actuated pump 400 while keeping the piston pump 458 liquid-filled (meaning the piston pump 458 does not need to be primed again). Thus, following the connection of the new liquid-actuated pump 400 to the pump unit 450, only the portion of the control fluid passage 460 between the pump 458 and the third valve 466 needs to be replenished with the control fluid.

[0077] Although not shown in Figure 5, the pumping system 490 may also include a control system, which optionally includes a PID controller or other type of feedback control, and the control system is configured to control the operation of the pump 458 and to actuate the valves of the pumping system 490. The control system may be configured to open certain valves and close others in response to the piston pump 458 being in a particular position. For example, when the control system determines that the piston pump 458 has reached the end of its stroke (which can be monitored, for example, using embedded software), it may be configured to actuate a valve from the valve state shown in Figure 6B to the valve state shown in Figure 6A.

[0078] Furthermore, the control system can be configured to receive inputs from a pressure sensor 486 and a bubble detector 488. For example, the control system can be configured to open the third valve 466 in response to input from the pressure sensor 486 indicating that the pressure of the control fluid between the first valve 462 and the third valve 466 exceeds a threshold pressure. As another example, the control system can be configured to close the third valve 466 in response to input from the bubble detector 488 indicating that there are no bubbles in the flow of the control fluid through the control fluid channel 460. In particular, the control system can be configured to monitor the output from the bubble detector 488 over time and close the third valve 466 in response to determining that there have been no bubbles in the control fluid channel 460 for a predetermined period of time. The control system can also be configured to control the operation of the air supply unit 482, allowing the control fluid channel 460 to be drained and the liquid-operated pump 400 to be disconnected from the pump unit.

[0079] Figures 6A to 68 show the valve states of the pumping system 490 during priming (Figures 6A and 6B), during operation (Figure 7), and during drain discharge of the pumping system (Figure 8). In Figures 6A to 68, valves filled in black indicate that the valve is open (i.e., allowing fluid passage), while valves filled in white indicate that the valve is closed (i.e., not allowing fluid passage). The rinse reservoir valve 472 is closed during priming, operation, and drain discharge of the pumping system. This is because rinsing the components of the control fluid flow path is a separate process not shown in Figures 6A to 68.

[0080] During the priming of the pumping system 490, as shown in Figures 6A and 6B, the first valve 462, the third valve 466, and the fourth valve 468 are all initially open (Figure 6A), while the second valve 464, the air supply valve 484, and the waste outlet valve 470 are closed. This arrangement of valves allows the control fluid from the reservoir 456a to be drawn into the piston pump 458 through the degassing device 480. Subsequently, the first valve 462 is closed and the second valve 464 is opened (Figure 6B), which allows the piston pump 458 to drive the control fluid through the control fluid passage and bubble detector 488 of the liquid-actuated pump 400 before returning to the reservoir 456b. The configuration shown in Figures 6A and 6B is then repeated (for example, by the control system of the pumping system 490) until a predetermined volume of control fluid is present between the first valve 462 and the third valve 466. Given that the second valve 464 is closed during the filling of the piston pump 458 (as shown in Figure 6A), it is recognized that the state of the third valve 466 and the waste outlet valve 470 is not important. However, during the discharge of the piston pump 458 (Figure 6B), the third valve 466 is open and the waste outlet valve 470 is closed.

[0081] The pumping system 490 is primed to ensure that a predetermined volume of control fluid is present between the first valve 462 and the third valve 466 (i.e., that the control fluid is in contact with the diaphragm of the liquid-actuated pump 400). The degassing device 480 and bubble detector 488 are used to verify that there are no air bubbles in the control fluid passing through the third valve 466, minimizing or eliminating the risk that the captured volume of control fluid contains air bubbles when the first valve 462 and the third valve 466 are closed.

[0082] To calibrate the position of pump 458 with the position of the diaphragm of the liquid-actuated pump 400, a predetermined volume of control fluid is initially trapped between the first valve 462 and the third valve 466 by closing the first valve 462 and the third valve 466 (for example, by the control system). Pump 458 is then used to supply positive pressure to the trapped volume of fluid, which deforms the diaphragm of the liquid-actuated pump 400. When the diaphragm reaches the bottom of the pump chamber of the liquid-actuated pump 400 (i.e., when the volume of the process fluid portion of the pump chamber becomes zero), the pressure at the inlet to the third valve 466 increases. Since the third valve 466 is a pressure control valve, any excess pressure from the pump causes the control fluid to flow through the third valve 466 until pump 458 reaches the end of its stroke. At that point, pump 458 is at the end of its stroke, and the diaphragm is in its maximum positive displacement position, which means that pump 458 and the diaphragm are calibrated.

[0083] Excess control fluid leakage through the third valve 466 can be achieved by setting the pressure control valve to allow control fluid flow when the pressure of the control fluid between the pump 458 and the third valve 466 exceeds approximately 0.2 bar to 0.3 bar. The piston position of the pump 458 can be monitored using embedded software that reads the piston position, which allows the end position of the piston (i.e., the end of the stroke of the pump 458) to be determined by the control system.

[0084] The remaining volume of the captured control fluid (i.e., the initial volume captured between the first valve 462 and the third valve 466 minus any control fluid that flowed through the third valve 466 as a result of excess pressure from the pump 458) can then be used during operation to drive the movement of the process fluid. Before the operation of the pumping system 190 (i.e., once calibration is complete), the threshold pressure of the third valve 466 can be increased (e.g., by the control system) to a higher pressure (e.g., at least 6 bar) to ensure that a predetermined volume of control fluid is captured between the first valve 462 and the third valve 466. Consequently, calibration of the liquid-actuated pump 400 and the pump unit can be achieved without the use of sensors to detect the position of the diaphragm. During the priming and calibration process, the pressure of the control fluid captured between the first valve 462 and the second valve 466 can be monitored using a pressure sensor 486.

[0085] Alternatively, the third valve 466 can operate as a "pulsating" valve, which is periodically opened for short periods (e.g., less than 0.05 seconds) to release excess pressure, allowing the pressure of the captured volume of control fluid to be maintained within a set pressure range (e.g., between 0.2 bar and 0.5 bar). In this case, the third valve 466 can be implemented as an on / off valve rather than a pressure control valve. The pressure of the control fluid captured between the first valve 462 and the third valve 466 can be monitored (e.g., using a pressure sensor 486), which can provide an input to a control system that controls the operation of the third valve 466 (e.g., opening the third valve 466 when the pressure monitored by the pressure sensor 486 exceeds 0.5 bar).

[0086] During the operation of the pumping system 490, all valves are closed except for the second valve 464, as shown in Figure 7. This means that a predetermined volume of control fluid is trapped between the first valve 462 and the third valve 466. The piston pump 458 can be used to pressurize the trapped volume of control fluid, and it applies the pressure supplied by the piston pump 458 to the diaphragm of the pump chamber of the liquid-actuated pump 400. This causes deformation of the liquid-actuated pump 400, which drives the movement of process fluid in the process fluid passage of the liquid-actuated pump 400.

[0087] During drain discharge from the pumping system 490, the air supply valve 484 is opened (for example, by the control system) along with the first valve 462, the second valve 464, and the waste outlet valve 470, as shown in Figure 8. The other valves (i.e., the third valve 466 and the fourth valve 468) are closed. Opening the air supply valve 484 causes air to be supplied from the air supply section 482 to the control fluid passage 460, allowing the fluid in the control fluid passage 460 to be pushed out to the waste outlet section via the waste outlet valve 470. Closing the fourth valve 468 prevents air from being supplied in the reverse direction (i.e., to the reservoir 456a via the degassing device 480). Draining the control fluid from the control fluid passage 460 allows the liquid-operated pump 400 to be disconnected from the pump unit without the outflow of control fluid, thereby improving the ease of disconnecting the liquid-operated pump 400 from the pump unit (for example, for disposal or cleaning of the liquid-operated pump 400). In addition, since the drained control fluid is mixed with air, it is preferable to drain the control fluid to the waste outlet. Therefore, draining the control fluid to the waste outlet avoids routing air bubbles into the control fluid reservoir.

[0088] Figure 9 is a flowchart of Method 500 for performing a pumping operation to pump process fluid using a pumping system including a liquid-actuated pump and a pump unit. Method 500 can be implemented using the pumping systems 190, 290, 390, and 490 described above. In particular, Method 500 can be implemented using a control system for the pumping system (for example, as described above with reference to Figure 5). Thus, the operation of the pumping system (described with reference to Figure 11) can be performed automatically under the control of the control system. In addition, priming and calibration of the pumping system (described with reference to Figure 10) can be performed automatically under the control of the control system, which can receive input from embedded pump software, one or more pressure sensors, and / or one or more bubble detectors. Furthermore, draining of the pumping system (described with reference to Figure 12) can also be performed automatically under the control of the control system.

[0089] In 502, a liquid-operated pump is connected to the pump unit.

[0090] In 504, a control fluid is supplied by the pump unit to prime the pumping system. Priming the pumping system involves capturing a predetermined volume of control fluid in a portion of the control fluid flow path, the portion of which includes the pump of the pump unit and the control fluid portion of the pump chamber of a liquid-operated pump, the control fluid portion being partially defined by the flexible diaphragm of the pump chamber. The priming of the pumping system is described in more detail below with reference to Figure 10.

[0091] When the pumping system is primed, the captured volume of control fluid in the control fluid channel is displaced in 506 to pump the process fluid (e.g., process fluid). Specifically, the displacement of the captured volume of control fluid causes the displacement of the flexible diaphragm in the pump chamber of the liquid-actuated pump, which in turn changes the volume of the process fluid portion of the pump chamber, which is also partially defined by the flexible diaphragm. The change in the volume of the process fluid portion drives the movement of the process fluid in the process fluid channel of the liquid-actuated pump, where the process fluid channel includes the process fluid portion. The operation of the pumping system for pumping the process fluid is described in more detail below with reference to Figure 11.

[0092] As the process fluid is pumped, as required by the bioprocessing operation carried out using the pumping system, a gas (e.g., air) is supplied in 508 to drain the pumping system. Specifically, air is supplied to displace the captured volume of control fluid from the control fluid flow path. Drainage of the pumping system is described in more detail below with reference to Figure 12.

[0093] Once the pumping system has drained, the liquid-operated pump can be disconnected from the pump unit at 510. Given that the pumping system has drained, the risk of control fluid leakage or spillage during the disconnection of the liquid-operated pump is minimized.

[0094] Following the disconnection of the liquid-operated pump, the components of the pump unit can be cleaned by rinsing with a control fluid. Another liquid-operated pump can then be connected to the pump unit to pump process fluid required for another bioprocessing operation.

[0095] Figure 10 is a flowchart of method 600 for priming the pumping system. Method 600 can be implemented using any of the pumping systems 190, 290, 390, and 490 described above, and can be implemented to carry out step 504 of method 500.

[0096] In 602, the control fluid is pumped through the control fluid passage. The control fluid is pumped from the upstream reservoir using the pump of the pump unit. Pumping the control fluid may first involve opening one or more valves between the upstream reservoir and the pump, closing the valve between the pump of the pump unit and the liquid-actuated pump, and applying negative pressure using the pump of the pump unit to draw the control fluid from the upstream reservoir into the pump. Pumping the control fluid may then involve closing one or more valves between the upstream reservoir and the pump, opening the valve between the pump of the pump unit and the liquid-actuated pump, and applying positive pressure using the pump of the pump unit while the valve between the diaphragm of the liquid-actuated pump and the downstream reservoir is open. In examples where the control fluid passage is a circuit, the downstream reservoir may be the same as the upstream reservoir or may be connected to the upstream reservoir.

[0097] In one example, pumping the control fluid includes pumping the control fluid through a degassing device located upstream of a valve between the upstream reservoir and the pump. In addition, pumping the control fluid may include pumping the control fluid through a bubble detector located downstream of a valve between the diaphragm of a liquid-actuated pump and the downstream reservoir.

[0098] Once the portion of the control fluid passage between the pump and the diaphragm of the pump chamber is filled with the control fluid, then in 604, in addition to closing the valve between the diaphragm and the downstream reservoir, the valve between the upstream reservoir and the pump is closed. Closing these valves traps a predetermined volume of control fluid between the valves.

[0099] In one example, when a bubble detector detects that there are no bubbles in the control fluid flowing through the control fluid channel, the valve between the upstream reservoir and the pump, and the valve between the diaphragm and the downstream reservoir are closed.

[0100] Once the valves between the upstream reservoir and the pump, and between the diaphragm and the downstream reservoir, are closed, the pump position is then calibrated relative to the diaphragm position at 606. Calibrating the pump position relative to the diaphragm position may include supplying positive pressure from the pump and deforming the diaphragm to its maximum positive displacement position. At this point, the diaphragm cannot be displaced any further, and the volume of the process fluid portion of the pump chamber is zero.

[0101] When the diaphragm reaches its maximum displacement, the pump continues to supply positive pressure until the pump reaches its maximum positive displacement position (for example, the end of its stroke in the case of a piston pump). During this continuous supply of positive pressure, the excess pressure from the pump causes the control fluid to flow through a valve between the diaphragm and the downstream reservoir. This is because this valve is a pressure control valve. Once the pump reaches its maximum displacement position, the pump's maximum positive displacement position is then calibrated against the diaphragm's maximum positive displacement position.

[0102] Figure 11 is a flowchart of Method 700 for operating a pumping system for pumping process fluid. Method 700 can be implemented using any of the pumping systems 190, 290, 390, and 490 described above, and can be implemented to carry out step 506 of Method 500.

[0103] In 702, a negative pressure is supplied using the pump to displace the diaphragm of the liquid-operated pump and to draw process fluid into the pump chamber. The negative pressure can be supplied first in method 700, because, following the calibration of the pump position relative to the diaphragm position in 606, the diaphragm can be in its maximum positive displacement position. The negative pressure supplied using the pump in 702 displaces the diaphragm of the liquid-operated pump, causing the volume of the process fluid portion of the pump chamber to increase (for example, from zero volume of the process fluid portion during calibration in 606). The increase in the volume of the process fluid portion draws process fluid into the process fluid portion through the process fluid passages.

[0104] If the liquid-operated pump includes an active valve, supplying negative pressure in 702 may include opening a first valve located upstream of the pump chamber in the process fluid flow path and closing a second valve located downstream of the pump chamber in the process fluid flow path.

[0105] In 704, a positive pressure is supplied using the pump to displace the diaphragm of the liquid-operated pump and to dispense process fluid from the pump chamber. The positive pressure supplied by the pump in 704 displaces the diaphragm of the liquid-operated pump, causing a reduction in the volume of the process fluid portion of the pump chamber (i.e., as a result of a corresponding increase in the volume of the control fluid portion of the pump chamber). The reduction in the volume of the process fluid portion pushes the process fluid out of the process fluid portion through the process fluid passage.

[0106] If the liquid-operated pump includes an active valve, supplying positive pressure in 704 may include closing a first valve located upstream of the pump chamber in the process fluid flow path and opening a second valve located downstream of the pump chamber in the process fluid flow path.

[0107] Optionally, the pump unit can be used to supply pressure to the two pump chambers of a liquid-operated pump. Thus, the pump used to supply positive pressure in 704 can be the first pump, and the positive pressure supplied in 704 can displace the diaphragm of the first pump chamber of the liquid-operated pump. In this case, while the first pump supplies positive pressure in 704, a second pump can be used to supply negative pressure to displace the diaphragm of the second pump chamber of the liquid-operated pump and to draw process fluid into the second pump chamber (i.e., in the same manner as described above in relation to 702).

[0108] In 706, steps 702 and 704 are repeated until the required volume of process fluid is pumped (i.e., until the pumping operation is complete). If the pump unit is used to supply pressure to two pump chambers of a liquid-operated pump, then in 706 (as described with reference to 702), it is possible to supply positive pressure using the second pump to displace the diaphragm of the second pump chamber and to dispense process fluid from the second pump chamber during the repeated supply of negative pressure using the first pump. By operating the pumping system in this way, one pump of the pump unit is always used in 706 to dispense process fluid from the pump chamber, and it means that the pumping system can be used to drive a continuous and pulsation-free supply of process fluid.

[0109] Figure 12 is a flowchart of method 800 for draining the pumping system. Method 800 can be implemented using any of the pumping systems 190, 290, 390, and 490 described above, and can be implemented to carry out step 508 of method 500.

[0110] Once the required volume of process fluid has been pumped using the pumping system, in 802, it is possible to open the valve between the upstream reservoir and the pump, in addition to opening the valve between the diaphragm and the waste outlet. To prevent the control fluid from being drained into the downstream reservoir, the valve between the diaphragm and the downstream reservoir can be kept closed. By opening these valves, a predetermined volume of control fluid is no longer trapped between the pump and the diaphragm.

[0111] In 804, the air supply valve is opened. Opening the air supply valve creates fluid communication between the control fluid passage and the air supply unit. The air supply valve is located upstream of the valve between the upstream reservoir and the pump, but (if present) downstream of the degassing unit, allowing the air supply unit to be connected to the control fluid passage. To prevent air from being supplied to the upstream reservoir via the degassing unit, an additional valve may be closed between the degassing unit and the connection point of the air supply unit to the control fluid passage.

[0112] When the air supply valve is opened, air is then supplied at 806 to displace the control liquid from the control liquid passage. The air supplied at 806 can push the control liquid through the control liquid passage to the waste outlet. It is preferable to drain the pumping system to the waste outlet (rather than to the control liquid reservoir) because the drained control liquid will be mixed with the air supplied by the air supply unit.

[0113] When the control fluid is removed from the control fluid passage, the air supply is stopped at 808. Stopping the air supply may include closing the air supply valve. At this point, the liquid-operated pump can be disconnected from the pump unit without the outflow of the control fluid.

[0114] Furthermore, the control system for the pumping system can also be used to implement other methods related to the pumping system. For example, the control system can be configured to control the pumping system to replace the control fluid, or to calibrate the pumping system to correct drift or degassing problems.

[0115] Variations or modifications of the systems and methods described herein are presented in the following paragraphs.

[0116] The pumping systems described above are explained with reference to piston pumps in particular, but other types of pumps can also be used to drive the movement of the captured volume of liquid.

[0117] Figures 1, 3, and 4 show that the control fluid is returned to the reservoir (from which the control fluid is initially supplied) (for example, during the priming of the pumping system), but in an alternative example, the control fluid received through the pump unit inlet 152 can be routed to a separate waste chamber during the priming of the pumping system. In other words, the control fluid flow path 160 is not necessarily a circuit. Similarly, Figures 1 and 4 show that the control fluid can be drained to the waste outlet, but in an alternative example, the waste outlet may not be included, and the control fluid can simply be drained to the control fluid reservoir.

[0118] In one example, multiple reservoirs can be implemented, allowing for the selection of different fluids at the inlet to the control fluid channel 160. For example, after disconnecting the liquid-operated pump 400, a cleaning procedure can be initiated by connecting pump 158 to a cleaning fluid reservoir, thereby cleaning a portion of the control fluid channel 160 within the pump unit 150. Once the components of pump unit 150 are cleaned, pump 158 can be reconnected to the control fluid reservoir 156, allowing the control fluid channel 160 to be replenished with control fluid for subsequent pumping operations.

[0119] In the example shown in Figure 1, the first valve 162 is located between the reservoir 156 and the pump 158, and the third valve 166 is located between the pump unit inlet 152 and the reservoir 156. However, in alternative arrangements, the pump 158 can be located between the reservoir 156 and the pump unit inlet 152, the first valve 162 can be located between the reservoir 156 and the pump unit outlet 154, and the third valve 166 can be located between the reservoir 156 and the pump 158.

[0120] Therefore, in both of these examples, the first valve 162 is upstream of both the liquid-operated pump 100 and the pump 158, the second valve 164 is between the liquid-operated pump 100 and the pump 158, and the third valve 166 is downstream of both the liquid-operated pump 100 and the pump 158. Thus, one of the valves 162, 166 is positioned between the reservoir 156 and the pump 158. However, the other of the valves 162, 166 does not need to be a component of the pump unit 150. In addition, the second valve 164 does not need to be a component of the pump unit 150. For example, the other of the valves 162, 166 can be a component of the liquid-operated pump 100, and the second valve 164 can be a component of the liquid-operated pump 100. Therefore, the pump unit 150 may include only one of the valves 162 and 166, which can be closed (i.e., in conjunction with the closing of the other of the valves 162 and 166 implemented in the liquid-operated pump 100) to cause a predetermined volume of control fluid to be trapped in a portion of the control fluid flow path 160. However, incorporating both valves 162, 166 and the second valve 164 into the pump unit 150 is advantageous in minimizing the number of parts in the liquid-operated pump 100, and consequently, in minimizing the cost, complexity, and material usage of the liquid-operated pump 100.

[0121] Although not shown in the diagram, the connection between the fluid-operated pump 100 and the pump unit 150 may include a valve to prevent the outflow of control fluid during connection and disconnection of the fluid-operated pump 100 (thus ensuring a dry connection and dry removal). Such a valve may be open when the fluid-operated pump 100 is connected to the pump unit 150 and closed when the fluid-operated pump 100 is removed from the pump unit 150. Such a valve may be implemented in the fluid-operated pump 100, the pump unit 150, and / or in the tubing connecting the fluid-operated pump 100 and the pump unit 150. The valve may be an active valve that is operated under user control before connection and / or disconnection of the fluid-operated pump 100 and the pump unit 150. Alternatively, the valve may be operated by the action of connecting and / or disconnecting the fluid-operated pump 100 and the pump unit 150 (e.g., one or more duckbill valves that are opened by the insertion of a connector).

[0122] The term “pump unit” as used herein is not intended to require that all components of the pump unit be integrated into a single device. Instead, the components of the pump unit can be provided as modular components that are connected together to form a system of interconnected components. For example, a first modular component may include one or more piston pumps, a second modular component may include a reservoir, and a third modular component may include a valve manifold. Each of these components can be connected together to provide the functionality of the pump unit described in the above-described implementations.

[0123] In addition, although liquid-operated pumps and pump units have been described above as separate components, it will be recognized that the same functionality can be provided by integrating the liquid-operated pump and pump unit into a single component. Therefore, liquid-operated pumps and pump units can be provided in the form of an integrated component as an alternative example of connecting a liquid-operated pump to a pump unit. However, it is preferable to provide a connectable liquid-operated pump. This is because it allows a low-cost, typically single-use pumping component to be used to pump process fluids by connecting a low-cost pumping component to a typically higher-cost pump unit. In addition, such an arrangement allows the pump unit to be used with multiple single-use liquid-operated pumps.

[0124] The methods described can be implemented using computer-executable instructions. Computer program products or computer-readable media can contain or store computer-executable instructions. Computer program products or computer-readable media can include hard disk drives, flash memory, read-only memory (ROM), CDs, DVDs, caches, random access memory (RAM), and / or any other storage media in which information is stored for any duration (e.g., for a long period, permanently, for a short period, for temporary buffering, and / or for caching information). Computer programs can contain computer-executable instructions. Computer-readable media can be tangible or non-temporary computer-readable media. The term "computer-readable" includes "machine-readable."

[0125] The singular terms "a" and "an" should not be interpreted as meaning "only." Rather, unless otherwise stated, they should be interpreted as meaning "at least one" or "one or more." The phrase "comprising" and its derivatives (including "comprises" and "comprise") include each of the listed features, but do not exclude the inclusion of one or more further features.

[0126] The above-described implementations are merely illustrative and should be considered in all respects as illustrative only, and not as limiting. It should be recognized that variations of the described implementations can be manufactured without departing from the scope of the present invention. It should also be clear that there are many variations that are not described but fall within the scope of the appended claims. [Explanation of Symbols]

[0127] 100 Liquid-operated pumps 110 Process fluid flow path 112 Process fluid inlet 114 Process fluid outlet 116 First valve 118 Second valve 120 Controlled liquid flow path 122 Control liquid inlet 124 Control liquid outlet section 130 Pump Chamber 132 Diaphragm 134 Process fluid section 136 Control fluid section 148 Waste Disposal Section 150 Pump Unit 152 Pump unit inlet 154 Pump unit outlet 156 Reservoir 158 pumps 160 Controlled liquid flow path 162 First valve 164 Second valve 166 Third Valve 170 Waste Outlet Valve 190 Pumping System 200 Second liquid-operated pump 210a First process fluid channel 210b Second process fluid channel 212 Process fluid inlet 214 Process fluid outlet 216a First valve 216b Third valve 218a Second valve 218b Fourth valve 220a Controlled liquid flow path 220b Second control fluid channel 230 Pump Chamber 230a First pump chamber 230b Second pump chamber 250 Second pump unit 256 Reservoir 258 pumps 258a First pump 258b Second pump 260 Controlled liquid flow path 260a First control fluid channel 260b Second control fluid channel 262a First valve 262b Fourth valve 264a Second valve 264b Fifth valve 266a Third valve 266b The sixth valve 290 Second pumping system 300 Liquid-operated pumps 310a First process fluid channel 310b Second process fluid channel 310c Third process fluid channel 310d Fourth process fluid channel 312 Process fluid inlet 312a First process fluid inlet 312b Second process fluid 314 Process fluid outlet 314a First process fluid outlet 314b Second process fluid outlet 330 Pump Chamber 350 Pump Unit 358a First pump 358b Second pump 358c Third pump 358d The fourth pump 390 Third Pumping System 400 Liquid-operated pumps 456a Reservoir 456b Reservoir 456c Rinse Reservoir 458 Piston pump 460 Controlled liquid flow path 462 First valve 464 Second valve 466 Third valve 468 The fourth valve 470 Waste Outlet Valve 472 Rinse Reservoir Valve 480 Degassing unit 482 Air supply unit 484 Air supply valve 486 Pressure Sensor 488 Bubble detector 490 Pumping System

Claims

1. Liquid-operated pumps (100, 200, 300, 400) for bioprocessing systems, wherein the pumps (100, 200, 300, 400) are, Pump chambers (130, 230, 330) and A flexible diaphragm (132) is configured to form a barrier between the control fluid portion (136) of the pump chamber (130, 230, 330) and the process fluid portion (134) of the pump chamber (130, 230, 330), The process fluid passages (110, 210, 310) include the process fluid portion (134) of the pump chamber (130, 230, 330), Controlled fluid flow paths (120, 220) and It is equipped with, The control fluid flow paths (120, 220) are The inlet portion (122) to the aforementioned pumps (100, 200, 300, 400), The outlet section (124) from the aforementioned pumps (100, 200, 300, 400), The control liquid portion (136) of the pump chamber (130, 230, 330), It is equipped with, Liquid-operated pumps (100, 200, 300, 400) wherein the control fluid channels (120, 220) are configured to contain at least a portion of the volume of the captured control fluid, and the displacement of the captured control fluid causes deformation of the flexible diaphragm (132), and the deformation of the flexible diaphragm (132) causes movement of the process fluid in the process fluid channels (110, 210, 310).

2. The liquid-operated pump (100, 200, 300, 400) according to claim 1, wherein the pumps (100, 200, 300, 400) are configured to connect to pump units (150, 250, 350) configured to displace the captured control fluid, and at least a portion of the volume of the captured control fluid is optionally housed within the pump units (150, 250, 350).

3. The inlet portion (122) is configured to receive the control fluid from the pump unit outlet portion (154) of the pump unit (150, 250, 350), The liquid-operated pump (100, 200, 300, 400) according to claim 2, wherein the outlet portion (124) is configured to supply the control liquid to the pump unit inlet portion (152) of the pump unit (150, 250, 350).

4. The process fluid passages (110, 210) are A first valve (116, 216) is disposed between the process fluid inlet (112, 212, 312) and the process fluid portion (134) of the pump chamber (130, 230, 330), A second valve (118, 218) is disposed between the process fluid portion (134) and the process fluid outlet portion (114, 214, 314) of the pump chamber (130, 230, 330) and A liquid-operated pump (100, 200, 300, 400) according to any one of claims 1 to 3, further comprising:

5. Each of the first valves (116, 216) and the second valves (118, 218) is a check valve, or The liquid-operated pump (100, 200, 300, 400) according to claim 4, wherein each of the first valves (116, 216) and the second valves (118, 218) is a fluid-operated membrane valve.

6. A second pump chamber (230b) is connected in parallel with the pump chamber (230a), A second flexible diaphragm is configured to form a barrier between the control fluid portion of the second pump chamber (230b) and the process fluid portion of the second pump chamber (230b), The second process fluid passages (210b, 310b, 310c, 310d) include the process fluid portion of the second pump chamber (230b), Second control fluid channel (220b) and It further includes, The second control fluid channel (220b) is The second inlet to the pump (200, 300, 400), The second outlet from the aforementioned pump (200, 300, 400), The control liquid portion of the second pump chamber (230b) and Includes, The liquid-operated pump (200, 300, 400) according to any one of claims 1 to 5, wherein the second control fluid channel (220b) is configured to contain at least a portion of the volume of the second captured control fluid, and the displacement of the second captured control fluid causes deformation of the second flexible diaphragm, and the deformation of the second flexible diaphragm causes movement of the process fluid in the second process fluid channels (210b, 310b, 310c, 310d).

7. The liquid-operated pump (200, 300, 400) according to claim 6, further comprising process fluid inlets (212, 312), wherein each of the process fluid passages (210a, 310a) and the second process fluid passages (210b, 310b) is configured to receive the process fluid through the process fluid inlets (212, 312).

8. The liquid-operated pump (300, 400) according to claim 6, further comprising a first process fluid inlet (312a) and a second process fluid inlet (312b), wherein the process fluid passage (310a) is configured to receive a first process fluid through the first process fluid inlet (312a), and the second process fluid passages (310c, 310d) are configured to receive a second process fluid through the second process fluid inlet (312b), wherein the second process fluid is different from the first process fluid.

9. Pump units (150, 250, 350) for a bioprocessing system, wherein the pump units are A pump unit outlet (154) configured for connection to the control liquid inlet (122) of a liquid-operated pump (100, 200, 300, 400), A pump unit inlet (152) configured for connection to the control liquid outlet (124) of the liquid-operated pumps (100, 200, 300, 400), wherein the control liquid flow path (160, 260, 460) includes the pump unit outlet (154), the liquid-operated pumps (100, 200, 300, 400), and the pump unit inlet (152), Pumps (158, 258, 358, 458) configured to drive the movement of the control liquid in the control liquid flow path (160, 260, 460), One or more valves (162, 262, 462, 166, 266, 466) configured to cause a predetermined volume of control fluid to be trapped in a portion of the control fluid flow path (160, 260, 460) including the pumps (158, 258, 358, 458) and the liquid-operated pumps (100, 200, 300, 400), wherein the movement of the pumps (158, 258, 358, 458) causes the displacement of the trapped control fluid, Pump units (150, 250, 350), including the above.

10. The pump unit (150, 250, 350) according to claim 9, wherein the pump unit (150, 250, 350) is configured to connect to reservoirs (156, 256, 456) configured to store the control fluid, and the pump (158, 258, 358, 458) is configured to drive the movement of the control fluid from the reservoirs (156, 256, 456) to the control fluid flow path (160, 260, 460).

11. The control liquid comprises a blend of water and alcohol, wherein the alcohol is optionally ethanol, according to the pump unit (150, 250, 350) of claim 9 or 10.

12. The pump unit (150, 250, 350) according to any one of claims 9 to 11, further comprising a pressure sensor (486) configured to detect the pressure of a predetermined volume of control fluid trapped in the portion of the control fluid flow path (160, 260, 460).

13. The pump unit (150, 250, 350) according to any one of claims 9 to 12, further comprising a degassing device (480) disposed upstream of the pumps (150, 250, 350) in the control liquid flow path (160, 260, 460).

14. The pump unit (150, 250, 350) according to any one of claims 9 to 13, further comprising a bubble detector (488) configured to detect whether gas bubbles are present in the control liquid flowing through the control liquid channels (160, 260, 460).

15. The one or more valves (162, 262, 462, 166, 266, 466) are, In the control fluid flow path (160, 260, 460), the first valves (162, 262, 462) are located upstream of the pumps (158, 258, 358, 458) and the liquid-operated pumps (100, 200, 300, 400), In the control fluid flow path (160, 260, 460), a second valve (164, 264, 464) is disposed between the pump (158, 258, 358, 458) and the liquid-operated pump (100, 200, 300, 400), In the control fluid flow path (160, 260, 460), a third valve (166, 266, 466) is located downstream of the pumps (158, 258, 358, 458) and the liquid-operated pumps (100, 200, 300, 400), A pump unit (150, 250, 350) according to any one of claims 9 to 14, including the following:

16. The pump unit (150, 250, 350) according to claim 15, wherein the third valve (166, 266, 466) is a pressure control valve configured to allow the flow of the control fluid when the pressure of the control fluid trapped in the portion of the control fluid passage (160, 260, 460) exceeds a predetermined pressure.

17. The pump unit (150, 250, 350) according to any one of claims 9 to 16, wherein the pumps (158, 258, 358, 458) are displacement pumps.

18. A method for pumping process fluid in a bioprocessing system, wherein the method is: The step of providing liquid-operated pumps (100, 200, 300, 400) and pump units (150, 250, 350), wherein the liquid-operated pumps (100, 200, 300, 400) are, Pump chambers (130, 230, 330), and, A flexible diaphragm (132) is configured to form a barrier between the control fluid portion (136) and the process fluid portion (134) of the pump chamber (130, 230, 330). Steps including, A step of capturing a predetermined volume of control liquid in a portion of a control liquid channel (160, 260, 460), wherein the portion of the control liquid channel (160, 260, 460) includes the pumps (158, 258, 358, 458) of the pump unit (150, 250, 350) and the control liquid portion (136) of the pump chamber (130, 230, 330). The steps include using the pumps (158, 258, 358, 458) to displace the captured control fluid, deform the flexible diaphragm (132), and cause the movement of process fluid in the process fluid passages (110, 210, 310) including the process fluid portion (134) of the pump chambers (130, 230, 330), and Methods that include...

19. The method according to claim 18, wherein the step of providing the liquid-operated pumps (100, 200, 300, 400) and the pump units (150, 250, 350) includes the step of connecting the liquid-operated pumps (100, 200, 300, 400) to the pump units (150, 250, 350).

20. The portion of the control liquid flow path (160, 260, 460) is In the control fluid flow path (160, 260, 460), the valves (162, 262, 462) located upstream of the pumps (158, 258, 358, 458) of the pump unit (150) and the liquid-operated pumps (100, 200, 300, 400) are connected. In the control fluid flow path (160, 260, 460), the valves (166, 266, 466) located downstream of the pumps (148, 258, 358, 458) of the pump unit (150) and the liquid-operated pumps (100, 200, 300, 400) are connected. It is located between, The step of capturing the predetermined volume of control liquid in the portion of the control liquid flow path (160, 260, 460) is: The steps include pumping the control liquid through the control liquid passages (160, 260, 460) using the pumps (158, 258, 358, 458) until the portion of the control liquid passages (160, 260, 460) is filled with the control liquid, The steps include closing the valves (162, 262, 462) located upstream of the pumps (158, 258, 358, 458) of the pump unit (150) and the liquid-operated pumps (100, 200, 300, 400) in the control liquid flow path (160, 260, 460), The steps include closing the valves (164, 264, 464) located downstream of the pumps (148, 258, 358, 458) of the pump unit (150) and the liquid-operated pumps (100, 200, 300, 400) in the control fluid flow path (160, 260, 460), The method according to claim 18 or claim 19, including the method according to claim 19.

21. The method according to any one of claims 18 to 20, wherein the step of capturing the predetermined volume of control liquid in the portion of the control liquid flow path (160, 260, 460) includes the step of pumping the control liquid through a degassing device (480) located upstream of the pumps (158, 258, 358, 458) in the control liquid flow path (160, 260, 460).

22. The step of capturing the predetermined volume of control liquid in the portion of the control liquid flow path (160, 260, 460) is: A step of using a bubble detector (488) to detect whether gas bubbles are present in the control liquid flowing through the portion of the control liquid flow path (160, 260, 460), In response to detecting that the control liquid flowing through the portion of the control liquid flow path (160, 260, 460) does not contain gas bubbles, the steps include capturing a predetermined volume of the control liquid, The method according to any one of claims 18 to 21, including the method described in any one of claims 18 to 21.

23. The method further includes a step of calibrating the maximum displacement position of the pumps (158, 258, 358, 458) with respect to the maximum displacement position of the flexible diaphragm (132), wherein the calibration is performed The steps include supplying positive pressure using the pumps (158, 258, 358, 458) to displace the captured liquid until the flexible diaphragm (132) is deformed to its maximum displacement position, The steps include: continuing to supply positive pressure using the pumps (158, 258, 358, 458) until the pumps (158, 258, 358, 458) reach their maximum displacement position; The method according to any one of claims 18 to 22, including the method described in any one of claims 18 to 22.

24. The method according to any one of claims 18 to 23, further comprising the step of supplying gas to displace the captured control liquid from the portion of the control liquid flow path (160, 260, 460).

25. The method according to any one of claims 18 to 24, further comprising the step of detecting the pressure of the captured control fluid using a pressure sensor (486).

26. The aforementioned liquid-operated pumps (200, 300, 400) are, A second pump chamber (230b) is connected in parallel with the pump chamber (230a), A second flexible diaphragm (132) is configured to form a barrier between the control fluid portion (136) and the process fluid portion (134) of the second pump chamber (230b), and Includes, The aforementioned method, A step of capturing a second volume of control liquid in a portion of a second control liquid channel (260b), wherein the portion of the second control liquid channel (260b) includes the second pumps (258b, 358b) of the pump unit (250, 350) and the control liquid portion (136) of the second pump chamber (230b), A step of supplying positive pressure using the pumps (258a, 358a) to displace the captured control fluid, wherein the displacement of the captured control fluid deforms the flexible diaphragm (132) and dispenses the process fluid from the process fluid portion (134) of the pump chamber (230a), Steps include supplying positive pressure using the pumps (258a, 358a), supplying negative pressure using the second pumps (258b, 358b) to displace the second captured control fluid, wherein the displacement of the second captured control fluid deforms the second flexible diaphragm (132) and draws the process fluid into the process fluid portion (134) of the second pump chamber (230b), and The method according to any one of claims 18 to 25, further comprising:

27. A step of supplying negative pressure using the pumps (258a, 358a) to displace the captured control fluid, wherein the displacement of the captured control fluid deforms the flexible diaphragm (132) and draws the process fluid into the process fluid portion (134) of the pump chamber (230a), During the step of supplying negative pressure using the pumps (258a, 358a), positive pressure is supplied using the second pumps (258b, 358b) to displace the second captured control fluid, the displacement of the second captured control fluid deforms the second flexible diaphragm (132) and dispenses process fluid from the process fluid portion (134) of the second pump chamber (230b), and The method according to claim 26, further comprising:

28. A thermoplastic elastomer (TPE) for use as a flexible diaphragm (132), wherein the TPE is At least one elastomer material, At least one thermoplastic material having a glass transition temperature (Tg) of approximately 65°C to approximately 95°C Thermoplastic elastomer (TPE), including

29. The TPE according to claim 28, wherein the at least one elastomer material comprises a SEBS (styrene-ethylene-butadiene-styrene) matrix.

30. The TPE according to claim 29, wherein the at least one elastomer material further comprises a soft segment and a hard segment therein.

31. The TPE according to claim 30, wherein the soft segment comprises polyethylene and / or polybutadiene, and / or the hard segment comprises polystyrene.

32. The TPE according to any one of claims 28 to 31, wherein at least one thermoplastic material has a glass transition temperature (Tg) of about 70°C to about 85°C, for example, about 75°C to about 80°C.

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