Microphysiological system

Abstract

This microphysiological system comprises: an inflow-side extraction unit that externally extracts, from an inflow medium which flows into a cell accommodation part accommodating cells, a trace of the inflow medium; and an outflow-side extraction unit that externally extracts, from an outflow medium which flows out from the cell accommodation part, a trace of the outflow medium.

Description

Biomimetic system

[0001] The present invention relates to a biomimetic system.

[0002] Conventionally, a technique for culturing cells or tissues using a microfluidic device that imitates the physiological environment of an organism is known (see Patent Document 1).

[0003] Japanese National Publication of International Patent Application No. 2022-519256

[0004] In the culture technique as described above, fluid components in the microfluidic device are monitored by a sensor to grasp the progress of culture. In such monitoring, when the sensor is arranged inside the microfluidic device, the material of the sensor (for example, an enzyme, a chemical substance, a metal, or a polymer) may elute into the fluid and adversely affect the culture environment.

[0005] The present invention has been made in view of such circumstances, and an object of the present invention is to provide a biomimetic system capable of extracting a culture medium, which is a monitoring target, from the biomimetic system.

[0006] One aspect of the biomimetic system according to the present invention comprises: an inflow-side extraction unit that extracts a trace amount of the inflow medium to the outside from the inflow medium flowing into a cell accommodating unit that accommodates cells; and an outflow-side extraction unit that extracts a trace amount of the outflow medium to the outside from the outflow medium flowing out of the cell accommodating unit.

[0007] According to the present invention, a biomimetic system capable of extracting a culture medium, which is a monitoring target, from the biomimetic system can be provided.

[0008] Figure 1 is a perspective view of a culture apparatus in which the biomimetic system according to Embodiment 1 of the present invention is arranged. Figure 2 is a block diagram showing the functional configuration of the biomimetic system. Figure 3 is a perspective view showing the structure of the biomimetic system. Figure 4 is a perspective view of a culture medium preparation unit. Figure 5 is an exploded perspective view of the culture medium preparation unit. Figure 6 is a perspective view of a microfluidic device. Figure 7 is a cross-sectional view of the microfluidic device. Figure 8 is a flowchart of a cell culture method and a test method performed using the biomimetic system. Figure 9 is a block diagram showing the functional configuration of the biomimetic system according to Embodiment 2 of the present invention. Figure 10 is a block diagram showing the functional configuration of the biomimetic system according to Embodiment 3 of the present invention. Figure 11 is a block diagram showing the functional configuration of the biomimetic system according to Embodiment 4 of the present invention. Figure 12 is a block diagram showing the functional configuration of the biomimetic system according to Embodiment 5 of the present invention. Figure 13 is a block diagram showing the functional configuration of the biomimetic system according to Embodiment 6 of the present invention. Figure 14 is a block diagram showing the functional configuration of the biomimetic system according to Embodiment 7 of the present invention. Figure 15A is a block diagram showing a part of the functional configuration of the biomimetic system according to Embodiment 8 of the present invention. Figure 15B is a block diagram showing a modified example of the biomimetic system according to Embodiment 8. Figure 16 is a block diagram showing a part of the functional configuration of the biomimetic system according to Embodiment 9 of the present invention. Figure 17 is a schematic diagram showing a modified microfluidic device. Figure 18 is a block diagram showing a part of the functional configuration of a biomimetic system according to Embodiment 10 of the present invention.

[0009] The biomimetic system according to the present invention will be described below with reference to the drawings. The same reference numerals will be used for the same components. The information described below, along with the accompanying drawings, is for illustrative purposes only and does not represent the only possible embodiment.

[0010] [Embodiment 1] A biomimetic system 1 according to Embodiment 1 of the present invention will be described with reference to Figures 1 to 8.

[0011] Biomimetic systems are microphysiological systems that mimic the physiological environment of living organisms (for example, humans). Such biomimetic systems are utilized in a wide range of fields, including cell culture, drug discovery, disease models, regenerative medicine, toxicity assessment, environmental research, and food science.

[0012] Here, we will briefly explain examples of the use of biomimetic systems in the field of drug discovery. Drug discovery is the process of developing new pharmaceuticals and generally includes target discovery, compound discovery, compound optimization, preclinical trials, and clinical trials.

[0013] Animal testing is conducted at each of these stages. In recent years, this animal testing has raised ethical concerns from an animal welfare perspective. Furthermore, animal testing is expensive and takes a long time (several months to several years), which can reduce the efficiency of drug discovery.

[0014] Therefore, in recent years, the biomimetic system 1 according to this embodiment is expected to be used as an alternative to animal testing.

[0015] For example, in the target discovery process, a disease model is constructed using the biomimetic system 1, the disease state is reproduced, and the target on which the drug acts is discovered and evaluated. The disease model constructed by such a biomimetic system 1 is an example of a biomimetic model.

[0016] Furthermore, in the compound discovery process, a disease model is constructed using the biomimetic system 1, the disease state is reproduced, and compounds that act on the target (in other words, pharmaceuticals) are searched for. The disease model constructed by such a biomimetic system 1 is an example of a biomimetic model.

[0017] Furthermore, in the compound optimization process, an animal biomimetic model that mimics the physiological environment of an animal (for example, a mouse or monkey) is constructed using the biomimetic system 1, and the pharmacological effects and side effects of the compounds identified in the compound discovery process are verified. Such an animal biomimetic model constructed by the biomimetic system 1 is an example of a biomimetic model.

[0018] Furthermore, in the preclinical trial stage, an animal biomimetic model that mimics the physiological environment of an animal (for example, a mouse or monkey) is constructed using biomimetic system 1, and the safety and efficacy of the compounds identified in the compound discovery stage are verified. Such an animal biomimetic model constructed using biomimetic system 1 is an example of a biomimetic model.

[0019] Furthermore, in the clinical trial process, a human-mimicking model that mimics the human physiological environment is constructed using biomimicking system 1, and the safety and efficacy of the compound against this human-mimicking model are verified. Such a human-mimicking model constructed using biomimicking system 1 is an example of a biomimicking model.

[0020] As described above, the biomimetic system 1 is used in each step of drug discovery, mainly for constructing biomimetic models and processing the constructed biomimetic models. In the biomimetic system 1 according to this embodiment, both the construction of biomimetic models and processing of these biomimetic models can be performed within a single system.

[0021] The configuration of the biomimetic system 1 according to this embodiment will be described below. Figure 1 is a schematic diagram of the culture apparatus 9 in which the biomimetic system 1 is arranged.

[0022] (Culture apparatus) The culture apparatus 9 is, for example, an incubator, and has a box section 91 and a door section 92. The box section 91 is box-shaped with an open front and has a culture space 911 inside. The box section 91 also has shelf sections 912 for dividing the culture space 911 into multiple regions. Figure 1 shows one shelf section 912.

[0023] The door section 92 is provided on the front of the box section 91 and is configured to be openable and closable. The culture apparatus 9 also has environmental adjustment means (not shown) for appropriately adjusting the environment of the culture space 911. The environmental adjustment means include, for example, humidity adjustment means, temperature adjustment means, and air adjustment means.

[0024] The humidity control means consists of, for example, a steam humidification method, an evaporative humidification method, or an ultrasonic humidification method. Such humidity control means adjust the humidity of the culture space 911 to a set humidity. The temperature control means consists of, for example, a heater provided in the box portion 91. Such temperature control means adjust the temperature of the culture space 911 to a set temperature. The air control means adjusts the gas concentration (specifically, O) of the culture space 911. ２ Concentration, CO ２ Concentration, and N ２ Adjust the concentration to the set gas concentration.

[0025] In the biomimetic system 1 according to this embodiment, the housing 2 containing the biomimetic unit 3 is placed on the shelf 912 and positioned in the culture space 911, as shown in Figure 1. The control device 6 of the biomimetic system 1 is positioned outside the culture apparatus 9.

[0026] The culture space 911 preferably has a volume capable of accommodating multiple housings 2. Specifically, in this embodiment, the culture space 911 has a volume capable of accommodating at least six housings 2.

[0027] In this embodiment, the biomimetic unit 3 and the control device 6 are connected by wired or wireless communication means. The control device 6 may be incorporated into the culture apparatus 9.

[0028] Next, an example of the specific configuration of the biomimetic system 1 will be described with reference to Figures 2 to 7. Figure 2 is a block diagram showing the functional configuration of the biomimetic system 1. Figure 3 is a perspective view showing the structure of the biomimetic system 1.

[0029] (Biomimicry System) The biomimicry system 1 comprises a housing 2, a biomimicry unit 3, and a control device 6.

[0030] (Housing) The housing 2 is a component that unitizes multiple devices that make up the biomimetic system 1. The housing 2 supports the biomimetic unit 3. Specifically, the housing 2 has a base 21 and a housing 22.

[0031] The base portion 21 is provided at the lower end of the housing 2 and is the part that is placed on the shelf portion 912 of the culture apparatus 9. The base portion 21 has a device support portion 211 on its upper surface.

[0032] The device support portion 211 is an example of a support portion and supports the microfluidic device 5, described later, in a detachable manner. The device support portion 211 is provided at the center and front end of the base portion 21 in the left-right direction. The device support portion 211 is a recess with an opening on the top and front surfaces.

[0033] Furthermore, the base portion 21 has an inflow-side culture medium receiving portion 212 and an outflow-side culture medium receiving portion 213 positioned on either side of the device support portion 211.

[0034] The inflow-side culture medium receiving section 212 is positioned below the inflow-side extraction section 351d, which is provided in the extraction section 35 described later, when in use. The inflow-side culture medium receiving section 212 is, for example, a small container with an open top. The inflow-side culture medium receiving section 212 contains the culture medium discharged from the inflow-side extraction section 351d.

[0035] In this embodiment, the inflow-side culture medium receiving portion 212 is fixed to the front end of the base portion 21 in a non-movable state. However, the inflow-side culture medium receiving portion 212 may be fixed to the front end of the base portion 21 in a movable state. In this case, the inflow-side culture medium receiving portion 212 may be configured to be movable forward from the front end of the base portion 21.

[0036] The outflow-side culture medium receiving section 213 is positioned below the outflow-side extraction section 352d, which is provided in the extraction section 35 described later, when in use. The outflow-side culture medium receiving section 213 is, for example, a small container with an open top. The outflow-side culture medium receiving section 213 contains the culture medium discharged from the outflow-side extraction section 352d.

[0037] In this embodiment, the outflow-side culture medium receiving portion 213 is fixed to the front end of the base portion 21 in a non-movable state. However, the outflow-side culture medium receiving portion 213 may be fixed to the front end of the base portion 21 in a movable state. In this case, the outflow-side culture medium receiving portion 213 may be configured to be movable forward from the front end of the base portion 21.

[0038] The housing section 22 is box-shaped with an open bottom and is positioned above the base section 21. The housing section 22 is positioned to cover the top surface of the base section 21 from above. The housing section 22 has a housing space inside for housing the biomimetic unit 3. Such a housing section 22 is supported on the base section 21 in a manner that allows it to be attached to or detached from the base section 21.

[0039] (Biomimic Unit) The biomimic unit 3 includes a reservoir tank 31, a pump 32, a flow meter 33, a culture medium preparation unit 34, a microfluidic device 5, and an extraction unit 35. The biomimic unit 3 has a plurality of channels L11 to L15 connecting these elements 31 to 35, 5.

[0040] Here, we will briefly explain the circuit configuration of the biomimetic unit 3. In the biomimetic unit 3, the culture medium contained in the reservoir tank 31 is circulated within the biomimetic unit 3 by the pump 32.

[0041] The culture medium delivered by pump 32 is indicated by arrow A in Figure 2. １ The system circulates in the direction indicated. A biomimetic system in which culture medium delivered by a pump circulates within a biomimetic unit is called a "circulating biomimetic system."

[0042] With the reservoir tank 31 as the reference point, the direction in which the culture medium flows (i.e., arrow A) １ The direction indicated by the arrow is considered the downstream side. Also, with the reservoir tank 31 as the reference point, the side opposite to the direction in which the culture medium flows is considered the upstream side.

[0043] A pump 32 is provided downstream of the reservoir tank 31. The reservoir tank 31 and the pump 32 are connected by a flow path L11. A flow meter 33 is also provided downstream of the pump 32. The pump 32 and the flow meter 33 are connected by a flow path L12.

[0044] Furthermore, a culture medium preparation unit 34 is provided downstream of the flow meter 33. The flow meter 33 and the culture medium preparation unit 34 are connected by a flow path L13. A microfluidic device 5 is provided downstream of the culture medium preparation unit 34.

[0045] The culture medium preparation unit 34 and the microfluidic device 5 are connected by a channel L14. Channels L12, L13, and L14 are examples of inflow channels through which the culture medium (i.e., inflow medium) flows into the microfluidic device 5.

[0046] Furthermore, a reservoir tank 31 is provided downstream of the microfluidic device 5. The microfluidic device 5 and the reservoir tank 31 are connected by a channel L15. Channel L15 is an example of an outflow channel through which the culture medium (i.e., the outflow medium) flowing out of the microfluidic device 5 flows.

[0047] The culture medium, delivered from the reservoir tank 31 by the pump 32, flows through the flow meter 33, the culture medium preparation unit 34, and the microfluidic device 5 in that order, before returning to the reservoir tank 31.

[0048] In this specification, the culture medium that flows through channels L12, L13, and L14 and enters the microfluidic device 5 is referred to as the inflow medium. The culture medium that flows out of the microfluidic device 5 and enters through channel L15 is referred to as the outflow medium. The following describes the various components of the biomimetic unit 3.

[0049] The reservoir tank 31 contains the culture medium. The pump 32, under the control of the control device 6, pumps the culture medium contained in the reservoir tank 31. The pump 32 is connected to the control device 6. The control device 6 is an example of a control unit that controls the pump 32.

[0050] Note that in Figure 2, the wiring connecting the pump 32 and the control device 6 is omitted. Ideally, the pump 32 should be a pump capable of precisely controlling the flow rate of the culture medium being delivered.

[0051] The control device 6 essentially has a configuration in which a processor, volatile memory (e.g., RAM), and storage device (e.g., HDD or SSR) are connected by a bus. The control device 6 may also consist of a single-chip LSI. For example, the control device 6 realizes the control processing of the biomimetic unit 3 by reading a program stored in non-volatile memory (not shown) into a buffer memory (not shown) and executing it.

[0052] The flow meter 33 is an example of a flow detection unit and acquires information regarding the flow rate of the culture medium passing through it. The flow meter 33 sends the acquired flow rate information to the control device 6. Therefore, the flow meter 33 is connected to the control device 6.

[0053] The control device 6 controls the pump 32 based on flow rate information obtained from the flow meter 33. Note that in Figure 2, the wiring connecting the flow meter 33 and the control device 6 is omitted.

[0054] The culture medium preparation unit 34 has an oxygen introduction function for introducing oxygen into the culture medium delivered by the pump 32, and / or a bubble removal function for removing bubbles from the culture medium. The culture medium preparation unit 34 is an example of an oxygen introduction section and / or a bubble removal section. The culture medium preparation unit 34 has a structure in which multiple components are stacked vertically.

[0055] Specifically, the culture medium preparation unit 34 has, from bottom to top, a base 341, an oxygen permeable membrane 342, a sheet 343, and a plate 344.

[0056] The base 341 has a main body portion 341a, a culture medium inlet portion 341b, and a culture medium outlet portion 341c.

[0057] The main body 341a is rectangular in shape in plan view and is located at the bottom of the culture medium preparation unit 34. The main body 341a is made of synthetic resin. The synthetic resin constituting the main body 341a may be, for example, polystyrene or polyolefin.

[0058] The main body 341a has a storage section 341d which is formed by a recess with an open top surface. The storage section 341d is a space for storing culture media.

[0059] The main body 341a has an inflow-side through-hole (not shown) that connects the first end (i.e., the upstream end) of the containment section 341d to the outside. The culture medium flows into the containment section 341d through the inflow-side through-hole.

[0060] The main body 341a has an outlet-side through-hole (not shown) that connects the second end (i.e., the downstream end) of the containment section 341d to the outside. The culture medium flows out from the containment section 341d through the outlet-side through-hole.

[0061] The culture medium inlet 341b is an axial member having a through-hole in its center. The through-hole constitutes a channel through which the culture medium passes.

[0062] The culture medium inlet 341b has a first joint and a second joint. The first joint is provided at one end of the culture medium inlet 341b (in other words, the upstream end). The second joint is provided at the other end of the culture medium inlet 341b (in other words, the downstream end).

[0063] The culture medium inlet 341b is fixed to the main body 341a with its second joint inserted into the inlet-side through-hole of the main body 341a. The first joint of the culture medium inlet 341b is connected to the flow path L13. The culture medium flowing through the flow path L13 flows into the containment section 341d of the main body 341a through the first joint of the culture medium inlet 341b.

[0064] The culture medium outlet section 341c is an axial member having a through hole in its center. The through hole constitutes a channel through which the culture medium passes. The culture medium outlet section 341c has a first joint section and a second joint section.

[0065] The first joint is located at one end of the culture medium outlet section 341c (in other words, the upstream end). The second joint is located at the other end of the culture medium outlet section 341c (in other words, the downstream end).

[0066] The culture medium outlet section 341c is fixed to the main body section 341a with its first joint inserted into the outlet-side through-hole of the main body section 341a. The second joint of the culture medium outlet section 341c is connected to the flow path L14. The culture medium contained in the storage section 341d of the main body section 341a flows out into the flow path L14 through the second joint of the culture medium inlet section 341b.

[0067] The oxygen permeable membrane 342 is rectangular in shape when viewed from above and is positioned on the base 341 (specifically, the main body portion 341a).

[0068] The oxygen permeable membrane 342 is composed of, for example, an oxygen-permeable film. The material constituting the oxygen permeable membrane 342 may be polyethylene, polypropylene, or polyethylene terephthalate. The material of the oxygen permeable membrane 342 is appropriately selected considering chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0069] The oxygen permeable membrane 342 is positioned to cover the housing portion 341d of the main body portion 341a from above.

[0070] The sheet 343 is rectangular in shape in plan view and is placed on the oxygen permeable membrane 342. The sheet 343 presses the oxygen permeable membrane 342 against the base 341 (specifically, the main body portion 341a).

[0071] Sheet 343 is composed of an oxygen-permeable sheet. The material constituting sheet 343 may be polyethylene, polypropylene, or polyethylene terephthalate. The material of sheet 343 is appropriately selected considering chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0072] Plate 344 is rectangular in plan view and is positioned at the top of the culture medium preparation unit 34. Plate 344 is made of synthetic resin. The synthetic resin constituting plate 344 may be, for example, polystyrene or polyolefin.

[0073] The synthetic resin constituting plate 344 is selected as appropriate, taking into consideration chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0074] The plate 344 has a plate-side through hole 344a that constitutes the adjustment space 34a. The plate-side through hole 344a is a through hole that penetrates the plate 344 in the vertical direction. The shape of the plate-side through hole 344a in plan view is smaller than the shape of the housing portion 341d provided in the base 341 (specifically, the main body portion 341a) in plan view.

[0075] In other words, the outer periphery shape of the plate-side through-hole 344a in a plan view is contained within the outer periphery shape of the housing section 341d in a plan view. The outer periphery shape of the plate-side through-hole 344a in a plan view is appropriately determined according to the performance required for the oxygen introduction function and bubble removal function of the culture medium preparation unit 34.

[0076] The base 341, oxygen permeable membrane 342, sheet 343, and plate 344, having the configuration described above, are fixed together by a plurality of fastening components 345 (for example, bolts) inserted through each of these elements 341 to 344.

[0077] In this embodiment, multiple fastening components 345 are inserted into multiple fastening holes 346 provided in the culture medium preparation unit 34. The fastening holes 346 are multiple through holes that penetrate the culture medium preparation unit 34 in the vertical direction. Each of the elements 341 to 344 is provided with through holes that constitute the fastening holes 346.

[0078] The microfluidic device 5 will now be described. The microfluidic device 5 is rectangular in shape and has a cell-containing space 51a inside. Cells can be cultured in such a microfluidic device 5 within the cell-containing space 51a. The microfluidic device 5 is an example of a culture vessel.

[0079] Furthermore, the microfluidic device 5 is an example of a cell containment section. That is, the entire microfluidic device 5 can be considered as a cell containment section. Alternatively, the cell containment space 51a, which is a part of the microfluidic device 5, can also be considered as a cell containment section.

[0080] The microfluidic device 5 includes a device body 51, a cell containment space 51a, a culture medium inlet 52, a culture medium outlet 53, an oxygen introduction section 54, and a bubble removal section 55.

[0081] The device body 51 has a cell containment space 51a inside. The cell containment space 51a is a space provided inside the device body 51 that contains cells to be cultured (hereinafter referred to as "target cells"). The cell containment space 51a extends in the longitudinal direction of the microfluidic device 5 (in other words, the device body 51).

[0082] In this embodiment, the volume of the cell containment space 51a is set to a size that ensures the cells within the cell containment space 51a receive a sufficient supply of oxygen.

[0083] The culture medium inlet 52 is an example of an inlet and has a channel that connects the cell containment space 51a to the outside. The culture medium inlet 52 is provided on the upper surface of the device body 51 at one end in the longitudinal direction (hereinafter referred to as the "first end of the microfluidic device 5").

[0084] The culture medium inlet 52 is connected to one end of the cell containment space 51a in the longitudinal direction (hereinafter referred to as the "first end of the cell containment space 51a"). The culture medium flows into the first end of the cell containment space 51a through the culture medium inlet 52.

[0085] The culture medium flowing into the cell containment space 51a is called the inflow medium. The first end of the cell containment space 51a is also the upstream end of the cell containment space 51a.

[0086] The culture medium outflow section 53 is an example of an outflow section and has a channel that connects the cell containment space 51a to the outside. The culture medium outflow section 53 is provided on the upper surface of the device body 51 at the other end in the longitudinal direction (hereinafter referred to as the "second end of the microfluidic device 5").

[0087] The culture medium outlet 53 is connected to the other end of the cell containment space 51a in the longitudinal direction (hereinafter referred to as the "second end of the cell containment space 51a"). The culture medium flows out from the second end of the cell containment space 51a through the culture medium outlet 53. The culture medium that flows out from the cell containment space 51a is referred to as the outflow culture medium. The second end of the cell containment space 51a is also the downstream end of the cell containment space 51a.

[0088] The oxygen introduction unit 54 has an oxygen introduction space 54a that connects the cell containment space 51a to the outside in a manner that allows for the movement of air (in other words, oxygen). The oxygen introduction unit 54 is located on the upper surface of the device body 51, in the central part in the longitudinal direction.

[0089] The oxygen introduction space 54a is connected to the central part of the cell containment space 51a in the longitudinal direction. Air is introduced into the cell containment space 51a from outside the microfluidic device 5 through the oxygen introduction space 54a.

[0090] The bubble removal section 55 has a space that connects the cell containment space 51a to the outside in a manner that allows for the movement of air (in other words, oxygen). In this embodiment, the bubble removal section 55 has an inlet-side bubble removal section 56 and an outlet-side bubble removal section 57.

[0091] The inlet-side bubble removal section 56 is provided on the upper surface of the device body 51, between the oxygen introduction section 54 and the culture medium inlet section 52. The inlet-side bubble removal section 56 has a bubble removal space 56a that connects the cell containment space 51a to the outside in a manner that allows for the movement of air (in other words, oxygen).

[0092] The outflow-side bubble removal section 57 is provided on the upper surface of the device body 51, between the oxygen introduction section 54 and the culture medium outflow section 53. The outflow-side bubble removal section 57 has a bubble removal space 57a that connects the cell containment space 51a to the outside in a manner that allows for the movement of air (in other words, oxygen).

[0093] The bubble removal spaces 56a and 57a are connected to the cell containment space 51a. Bubbles contained in the culture medium flowing through the cell containment space 51a are discharged to the outside through the bubble removal spaces 56a and 57a.

[0094] The specific configuration of the microfluidic device 5 will be described below with reference to Figures 6 and 7. The microfluidic device 5 has a structure in which multiple components are stacked vertically.

[0095] First, let me explain the specific configuration of the device body 51. The device body 51 has, from bottom to top, a lower plate 511, a lower sheet 512, a base 513, an upper sheet 514, and an upper plate 515.

[0096] The lower plate 511 is rectangular in shape in plan view and is located at the very bottom of the device body 51. The lower plate 511 is made of synthetic resin. The synthetic resin constituting the lower plate 511 may be, for example, polystyrene or polyolefin. Plan view means the view of the microfluidic device 5 from above.

[0097] The synthetic resin constituting the lower plate 511 is selected as appropriate, taking into consideration chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0098] The lower sheet 512 is rectangular in shape in plan view and is positioned above the lower plate 511. The lower sheet 512 is made of, for example, silicone resin. The silicone resin constituting the lower sheet 512 may be, for example, polydimethylsiloxane (PDMS).

[0099] The silicone resin constituting the lower sheet 512 is appropriately selected considering factors such as chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0100] The lower sheet 512 is positioned between the lower plate 511 and the base 513 and functions as a sealing member. The lower sheet 512 has a lower through-hole 512a that forms the cell containment space 51a. The lower through-hole 512a is a roughly rhomboid through-hole that penetrates the lower sheet 512 vertically and extends in the longitudinal direction.

[0101] The base 513 is rectangular in shape in plan view and is positioned above the lower sheet 512. The base 513 is made of synthetic resin. The synthetic resin constituting the base 513 may be, for example, polystyrene or polyolefin.

[0102] The synthetic resin constituting the base 513 is selected as appropriate, taking into consideration chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0103] The base 513 is positioned between the lower sheet 512 and the upper sheet 514. The base 513 constitutes the core of the device body 51. The base 513 has a base-side through-hole 513a that forms the cell containment space 51a.

[0104] The base-side through-hole 513a is a roughly diamond-shaped through-hole that penetrates the base 513 vertically and extends in the longitudinal direction. The external shape of the base-side through-hole 513a in a plan view is the same as the external shape of the lower through-hole 512a in a plan view.

[0105] The upper sheet 514 is rectangular in shape in plan view and is positioned above the base 513. The upper sheet 514 is made of, for example, silicone resin. The silicone resin constituting the upper sheet 514 may be, for example, polydimethylsiloxane (PDMS).

[0106] The silicone resin constituting the upper sheet 514 is selected as appropriate, taking into consideration chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0107] The upper sheet 514 is positioned between the base 513 and the upper plate 515 and functions as a sealing member. The upper sheet 514 has an upper through-hole 514a that forms a cell containment space 51a. The upper through-hole 514a is a roughly rhomboid through-hole that penetrates the upper sheet 514 vertically and extends in the longitudinal direction.

[0108] The external shape of the upper through-hole 514a in a plan view is consistent with the external shape of the lower through-hole 512a and the base-side through-hole 513a in a plan view.

[0109] The upper plate 515 is rectangular in shape in plan view and is positioned at the very top of the device body 51. The upper plate 515 is made of synthetic resin. The synthetic resin constituting the upper plate 515 may be, for example, polystyrene or polyolefin.

[0110] The synthetic resin constituting the upper plate 515 is selected as appropriate, taking into consideration chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0111] The upper plate 515 has, in order from one end in the longitudinal direction (i.e., the upstream side), an inlet hole 515a, an inlet-side bubble removal hole 515b, an oxygen introduction hole 515c, an outlet-side bubble removal hole 515d, and an outlet hole 515e.

[0112] The inlet hole 515a is provided at one end of the upper plate 515 in the longitudinal direction (i.e., the upstream end) and is a through hole that penetrates the upper plate 515 in the vertical direction.

[0113] The outflow hole 515e is provided at the other end (i.e., the downstream end) in the longitudinal direction of the upper plate 515 and is a through hole that penetrates the upper plate 515 in the vertical direction.

[0114] The oxygen introduction hole 515c is located in the center of the upper plate 515 in the longitudinal direction and is a through hole that penetrates the upper plate 515 in the vertical direction. The oxygen introduction hole 515c constitutes the oxygen introduction space 54a.

[0115] The inlet-side bubble removal hole 515b is provided in the longitudinal direction of the upper plate 515 between the inlet hole 515a and the oxygen introduction hole 515c, and is a through hole that penetrates the upper plate 515 in the vertical direction. The inlet-side bubble removal hole 515b constitutes the bubble removal space 56a.

[0116] The outflow-side bubble removal hole 515d is provided in the longitudinal direction of the upper plate 515 between the outflow hole 515e and the oxygen introduction hole 515c, and is a through hole that penetrates the upper plate 515 in the vertical direction. The outflow-side bubble removal hole 515d constitutes the bubble removal space 57a.

[0117] The lower plate 511, lower sheet 512, base 513, upper sheet 514, and upper plate 515, having the configuration described above, are fixed together by a plurality of fastening components 58 (for example, bolts) inserted through each of these elements 511 to 515. Note that each of the elements 511 to 515 may also be fixed by welding.

[0118] In this embodiment, multiple fastening components 58 are inserted into multiple fastening holes 59 provided in the device body 51. The fastening holes 59 are multiple through holes that penetrate the device body 51 in the vertical direction. Each of the elements 511 to 515 is provided with through holes that constitute the fastening holes 59.

[0119] The culture medium inlet 52 is an axial member having a through hole 521 in its center. The through hole 521 constitutes a channel through which the incoming culture medium passes. The culture medium inlet 52 has a first joint 522 and a second joint 523.

[0120] The first joint 522 is provided at one end (i.e., the upper end) of the culture medium inlet 52. The second joint 523 is provided at the other end (i.e., the lower end) of the culture medium inlet 52.

[0121] The culture medium inlet 52 is fixed to the device body 51 with the second joint 523 inserted into the inlet hole 515a of the upper plate 515. In this state, the first joint 522 is connected to the downstream end of the flow path L14.

[0122] The culture medium outlet section 53 is an axial member having a through hole in its center. The through hole 531 constitutes a flow path through which the outflowed culture medium passes. The culture medium outlet section 53 has a first joint section 532 and a second joint section 533.

[0123] The first joint 532 is provided at one end (i.e., the upper end) of the culture medium outlet 53. The second joint 533 is provided at the other end (i.e., the lower end) of the culture medium outlet 53.

[0124] The culture medium outlet section 53 is fixed to the device body 51 with the second joint section 533 inserted into the outlet hole 515e of the upper plate 515. In this state, the first joint section 532 is connected to the upstream end of the flow path L15.

[0125] Next, the specific configuration of the oxygen introduction section 54 will be described. The oxygen introduction section 54 has, from bottom to top, a sheet 541, an oxygen permeable membrane 542, and a plate 543.

[0126] The sheet 541 is rectangular in shape in plan view and is located at the bottom of the oxygen introduction section 54. The sheet 541 is made of, for example, silicone resin. The silicone resin constituting the sheet 541 may be, for example, polydimethylsiloxane (PDMS).

[0127] The sheet 541 has sheet-side through holes 541a that constitute the oxygen introduction space 54a. The sheet-side through holes 541a are through holes that penetrate the sheet 541 in the vertical direction. The shape of the sheet-side through holes 541a in plan view matches the shape of the oxygen introduction holes 515c in the upper plate 515 in plan view.

[0128] The oxygen permeable membrane 542 is rectangular in plan view and is placed on the sheet 541. The oxygen permeable membrane 542 is made of, for example, an oxygen-permeable film. The material constituting the oxygen permeable membrane 542 may be polyethylene, polypropylene, or polyethylene terephthalate.

[0129] The oxygen permeable membrane 542 is positioned to cover the sheet-side through-holes 541a of the sheet 541 from above.

[0130] The plate 543 is rectangular in shape in plan view and is positioned at the top of the oxygen introduction section 54. The plate 543 is made of synthetic resin. The synthetic resin constituting the plate 543 may be, for example, polystyrene or polyolefin.

[0131] The synthetic resin constituting plate 543 is selected appropriately, taking into consideration chemical stability, mechanical strength, processability, biocompatibility, heat resistance, and productivity.

[0132] The plate 543 has plate-side through-holes 543a that constitute the oxygen introduction space 54a. The plate-side through-holes 543a are through-holes that penetrate the plate 543 in the vertical direction. The shape of the plate-side through-holes 543a in plan view matches the shape of the oxygen introduction holes 515c in the upper plate 515 and the sheet-side through-holes 541a in the sheet 541 in plan view.

[0133] The plate 543 is positioned to cover the oxygen permeable membrane 542 from above. The oxygen introduction section 54 having this configuration is fixed to the central part of the upper surface of the device body 51 by fastening components 544.

[0134] The oxygen introduction section 54 is positioned to cover the oxygen introduction hole 515c in the upper plate 515 from above. In this state, the oxygen introduction space 54a is formed by the plate-side through hole 543a and sheet-side through hole 541a of the oxygen introduction section 54, and the oxygen introduction hole 515c in the upper plate 515.

[0135] The oxygen introduction space 54a extends in the vertical direction. The oxygen introduction space 54a connects the cell containment space 51a to the outside. An oxygen permeable membrane 542 is positioned in the middle of the oxygen introduction space 54a in the direction of extension. The oxygen permeable membrane 542 controls the amount of air introduced from the outside into the cell containment space 51a to an appropriate amount.

[0136] Next, the specific configuration of the bubble removal unit 55 will be described. The bubble removal unit 55 has an inlet-side bubble removal unit 56 and an outlet-side bubble removal unit 57. The basic configuration of the inlet-side bubble removal unit 56 and the outlet-side bubble removal unit 57 is the same as the configuration of the oxygen introduction unit 54 described above.

[0137] The inlet-side bubble removal section 56 has, from bottom to top, a sheet 561, an oxygen permeable membrane 562, and a plate 563. The configuration of the sheet 561, oxygen permeable membrane 562, and plate 563 is substantially the same as the configuration of the sheet 541, oxygen permeable membrane 542, and plate 543 of the oxygen introduction section 54 described above.

[0138] The inlet-side bubble removal section 56 is fixed to the upper surface of the device body 51 by fastening components 564. The inlet-side bubble removal section 56 is positioned to cover the inlet-side bubble removal hole 515b in the upper plate 515 from above. In this state, a bubble removal space 56a is formed by the plate-side through hole 563a and sheet-side through hole 561a of the inlet-side bubble removal section 56, and the inlet-side bubble removal hole 515b in the upper plate 515.

[0139] The bubble removal space 56a extends in the vertical direction. The bubble removal space 56a connects the cell containment space 51a to the outside. An oxygen permeable membrane 562 is positioned in the middle of the bubble removal space 56a in the direction of its extension. Bubbles contained in the culture medium in the cell containment space 51a are discharged to the outside through the bubble removal space 56a.

[0140] The outflow-side bubble removal section 57 has, from bottom to top, a sheet 571, an oxygen permeable membrane 572, and a plate 573. The configuration of the sheet 571, oxygen permeable membrane 572, and plate 573 is substantially the same as the configuration of the sheet 541, oxygen permeable membrane 542, and plate 543 of the oxygen introduction section 54 described above.

[0141] The outlet-side bubble removal section 57, having this configuration, is fixed to the upper surface of the device body 51 by fastening components 574. The outlet-side bubble removal section 57 is positioned to cover the outlet-side bubble removal hole 515d in the upper plate 515 from above. In this state, a bubble removal space 57a is formed by the plate-side through hole 573a and sheet-side through hole 571a of the outlet-side bubble removal section 57, and the outlet-side bubble removal hole 515d in the upper plate 515.

[0142] The bubble removal space 57a extends in the vertical direction. The bubble removal space 57a connects the cell containment space 51a to the outside. An oxygen permeable membrane 572 is positioned in the middle of the bubble removal space 57a in the direction of its extension. Bubbles contained in the culture medium in the cell containment space 51a are discharged to the outside through the bubble removal space 57a.

[0143] The microfluidic device 5, having the configuration described above, is supported in a detachable manner on the device support portion 211 provided on the base portion 21 of the housing 2 during cell culture (in other words, during use).

[0144] The worker removes the housing section 22 from the base section 21 and inserts the microfluidic device 5 into the device support section 211 from the front. Then, the worker places the housing section 22 over the base section 21 from above.

[0145] When the housing section 22 is fixed to the base section 21, the end of the flow path L14 is attached to the first joint section 522 of the culture medium inlet section 52. Also, when the housing section 22 is fixed to the base section 21, the end of the flow path L15 is attached to the first joint section 532 of the culture medium outlet section 53.

[0146] Next, the extraction unit 35 will be described. The extraction unit 35 extracts a small amount of culture medium from the culture medium flowing through the biomimetic unit 3 and brings it outside the biomimetic unit 3. The extraction unit 35 has an inflow side extraction unit 351 and an outflow side extraction unit 352.

[0147] The inflow extraction unit 351 extracts a small amount of inflow medium from the inflow medium flowing into the microfluidic device 5 and releases it to the outside. "Outside" refers to the area outside the biomimetic unit 3. Alternatively, "outside" may refer to the area outside the housing 2.

[0148] Specifically, the inflow extraction unit 351 extracts a small amount of culture medium from the culture medium flowing through the channel L13 (i.e., the inflow medium). Hereinafter, the culture medium extracted by the inflow extraction unit 351 will be referred to as the extracted inflow medium. The inflow extraction unit 351 may also extract a small amount of culture medium from the culture medium flowing through the channel L14 (i.e., the inflow medium).

[0149] The inlet side extraction unit 351 includes an inlet side extraction channel 351a, an inlet side first valve 351b, an inlet side second valve 351c, an inlet side extraction section 351d, and an inlet side valve drive section 351e.

[0150] The inflow side extraction channel 351a has its first end (in other words, its upstream end) connected to the middle section of the channel L13. The connection between the inflow side extraction channel 351a and the channel L13 is made up of a valve such as a septum or a three-way valve.

[0151] The connection position between the inflow extraction channel 351a and the channel L13 is not particularly limited. From the viewpoint of extracting the inflow medium immediately before it flows into the microfluidic device 5, it is preferable that the connection position between the inflow extraction channel 351a and the channel L13 be a position in the channel L13 that is close to the microfluidic device 5.

[0152] The second end of the inflow side extraction channel 351a (in other words, the downstream end) is connected to the inflow side extraction section 351d.

[0153] The inlet-side first valve 351b is located in the middle of the inlet-side extraction passage 351a. The inlet-side first valve 351b is, for example, a pinch valve. The state of the inlet-side first valve 351b is controlled by the control device 6 driving the inlet-side valve drive unit 351e.

[0154] When the inlet-side first valve 351b is open, the culture medium in the inlet-side extraction channel 351a (i.e., the inflow medium) flows toward the inlet-side extraction section 351d. When the inlet-side first valve 351b is closed, the culture medium in the inlet-side extraction channel 351a (i.e., the inflow medium) is blocked by the inlet-side first valve 351b.

[0155] The position of the inlet-side first valve 351b in the inlet-side extraction channel 351a is not particularly limited. Furthermore, the inlet-side first valve 351b is not particularly limited as long as it is a valve that can be switched between an open state and a closed state.

[0156] The inflow-side second valve 351c is located in the flow path L13, closer to the microfluidic device 5 (in other words, the culture medium preparation unit 34) than the connection point between the flow path L13 and the inflow-side extraction flow path 351a.

[0157] The inlet-side second valve 351c is, for example, a pinch valve. The state of the inlet-side second valve 351c is controlled by the control device 6 driving the inlet-side valve drive unit 351e.

[0158] When the inflow-side second valve 351c is open, the culture medium in the flow path L13 (i.e., the inflow medium) flows toward the microfluidic device 5 (in other words, the culture medium preparation unit 34).

[0159] When the inflow-side second valve 351c is closed, the culture medium in the flow path L13 (i.e., the inflow culture medium) is blocked by the inflow-side second valve 351c.

[0160] Furthermore, the inlet-side second valve 351c is not particularly limited as long as it is a valve that can be switched between an open state and a closed state. Also, the inlet-side second valve 351c may be omitted.

[0161] The inflow extraction unit 351d extracts a small amount of the inflow medium from the culture medium flowing into the microfluidic device 5 (i.e., the inflow medium) to the outside. In other words, the inflow extraction unit 351d extracts a small amount of the inflow medium to the outside of the channel L13.

[0162] Specifically, the inflow extraction unit 351d extracts a small amount of culture medium (i.e., inflow culture medium) from the inflow extraction channel 351a.

[0163] The inlet-side extraction unit 351d is a nozzle capable of extracting a small amount of liquid. The amount of culture medium extracted by the inlet-side extraction unit 351d is, for example, 0.1 μL to 5.0 μL.

[0164] The culture medium extracted by the inflow-side extraction unit 351d is contained in the inflow-side culture medium receiving unit 212 provided on the base 21 of the housing 2.

[0165] The inlet valve drive unit 351e switches the state of the inlet first valve 351b and the inlet second valve 351c.

[0166] The operation of the inlet valve drive unit 351e is controlled by the control device 6. Therefore, the inlet valve drive unit 351e is connected to the control device 6. Note that in Figure 2, the wiring connecting the inlet valve drive unit 351e and the control device 6 is omitted.

[0167] The inlet valve drive unit 351e includes, for example, a motor and an operating unit. The motor is driven under the control of the control device 6 and operates the operating unit. The operating unit switches the state of the inlet first valve 351b and the inlet second valve 351c.

[0168] When the control device 6 extracts the culture medium (i.e., the inflow medium) from the flow path L13, it drives the inflow valve drive unit 351e to open the inflow first valve 351b and close the inflow second valve 351c.

[0169] In this state, the culture medium in the channel L13 (i.e., the incoming medium) is blocked by the inflow-side second valve 351c. Therefore, the culture medium in the channel L13 (i.e., the incoming medium) does not flow into the microfluidic device 5.

[0170] Furthermore, the culture medium in the flow path L13 (i.e., the inflow medium) flows into the inflow side extraction section 351d through the inflow side extraction flow path 351a. The culture medium that flows into the inflow side extraction section 351d (i.e., the inflow medium) is then extracted by the inflow side extraction section 351d.

[0171] The interval at which the culture medium is extracted by the inflow extraction unit 351d (hereinafter referred to as the "inflow culture medium extraction interval") may be, for example, 30 seconds or more. Specifically, the inflow culture medium extraction interval may be 1 minute. The inflow culture medium extraction interval may be determined as appropriate. The inflow culture medium extraction interval may be set as appropriate.

[0172] Furthermore, after extracting the culture medium (i.e., the inflow culture medium) from the flow path L13, the control device 6 drives the inflow valve drive unit 351e to close the inflow first valve 351b and open the inflow second valve 351c.

[0173] In this state, the culture medium in channel L13 (i.e., the incoming medium) does not flow through the inflow side extraction channel 351a. On the other hand, the culture medium in channel L13 (i.e., the incoming medium) flows into the microfluidic device 5 by passing through the inflow side second valve 351c.

[0174] As described above, in this embodiment, the control device 6 controls the state of the inlet-side first valve 351b and the inlet-side second valve 351c via the inlet-side valve drive unit 351e. If the inlet-side second valve 351c is omitted, the control device 6 only needs to control the state of the inlet-side first valve 351b via the inlet-side valve drive unit 351e.

[0175] The outflow-side extraction unit 352 extracts a small amount of the outflow medium from the outflow medium flowing out of the microfluidic device 5. Specifically, the outflow-side extraction unit 352 extracts a small amount of medium from the medium flowing through the channel L15 (i.e., the outflow medium). Hereinafter, the medium extracted by the outflow-side extraction unit 352 will be referred to as the extracted inflow medium.

[0176] The outlet side extraction unit 352 includes an outlet side extraction channel 352a, an outlet side first valve 352b, an outlet side second valve 352c, an outlet side extraction section 352d, and an outlet side valve drive section 352e.

[0177] The first end (in other words, the upstream end) of the outflow side extraction channel 352a is connected to the middle section of the channel L15. The connection position between the outflow side extraction channel 352a and the channel L15 is not particularly limited.

[0178] From the viewpoint of extracting the culture medium immediately before it flows out from the microfluidic device 5, it is preferable that the connection position between the outflow-side extraction channel 352a and the channel L15 be a position close to the microfluidic device 5 in the channel L15.

[0179] The second end of the outflow side extraction channel 352a (in other words, the downstream end) is connected to the outflow side extraction section 352d.

[0180] The first outlet valve 352b is located in the middle of the outlet extraction channel 352a. The first outlet valve 352b is, for example, a pinch valve. The state of the first outlet valve 352b is controlled by the control device 6 driving the outlet valve drive unit 352e.

[0181] When the first outlet valve 352b is open, the culture medium in the outlet extraction channel 352a (i.e., the outlet medium) flows toward the outlet extraction section 352d. When the first outlet valve 352b is closed, the culture medium in the outlet extraction channel 352a (i.e., the outlet medium) is blocked by the first outlet valve 352b.

[0182] The position of the first outlet valve 352b in the outlet extraction channel 352a is not particularly limited. Furthermore, the first outlet valve 352b is not particularly limited as long as it is a valve that can be switched between an open state and a closed state.

[0183] The second outlet valve 352c is located in the flow path L15 at a position further from the microfluidic device 5 than the connection point between the flow path L15 and the outlet extraction flow path 352a (in other words, at a downstream position). The second outlet valve 352c is, for example, a pinch valve. The state of the second outlet valve 352c is controlled by the control device 6 driving the outlet valve drive unit 352e.

[0184] When the second outlet valve 352c is open, the culture medium in the flow path L15 (i.e., the outflow medium) flows toward the reservoir tank 31. When the second outlet valve 352c is closed, the culture medium in the flow path L15 (i.e., the outflow medium) is blocked by the second outlet valve 352c.

[0185] Furthermore, the second outlet valve 352c is not particularly limited as long as it is a valve that can be switched between an open state and a closed state. Also, the second outlet valve 352c may be omitted.

[0186] The outflow-side extraction unit 352d extracts a small amount of the culture medium flowing out of the microfluidic device 5 (i.e., the outflow medium) to the outside. In other words, the outflow-side extraction unit 352d extracts a small amount of the outflow medium to the outside of the flow path L15.

[0187] Specifically, the outflow-side extraction unit 352d extracts a small amount of culture medium (i.e., outflow culture medium) from the outflow-side extraction channel 352a.

[0188] The outflow-side extraction unit 352d is a nozzle capable of extracting a small amount of liquid. The amount of culture medium extracted by the outflow-side extraction unit 352d is, for example, 0.1 μL to 5.0 μL.

[0189] The culture medium extracted by the outflow side extraction unit 352d is contained in the outflow side culture medium receiving unit 213 provided on the base 21 of the housing 2.

[0190] The outlet valve drive unit 352e switches the state of the outlet first valve 352b and the outlet second valve 352c.

[0191] The operation of the outlet valve drive unit 352e is controlled by the control device 6. Therefore, the outlet valve drive unit 352e is connected to the control device 6. Note that in Figure 2, the wiring connecting the outlet valve drive unit 352e and the control device 6 is omitted.

[0192] The outlet valve drive unit 352e includes, for example, a motor and an operating unit. The motor is driven under the control of the control device 6 and operates the operating unit. The operating unit switches the state of the outlet first valve 352b and the outlet second valve 352c.

[0193] When the control device 6 extracts the culture medium (i.e., the outflow culture medium) from the flow path L15, it drives the outflow-side valve drive unit 352e to open the first outflow-side valve 352b and close the second outflow-side valve 352c.

[0194] In this state, the culture medium in the flow path L15 (i.e., the incoming culture medium) is blocked by the outflow side second valve 352c.

[0195] Furthermore, the culture medium in the flow path L15 (i.e., the outflow medium) flows into the outflow side extraction section 352d through the outflow side extraction flow path 352a. The culture medium that flows into the outflow side extraction section 352d is then extracted by the outflow side extraction section 352d.

[0196] The interval at which the culture medium is extracted by the outflow side extraction unit 352d (hereinafter referred to as the "outflow culture medium extraction interval") may be, for example, 30 seconds or more and 3 minutes or less. Specifically, the outflow culture medium extraction interval may be 1 minute. The outflow culture medium extraction interval may be determined as appropriate.

[0197] Furthermore, after extracting the culture medium (i.e., the outflow culture medium) from the flow path L15, the control device 6 drives the outflow valve drive unit 352e to close the first outflow valve 352b and open the second outflow valve 352c.

[0198] In this state, the culture medium in channel L15 (i.e., the efflux medium) does not flow through the efflux-side extraction channel 352a. On the other hand, the culture medium in channel L15 (i.e., the efflux medium) flows into the reservoir tank 31 through the efflux-side second valve 352c.

[0199] As described above, in this embodiment, the control device 6 controls the state of the outlet-side first valve 352b and the outlet-side second valve 352c via the outlet-side valve drive unit 352e. If the outlet-side second valve 352c is omitted, the control device 6 only needs to control the state of the outlet-side first valve 352b via the outlet-side valve drive unit 352e.

[0200] Furthermore, the timing of the extraction of small amounts of inflow and outflow media by the extraction unit 35 may be the same or different.

[0201] The configuration of the biomimetic system 1 according to this embodiment has been described above. Now, with reference to Figure 8, cell culture and testing performed using the biomimetic system 1 will be described. Figure 8 shows the cell culture preparation step, the cell culture step, and the testing step.

[0202] (Step S101) First, in step S101 of Figure 8, the operator seeds cells (i.e., target cells) into a microfluidic device. The operator selects a microfluidic device from among several types of microfluidic devices that has suitable performance for the target cells (for example, the shape and volume of the cell containment space). The following explanation assumes that the operator has selected microfluidic device 5.

[0203] The operator seeds the target cells into the cell containment space 51a of the microfluidic device 5. Specifically, the operator places the cell suspension containing the target cells into a seeding device (e.g., a pipette or syringe).

[0204] Then, the operator inserts an instrument into the culture medium inlet 52 or culture medium outlet 53 of the microfluidic device 5 and injects the cell suspension into the cell containment space 51a. After a while, the target cells contained in the cell suspension will engraft at the bottom of the cell containment space 51a.

[0205] The culture medium inlet 52 and culture medium outlet 53 are examples of ports that allow target cells to be introduced into the microfluidic device 5 from outside the microfluidic device 5.

[0206] The target cells may be placed inside the microfluidic device while supported by an accessory capable of carrying cells (e.g., a culture vessel). In this case, the microfluidic device is provided with a port through which the accessory carrying the target cells can be introduced from outside the microfluidic device into the microfluidic device. Such a port may be, for example, a through-hole provided in the center of the top surface of the microfluidic device. Such a through-hole may also function as an oxygen introduction port. The position of the port is not particularly limited.

[0207] (Step S102) Next, in step S102 of Figure 8, the worker removes the housing section 22 from the base section 21 and attaches the microfluidic device 5 to the device support section 211 provided on the base section 21 of the housing 2. In this state, the housing section 22 houses the other components of the biomimetic unit 3 besides the microfluidic device 5.

[0208] The operator then places the culture medium into the reservoir tank 31. The culture medium is selected appropriately according to the target cells. The culture medium may contain glucose at a predetermined concentration.

[0209] The glucose concentration must be maintained at an appropriate level, taking into account the amount of glucose consumed by the target cells in the cell containment space 51a. In addition to glucose, the culture medium may also contain other components necessary to adapt to the breeding conditions of animals used in animal experiments.

[0210] Then, the worker assembles the housing section 22 onto the base section 21. Once the housing section 22 is assembled to the base section 21, the first joint section 522 provided at the culture medium inlet section 52 of the microfluidic device 5 is automatically connected to the downstream end of the flow path L14.

[0211] Furthermore, once the housing section 22 is assembled to the base section 21, the first joint section 532 provided on the culture medium outlet section 53 of the microfluidic device 5 is automatically connected to the upstream end of the flow path L15.

[0212] In this way, when the microfluidic device 5 is mounted on the device support portion 211 and the housing portion 22 is assembled above the base portion 21, the microfluidic device 5 is connected to the flow path L14 and flow path L15 without any special positioning work.

[0213] (Step S103) Next, in step S103 of Figure 8, the operator places the biomimetic system 1 (specifically, the housing 2 containing the biomimetic unit 3) into the culture apparatus 9, as shown in Figure 1. In this state, the control device 6 is placed outside the culture apparatus 9.

[0214] The operator operates the control panel of the culture apparatus 9 to set the environment of the culture space 911. The operator sets the environment of the culture space 911 to be suitable for the living environment of the animals used in animal experiments.

[0215] Specifically, the operator sets the target temperature of the culture space 911 (for example, 37°C). The temperature control means of the culture apparatus 9 functions to maintain the temperature of the culture space 911 at the target temperature. The operator also controls the gas concentration of the culture space 911 (for example, O ２ Concentration, CO ２ Concentration, N ２ The operator sets a target concentration (for example, 5%). The air conditioning means of the culture apparatus 9 functions to maintain the gas concentration in the culture space 911 at the target concentration. The operator also sets a target humidity for the culture space 911. The humidity conditioning means of the culture apparatus 9 functions to maintain the humidity in the culture space 911 at the target humidity.

[0216] Furthermore, the environmental settings may include not only items that can be achieved by the functions of the culture device 9, but also items that can be achieved through means other than the functions of the culture device 9. For example, the environmental settings may include temperature, humidity, airflow rate, ventilation rate, illuminance, noise level, odor level, and atmospheric pressure level.

[0217] The steps S101 to S103 described above constitute the preparation process. The worker may perform any steps other than those described above during the preparation process.

[0218] Next, the operator performs a cell culture process using the biomimetic system 1 to culture the target cells. The cell culture process is described below. The operator or the control device 6 is the main entity that performs the cell culture process.

[0219] (Step S104) In step S104 of Figure 8, the control device 6 starts culturing the target cells. Specifically, the control device 6 drives the pump 32 to circulate the culture medium contained in the reservoir tank 31 within the biomimetic unit 3. The discharge volume of the pump 32 is set appropriately according to the target cells.

[0220] In this embodiment, the discharge rate of the pump 32 is adjusted so that the culture medium circulates within the biomimetic unit 3 at a rate of 0.5 μL / min. The discharge rate of the pump 32 may be set appropriately within a range that allows the culture medium to circulate within the biomimetic unit 3 at a rate of 0.5 μL / min or more.

[0221] (Step S105) Next, in step S105 of Figure 8, the control device 6 monitors the culture status. This step is called the monitoring step. The monitoring step is a step included in the cell culture step.

[0222] In the monitoring process, the control device 6 controls the inflow-side extraction unit 351 of the extraction unit 35 to extract a small amount of inflow medium and a small amount of outflow medium. This process is referred to as the medium extraction process.

[0223] The method for extracting trace amounts of inflow and outflow media is as previously described. The inflow media extracted by the inflow-side extraction unit 351 is contained in the inflow-side media receiving section 212 provided on the base 21 of the housing 2.

[0224] Furthermore, the effluent culture medium extracted by the inflow-side extraction unit 351 is contained in the effluent-side culture medium receiving section 213 provided on the base 21 of the housing 2.

[0225] Next, the operator uses a detection device (not shown), such as a biosensor, to detect information about the influent medium from the trace amount of influent medium contained in the influent medium receiving section 212. The information about the influent medium includes the concentration of glucose and / or lactic acid contained in the trace amount of influent medium. The information about the influent medium may also include the concentration of albumin, ammonia, and / or urea contained in the trace amount of influent medium.

[0226] Furthermore, the operator uses a detection device (not shown), such as a biosensor, to detect information about the effluent medium from the trace amount of effluent medium contained in the effluent medium receiving section 213. The information about the effluent medium includes the concentration of glucose and / or lactic acid contained in the trace amount of effluent medium. The information about the effluent medium may also include the concentration of albumin, ammonia, and / or urea contained in the trace amount of effluent medium.

[0227] Glucose is the primary energy source for cells. When the influx medium flows into the cell containment space 51a of the microfluidic device 5, the target cells in the cell containment space 51a proliferate using the glucose contained in the influx medium as an energy source.

[0228] During this process, lactic acid is produced as a metabolite of glucose. The produced lactic acid accumulates in the culture medium within the cell containment space 51a and flows out from the microfluidic device 5 along with the culture medium.

[0229] The operator can understand the changes in glucose and lactate in the microfluidic device 5 based on the concentrations of glucose and lactate in the inflow medium and the concentrations of glucose and lactate in the outflow medium.

[0230] For example, the energy consumption of target cells within the microfluidic device 5 can be determined from changes in glucose concentration. A rapid decrease in glucose concentration indicates that the target cells are actively proliferating and metabolizing.

[0231] Furthermore, changes in lactic acid concentration allow us to understand the metabolic state of cells within the microfluidic device 5. High lactic acid concentrations can lower the pH of the culture medium, potentially harming cells. A rapid increase in lactic acid concentration indicates that the cells are under stress.

[0232] In this way, the operator can understand the cell culture status within the microfluidic device 5 by monitoring the glucose and / or lactate concentrations in the inflow and outflow media. Furthermore, it is possible to numerically manage the culture state based on the glucose and / or lactate concentrations in the inflow and outflow media. Preferably, the glucose concentration in the inflow and outflow media is 0.1 mM to 30 mM. Also, preferably, the lactate concentration in the inflow and outflow media is 0.1 mM to 30 mM.

[0233] In this embodiment, the operator uses a detection device (not shown), such as a biosensor, to detect information regarding the incoming culture medium and information regarding the outgoing culture medium. However, as in Embodiment 2 described later, if the biomimetic system 1B is equipped with a detection device 7, the control device 6 may control the detection device 7 and autonomously detect information regarding the incoming culture medium and information regarding the outgoing culture medium.

[0234] (Step S106) Next, in step S106 of Figure 8, the operator or the control device 6 determines whether the test preparation is complete based on the information regarding the incoming culture medium and the information regarding the outgoing culture medium.

[0235] The operator may review the information regarding the incoming and outgoing culture media and determine whether the test preparation is complete.

[0236] Furthermore, the control device 6 may determine whether or not the test preparation is complete based on the information regarding the incoming culture medium and the information regarding the outgoing culture medium entered by the operator.

[0237] One example of a condition for completing test preparation (hereinafter referred to as "completion condition") is when the information regarding the incoming medium and the outgoing medium indicates that the target cells in the cell containment space 51a have grown sufficiently. Another example of a completion condition is when the information regarding the incoming medium and the outgoing medium indicates that a problem has occurred with the target cells in the cell containment space 51a.

[0238] If it is determined in step S106 that the test preparation is complete (YES in step S106), the operator or the control device 6 proceeds to step S107.

[0239] Furthermore, if it is determined in step S106 that there is a problem with the target cells in the cell containment space 51a, the operator or the control device 6 may terminate the cell culture.

[0240] If it is determined in step S106 that the test preparation is not complete ("NO" in step S106), the operator or the control device 6 proceeds to step S105. In this case, the monitoring process is repeated in step S105.

[0241] The steps S104 to S106 described above constitute the cell culture process. The operator may perform steps other than those described above during the cell culture process.

[0242] Next, the operator performs a test process using the biomimetic system 1 to conduct the desired test on the target cells. The test process is described below. The operator or the control device 6 is the entity that performs the test process.

[0243] The target cells cultured in the cell culture process described above correspond to animal cells in animal testing. If the target cells are cells that make up an animal organ (for example, liver, heart, kidney, or pancreas), the microfluidic device 5 can be considered an organ-mimicking model that reproduces the function of the animal organ. Hereinafter, animal organs will be referred to as target organs.

[0244] In this case, the biomimetic unit 3 can be considered an animal biomimetic model that mimics the biological environment of an animal, including the target organ. The target cells may be normal cells (hereinafter referred to as "normal cells") or diseased cells (hereinafter referred to as "disease cells").

[0245] (Step S107) In step S107 of Figure 8, the operator performs a test on the target cells. The test is, for example, a test to confirm the safety and efficacy of a newly generated compound (hereinafter referred to as the "test substance") in drug discovery. The type of test may be selected as appropriate depending on the purpose.

[0246] Furthermore, if the purpose is cell culture, the testing step may be omitted. In this case, the operator may perform observation or analysis of the cultured target cells instead of the testing step.

[0247] In the testing process, when confirming the safety and efficacy of a test substance, the operator, for example, adds the test substance to the culture medium in the reservoir tank 31. The culture medium containing the test substance then circulates within the biomimetic unit 3. When the culture medium containing the test substance flows into the microfluidic device 5, the test substance is supplied to the target cells.

[0248] In this process, the operator can confirm the effect of the test substance based on the information regarding the incoming and outgoing culture media detected by the detection device (not shown).

[0249] Specifically, the efficacy and pharmacology of the test substance can be confirmed based on the glucose and lactate concentrations in the influent and efflux media. The type of information obtained in the test to evaluate the test substance will be appropriately selected according to the type and purpose of the test.

[0250] Furthermore, the operator can confirm the effect of the test substance by observing the target cells within the microfluidic device 5.

[0251] The operator observes the target cells using a microscope or other device while the cells are contained within the microfluidic device 5. In this case, it is desirable that the microfluidic device 5 be made of a transparent material that allows the cell containment space 51a to be viewed from the outside.

[0252] Furthermore, the operator may observe the target cells extracted from the microfluidic device 5. In this case, it is desirable that the microfluidic device 5 has a structure that allows the target cells to be extracted from the cell containment space 51a.

[0253] Afterward, the worker terminates the test at the desired time.

[0254] (Operation and Effects of this Embodiment) In the biomimetic system 1 of this embodiment, having the configuration described above, the extraction unit 35 extracts a small amount of inflow medium and a small amount of outflow medium to the outside of the biomimetic unit 3 (in other words, the flow path L13 and flow path L15). Then, information about the inflow medium and information about the outflow medium are obtained from the extracted small amounts of inflow medium and outflow medium. For this reason, it is not necessary to install the detection device in a position that is in direct contact with the culture medium inside the biomimetic unit 3. Consequently, the material of the detection device (for example, enzymes, chemicals, metals, or polymers) does not leach into the culture medium inside the biomimetic unit 3 and adversely affect the culture environment.

[0255] Furthermore, in the biomimetic system 1 of this embodiment, it is not necessary to position the detection device in a location that directly contacts the culture medium within the biomimetic unit 3. Therefore, the detection device does not undergo a chemical reaction with the target substance (for example, glucose and lactic acid), and no reaction products are produced. Consequently, such reaction products do not adversely affect the culture environment.

[0256] Furthermore, in the biomimetic system 1 of this embodiment, it is not necessary to position the detection device in a location that directly contacts the culture medium within the biomimetic unit 3. Therefore, there is no need to secure space for arranging the detection device within the microfluidic device 5, which enables miniaturization of the microfluidic device 5.

[0257] Furthermore, in the biomimetic system 1 according to this embodiment, the microfluidic device 5 (specifically, the bubble removal unit 55) and the culture medium preparation unit 34 remove bubbles from the culture medium circulating in the biomimetic unit 3. If bubbles are present in the culture medium, adverse effects such as damage to target cells, disruption of the culture medium flow, decreased measurement accuracy of the flow meter 33, and decreased performance of the pump 32 may occur. The biomimetic system 1 according to this embodiment can suppress such adverse effects of bubbles.

[0258] Furthermore, in the biomimetic system 1 according to this embodiment, oxygen is introduced into the culture medium circulating through the biomimetic unit 3 by the microfluidic device 5 (specifically, the oxygen introduction unit 54) and the culture medium preparation unit 34. Since cells consume oxygen, supplying appropriate oxygen to the culture medium can suppress hypoxic conditions and improve cell viability. In addition, supplying appropriate oxygen to the culture medium is extremely important when the biomimetic system 1 mimics the biological environment of animals or humans. Moreover, if the culture medium is in a hypoxic state, the cell's response to the test substance may change, potentially leading to erroneous evaluation results in the testing process. In the biomimetic system 1 according to this embodiment, the oxygen concentration of the culture medium can be maintained at an appropriate concentration, thus enabling highly accurate evaluation results in the testing process.

[0259] [Embodiment 2] Next, with reference to Figure 9, a biomimetic system 1B according to Embodiment 2 of the present invention will be described. Figure 9 is a diagram corresponding to Figure 2 described above, and is a block diagram showing the functional configuration of the biomimetic system 1B.

[0260] The configuration of the biomimetic system 1B according to this embodiment will be described below. The biomimetic system 1B has a configuration common to the biomimetic system 1 according to Embodiment 1 described above (hereinafter referred to as the "common configuration"). A detailed explanation of the common configuration will be omitted, and the explanation of the common configuration in Embodiment 1 described above can be appropriately adapted and used as needed.

[0261] Furthermore, the biomimetic system 1B has a configuration different from the biomimetic system 1 according to Embodiment 1 described above (hereinafter referred to as "additional configuration"). Such additional configuration can also be applied to the biomimetic system 1 according to Embodiment 1 described above, to the extent that it is not technically contradictory. The following description will focus on the additional configuration of the biomimetic system 1B.

[0262] In Figure 9, the reference numerals for common components are the same as those for common components in Embodiment 1 described above. Furthermore, the biomimetic system 1B according to this embodiment is also used in a state where it is placed within the culture apparatus 9 shown in Figure 1. Therefore, the description of the culture apparatus 9 can be appropriately based on the description of the culture apparatus 9 in Embodiment 1 described above. In addition, Figures 3 and 8 may be appropriately referenced in the description of the biomimetic system 1B according to this embodiment.

[0263] The biomimetic system 1B comprises a housing 2, a biomimetic unit 3B, and a control device 6. The configuration of the housing 2 and the control device 6 is the same as that of the housing 2 and the control device 6 in the embodiment 1 described above.

[0264] (Biomimic Unit) The biomimetic unit 3B has a reservoir tank 31, a pump 32, a flow meter 33, a culture medium preparation unit 34, a microfluidic device 5, and an extraction unit 35, which are common components with the biomimetic unit 3 in the above-described embodiment 1.

[0265] Furthermore, the biomimetic unit 3B has a common configuration with the biomimetic unit 3 in the above-described embodiment 1, which includes multiple channels L11 to L15 connecting these elements 31 to 35 and the microfluidic device 5. Therefore, the biomimetic system 1B is a circulating biomimetic system.

[0266] Furthermore, the biomimetic unit 3B includes a detection device 7 as an additional component to the biomimetic unit 3 in the above-described embodiment 1. The detection device 7 will be described below.

[0267] In the monitoring process shown in step S105 of Figure 8, the detection device 7 automatically detects information about the incoming medium from the small amount of incoming medium contained in the incoming medium receiving section 212.

[0268] Furthermore, in the monitoring process shown in step S105 of Figure 8, the detection device 7 automatically detects information about the effluent medium from the small amount of effluent medium contained in the effluent medium receiving section 213.

[0269] The detection operation of the detection device 7 is controlled by the control device 6. Therefore, the detection device 7 is connected to the control device 6. The detection device 7 and the control device 6 are connected by wired or wireless communication means. Note that in Figure 9, the means for connecting the detection device 7 and the control device 6 are omitted.

[0270] The detection device 7 is placed in the culture space 911 of the culture apparatus 9 when in use. From the viewpoint of miniaturizing the biomimetic unit 3B, it is desirable that the detection device 7 be unitized with the housing 2 by a support member (not shown).

[0271] The detection device 7 includes an inlet-side sensor 71 and an outlet-side sensor 72.

[0272] The inflow-side sensor 71 is an example of an inflow-side detection unit. The inflow-side sensor 71 detects information about the inflow medium from the small amount of inflow medium contained in the inflow-side medium receiving unit 212.

[0273] In this embodiment, the inflow sensor 71 detects information regarding the incoming culture medium at a predetermined first time interval (for example, 1 minute). The first time interval may be 30 seconds or longer. The first time interval may be set as appropriate.

[0274] Furthermore, the outflow-side sensor 72 is an example of an outflow-side detection unit. The outflow-side sensor 72 detects information about the outflow medium from the small amount of outflow medium contained in the outflow-side medium receiving unit 213.

[0275] In this embodiment, the outflow sensor 72 detects information regarding the incoming culture medium at a predetermined second time interval (for example, 1 minute). The second time interval may be 30 seconds or longer. The second time interval may be set as appropriate.

[0276] From the viewpoint of suppressing contamination of the inflow-side sensor 71, it is desirable that the inflow-side sensor 71 be stored in a predetermined position in the culture space 911 when it is not detecting information about the inflow culture medium. In this case, it is desirable that the detection device 7 be provided with means for positioning the inflow-side sensor 71 in the inflow-side culture medium receiving section 212 when it is detecting information about the inflow culture medium.

[0277] Furthermore, from the viewpoint of suppressing contamination of the outflow-side sensor 72, it is desirable that the outflow-side sensor 72 be stored in a predetermined position in the culture space 911 when it is not detecting information about the outflow culture medium. In this case, it is desirable that the detection device 7 be provided with means for positioning the outflow-side sensor 72 in the outflow-side culture medium receiving section 213 when it is detecting information about the outflow culture medium.

[0278] The detection device 7 sends the acquired information regarding the incoming and outgoing culture media to the control device 6. Based on the information regarding the incoming and outgoing culture media acquired from the detection device 7, the control device 6 controls the operation of the biomimetic unit 3B (specifically, the pump 32).

[0279] Furthermore, the control device 6 determines in step S106 of Figure 8 whether or not the test preparation is complete, based on the information regarding the incoming culture medium and the information regarding the outgoing culture medium obtained from the detection device 7.

[0280] According to the biomimetic system 1B of this embodiment, which has the configuration described above, in the monitoring step shown in step S105 of Figure 8, the detection device 7 automatically acquires information regarding the incoming culture medium and the outgoing culture medium. This configuration automates the monitoring step of the biomimetic system 1B. The other operations and effects of the biomimetic system 1B according to this embodiment are the same as those of the biomimetic system 1 according to Embodiment 1 described above.

[0281] [Embodiment 3] Next, with reference to Figure 10, a biomimetic system 1C according to Embodiment 3 of the present invention will be described. Figure 10 is a diagram corresponding to Figure 2 described above, and is a block diagram showing the functional configuration of the biomimetic system 1C.

[0282] The configuration of the biomimetic system 1C according to this embodiment will be described below. The biomimetic system 1C has a common configuration with the biomimetic systems 1 and 1B according to embodiments 1 and 2 described above. A detailed explanation of such a common configuration will be omitted, and the explanation of the common configuration in embodiments 1 and 2 described above can be appropriately adapted and used.

[0283] Furthermore, the biomimetic system 1C has a configuration different from that of the biomimetic systems 1 and 1B according to the embodiments 1 and 2 described above (hereinafter referred to as "additional configuration"). Such additional configuration can also be applied to the biomimetic systems 1 and 1B according to the embodiments 1 and 2 described above, to the extent that it is not technically contradictory. The following description will focus on the additional configuration of the biomimetic system 1C.

[0284] In Figure 10, the reference numerals for common components are the same as those for common components in Embodiments 1 and 2 described above. Furthermore, the biomimetic system 1C according to this embodiment is also used in a state where it is placed within the culture apparatus 9 shown in Figure 1. Therefore, the description of the culture apparatus 9 can be appropriately based on the description of the culture apparatus 9 in Embodiment 1 described above. In addition, Figures 3 and 8 may be appropriately referenced in the description of the biomimetic system 1C according to this embodiment.

[0285] The biomimetic system 1C comprises a housing 2, a biomimetic unit 3C, and a control device 6. The configuration of the housing 2 and the control device 6 is the same as that of the housing 2 and the control device 6 in the embodiment 1 described above.

[0286] (Biomimetic Unit) The biomimetic unit 3C has a reservoir tank 31, a pump 32, a flow meter 33, a culture medium preparation unit 34, a microfluidic device 5, and an extraction unit 35, which are common components with the biomimetic unit 3 in the above-described embodiment 1.

[0287] The biomimetic unit 3C has a plurality of channels L11 to L15 connecting these elements 31 to 34 and the microfluidic device 5, which are common to the biomimetic unit 3 in the above-described embodiment 1. Therefore, the biomimetic system 1C is a circulating biomimetic system.

[0288] The biomimetic unit 3C has a detection device 7 that is a common configuration with the biomimetic unit 3B in the above-described embodiment 2.

[0289] Furthermore, the biomimetic unit 3C includes a real-time monitoring sensor 36C as an additional component to the biomimetic units 3 and 3B in the embodiments 1 and 2 described above. The real-time monitoring sensor 36C will be described below.

[0290] The real-time monitoring sensor 36C is installed inside the reservoir tank 31. The real-time monitoring sensor 36C acquires information about the culture medium (hereinafter referred to as "storage medium") inside the reservoir tank 31 in real time.

[0291] Information regarding the storage medium includes the concentration of glucose and / or lactate contained in the storage medium. Such information regarding the storage medium is used to understand and manage the overall status of the biomimetic unit 3C. Information regarding the storage medium may also include the concentration of oxygen contained in the storage medium and / or the pH of the storage medium.

[0292] The real-time monitoring sensor 36C may be any biosensor capable of acquiring information about the stored medium in the reservoir tank 31 in real time. The information about the stored medium may include the concentration of albumin, ammonia, and / or urea contained in the stored medium.

[0293] The operation of the real-time monitoring sensor 36C is controlled by the control device 6. Therefore, the real-time monitoring sensor 36C is connected to the control device 6. The real-time monitoring sensor 36C and the control device 6 are connected by wired or wireless communication means. Note that in Figure 10, the means for connecting the real-time monitoring sensor 36C and the control device 6 are omitted.

[0294] The real-time monitoring sensor 36C sequentially sends information about the storage medium to the control device 6. Based on the information about the storage medium obtained from the real-time monitoring sensor 36C, the control device 6 grasps and manages the status of the entire biomimetic unit 3.

[0295] Specifically, the control device 6 may control the operation of the pump 32 (in other words, the discharge volume) based on information about the stored culture medium obtained from the real-time monitoring sensor 36C.

[0296] Furthermore, the control device 6 may notify the user of the overall status of the biomimetic unit 3 based on information about the storage medium obtained from the real-time monitoring sensor 36C. The control device 6 may also display the overall status of the biomimetic unit 3 on a display device (not shown) connected to the control device 6.

[0297] In the biomimetic system 1C according to this embodiment, which has the configuration described above, the control device 6 can grasp and manage the status of the entire biomimetic unit 3 based on information about the storage medium obtained from the real-time monitoring sensor 36C. This improves the reproducibility of cell culture and allows for the acquisition of uniform and high-quality cells in the culture process. Furthermore, this improves the accuracy of tests in the testing process and increases the reliability of test results. In addition, the reduction in cell culture failures can reduce the cost of cell culture. Other functions and effects of the biomimetic system 1C according to this embodiment are the same as those of the biomimetic systems 1 and 1B according to embodiments 1 and 2 described above.

[0298] [Embodiment 4] Next, with reference to Figure 11, the biomimetic system 1D according to Embodiment 4 of the present invention will be described. Figure 11 is a diagram corresponding to Figure 2 described above, and is a block diagram showing the functional configuration of the biomimetic system 1D.

[0299] Hereinafter, the configuration of the biomimetic system 1D according to the present embodiment will be described. The biomimetic system 1D has a common configuration with the biomimetic system 1 according to the first embodiment described above. Detailed description of such a common configuration is omitted, and the description of the common configuration in the first embodiment described above can be appropriately read and incorporated herein by reference.

[0300] In addition, the biomimetic system 1D has a configuration different from that of the biomimetic system 1 according to the first embodiment described above (hereinafter referred to as "additional configuration"). Such an additional configuration can also be applied to the biomimetic system 1 according to the first embodiment described above within a technically consistent range. Hereinafter, the description will focus on the additional configuration included in the biomimetic system 1D.

[0301] In Fig. 11, the reference numerals of the common configuration are the same as the reference numerals of the common configuration in the first embodiment described above. The biomimetic system 1D according to the present embodiment is also used in a state of being disposed in the culture apparatus 9 shown in Fig. 1. Therefore, for the description of the culture apparatus 9, the description of the culture apparatus 9 in the first embodiment described above can be appropriately incorporated herein by reference. Furthermore, in the description of the biomimetic system 1D according to the present embodiment, Fig. 3 and Fig. 8 may be appropriately incorporated herein by reference.

[0302] The biomimetic system 1D includes a housing 2, a biomimetic unit 3D, and a control device 6. The configurations of the housing 2 and the control device 6 are the same as the configurations of the housing 2 and the control device 6 in the first embodiment described above.

[0303] (Biomimetic Unit) The biomimetic unit 3D includes a reservoir tank 31, a pump 32, a flow meter 33, a medium adjustment unit 34, a microchannel device 5, and an extraction unit 35 as a common configuration with the biomimetic unit 3 in the first embodiment described above.

[0304] The biomimetic unit 3D includes a plurality of channels L11 to L15 connecting each of these elements 31 to 35 and the microchannel device 5 ａ . The channels L11 to L14 are a common configuration with the biomimetic unit 3 in the first embodiment described above. However, the channel L15 ａIn this case, the element to be connected is different from the flow path L15 in the embodiment 1 described above.

[0305] In the biomimetic unit 3D according to this embodiment, L15 ａ The upstream end of is connected to the culture medium outflow section 53 (see Figure 7) of the microfluidic device 5. Also, L15 ａ The downstream end of the device is not connected to the reservoir tank 31, but is connected to the discharge tank 37D.

[0306] The biomimetic unit 3D includes a discharge tank 37D as an additional component to the biomimetic unit 3 in the above-described embodiment 1. The discharge tank 37D is located downstream of the microfluidic device 5.

[0307] Discharge tank 37D is L15 ａ It is connected to the microfluidic device 5 via this. Such a discharge tank 37D contains the culture medium that flows out from the microfluidic device 5 (i.e., the discharged culture medium).

[0308] In this embodiment, the biomimetic unit 3D has an outflow side extraction unit 352 of the extraction unit 35, which is located in the flow path L15. ａ It is located in the flow path L15. Therefore, the outflow side extraction unit 352 is located in the flow path L15. ａ A small amount of culture medium is extracted from the flowing culture medium (i.e., the effluent culture medium) and brought to the outside. In addition, the configuration of the effluent side extraction unit 352 in this embodiment is the same as the configuration of the effluent side extraction unit 352 in the above-described embodiment 1.

[0309] As described above, the elements 5, 35-34 that constitute the biomimetic unit 3D are not connected in a ring. Therefore, the culture medium delivered by the pump 32 flows only in one direction within the biomimetic unit 3D, from the reservoir tank 31 to the discharge tank 37D, and does not circulate. Such a biomimetic system is called a "non-circulating biomimetic system" or a "one-way biomimetic system."

[0310] In the biomimetic system 1D according to this embodiment, which has the configuration described above, the culture medium that has passed through the microfluidic device 5 (i.e., the efflux medium) is discharged into the discharge tank 37D. As a result, the culture medium that has effluxed from the microfluidic device 5 (i.e., the efflux medium) does not pass through the microfluidic device 5 again. With this configuration, the microfluidic device 5 can be constantly supplied with fresh culture medium (i.e., the influx medium). Since the biomimetic system 1D according to this embodiment does not reuse the culture medium and can always maintain a fresh state, it is effective in stabilizing the supply of nutrients to the target cells in the microfluidic device 5 and maintaining an optimal culture environment.

[0311] Furthermore, in the biomimetic system 1D according to this embodiment, the state of the culture medium supplied to the microfluidic device 5 is maintained at a constant level, so that nutrients (i.e., glucose) can be stably supplied to the target cells in the microfluidic device 5 during the cell culture process. This makes it possible to obtain stable culture results in the cell culture process. After performing the cell culture process with the biomimetic system 1D according to this embodiment, the testing process can also be performed with the biomimetic system 1 in Embodiment 1 described above. In this case, it is desirable that the biomimetic system 1D be configured so that the operator can switch to the configuration of the biomimetic system 1 in Embodiment 1. The other functions and effects of the biomimetic system 1D according to this embodiment are the same as those of the biomimetic systems 1, 1B, and 1C according to Embodiments 1 to 3 described above.

[0312] [Embodiment 5] Next, with reference to Figure 12, a biomimetic system 1E according to Embodiment 5 of the present invention will be described. Figure 12 is a diagram corresponding to Figures 2 and 11 described above, and is a block diagram showing the functional configuration of the biomimetic system 1E.

[0313] The configuration of the biomimetic system 1E according to this embodiment will be described below. The biomimetic system 1E has a common configuration with the biomimetic systems 1 and 1D according to Embodiment 4 described above. A detailed explanation of such a common configuration will be omitted, and the explanation of the common configuration in Embodiments 1 and 4 described above can be appropriately adapted and used as needed.

[0314] Furthermore, the biomimetic system 1E has a configuration that differs from the biomimetic system 1D according to Embodiment 4 described above (hereinafter referred to as the "additional configuration"). Except for the additional configuration, the configuration of the biomimetic system 1E is the same as that of the biomimetic system 1D according to Embodiment 4 described above. The following description will focus on the additional configuration of the biomimetic system 1E. The additional configuration can also be applied to the biomimetic system 1D according to Embodiment 4 described above, to the extent that it is not technically contradictory.

[0315] Furthermore, in Figure 12, the reference numerals for common components are the same as those for common components in Embodiments 1 and 4 described above. Also, the biomimetic system 1E according to this embodiment is used in a state where it is placed inside the culture apparatus 9 shown in Figure 1. Therefore, the description of the culture apparatus 9 can be appropriately adapted from the description of the culture apparatus 9 in Embodiment 1 described above. Furthermore, in the description of the biomimetic system 1E according to this embodiment, Figures 3 and 8 may also be appropriately adapted.

[0316] The biomimetic system 1E comprises a housing 2, a biomimetic unit 3E, and a control device 6. The configuration of the housing 2 and the control device 6 is the same as that of the housing 2 and the control device 6 in the embodiments 1 and 4 described above.

[0317] (Biomimic Unit) The biomimetic unit 3E has a reservoir tank 31, a pump 32, a flow meter 33, a culture medium preparation unit 34, a microfluidic device 5, an extraction unit 35, and a discharge tank 37D, which are common components with the biomimetic unit 3D in the above-described embodiment 4.

[0318] Furthermore, the biomimetic unit 3E has multiple channels L11 to L15 connecting these elements 31 to 35, 37D and the microfluidic device 5. ａ It has. Flow paths L11 to L15 ａ This is a common configuration with the biomimetic unit 3D in the above-described embodiment 4. Therefore, the biomimetic unit 3E is a non-circular biomimetic system.

[0319] The biomimetic unit 3E includes a detection device 7 as an additional component to the biomimetic unit 3D in the above-described embodiment 4. The configuration of the detection device 7 is the same as that of the detection device 7 in the above-described embodiment 2. Therefore, the description of the detection device 7 in the above-described embodiment 2 may be appropriately adapted and used in reference to the detection device 7.

[0320] According to the biomimetic system 1E of this embodiment, which has the configuration described above, in the monitoring step shown in step S105 of Figure 8, the detection device 7 automatically acquires information regarding the incoming culture medium and information regarding the outgoing culture medium. This configuration automates the monitoring step of the biomimetic system 1E. The other functions and effects of the biomimetic system 1E according to this embodiment are the same as those of the biomimetic systems 1 and 1D according to embodiments 1 and 4 described above.

[0321] [Embodiment 6] Next, with reference to Figure 13, the biomimetic system 1F according to Embodiment 6 of the present invention will be described. Figure 13 is a diagram corresponding to Figures 2 and 11 described above, and is a block diagram showing the functional configuration of the biomimetic system 1F.

[0322] The configuration of the biomimetic system 1F according to this embodiment will be described below. The biomimetic system 1F has a common configuration with the biomimetic systems 1, 1D, and 1E according to embodiments 1, 4, and 5 described above. A detailed explanation of such a common configuration will be omitted, and the explanation of the common configuration in embodiments 1, 4, and 5 described above can be appropriately adapted and used as needed.

[0323] Furthermore, the biomimetic system 1F has a different configuration (hereinafter referred to as the "additional configuration") from the biomimetic system 1E according to the above-described embodiment 5. Except for the additional configuration, the configuration of the biomimetic system 1F is the same as that of the biomimetic system 1E according to the above-described embodiment 5. The following description will focus on the additional configuration of the biomimetic system 1F. The additional configuration can also be applied to the biomimetic system 1E according to the above-described embodiment 5, to the extent that it is not technically contradictory.

[0324] Furthermore, in Figure 13, the reference numerals for common components are the same as those for common components in Embodiments 1, 4, and 5 described above. Also, the biomimetic system 1F according to this embodiment is used in a state where it is placed inside the culture apparatus 9 shown in Figure 1. Therefore, the description of the culture apparatus 9 can be appropriately adapted from the description of the culture apparatus 9 in Embodiment 1 described above. Furthermore, in the description of the biomimetic system 1E according to this embodiment, Figures 3 and 8 will be appropriately adapted.

[0325] The biomimetic system 1F comprises a housing 2, a biomimetic unit 3F, and a control device 6. The configuration of the housing 2 and the control device 6 is the same as that of the housing 2 and the control device 6 in the embodiments 1, 4, and 5 described above.

[0326] (Biomimic Unit) The biomimetic unit 3F has a reservoir tank 31, a pump 32, a flow meter 33, a culture medium preparation unit 34, a microfluidic device 5, an extraction unit 35, a discharge tank 37D, and a detection device 7, which are common components with the biomimetic unit 3E in the above-described embodiment 5.

[0327] Furthermore, the biomimetic unit 3F has multiple channels L11 to L15 connecting these elements 31 to 35, 37D and the microfluidic device 5. ａ It has. Flow paths L11 to L15 ａ This is a common configuration with the biomimetic unit 3E in the above-described embodiment 5. Therefore, the biomimetic unit 3F is a non-circular biomimetic system.

[0328] The biomimetic unit 3F includes a real-time monitoring sensor 36C as an additional component to the biomimetic unit 3E in the above-described embodiment 5.

[0329] In this embodiment, the real-time monitoring sensor 36C is located inside the discharge tank 37D. Therefore, the real-time monitoring sensor 36C acquires information about the discharge medium in real time from the culture medium (i.e., the discharged culture medium) inside the discharge tank 37D.

[0330] The configuration of the other real-time monitoring sensor 36C is the same as that of the real-time monitoring sensor 36C in Embodiment 3 described above. Therefore, the description of the real-time monitoring sensor 36C in Embodiment 3 described above may be appropriately adapted and applied to the real-time monitoring sensor 36C in this embodiment.

[0331] According to the biomimetic system 1F of this embodiment, which has the configuration described above, the control device 6 can grasp and manage the status of the entire biomimetic unit 3F based on the information on the discharged culture medium obtained from the real-time monitoring sensor 36C. This improves the reproducibility of cell culture and allows for the acquisition of uniform and high-quality cells in the culture process. Furthermore, this improves the accuracy of tests in the testing process and increases the reliability of test results. In addition, the reduction in cell culture failures can reduce the cost of cell culture. Other functions and effects of the biomimetic system 1F according to this embodiment are the same as those of the biomimetic systems 1, 1D, and 1E according to embodiments 1, 4, and 5 described above.

[0332] [Embodiment 7] Next, with reference to Figure 14, the biomimetic system 1G according to Embodiment 7 of the present invention will be described. Figure 14 is a diagram corresponding to Figure 2 described above, and is a block diagram showing the functional configuration of the biomimetic system 1G.

[0333] The configuration of the biomimetic system 1G according to this embodiment will be described below. The biomimetic system 1G has a common configuration with the biomimetic systems 1, 1B, and 1C according to embodiments 1 to 3 described above. A detailed explanation of such a common configuration will be omitted, and the explanation of the common configuration in embodiments 1 to 3 described above can be appropriately adapted and used as needed.

[0334] Furthermore, the biomimetic system 1G has a configuration different from that of the biomimetic systems 1, 1B, and 1C according to the embodiments 1 to 3 described above (hereinafter referred to as "additional configuration"). Such additional configuration can also be applied to the biomimetic systems 1, 1B, and 1C according to the embodiments 1 to 3 described above, to the extent that it is not technically contradictory. The following description will focus on the additional configuration of the biomimetic system 1G.

[0335] In Figure 14, the reference numerals for common components are the same as those for common components in Embodiments 1 to 3 described above. Furthermore, the biomimetic system 1G according to this embodiment is also used in a state where it is placed within the culture apparatus 9 shown in Figure 1. Therefore, the description of the culture apparatus 9 can be appropriately based on the description of the culture apparatus 9 in Embodiment 1 described above. In addition, Figures 3 and 8 may be appropriately referenced in the description of the biomimetic system 1G according to this embodiment.

[0336] The biomimetic system 1G comprises a housing 2, a biomimetic unit 3G, and a control device 6. The configuration of the housing 2 and the control device 6 is the same as that of the housing 2 and the control device 6 in the above-described embodiment 1.

[0337] (Biomimetic Unit) The biomimetic unit 3G has a reservoir tank 31, a pump 32, a flow meter 33, a culture medium preparation unit 34, a microfluidic device 5, and an extraction unit 35, which are common components with the biomimetic unit 3 in the embodiments 1 to 3 described above.

[0338] Furthermore, the biomimetic unit 3G has a detection device 7 as a common configuration with the biomimetic unit 3B in the above-described embodiment 2. In addition, the biomimetic unit 3G has a real-time monitoring sensor 36C as a common configuration with the biomimetic unit 3C in the above-described embodiment 3.

[0339] The biomimetic unit 3G has a plurality of channels L11 to L15 connecting these elements 31 to 35 and the microfluidic device 5, which are common to the biomimetic unit 3 in the above-described embodiment 1. Therefore, the biomimetic system 1G is a circulating biomimetic system.

[0340] Furthermore, the biomimetic unit 3G includes a culture medium supply unit 38G and a test substance supply unit 39G as additional components to the biomimetic units 3, 3B, and 3C in the embodiments 1 to 3 described above. The culture medium supply unit 38G and the test substance supply unit 39G will be described below.

[0341] The culture medium supply unit 38G supplies new culture medium (hereinafter referred to as "additional culture medium") to the culture medium flowing into the microfluidic device 5 (i.e., the incoming culture medium). The culture medium supply unit 38G is located at a predetermined position in the flow path L13. For the sake of explanation, in Figure 14, the flow path L13 is shown as three flow paths L13 ａ , L13 ｂ , L13 ｃ I will explain it in two parts.

[0342] Specifically, the culture medium supply unit 38G is located downstream of the flow meter 33 and upstream of the test substance supply unit 39G. The culture medium flowing out from the flow meter 33 flows through the channel L13. ａ It flows into the culture medium supply unit 38G through the channel L13. ａ It is connected to the flow meter 33.

[0343] The culture medium supply unit 38G supplies additional culture medium to the culture medium passing through it, under the control of the control device 6. Therefore, the culture medium supply unit 38G is connected to the control device 6 by wired or wireless communication means. Note that in Figure 14, the means for connecting the culture medium supply unit 38G and the control device 6 are omitted.

[0344] The supplemental culture medium contains glucose at a predetermined concentration. The supplemental culture medium may also contain components other than glucose.

[0345] The control device 6 controls the operation of the culture medium supply unit 38G based on information regarding the incoming culture medium and the outgoing culture medium obtained from the detection device 7. Furthermore, the control device 6 controls the operation of the culture medium supply unit 38G based on information regarding the stored culture medium obtained from the real-time monitoring sensor 36C. The control device 6 is an example of a culture medium supply control unit.

[0346] The culture medium supply unit 38G may have a function to adjust the amount of additional culture medium supplied in accordance with the instructions of the control device 6. The culture medium supply unit 38G may also have a function to adjust the concentration of glucose contained in the additional culture medium. The operation of the culture medium supply unit 38G is set appropriately according to the purpose of the culture and testing processes.

[0347] The test substance supply unit 39G supplies the test substance to the culture medium (i.e., the inflow medium) flowing into the microfluidic device 5. The culture medium supply unit 38G is provided at a predetermined position in the flow path L13.

[0348] Specifically, the test substance supply unit 39G is located downstream of the culture medium supply unit 38G and upstream of the culture medium preparation unit 34. The test substance supply unit 39G is located in the flow path L13 ｂ It is connected to the culture medium supply unit 38G by the flow path L13. ｃ It is connected to the culture medium preparation unit 34.

[0349] The culture medium that flows out from the culture medium supply unit 38G (i.e., the incoming culture medium) flows through the channel L13 ｂ It flows into the test substance supply unit 39G through this.

[0350] The test substance supply unit 39G supplies the test substance to the culture medium passing through it, under the control of the control device 6. Therefore, the test substance supply unit 39G is connected to the control device 6 by wired or wireless communication means. Note that in Figure 14, the means for connecting the test substance supply unit 39G and the control device 6 are omitted.

[0351] The control device 6 controls the operation of the test substance supply unit 39G based on the information regarding the influent medium and the outfluent medium obtained from the detection device 7. In this case, the information regarding the influent medium may include the concentration of glucose, the concentration of lactic acid, and the concentration of the test substance contained in the influent medium. The information regarding the outfluent medium may also include the concentration of glucose, the concentration of lactic acid, and the concentration of the test substance contained in the outfluent medium. Furthermore, the information regarding the influent medium may include the concentration of albumin, the concentration of ammonia, and / or the concentration of urea contained in the influent medium. Furthermore, the information regarding the outfluent medium may include the concentration of albumin, the concentration of ammonia, and / or the concentration of urea contained in the outfluent medium.

[0352] Furthermore, the control device 6 controls the operation of the test substance supply unit 39G based on information about the storage medium obtained from the real-time monitoring sensor 36C. In this case, the information about the storage medium may include the concentration of glucose, the concentration of lactic acid, and the concentration of the test substance contained in the storage medium. The control device 6 is an example of a test substance supply control unit.

[0353] The test substance supply unit 39G may have a function to adjust the amount of test substance supplied to the culture medium preparation unit 34 in accordance with the instructions of the control device 6. The operation of supplying the test substance by such a test substance supply unit 39G is set as appropriate depending on the purpose in the culture process and the testing process.

[0354] As described above, in the biomimetic unit 3G of this embodiment, the culture medium supply unit 38G, the test substance supply unit 39G, the inflow side extraction unit 351, the microfluidic device 5, and the outflow side extraction unit 352 are arranged in that order from the upstream side.

[0355] Thus, in this embodiment, the extraction unit 35 passes through the culture medium supply unit 38G and the test substance supply unit 39G to the flow path L13 ｃ A small amount of culture medium is extracted from the culture medium flowing through it (i.e., the inflow medium) and brought to the outside. The other components of biomimetic system 1G are the same as those of biomimetic systems 1, 1B, and 1C according to embodiments 1 to 3 described above.

[0356] In the biomimetic system 1G according to this embodiment, having the above configuration, the culture medium supply unit 38G can add culture medium according to the state of the culture medium in the biomimetic unit 3G. This allows for the maintenance of an optimal culture environment by replenishing fresh culture medium even if glucose becomes insufficient during cell culture. Furthermore, since fresh culture medium can be supplied to the biomimetic unit 3G, long-term culture is possible. In addition, the additionally supplied culture medium dilutes waste products such as lactic acid produced by cell metabolism, thereby suppressing the adverse effects of these waste products on cells. Moreover, by keeping the components of the culture medium in the biomimetic unit 3G constant, it is possible to suppress variability in test results during the testing process.

[0357] Furthermore, in the biomimetic system 1G according to this embodiment, the test substance supply unit 39G can add the test substance according to the culture status of the target cells in the biomimetic unit 3G. This allows the test substance to be added at the appropriate timing according to the culture status of the target cells, making it easier to evaluate the effects of stepwise administration and changes in concentration of the test substance. In addition, since the test substance can be added according to the concentration of the test substance contained in the culture medium, the state of the culture medium can be optimally maintained. This allows the concentration of the test substance in the culture medium to be kept constant, thereby suppressing variability in test results during the testing process. Moreover, since the test substance can be added at the appropriate timing according to the culture status of the target cells, tests can be conducted considering the consumption of the test substance, and data closer to actual clinical trials can be obtained.

[0358] Furthermore, the other functions and effects of the biomimetic system 1G according to this embodiment are the same as those of the biomimetic system 1 according to Embodiment 1 described above.

[0359] [Embodiment 8] Next, a biomimetic system 1H according to Embodiment 8 of the present invention will be described with reference to Figure 15A. Figure 15A is a diagram corresponding to Figure 2 described above, and is a block diagram showing the functional configuration of the biomimetic system 1H. Note that in Figure 15A, the reservoir tank 31, pump 32, and flow meter 33 shown in Figure 2 are omitted.

[0360] The configuration of the biomimetic system 1H according to this embodiment will be described below. The biomimetic system 1H has a configuration common to the biomimetic system 1 according to Embodiment 1 described above (hereinafter referred to as the "common configuration"). A detailed explanation of the common configuration will be omitted, and the explanation of the common configuration in Embodiment 1 described above can be appropriately adapted and used as needed.

[0361] Furthermore, the biomimetic system 1H has a configuration different from the biomimetic system 1 according to Embodiment 1 described above (hereinafter referred to as "additional configuration"). Such additional configuration can also be applied to the biomimetic system 1 according to Embodiment 1 described above, to the extent that it is not technically contradictory. The following description will focus on the additional configuration of the biomimetic system 1H.

[0362] Furthermore, the additional configurations provided by the biomimetic system 1H according to this embodiment can also be applied to the biomimetic systems according to embodiments 2 to 7 described above. In addition, the additional configurations provided by the biomimetic system 1H according to this embodiment can be applied to both circulating and non-circulating biomimetic systems.

[0363] Furthermore, in Figure 15A, the reference numerals for common components are the same as those for common components in Embodiment 1 described above. Also, the biomimetic system 1H according to this embodiment is used in a state where it is placed inside the culture apparatus 9 shown in Figure 1. Therefore, the description of the culture apparatus 9 can be appropriately adapted from the description of the culture apparatus 9 in Embodiment 1 described above. Furthermore, in the description of the biomimetic system 1H according to this embodiment, Figures 3 and 8 may also be appropriately adapted.

[0364] The biomimetic system 1H comprises a housing 2, a biomimetic unit 3H, and a control device 6. The configuration of the housing 2 and the control device 6 is the same as that of the housing 2 and the control device 6 in the above-described embodiment 1.

[0365] (Biomimic Unit) The biomimetic unit 3H includes a reservoir tank 31 (see Figure 2), a pump 32 (see Figure 2), a flow meter 33 (see Figure 2), a culture medium preparation unit 34, microfluidic devices 5a and 5b, and an extraction unit 35.

[0366] The reservoir tank 31, pump 32, flow meter 33, culture medium preparation unit 34, and extraction unit 35 have the same configuration as the biomimetic unit 3 in the above-described embodiment 1.

[0367] The biomimetic unit 3H of this embodiment differs from the biomimetic unit 3 of Embodiment 1 described above in that it comprises two microfluidic devices 5a and 5b. The configuration of the microfluidic devices 5a and 5b is the same as the configuration of the microfluidic device 5 of Embodiment 1 described above.

[0368] In the biomimetic unit 3H of this embodiment, the microfluidic device 5a and the microfluidic device 5b are connected in series.

[0369] The microfluidic device 5a is positioned upstream of the microfluidic device 5b. The downstream end of the channel L14 is connected to the culture medium inlet 52 of the microfluidic device 5a.

[0370] The upstream end of channel L16 is connected to the culture medium outlet 53 of microfluidic device 5a. Channel L16 is a channel connecting microfluidic device 5a and microfluidic device 5b. Microfluidic device 5a corresponds to an example of the furthest upstream culture vessel.

[0371] The downstream end of channel L16 is connected to the culture medium inlet 52 of the microfluidic device 5b. The upstream end of channel L15 is connected to the culture medium outlet 53 of the microfluidic device 5b. The microfluidic device 5b corresponds to an example of the furthest downstream culture vessel.

[0372] The culture medium that flows from channel L14 into microfluidic device 5a (i.e., inflow medium) flows into microfluidic device 5b through channel L16. The culture medium that flows into microfluidic device 5b then flows out of microfluidic device 5b into channel L15. The culture medium that flows out of microfluidic device 5b is called the outflow medium.

[0373] In the biomimetic unit 3H of this embodiment, the flow path L14 corresponds to an example of an inflow side flow path. Also, in the biomimetic unit 3H of this embodiment, the flow path L15 corresponds to an example of an outflow side flow path.

[0374] Furthermore, the microfluidic devices 5a and 5b each represent examples of cell containment sections. Different target cells may be contained in the microfluidic devices 5a and 5b.

[0375] In this embodiment, the biomimetic unit 3H also extracts a small amount of culture medium from the culture medium flowing through the biomimetic unit 3H and brings it outside the biomimetic unit 3H. Specifically, the inflow extraction unit 351 extracts a small amount of culture medium from the culture medium flowing through the channel L13 (i.e., the inflow medium). In other words, the inflow extraction unit 351 extracts a small amount of culture medium from the culture medium flowing into the upstream microfluidic device 5a (i.e., the inflow medium).

[0376] Furthermore, the outflow-side extraction unit 352 extracts a small amount of culture medium from the culture medium flowing through the channel L15 (i.e., the outflow medium). In other words, the outflow-side extraction unit 352 extracts a small amount of culture medium from the culture medium that has flowed out from the downstream microfluidic device 5b (i.e., the outflow medium).

[0377] In this embodiment, the biomimetic system 1H has two microfluidic devices 5a and 5b connected in series. However, the number of microfluidic devices may be three or more (for example, four).

[0378] Although not shown in the diagram, multiple microfluidic devices can also be connected in series to a single microfluidic device. The other configurations of the biomimetic system 1H according to this embodiment are the same as those of the biomimetic system 1 according to Embodiment 1 described above.

[0379] In the biomimetic system 1H according to this embodiment, which has the configuration described above, two microfluidic devices 5a and 5b are connected in series. This allows the biomimetic unit 3H to mimic the interaction between organs via blood flow in the human body (for example, the liver and kidney). In other words, the biomimetic unit 3H can create an environment that is closer to that of a human or animal. Furthermore, according to the biomimetic system 1H of this embodiment, it is possible to evaluate the effect of compounds metabolized in upstream organs (in other words, test substances) in the human or animal body on downstream organs. The other functions and effects of the biomimetic system 1H according to this embodiment are the same as those of the biomimetic system 1 according to Embodiment 1 described above.

[0380] (Modification of Embodiment 8) Next, a modification of the biomimetic system 1H according to Embodiment 8 described above will be explained with reference to Figure 15B. Figure 15B is a block diagram showing the functional configuration of the biomimetic system 1Ha, which is a modification of the biomimetic system 1H. In the following, the configuration of the biomimetic system 1Ha will be explained, focusing on the configurations that differ from those of the biomimetic system 1H.

[0381] The biomimetic system 1Ha has an extraction unit 353 provided in the flow path L16. The extraction unit 353 has an extraction flow path 353a, a first valve 353b, a second valve 353c, an extraction section 353d, and a valve drive section 353e.

[0382] The configuration of the extraction channel 353a, the first valve 353b, the second valve 353c, the extraction section 353d, and the valve drive unit 353e is substantially the same as the configuration of the outlet side extraction channel 352a, the outlet side first valve 352b, the outlet side second valve 352c, the outlet side extraction section 352d, and the outlet side valve drive unit 352e of the outlet side extraction unit 352 described above.

[0383] Therefore, the configuration of the extraction unit 353 may be appropriately adapted from the description of the outflow side extraction unit 352 mentioned above. The culture medium extracted from the flow path L16 by the extraction unit 353 is contained in the culture medium receiving section 214 provided on the base 21 of the housing 2.

[0384] When viewed with reference to the microfluidic device 5a, the extraction unit 353 can be considered as an outflow-side extraction unit. In this case, the extraction section 353d of the extraction unit 353 corresponds to an example of an outflow-side extraction section.

[0385] On the other hand, when viewed with reference to the microfluidic device 5b, the extraction unit 353 can be considered as an inflow-side extraction unit. In this case, the extraction section 353d of the extraction unit 353 corresponds to an example of an inflow-side extraction section.

[0386] Furthermore, the biomimetic system 1Ha, like the biomimetic system 1H described above, has an inflow-side extraction unit 351 provided in the flow path L13 and an outflow-side extraction unit 352 provided in the flow path L15.

[0387] In this modified example, the culture medium flowing between the microfluidic device 5a and the microfluidic device 5b can be extracted. This makes it possible to understand the state of the culture medium after it has passed through the upstream microfluidic device 5a and before it flows into the downstream microfluidic device 5b. Therefore, it becomes easier to evaluate the changes in the culture medium between the microfluidic device 5a and the microfluidic device 5b.

[0388] [Embodiment 9] Next, a biomimetic system 1J according to Embodiment 9 of the present invention will be described with reference to Figure 16. Figure 16 is a diagram corresponding to Figure 2 described above, and is a block diagram showing the functional configuration of the biomimetic system 1J. Note that in Figure 16, the reservoir tank 31, pump 32, and flow meter 33 shown in Figure 2 are omitted.

[0389] The configuration of the biomimetic system 1J according to this embodiment will be described below. The biomimetic system 1J has a configuration common to the biomimetic system 1 according to Embodiment 1 described above (hereinafter referred to as the "common configuration"). A detailed explanation of the common configuration will be omitted, and the explanation of the common configuration in Embodiment 1 described above can be appropriately adapted and used as needed.

[0390] Furthermore, the biomimetic system 1J has a configuration different from the biomimetic system 1 according to Embodiment 1 described above (hereinafter referred to as "additional configuration"). Such additional configuration can also be applied to the biomimetic system 1 according to Embodiment 1 described above, to the extent that it is not technically contradictory. The following description will focus on the additional configuration of the biomimetic system 1J.

[0391] Furthermore, the additional configuration of the biomimetic system 1J according to this embodiment can also be applied to each of the biomimetic systems according to embodiments 2 to 7 described above. In addition, the additional configuration of the biomimetic system 1H according to this embodiment can be applied to both a circulating biomimetic system and a non-circulating biomimetic system.

[0392] Furthermore, in Figure 16, the reference numerals for common components are the same as those for common components in Embodiment 1 described above. Also, the biomimetic system 1J according to this embodiment is used in a state where it is placed within the culture apparatus 9 shown in Figure 1. Therefore, the description of the culture apparatus 9 can be appropriately based on the description of the culture apparatus 9 in Embodiment 1 described above. Furthermore, Figures 3 and 8 may be appropriately referenced in the description of the biomimetic system 1J according to this embodiment.

[0393] The biomimetic system 1J comprises a housing 2, a biomimetic unit 3J, and a control device 6. The configuration of the housing 2 and the control device 6 is the same as that of the housing 2 and the control device 6 in the above-described embodiment 1.

[0394] (Biomimic Unit) The biomimetic unit 3J includes a reservoir tank 31 (see Figure 2), a pump 32 (see Figure 2), a flow meter 33 (see Figure 2), culture medium preparation units 34A and 34B, microfluidic devices 5c and 5d, and an extraction unit 35J.

[0395] The reservoir tank 31, pump 32, and flow meter 33 are common components with the biomimetic unit 3 in the above-described embodiment 1.

[0396] The biomimetic unit 3J of this embodiment differs from the biomimetic unit 3 of Embodiment 1 described above in that it comprises two microfluidic devices 5c and 5d. The configuration of the microfluidic devices 5c and 5d is the same as that of the microfluidic device 5 of Embodiment 1 described above.

[0397] In the biomimetic unit 3J of this embodiment, a microfluidic device 5c and a microfluidic device 5d are connected in parallel. Microfluidic devices 5c and 5d each correspond to an example of a cell containment section. Different target cells may be contained in the microfluidic devices 5c and 5d.

[0398] In the biomimetic unit 3J of this embodiment, the flow path L13 in the above-described embodiment 1 is replaced by three flow paths L13 ｄ , L13 ｅ , L13 ｆ It is divided into parts.

[0399] Flow path L13 ｆ The upstream end is connected to the flow meter 33. Flow path L13 ｆ The downstream end is connected to branch section 801. Flow path L13 ｆ The branching section 801 creates a flow path L13 ｅ and flow path L13 ｆ It branches into two paths.

[0400] The branching portion 801 may be configured such that the number of flow channels connected to the branching portion 801 can be increased or decreased. The number of flow channels connectable to the branching portion 801 may be appropriately determined depending on the organism mimicked by the biomimetic unit 3J.

[0401] In the biomimetic unit 3J of the present embodiment, three flow channels L13 ｄ , L13 ｅ , L13 ｆ are connected to the branching portion 801. However, four or more flow channels may be connected to the branching portion 801. The flow channels L13 ｄ , L13 ｅ , L13 ｆ correspond to an example of inflow-side flow channels. Further, the flow channels L13 ｅ , L13 ｆ correspond to an example of inflow-side branch flow channels.

[0402] Further, the branching portion 801 may have a function (specifically, a valve) for controlling the flow of a medium (that is, inflow medium) into the flow channels L13 ｅ , L13 ｆ connected to the branching portion 801.

[0403] An upstream end of the flow channel L13 ｅ is connected to the branching portion 801. A downstream end of the flow channel L13 ｅ is connected to the medium adjustment unit 34A. The configuration of the medium adjustment unit 34A is the same as the configuration of the medium adjustment unit 34 in the above-described first embodiment.

[0404] An upstream end of the flow channel L13 ｆ is connected to the branching portion 801. A downstream end of the flow channel L13 ｆ is connected to the medium adjustment unit 34B. The configuration of the medium adjustment unit 34B is the same as the configuration of the medium adjustment unit 34 in the above-described first embodiment.

[0405] Further, the medium adjustment unit 34A is connected to the medium inflow portion 52 of the microchannel device 5c via the flow channel L14 ａ . The flow channel L14 ａ corresponds to an example of an inflow-side flow channel and an inflow-side branch flow channel.

[0406] Further, the medium adjustment unit 34B is connected via a flow path L14 ｂ to the medium inlet 52 of the microchannel device 5d. The flow path L14 ｂ corresponds to an example of an inflow-side flow path and an inflow-side branch flow path.

[0407] Further, an upstream end of a flow path L15 ｂ is connected to the medium outlet 53 of the microchannel device 5c. The flow path L15 ａ corresponds to an example of an outflow-side branch flow path.

[0408] Further, an upstream end of a flow path L15 ｃ is connected to the medium outlet 53 of the microchannel device 5d. The flow path L15 ｃ corresponds to an example of an outflow-side branch flow path.

[0409] The flow path L15 ｂ and the flow path L15 ｃ are collected into a flow path L15 ｄ by the collecting unit 802. A medium that has flowed out of the microchannel devices 5c and 5d (i.e., an outflow medium) flows through the flow path L15 ｂ , L15 ｃ , and L15 ｄ . Such flow path L15 ｂ , L15 ｃ , and L15 ｄ correspond to an example of an outflow-side flow path.

[0410] Also in the biomimetic unit 3J of the present embodiment, the extraction unit 35J extracts a trace amount of medium from the medium flowing through the biomimetic unit 3J to the outside of the biomimetic unit 3J.

[0411] In the biomimetic unit 3J of the present embodiment, the extraction unit 35J includes inflow-side extraction units 351A and 351B, and outflow-side extraction units 352A, 352B, and 352C.

[0412] The configurations of the inflow-side extraction units 351A and 351B are the same as those of the inflow-side extraction unit 351 in the first embodiment described above.

[0413] The configurations of the outflow side extraction units 352A, 352B, and 352C are the same as those of the outflow side extraction unit 352 in the above-described embodiment 1.

[0414] The inflow side extraction unit 351A is located in the flow path L13 ｅ It is located in the flow path L13. ｅ A small amount of influent medium is extracted from the medium flowing through it (i.e., the influent medium). The medium extracted by the influent side extraction unit 351A is the medium that flows into the microfluidic device 5c.

[0415] The inflow side extraction unit 351B is located in the flow path L13 ｆ It is located in the flow path L13. ｆ A small amount of influent medium is extracted from the medium flowing through it (i.e., the influent medium). The medium extracted by the influent side extraction unit 351B is the medium that flows into the microfluidic device 5d.

[0416] The outflow side extraction unit 352A is located in the flow path L15 ｂ It is located in the flow path L15. Therefore, the outflow side extraction unit 352A is located in the flow path L15. ｂ A small amount of influent medium is extracted from the flowing medium (i.e., the effluent medium). The medium extracted by the effluent extraction unit 352A is the medium that has flowed out from the microfluidic device 5c.

[0417] The outflow side extraction unit 352B is located in the flow path L15 ｃ It is located in the flow path L15. Therefore, the outflow side extraction unit 352B is located in the flow path L15. ｃ A small amount of influent medium is extracted from the flowing medium (i.e., the effluent medium). The medium extracted by the effluent extraction unit 352B is the medium that has flowed out from the microfluidic device 5d.

[0418] The outflow side extraction unit 352C is located in the flow path L15 ｄ It is located in the flow path L15. Therefore, the outflow side extraction unit 352C is located in the flow path L15. ｄA small amount of influent medium is extracted from the flowing medium (i.e., the efflux medium). The medium extracted by the efflux-side extraction unit 352C is the medium formed by the convergence of the medium effluxed from the microfluidic device 5c and the microfluidic device 5d.

[0419] In the biomimetic system 1J according to this embodiment, which has the configuration described above, two microfluidic devices 5c and 5d are connected in parallel. This allows the biomimetic unit 3J to mimic the interactions between organs that function in parallel in the human body. In other words, the biomimetic unit 3J can create an environment that is closer to that of the human or animal body. The other functions and effects of the biomimetic system 1J according to this embodiment are the same as those of the biomimetic system 1 according to Embodiment 1 described above.

[0420] (Note) In each of the embodiments described above, the extraction unit extracts a small amount of culture medium (specifically, inflow medium and outflow medium) from a channel connected to a microfluidic device. However, the extraction unit may directly extract a small amount of culture medium (specifically, inflow medium and outflow medium) from the microfluidic device.

[0421] The following will describe this configuration with reference to Figure 17. Figure 17 is a schematic cross-sectional view of a modified microfluidic device 5e. The microfluidic device 5e has a cell containment space 51b, an inflow channel 51c, and an outflow channel 51d inside.

[0422] The cell containment space 51b is an example of a cell containment section and is a space for containing cells. The inflow channel 51c is a channel connected to the upstream end of the cell containment space 51b. The inflow channel 51c is connected to the culture medium inflow section 52.

[0423] The outflow channel 51d is a channel connected to the downstream end of the cell containment space 51b. The outflow channel 51d is connected to the culture medium outflow section 53. The culture medium flowing into the cell containment space 51b (i.e., the inflow medium) flows through the inflow channel 51c.

[0424] Furthermore, the culture medium flowing out from the cell containment space 51b (i.e., the efflux medium) flows through the outflow channel 51d.

[0425] Furthermore, the inflow side extraction unit (not shown) of the extraction unit extracts a small amount of culture medium (i.e., inflow medium) from the inflow side channel 51c to the outside of the microfluidic device 5e. In addition, the outflow side extraction unit (not shown) of the extraction unit extracts a small amount of culture medium (i.e., inflow medium) from the outflow side channel 51d to the outside of the microfluidic device 5e. Such a configuration also falls within the technical scope of the present invention.

[0426] [Embodiment 10] Next, a biomimetic system 1K according to Embodiment 10 of the present invention will be described with reference to Figure 18. Figure 18 is a diagram corresponding to Figure 2 described above, and is a block diagram showing the functional configuration of the biomimetic system 1K. Note that in Figure 18, the reservoir tank 31, pump 32, and flow meter 33 shown in Figure 2 are omitted.

[0427] The biomimetic unit 3K constituting the biomimetic system 1K includes a reservoir tank 31 (see Figure 2), a pump 32 (see Figure 2), a flow meter 33 (see Figure 2), a culture medium preparation unit 34, a microfluidic device 5, and an extraction unit 35K. The biomimetic unit 3 also has a plurality of channels L11 to L15 (see Figure 2 for L11 and L12) connecting these elements.

[0428] In this embodiment, the biomimetic unit 3K differs from the biomimetic unit 35 shown in Figure 2 in the configuration of the extraction section 35K.

[0429] Specifically, the extraction unit 35K has an inlet extraction port 354 and an outlet extraction port 355.

[0430] The inflow-side extraction port 354 is located in the flow path L13. The inflow-side extraction port 354 is a part for extracting a small amount of culture medium from the flow path L13, through which the culture medium flows before it enters the microfluidic device 5 (i.e., the inflow culture medium), to the outside of the biomimetic unit 3K. Therefore, the inflow-side extraction port 354 is an example of an inflow-side extraction unit.

[0431] The outflow-side extraction port 355 is located in the flow path L15. The outflow-side extraction port 355 is a part for extracting a small amount of culture medium from the flow path L15, through which the culture medium flows after being discharged from the microfluidic device 5 (i.e., the discharged culture medium), to the outside of the biomimetic unit 3K. Therefore, the outflow-side extraction port 355 is an example of an outflow-side extraction unit.

[0432] As shown in Figure 18, in this embodiment, the inflow extraction port 354 and the outflow extraction port 355 may be configured to accommodate a syringe 358 (for example, a microsyringe or microneedle).

[0433] The user may insert syringe 358 into at least one of the inflow extraction port 354 and the outflow extraction port 355 to extract the culture medium. This allows for the extraction of a small amount of the culture medium flowing through channel L13 and channel L15 at a desired timing.

[0434] The user can extract the culture medium before it flows into the microfluidic device 5 by inserting a syringe 358 into the inflow extraction port 354. The user can also extract the culture medium after it has passed through the microfluidic device 5 by inserting a syringe 358 into the outflow extraction port 355. This allows the user to compare and evaluate the state of the culture medium upstream and downstream of the microfluidic device 5.

[0435] The specific structures of the inflow extraction port 354 and the outflow extraction port 355 are not limited to the configuration shown in Figure 18. For example, the inflow extraction port 354 and the outflow extraction port 355 may be provided on the outer surface of the housing 2 (see Figure 3) that houses the biomimetic unit 3K. This makes it easier to sample the culture medium from the outside without opening the housing 2. Therefore, operability can be improved and the burden during work can be reduced. The syringe 358 may be a microsyringe, microneedle, or a similar micro-collection device.

[0436] According to the biomimetic system 1K according to the present embodiment having the above-described configuration, sampling of a culture medium can be performed with a simple configuration by using the inflow-side extraction port 354 and the outflow-side extraction port 355. This makes it easy to grasp changes in the state of the culture medium before and after the microchannel device 5, and improves convenience such as evaluation of the influence of a test substance. Other configurations, functions and effects are the same as those of the biomimetic system 1 according to Embodiment 1 described above.

[0437] The entire disclosure content of the specification, drawings and abstract contained in the Japanese application of Japanese Patent Application No. 2025-40391 filed on March 13, 2025 is incorporated herein by reference.

[0438] The biomimetic system according to the present invention can mimic the physiological environment of various organisms.

[0439] 1, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1J, 1K Biomimetic System 2 Housing 21 Base 211 Device support 212 Inlet side medium receiving section 213 Outlet side medium receiving section 214 Medium receiving section 22 Storage section 3, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3J, 1K Biomimetic Unit 31 Reservoir tank 32 Pump 33 Flow meter 34, 34A, 34B Medium preparation unit 34a Preparation space 341 Base 341a Main body 341b Medium inlet section 341c Medium outlet section 341d Storage section 342 Oxygen permeable membrane 343 Sheet 344 Plate 344a Plate side through hole 345 Fastening component 346 Fastening hole 35, 35J, 35K Extraction Unit 351 Inlet Extraction Unit 351a Inlet Extraction Channel 351b Inlet First Valve 351c Inlet Second Valve 351d Inlet Extraction Unit 351e Inlet Valve Drive Unit 352 Outlet Extraction Unit 352a Outlet Extraction Channel 352b Outlet First Valve 352c Outlet Second Valve 352d Outlet Extraction Unit 352e Outlet Valve Drive Unit 353 Extraction Unit 353a Extraction Channel 353b First Valve 353c Second Valve 353d Extraction Unit 353e Valve Drive Unit 354 Inlet Port 355 Outlet Port 358 Syringe 36C Real-time Monitoring Sensor 37D Discharge Tank 38G Culture Medium Supply Unit 39G Test Substance Supply Unit 5, 5a, 5b, 5c, 5d, 5e Microfluidic device 51 Device body 511 Lower plate 512 Lower sheet 512a Lower through hole 513 Base 513a Base-side through hole 514 Upper sheet 514a Upper through hole 515 Upper plate 515a Inlet hole 515b Inlet-side bubble removal hole 515c Oxygen introduction hole 515d Outlet-side bubble removal hole 515e Outlet hole 51a, 51b Cell containment space 51c Inlet-side channel 51d Outlet-side channel 52 Culture medium inlet section 521 Through hole 522 First joint section 523 Second joint section 53 Culture medium outlet section 531 Through hole 532 First joint section 533 Second joint section54 Oxygen introduction part 54a Oxygen introduction space 541 Sheet 541a Sheet-side through hole 542 Oxygen permeable membrane 543 Plate 543a Plate-side through hole 544 Fastening part 55 Bubble removal part 56 Inflow-side bubble removal part 56a Bubble removal space 561 Sheet 561a Sheet-side through hole 562 Oxygen permeable membrane 563 Plate 563a Plate-side through hole 564 Fastening part 57 Outflow-side bubble removal part 57a Bubble removal space 571 Sheet 571a Sheet-side through hole 572 Oxygen permeable membrane 573 Plate 573a Plate-side through hole 574 Fastening part 58 Fastening part 59 Fastening hole 6 Control device 7 Detection device 71 Inflow-side sensor 72 Outflow-side sensor 801 Branch part 802 Concentration part 9 Culture device 91 Box part 911 Culture space 912 Shelf part 92 Door part L １１ , L １２ , L １３、 L13 ａ , L13 ｂ , L13 ｃ Channel L １４ , L14 ａ , L14 ｂ , L １５ , L15 ａ , L15 ｂ , L15 ｃ , L15 ｄ , L １６ Channel

Claims

1. A biomimetic system comprising: an inflow-side extraction unit for extracting a small amount of inflow medium from an inflow medium flowing into a cell-containing section for containing cells; and an outflow-side extraction unit for extracting a small amount of outflow medium from an outflow medium flowing out of the cell-containing section.

2. The biomimetic system according to claim 1, further comprising an inflow channel through which the incoming culture medium flows, and an outflow channel through which the outflow culture medium flows, wherein the inflow extraction unit extracts the minute amount of the incoming culture medium to the outside of the inflow channel, and the outflow extraction unit extracts the minute amount of the outflow culture medium to the outside of the outflow channel.

3. The biomimetic system according to claim 1, further comprising: an inflow-side detection unit for detecting information about the inflow medium from the trace amount of inflow medium extracted by the inflow-side extraction unit; and an outflow-side detection unit for detecting information about the outflow medium from the trace amount of outflow medium extracted by the outflow-side extraction unit, wherein the information about the inflow medium includes the concentration of glucose and / or lactic acid contained in the trace amount of inflow medium, and the information about the outflow medium includes the concentration of glucose and / or lactic acid contained in the trace amount of outflow medium.

4. The biomimetic system according to claim 3, wherein the inflow side detection unit detects information regarding the inflow culture medium at predetermined first time intervals, and the outflow side detection unit detects information regarding the outflow culture medium at predetermined second time intervals.

5. The biomimetic system according to claim 1, further comprising: a pump for delivering the influent medium; and a control unit for controlling the pump based on information about the influent medium detected from the trace amount of influent medium and information about the efflux medium detected from the trace amount of efflux medium.

6. The biomimetic system according to claim 1, further comprising: a pump for delivering the incoming culture medium; a flow rate detection unit for detecting the flow rate of the incoming culture medium; and a control unit for controlling the pump based on the flow rate detected by the flow rate detection unit.

7. The biomimetic system according to claim 1, further comprising: a pump for delivering the incoming culture medium; an oxygen introduction unit for introducing oxygen into the incoming culture medium delivered by the pump, and / or a bubble removal unit for removing bubbles from the incoming culture medium.

8. The biomimetic system according to claim 1, further comprising: an inflow channel through which the inflow medium flows; an outflow channel through which the outflow medium flows; and a support for detachably supporting a culture vessel having a cell containment section, wherein the inflow channel is connected to the inflow section of the culture vessel mounted on the support, and the outflow channel is connected to the outflow section of the culture vessel mounted on the support.

9. The biomimetic system according to claim 1, further comprising an inflow channel through which the incoming culture medium flows, and an outflow channel through which the outflow culture medium flows, wherein the cell containment section is composed of a plurality of culture vessels connected in series and containing different cells, the inflow channel is connected to the upstream culture vessel among the plurality of culture vessels, and the outflow channel is connected to the downstream culture vessel among the plurality of culture vessels.

10. The biomimetic system according to claim 1, further comprising: an inflow channel through which the incoming culture medium flows; and an outflow channel through which the outgoing culture medium flows, wherein the cell containment section is composed of a plurality of culture vessels connected in parallel and containing different cells, the inflow channel has a plurality of inflow branched channels connected to each of the plurality of culture vessels, the outgoing channel has a plurality of outgoing branched channels connected to each of the plurality of culture vessels, the inflow extraction section is provided in each of the plurality of inflow branched channels, and the outgoing extraction section is provided in each of the plurality of outgoing branched channels.

11. The biomimetic system according to claim 10, wherein the outflow channel has a consolidation channel that consolidates a plurality of the outflow branch channels, and the outflow extraction unit is provided in the consolidation channel.

12. The biomimetic system according to claim 10, wherein the inflow channel has a branch section to which the upstream end of the inflow branch channel is connected, and the branch section is configured to increase or decrease the number of inflow branch channels connected to the branch section.

13. The biomimetic system according to claim 12, wherein the branching portion has valves that control the flow of the inflow culture medium to a plurality of inflow-side branching channels connected to the branching portion.

14. The biomimetic system according to claim 1, further comprising: a culture medium supply unit that supplies new culture medium to the inflow culture medium; and a culture medium supply control unit that controls the amount of culture medium supplied by the culture medium supply unit based on information about the inflow culture medium detected from the trace amount of inflow culture medium and information about the outflow culture medium detected from the trace amount of outflow culture medium.

15. The biomimetic system according to claim 1, further comprising: a test substance supply unit that supplies a test substance to the inflow medium; and a test substance supply control unit that controls the amount of the test substance supplied by the test substance supply unit based on information about the inflow medium detected from the trace amount of inflow medium and information about the efflux medium detected from the trace amount of efflux medium.

16. The biomimetic system according to claim 1, further comprising a culture medium supply unit for supplying new culture medium to the incoming culture medium, and a test substance supply unit for supplying a test substance to the incoming culture medium, wherein the units are arranged in the order from the upstream side: the culture medium supply unit, the test substance supply unit, the incoming side extraction unit, the cell containment unit, and the outgoing side extraction unit.

17. The biomimetic system according to claim 1, further comprising a culture vessel having the cell containment section, wherein the culture vessel has an oxygen introduction section for supplying oxygen to the culture medium in the cell containment section.

18. The biomimetic system according to claim 1, further comprising a culture vessel having the cell containment section, wherein the culture vessel has a bubble removal section for removing bubbles from the culture medium in the cell containment section.

19. The biomimetic system according to claim 1, further comprising a culture vessel having the cell containment section, wherein the culture vessel has a port through which the cells or an accessory carrying the cells can be introduced from outside the cell containment section into the cell containment section.

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