Biological function chip

Abstract

To provide a compact biological function chip having an ECF-using micro pump built in.SOLUTION: A biological function chip 10 has an elastic film 12 including a face capable of culturing cells, an upper plate 11 and a lower plate 13 for holding the elastic film 12, pressure chambers PC1, PC2, drive paths DP1, DP2 connected to the pressure chambers PC1, PC2, a working fluid injected into the pressure chambers PC1, PC2 and the drive paths DP1, DP2, and an electrode unit 16 disposed in the drive paths DP1, DP2. Applying DC voltage to the electrode unit 16 causes the working fluid to move inside the drive paths DP1, DP2 for a change in the pressure of the pressure chambers PC1, PC2, thereby giving the first elastic film 12 tensile stress.SELECTED DRAWING: Figure 5A

Description

[Technical Field]

[0001] The present invention relates to a biofunction chip. [Background technology]

[0002] In general, new drug development involves cell culture or animal testing to confirm the safety of a drug before clinical trials. However, because cultured cells are different from actual human cells, there is a risk that the drug's effects may not be properly evaluated. In addition, animal testing involving the administration of drugs whose safety has not been confirmed has been criticized from the perspective of animal welfare. Therefore, a different experimental platform than the conventional one is needed.

[0003] In response to this, Patent Document 1 discloses a microchip-type biofunctional chip that can serve as a new experimental platform. According to the biofunctional chip in Patent Document 1, alveolar epithelial cells are cultured on the upper side of a central porous membrane, and vascular endothelial cells on the lower side, and by driving the walls perpendicular to the membrane from the left and right with a vacuum pump, periodic expansion and contraction is generated, providing the cultured cells with a mechanical stimulus due to stretching, making it possible to reproduce the cellular environment of alveoli in vivo. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2016 / 010861 Summary of the Invention [Problem to be solved by the invention]

[0005] Although the biofunction chip in Patent Document 1 is relatively small, it requires peripheral equipment such as a vacuum pump and a syringe pump, as well as piping, and the installation of these devices results in a unit including the enlarged biofunction chip that cannot be accommodated in an incubator. For this reason, there is a need for a more compact biofunction chip that includes the pump.

[0006] In recent years, research on micropumps using functional fluids has been underway. Functional fluids are a general term for fluids that exhibit specific functions in response to external stimuli. Examples of functional fluids include magnetic fluids, magnetorheological fluids, electro-rheological fluids, and electro-conjugate fluids, and actuators using these fluids are already being used in industrial products and the like.

[0007] One type of functional fluid, the electro-conjugate fluid (hereinafter referred to as ECF), is a functional fluid that generates active flow when a DC voltage is applied. A pump using ECF is expected to be a hydraulic source suitable for a small fluid distribution system because it can generate flow simply by applying a voltage to a minute electrode without requiring a mechanical structure.

[0008] Therefore, an object of the present invention is to provide a small biofunctional chip incorporating a micropump using ECF.

Means for Solving the Problems

[0009] To achieve the above object, one representative biofunctional chip of the present invention includes a first elastic membrane having a surface on which cells can be cultured, a holding plate for holding the first elastic membrane, a pressure chamber formed within the holding plate, a drive path connected to the pressure chamber, a working fluid injected into the pressure chamber and the drive path, and an electrode unit disposed within the drive path, and when a DC voltage is applied to the electrode unit, the working fluid moves within the drive path and the pressure in the pressure chamber changes, thereby applying tensile stress to the first elastic membrane.

Effects of the Invention

[0010] According to the present invention, it is possible to provide a small biofunctional chip incorporating a micropump using ECF. Problems, configurations, and effects other than those described above will be clarified by the following description of the embodiments.

Brief Description of the Drawings

[0011]

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BEST MODE FOR CARRYING OUT THE INVENTION

[0012] Hereinafter, embodiments of the present invention will be specifically described.

[0013] (First Embodiment) FIG. 1 is a perspective view of the biological function chip 10 according to the first embodiment, with the internal structure shown by dotted lines. FIG. 2 is a perspective view showing the biological function chip 10 disassembled. FIG. 3 is a perspective view of the upper plate shown in a state where the internal structure is seen through. The biological function chip 10 of the first embodiment is of a uniaxial tension double-sided pump drive type.

[0014] The biological function chip 10 has a thin substantially rectangular plate shape with a size of about 6 cm in length and 4 cm in width, for example, and is composed of an upper plate 11, an elastic membrane (hereinafter referred to as the first elastic membrane) 12, a lower plate 13, and a pump substrate 14. The upper plate 11 and the lower plate 13 constitute a holding plate. When the biological function chip 10 is formed using a semiconductor manufacturing process, it can be mass-produced despite having a fine structure. Also, its manufacturing method is not limited to a specific manufacturing method.

[0015] In FIG. 2, on the upper plate 11 made of a flexible material such as silicon rubber, a first inlet hole 11p, a second inlet hole 11q, a first outlet hole 11s, and a second outlet hole 11t formed near both ends in the longitudinal direction are formed so as to penetrate in the vertical direction, respectively.

[0016] Also, on the lower surface of the upper plate 11, as shown in FIG. 3, an upper left groove 11a with a rectangular cross-section, an upper middle groove 11b, and an upper right groove 11c are formed so as to extend in parallel along the longitudinal direction. A first upper partition wall 11d is formed between the upper left groove 11a and the upper middle groove 11b, and a second upper partition wall 11e is formed between the upper middle groove 11b and the upper right groove 11c.

[0017] The upper left groove 11a, the upper middle groove 11b, and the upper right groove 11c extend from the vicinity of the first inlet hole 11p to the vicinity of the first outlet hole 11s. The upper middle groove 11b and the first inlet hole 11p are connected via an upper side flow path groove 11g, and the upper middle groove 11b and the first outlet hole 11s are connected via an upper side flow path groove 11h.

[0018] Furthermore, on the upper plate 11, a first injection hole 11i, a second injection hole 11j, a third injection hole 11k, and a fourth injection hole 11m are formed so as to penetrate in the vertical direction, respectively. The first injection hole 11i is connected to one end of the upper left groove 11a via an injection groove 11n, and the second injection hole 11j is connected to the other end of the upper left groove 11a via an injection groove 11o. Also, the third injection hole 11k is connected to one end of the upper right groove 11c via an injection groove 11r, and the fourth injection hole 11m is connected to the other end of the upper right groove 11c via an injection groove 11u.

[0019] On both sides sandwiching the upper left groove 11a, the upper middle groove 11b, and the upper right groove 11c, a first rectangular opening 11v and a second rectangular opening 11w are formed through the upper plate 11 in the vertical direction. Flexible membrane members 15a and 15b are respectively adhered to the upper surfaces around the first rectangular opening 11v and the second rectangular opening 11w of the upper plate 11, closing the upper ends of the first rectangular opening 11v and the second rectangular opening 11w.

[0020] Adjacent to the first rectangular opening 11v and the second rectangular opening 11w, a first recess 111 and a second recess 113 are formed on the lower surface of the upper plate 11. The first rectangular opening 11v and the first recess 111 are connected by a communication groove 11x, and the second rectangular opening 11w and the second recess 113 are connected by a communication groove 11y.

[0021] Next, the lower plate 13 will be described. The lower plate 13 is also made of a flexible material such as silicon rubber. In FIG. 2, on the upper surface of the lower plate 13 having the same outer shape as the upper plate 11, an inlet-side recess 13q is formed corresponding to the second inlet hole 11q of the upper plate 11, and an outlet-side recess 13t is formed corresponding to the second outlet hole 11t.

[0022] Also, on the upper surface of the lower plate 13, a lower left groove 13a, a lower middle groove 13b, and a lower right groove 13c with a rectangular cross-section are respectively formed corresponding to the upper left groove 11a, the upper middle groove 11b, and the upper right groove 11c. Further, a first lower partition wall 13d is formed between the lower left groove 13a and the lower middle groove 13b, and a second lower partition wall 13e is formed between the lower middle groove 13b and the lower right groove 13c.

[0023] The lower middle groove 13b and the inlet-side recess 13q are connected via a lower flow path groove 13g, and the lower middle groove 13b and the outlet-side recess 13t are connected via a lower flow path groove 13h.

[0024] On both sides sandwiching the lower left groove 13a, the lower middle groove 13b, and the lower right groove 13c, a first hole 131, a first recess 132, a second hole 133, and a second recess 134 are formed so as to penetrate vertically. The first recess 132 communicates with the lower left groove 13a via the first groove 135, and the second recess 134 communicates with the lower right groove 13c via the second groove 136.

[0025] Next, the elastic membrane 12 will be described. In the elastic membrane 12 sandwiched between the upper plate 11 and the lower plate 13, a through hole 12q is formed corresponding to the second inlet hole 11q of the upper plate 11, and a through hole 12t is formed corresponding to the second outlet hole 11t. Also, in the elastic membrane 12, a through hole 121 is formed corresponding to the first hole 131 of the lower plate 13, and a through hole 123 is formed corresponding to the second hole 133.

[0026] The region of the elastic membrane 12 sandwiched between the upper middle groove 11b and the lower middle groove 13b is a porous part 125 in which a large number of fine holes are formed. For example, alveolar epithelial cells are cultured on the upper surface of the porous part 125, and vascular endothelial cells are cultured on the lower surface thereof.

[0027] On both sides of the porous part 125, a first opening 12a corresponding to the upper left groove 11a and the lower left groove 13a, and a second opening 12c corresponding to the upper right groove 11c and the lower right groove 13c are formed.

[0028] In FIG. 2, when the elastic membrane 12 is adhered to the lower surface of the upper plate 11, the open lower end of the upper middle groove 11b is shielded by the elastic membrane 12. At this time, the first upper partition wall 11d and the second upper partition wall 11e are joined to the elastic membrane 12 so as to sandwich the porous part 125, whereby the upper middle groove 11b is sealed. Also, the lower ends of the upper side flow path grooves 11g, 11h are shielded by the elastic membrane 12.

[0029] The space surrounded by the upper middle groove 11b and the elastic membrane 12 is defined as the upper test flow path UP, and the spaces surrounded by the upper flow path grooves 11g, 11h and the elastic membrane 12 are defined as the upper communication paths UP1 and UP2, respectively. The alveolar epithelial cells cultured on the upper surface of the porous portion 125 can come into contact with the liquid passing through the upper test flow path UP. Here, the first inlet hole 11p is connected to the upper test flow path UP via the upper communication path UP1, and the first outlet hole 11s is connected to the upper test flow path UP via the upper communication path UP2.

[0030] In FIG. 2, when the elastic membrane 12 is adhered to the lower surface of the upper plate 11, the lower ends of the first rectangular opening 11v and the communication groove 11x are shielded by the elastic membrane 12. The first rectangular opening 11v with its upper and lower ends shielded constitutes the first reservoir RV1.

[0031] Furthermore, when the elastic membrane 12 is adhered to the lower surface of the upper plate 11, the lower ends of the second rectangular opening 11w and the communication groove 11y are shielded by the elastic membrane 12. The second rectangular opening 11w with its upper and lower ends shielded constitutes the second reservoir RV2.

[0032] Furthermore, when the elastic membrane 12 is adhered to the lower surface of the upper plate 11, the communication groove 11x with its lower end shielded constitutes a part of the first drive path DP1 described later, and the communication groove 11y with its lower end shielded constitutes a part of the second drive path DP2 described later.

[0033] Also, when the elastic membrane 12 is adhered to the lower surface of the upper plate 11, the open lower ends of the first injection hole 11i and the injection groove 11n, and the open lower ends of the second injection hole 11j and the injection groove 11o are shielded by the elastic membrane 12, and injection paths PP1 and PP2 communicating with the first pressure chamber PC1 described later are respectively formed. Also, the open lower ends of the third injection hole 11k and the injection groove 11r, and the open lower ends of the fourth injection hole 11m and the injection groove 11u are shielded by the elastic membrane 12, and injection paths PP3 and PP4 communicating with the second pressure chamber PC2 described later are formed.

[0034] In FIG. 2, when the elastic film 12 is further adhered to the upper surface of the lower plate 13, the open upper end of the lower middle groove 13b is shielded by the elastic film 12. At this time, the first lower partition wall 13d and the second lower partition wall 13e facing the first upper partition wall 11d and the second upper partition wall 11e are joined to the elastic film 12 so as to sandwich the porous portion 125, whereby the lower middle groove 13b is sealed. Also, the upper ends of the lower side flow path grooves 13g and 13h are shielded by the elastic film 12.

[0035] The space surrounded by the lower middle groove 13b and the elastic film 12 is defined as the lower side test flow path LP, and the spaces surrounded by the lower side flow path grooves 13g and 13h and the elastic film 12 are defined as the lower side communication paths LP1 and LP2, respectively. The vascular endothelial cells cultured on the lower surface of the porous portion 125 can come into contact with the liquid passing through the lower side test flow path LP.

[0036] Via the first opening 12a of the elastic film 12, the upper left groove 11a and the lower left groove 13a communicate with each other, and the upper right groove 11c and the lower right groove 13c communicate with each other. Also, the upper ends of the first groove 135 and the second groove 136 are shielded by the elastic film 12. The first pressure chamber PC1 is formed by the upper left groove 11a and the lower left groove 13a, and the second pressure chamber PC2 is formed by the upper right groove 11c and the lower right groove 13c.

[0037] Also, the first groove 135 shielded by the elastic film 12 constitutes a part of the first drive path DP1 so as to communicate the first pressure chamber PC1 and the first recess 132, and the second groove 136 shielded by the elastic film 12 constitutes a part of the second drive path DP2 so as to communicate the second pressure chamber PC2 and the second recess 134.

[0038] With both surfaces of the elastic film 12 adhered to the upper plate 11 and the lower plate 13, the second inlet hole 11q and the inlet side recess 13q communicate with each other via the through hole 12q, and the second outlet hole 11t and the outlet side recess 13t communicate with each other via the through hole 12t. The second inlet hole 11q communicates with the lower side test flow path LP via the lower side communication path LP1, and the second outlet hole 11t communicates with the lower side test flow path LP via the lower side communication path LP2.

[0039] Next, the pump substrate 14 will be described. The pump substrate 14 shows an example in which a plate with grooves or holes penetrating vertically, for example, is combined with a flat plate, but it may be formed from a single plate material. The same applies to the embodiments described later.

[0040] On the upper surface of the pump substrate 14, a meandering first meandering groove 147 and a second meandering groove 148 are formed. In the first meandering groove 147 and the second meandering groove 148, a plurality of electrode units 16 arranged in series and a power supply wiring (not shown) are formed. By joining the lower plate 13 to the upper surface of the pump substrate 14, drive paths DP1 and DP2 are formed, and the electrode units 16 are arranged in the drive paths DP1 and DP2. The drive paths DP1 and DP2 filled with ECF and the electrode units 16 constitute a micropump.

[0041] A recess 141 is formed at one end of the first meandering groove 147, and a recess 142 is formed at the other end. Also, a recess 143 is formed at one end of the second meandering groove 148, and a recess 144 is formed at the other end.

[0042] When the pump substrate 14 is joined to the lower plate 13, the recess 141 communicates with the first recess 111 through the first hole 131 of the lower plate 13 and the through-hole 121 of the elastic film 12. Therefore, one end of the first drive path DP1 is connected to the first reservoir RV1. Also, since the recess 142 communicates with the first recess 132, the other end of the first drive path DP1 is connected to the first pressure chamber PC1.

[0043] Also, when the pump substrate 14 is joined to the lower plate 13, the recess 143 communicates with the second recess 113 through the second hole 133 of the lower plate 13 and the through-hole 123 of the elastic film 12. Therefore, one end of the second drive path DP2 is connected to the second reservoir RV2. Also, since the recess 144 communicates with the second recess 134, the other end of the second drive path DP2 is connected to the second pressure chamber PC2.

[0044] FIG. 4 is a diagram schematically showing the electrode unit 16 disposed in the first drive path DP1 and the second drive path DP2. The electrode unit 16 has a slit electrode (also referred to as a positive electrode) 16a and a triangular prism electrode (also referred to as a negative electrode) 16b. Other electrode units 16 also have the same configuration. The pump substrate 14 and the lower plate 13 (not shown in FIG. 4) that constitute the inner wall of the first drive path DP1 are each formed of an insulator.

[0045] The slit electrodes 16a are arranged on both sides with a gap across the axis of the drive path DP1 (or DP2). On the other hand, the triangular prism electrodes 16b have their pointed tips facing the gaps of the slit electrodes 16a.

[0046] A DC voltage of several tens of V to several tens of kV can be applied to the slit electrodes 16a and the triangular prism electrodes 16b from a DC power source. The slit electrodes 16a are connected to the positive electrode side, and the triangular prism electrodes 16b are connected to the negative electrode side.

[0047] In FIG. 2, the biological function chip 10 is formed by laminating and bonding the pump substrate 14, the lower plate 13, the elastic film 12, and the upper plate 11. First, in the state before bonding the film members 15a and 15b, the ECF is injected into the pressure chambers PC1 and PC2 as follows.

[0048] Referring to FIG. 1, when the ECF is injected from the injection hole 11i, the injected ECF fills the first pressure chamber PC1 through the injection path PP1 and further reaches the first reservoir RV1 through the first drive path DP1. The excess ECF passes through the injection path PP2 from the first pressure chamber PC1 and overflows outside through the injection hole 11j. After the injection is completed, the injection hole 11i and the injection hole 11j are closed using a clamp or the like, and the upper part of the first reservoir RV1 is shielded by the film member 15a. However, the method of closing the injection port is not limited to the above.

[0049] Similarly, when ECF is injected from the injection hole 11k, the injected ECF fills the second pressure chamber PC2 via the injection path PP3, and further reaches the second reservoir RV2 via the second drive path DP2. The surplus ECF passes from the second pressure chamber PC2 through the injection path PP4 and overflows outside from the injection hole 11m. After the injection is completed, the injection holes 11k and 11m are closed using a clamp or the like, and the upper portion of the second reservoir RV2 is shielded by the membrane member 15b. However, the method of closing the injection port is not limited to the above. As the ECF, for example, the fluid described in U.S. Patent No. 6,495,071 is used, but it is not limited thereto.

[0050] (Operation of the biological function chip) FIG. 5A is a schematic cross-sectional view schematically showing the operation of the biological function chip 10 of the first embodiment. In FIG. 5A, a single electrode unit 16 is shown in the drive paths DP1 and DP2, but actually a plurality of electrode units 16 are arranged in series. Note that the triangular prism electrode 16b of the electrode unit 16 in the first drive path DP1 is arranged on the first pressure chamber PC1 side, and the triangular prism electrode 16b of the electrode unit 16 in the second drive path DP2 is arranged on the second pressure chamber PC2 side. Each electrode unit 16 is connected to a DC power supply DC, and the power supply is integrally controlled by a control device (not shown).

[0051] In advance, alveolar epithelial cells are cultured on the upper surface of the porous portion 125, and on the side surface thereof, a first upper partition wall 11d and a second upper partition wall 11e that form a part of the inner wall of the first pressure chamber PC1 are in close contact. Also, vascular endothelial cells are cultured on the lower surface of the porous portion 125, and on the side surface thereof, a first lower partition wall 13d and a second lower partition wall 13e that form a part of the inner wall of the second pressure chamber PC2 are in close contact.

[0052] Furthermore, air is injected from the first inlet hole 11p, and the injected air enters the upper test flow path UP through the upper communication path UP1 and touches the alveolar epithelial cells. The surplus air passes from the upper test flow path UP through the downstream upper communication path UP2 and is discharged from the first outlet hole 11s. Note that a liquid may be injected instead of air.

[0053] On one hand, blood is injected from the second inlet hole 11q, and the injected blood enters the lower test flow path LP through the lower communication path LP1 and touches the vascular endothelial cells. The excess blood passes through the downstream lower communication path LP2 from the lower test flow path LP and is discharged from the second outlet hole 11t. Note that the gas or liquid injected into the upper communication path UP1 and the lower communication path LP1 can be appropriately selected according to the cells to be cultured.

[0054] When a DC voltage is not applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive paths DP1 and DP2 by a signal from the control device, the internal pressures of the pressure chambers PC1 and PC2 are equivalent to the atmosphere. Therefore, as shown in Fig. 5A(a), the first upper partition wall 11d and the second upper partition wall 11e, and the first lower partition wall 13d and the second lower partition wall 13e are maintained in the state before deformation.

[0055] On the contrary, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive paths DP1 and DP2 by a signal from the control device, the ECF in the drive paths DP1 and DP2 flows toward the reservoirs RV1 and RV2 from the pressure chambers PC1 and PC2 as shown in Fig. 5A(b). The reservoirs RV1 and RV2 can increase the volume for storing the flowing ECF by the elastic deformation of the membrane members 15a and 15b.

[0056] Due to the flow of the ECF, the internal pressures of the pressure chambers PC1 and PC2 decrease. Therefore, the first upper partition wall 11d and the second upper partition wall 11e are biased to separate, and both sides of the alveolar epithelial cells are pulled in the left - right direction as shown in Fig. 5A(b). At the same time, the first lower partition wall 13d and the second lower partition wall 13e are biased to separate, and both sides of the vascular endothelial cells are also pulled in the left - right direction as shown in Fig. 5A(b). Thereby, stretching stimuli are applied to the alveolar epithelial cells and the vascular endothelial cells, and the environment of the alveoli in vivo can be reproduced.

[0057] When the power supply to the electrode unit 16 is stopped, the membrane members 15a and 15b return from elastic deformation. As a result, the ECF returns from the reservoirs RV1 and RV2 to the pressure chambers PC1 and PC2, and the internal pressure thereof returns to the original state. Thereby, the first upper partition wall 11d and the second upper partition wall 11e, and the first lower partition wall 13d and the second lower partition wall 13e return to the original positions shown in Fig. 5A(a). Therefore, the alveolar epithelial cells and the vascular endothelial cells also return to the original state. Further, the upper partition walls 11d and 11e, and the lower partition walls 13d and 13e return to the original positions by the elastic force of the membrane itself of the porous portion 125.

[0058] In this way, by repeating the power supply and power cut to the electrode unit 16, the alveolar epithelial cells and the vascular endothelial cells repeatedly perform the expansion and contraction operations. Therefore, like the human lung, the gas exchange between the oxygen in the alveoli and the carbon dioxide in the blood can be realized through the porous portion 125. According to the biological function chip 10 of this embodiment, for example, it is possible to reproduce the changes in blood caused by virus infection (airborne infection) by breathing, or to accurately evaluate how the efficiency of gas exchange changes when a chemical solution is injected into the blood, etc., without performing animal experiments.

[0059] (Modification example) Particularly in vivo, the blood flow becomes non-uniform near the branch of the blood vessel, and the mechanical stimulus due to the shear force applied to the vascular endothelial cells also becomes non-uniform. The biological function chip 10' according to a modification example including such a structure is shown below.

[0060] Fig. 5B is a perspective view showing the lower plate 13' of the biological function chip 10', and Fig. 5C is a top view of the lower plate 13'. In the biological function chip 10', since the configurations other than the lower plate 13' are the same as those in the first embodiment, the overlapping description is omitted.

[0061] The lower plate 13' is different from the lower plate 13 of the first embodiment in the shape of the lower middle groove 13b'. Since the other configurations are the same as those of the lower plate 13 of the first embodiment, the common configurations are denoted by the same reference numerals and the description thereof is omitted.

[0062] In FIG. 5C, at the center of the lower middle groove 13' sandwiched between the lower partition walls 13d and 13e, a central lower partition wall 13x extending parallel to the lower partition walls 13d and 13e is formed. Also, between the first lower partition wall 13d and the central lower partition wall 13x, a third lower partition wall 13y is formed. Further, between the central lower partition wall 13x and the second lower partition wall 13e, a fourth lower partition wall 13z is formed. The lengths of the third lower partition wall 13y and the fourth lower partition wall 13z are equal. The central lower partition wall 13x is formed long so as to protrude from both ends of the third lower partition wall 13y and the fourth lower partition wall 13z, but is formed shorter than the entire length of the lower middle groove 13'.

[0063] The lower middle groove 13b' is divided, from the upstream side, into a first portion BV1 in which only the lower partition walls 13d and 13e are arranged, a second portion BV2 in which only the central lower partition wall 13x is arranged between the lower partition walls 13d and 13e, a third portion BV3 in which the third lower partition wall 13y, the central lower partition wall 13x, and the fourth lower partition wall 13z are arranged between the lower partition walls 13d and 13e, a fourth portion BV4 in which only the central lower partition wall 13x is arranged between the lower partition walls 13d and 13e, and a fifth portion BV5 in which only the lower partition walls 13d and 13e are arranged.

[0064] Each flow path cross-section sandwiched between the partition walls becomes smaller from the first portion BV1 toward the third portion BV3, and becomes larger from the third portion BV3 toward the fifth portion BV5. Therefore, the first portion BV1 corresponds to a small artery in the human body with a relatively large flow path cross-section, the second portion BV2 corresponds to an arteriole with a smaller flow path cross-section than the small artery, the third portion BV3 corresponds to a capillary with the smallest flow path cross-section, the fourth portion BV4 corresponds to a venule, and the fourth portion BV4 corresponds to a small vein. Thus, for example, the branching structure of the capillaries in the alveoli can be reproduced.

[0065] FIG. 5D is a schematic cross-sectional view of the third portion BV3 schematically showing the operation of the biological function chip 10'. As shown in FIG. 5D, the upper ends of the central lower partition wall 13x, the third lower partition wall 13y, and the fourth lower partition wall 13z are in contact with and joined to the lower surface of the porous portion 125. For this reason, a micro cross-section passage (the first capillary A flow path is formed, a micro cross-section passage (second capillary flow path) is formed between the third lower partition wall 13y and the central lower partition wall 13x, a micro cross-section passage (third capillary flow path) is formed between the central lower partition wall 13x and the fourth lower partition wall 13z, and a micro cross-section passage (fourth capillary flow path) is formed between the fourth lower partition wall 13z and the second lower partition wall 13e.

[0066] The operation of the biological function chip 10’ is basically the same as that of the first embodiment. When no DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive paths DP1 and DP2 by a signal from the control device, the internal pressures of the pressure chambers PC1 and PC2 are equivalent to the atmosphere. Therefore, as shown in Fig. 5D(a), the first upper partition wall 11d, the second upper partition wall 11e, the third lower partition wall 13y, the central lower partition wall 13x, the fourth lower partition wall 13z, and the first lower partition wall 13d and the second lower partition wall 13e are maintained in the state before deformation.

[0067] On the contrary, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive paths DP1 and DP2 by a signal from the control device, the ECF in the drive paths DP1 and DP2 flows from the pressure chambers PC1 and PC2 toward the reservoirs RV1 and RV2 as shown in Fig. 5D(b). The reservoirs RV1 and RV2 can increase the volume for storing the flowing ECF by the elastic deformation of the membrane members 15a and 15b.

[0068] Due to the flow of the ECF, the internal pressures of the pressure chambers PC1 and PC2 decrease. Therefore, the first upper partition wall 11d and the second upper partition wall 11e are biased to separate, and both side surfaces of the alveolar epithelial cells are pulled in the left-right direction as shown in Fig. 5D(b). At the same time, the first lower partition wall 13d and the second lower partition wall 13e are biased to separate, and as the porous part 125 extends, the third lower partition wall 13y and the fourth lower partition wall 13z also deform, and both side surfaces of the vascular endothelial cells are pulled in the left-right direction as shown in Fig. 5D(b). Thereby, stretching stimuli are applied to the alveolar epithelial cells and the vascular endothelial cells, and the environment of the alveoli in the living body can be reproduced. A structure imitating the branching of capillaries like this modification example can be similarly incorporated into other embodiments hereafter.

[0069] (Second Embodiment) FIG. 6 is a perspective view of the biofunctional chip 10' according to the second embodiment, with the internal structure shown by dashed lines. FIG. 7 is a perspective view showing the biofunctional chip 10' disassembled. FIG. 8 is a perspective view of the upper plate shown in a state where the internal structure is seen through. Note that FIGS. 6 to 8 are shown in a state where the longitudinal axis is rotated 180 degrees with respect to FIGS. 1 to 3.

[0070] The biofunctional chip 10' of this embodiment is of a uniaxial tensile one-sided pump drive type. For the common configurations with respect to the first embodiment, the same reference numerals are given and redundant explanations are omitted.

[0071] The biofunctional chip 10' is formed by an upper plate 11', an elastic membrane 12', a lower plate 13', and a pump substrate 14' that do not have the structures related to the second drive path DP2 and the second reservoir RV2 of the first embodiment.

[0072] Instead, in the biofunctional chip 10', the drive path DP1 is connected to both the first pressure chamber PC1 and the second pressure chamber PC2. Specifically, in the pump substrate 14', it is branched from the serpentine path 147 into a branch path 147a and a branch path 147b. Further, the recess 142a formed at the end of the branch path 147a is communicated with the first recess 132 of the lower plate 13'. Also, the recess 142b formed at the end of the branch path 147a is communicated with the second recess 134 of the lower plate 13'. Thereby, the end of the drive path DP1 is connected to the first pressure chamber PC1 and the second pressure chamber PC2.

[0073] (Operation of the Biofunctional Chip) FIG. 9 is a schematic cross-sectional view similar to FIG. 5A schematically showing the operation of the biofunctional chip 10' of the second embodiment. Similar to the first embodiment, alveolar epithelial cells are cultured on the upper surface of the porous portion 125, and vascular endothelial cells are cultured on the lower surface thereof.

[0074] When no DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP1 by a signal from the control device, the internal pressures of the pressure chambers PC1 and PC2 are equal to the atmosphere. Therefore, as shown in FIG. 9(a), the first upper partition wall 11d, the second upper partition wall 11e, the first lower partition wall 13d, and the second lower partition wall 13e are maintained in the state before deformation.

[0075] On the other hand, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP1 by a signal from the control device, the ECF in the drive path DP1 flows from the pressure chambers PC1 and PC2 toward the reservoir RV1 as shown in FIG. 9(b). The reservoir RV1 can increase the volume for storing the flowing ECF by the elastic deformation of the membrane member 15a.

[0076] Due to the flow of the ECF, the internal pressures of the pressure chambers PC1 and PC2 decrease through the branch paths 147a and 147b. Therefore, the first upper partition wall 11d and the second upper partition wall 11e are biased to separate from each other, and both side surfaces of the alveolar epithelial cells are pulled in the left - right direction as shown in FIG. 9(b). At the same time, the first lower partition wall 13d and the second lower partition wall 13e are biased to separate from each other, and both side surfaces of the vascular endothelial cells are also pulled in the left - right direction as shown in FIG. 5A.

[0077] When the power supply to the electrode unit 16 is stopped, since the membrane members 15a and 15b return from the elastic deformation, the ECF returns from the reservoirs RV1 and RV2 to the pressure chambers PC1 and PC2, and their internal pressures return to the original state. As a result, the first upper partition wall 11d and the second upper partition wall 11e, and the first lower partition wall 13d and the second lower partition wall 13e return to the original positions shown in FIG. 9(a), so that the alveolar epithelial cells and the vascular endothelial cells also return to the original state. Furthermore, the elastic force of the membrane itself of the porous part 125 causes the upper partition walls 11d and 11e, and the lower partition walls 13d and 13e to return to the original positions.

[0078] According to the second embodiment, the configuration of the biological function chip 10' can be further simplified.

[0079] (Third Embodiment) FIG. 10 is a perspective view of the biological function chip 20 according to the third embodiment, and the internal structure is shown by a dotted line. FIG. 11 is a perspective view showing the biological function chip 20 disassembled. The biological function chip 20 of the third embodiment is of a diaphragm drive type.

[0080] The biological function chip 20 is composed of an upper plate 21, a first elastic membrane 22, an intermediate plate 23, a second elastic membrane 24, a lower plate 25, and a pump substrate 26. The upper plate 21, the intermediate plate 23, and the lower plate 25 constitute a holding plate.

[0081] In the rectangular plate-shaped upper plate 21, a circular central opening 21a is formed on one side in the short side direction, and on both sides sandwiching the central opening 21a, an inlet hole 21b and an outlet hole 21c having a smaller diameter than the central opening 21a are formed.

[0082] In the first elastic membrane 22 having the same outer shape as the upper plate 21, a porous portion 22a having a large number of fine holes is formed corresponding to the central opening 21a, and intermediate holes 22b, 22c are formed corresponding to the inlet hole 21b and the outlet hole 21c.

[0083] In the intermediate plate 23 having the same outer shape as the first elastic membrane 22, a long hole opening 23f is formed. The long hole opening 23f has a long hole central portion 23a corresponding to the central opening 21a, and long hole end portions 23b, 23c corresponding to the inlet hole 21b and the outlet hole 21c. Further, the long hole central portion 23a and the long hole end portions 23b, 23c are connected by flow paths 23d, 23e, respectively.

[0084] The second elastic membrane 24 is a rectangular shape with a larger area than the intermediate plate 23.

[0085] In the lower plate 25 having the same outer shape as the second elastic membrane 24, a lower opening 25a is formed corresponding to the long hole central portion 23a, and drive holes 25b, 25c are formed corresponding to the long hole end portions 23b, 23c.

[0086] Furthermore, on the lower plate 25, a central rectangular opening 25g is formed at a position protruding from the intermediate plate 23, and end rectangular openings 25h and 25i are formed on both sides sandwiching the central rectangular opening 25g.

[0087] On the upper surface of the pump substrate 26 having the same outer shape as the lower plate 25, a meandering central meandering groove 261 is formed, and meandering first meandering grooves 262 and second meandering grooves 263 are formed on both sides of the central meandering groove 261. One end of the central meandering groove 261 is a circular recess 26a disposed at a position corresponding to the lower opening 25a, and the other end is a rectangular recess 26g disposed at a position corresponding to the central rectangular opening 25g.

[0088] Also, one end of the first meandering groove 262 is a circular recess 26b disposed at a position corresponding to the drive hole 25b, and the other end is a rectangular recess 26h disposed at a position corresponding to the end rectangular opening 25h.

[0089] Furthermore, one end of the second meandering groove 263 is a circular recess 26c disposed at a position corresponding to the drive hole 25c, and the other end is a rectangular recess 26i disposed at a position corresponding to the end rectangular opening 25i.

[0090] In the central meandering groove 261, the first meandering groove 262, and the second meandering groove 263, a plurality of electrode units 16 arranged in series and a power supply wiring (not shown) are formed. The electrode unit 16 is the same as that shown in FIG. 5A.

[0091] The biological function chip 20 is formed by laminating and bonding the upper plate 21, the first elastic film 22, the intermediate plate 23, the second elastic film 24, the lower plate 25, and the pump substrate 26.

[0092] When the upper plate 21, the first elastic film 22, and the intermediate plate 23 are joined, the upper surface of the porous portion 22a is disposed within the central opening 21a, and the lower surface faces the central portion of the long hole 23a. Also, the inlet hole 21b communicates with the end portion of the long hole 23b via the intermediate hole 22b, and the outlet hole 21c communicates with the end portion of the long hole 23c via the intermediate hole 22c.

[0093] Here, an inlet port IP is formed by the inlet hole 21b and the intermediate hole 22b, and an outlet port OP is formed by the outlet hole 21c and the intermediate hole 22c.

[0094] Furthermore, when a lower plate 25 with a second elastic film 24 adhered to its upper surface is joined to the intermediate plate 23, the open lower ends of the flow paths 23d and 23e are shielded by the second elastic film 24, and an internal passage IT connecting both ends to the inlet port IP and the outlet port OP is formed. Inside the internal passage IT, the inside of the long hole end 23b constitutes a first valve chamber VC1 connected to the inlet port IP, and the inside of the long hole end 23c constitutes a second valve chamber VC2 connected to the outlet port OP.

[0095] Also, the upper end of the lower opening 25a, the upper ends of the drive holes 25b and 25c, and the upper end of the central rectangular opening 25g, and the upper ends of the end rectangular openings 25h and 25i are also shielded by the second elastic film 24. Here, the inside of the lower opening 25a shielded by the second elastic film 24 constitutes a central pressure chamber PCC, the inside of the drive hole 25b shielded by the second elastic film 24 constitutes a first pressure chamber PC1, and the inside of the drive hole 25c shielded by the second elastic film 24 constitutes a second pressure chamber PC2. Also, the inside of the central rectangular opening 25g shielded by the second elastic film 24 constitutes a central reservoir RVC, the inside of the end rectangular opening 25h shielded by the second elastic film 24 constitutes a first reservoir RV1, and the inside of the end rectangular opening 25i shielded by the second elastic film 24 constitutes a second reservoir RV2.

[0096] Furthermore, by joining the pump substrate 26 to the lower plate 25, the open upper end of the central meandering groove 261 is closed, forming a central drive path DPC, and the open upper ends of the first meandering groove 262 and the second meandering groove 263 are closed, forming drive paths DP1 and DP2. The electrode unit 16 is to be arranged inside the central drive path DPC and the drive paths DP1 and DP2. The second elastic film 24, the drive paths DP1 and DP2 containing the working fluid, and the pump substrate 26 constitute a valve mechanism.

[0097] (Operation of the biological function chip) Figs. 12 and 13 are schematic cross-sectional views schematically showing the operation of the biological function chip 20 of the third embodiment. Fig. 12 shows the A-A cross-section of Fig. 10, and Fig. 13 shows the B-B cross-section of Fig. 10.

[0098] In Figs. 12 and 13, a single electrode unit 16 is shown in the central drive path DPC and the drive paths DP1 and DP2. Actually, a plurality of electrode units 16 are arranged in series. Note that the triangular prism electrode 16b of the electrode unit 16 in the central drive path DPC is arranged on the side of the central pressure chamber PCC, the triangular prism electrode 16b of the electrode unit 16 in the first drive path DP1 is arranged on the side of the first reservoir RV1, and the triangular prism electrode 16b of the electrode unit 16 in the second drive path DP2 is arranged on the side of the second reservoir RV2. Each electrode unit 16 is connected to a DC power supply DC, and its power supply is integrally controlled by a control device (not shown).

[0099] Here, it is assumed that alveolar epithelial cells are cultured on the upper surface of the porous part 22a, and vascular endothelial cells are cultured on the lower surface thereof. The alveolar epithelial cells are in contact with air through the central opening 21a of the upper plate 21.

[0100] Furthermore, it is assumed that blood is injected from the inlet port IP, and the injected blood is discharged from the outlet port OP through the internal passage IT.

[0101] The valve operation of the biological function chip 20 will be described. When no DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive paths DP1 and DP2 by a signal from the control device, the internal pressures of the first pressure chamber PC1 and the second pressure chamber PC2 are equal to the atmosphere. Therefore, as shown in Fig. 12(a), the second elastic membrane 24 facing the first pressure chamber PC1 and the second pressure chamber PC2 and the first valve chamber VC1 and the second valve chamber VC2 is maintained in the state before deformation.

[0102] On the other hand, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP1 by a signal from the control device, the ECF in the drive path DP1 flows from the first reservoir RV1 toward the first pressure chamber PC1 as shown in Fig. 12(b). As a result, the second elastic film 24 facing the first reservoir RV1 elastically deforms, allowing the movement of the ECF from the first reservoir RV1.

[0103] Due to the flow of the ECF, the internal pressure of the first pressure chamber PC1 increases, causing the second elastic film 24 facing it to deform toward the first valve chamber VC1 and close the inlet port IP. As a result, the inflow of blood through the inlet port IP is blocked.

[0104] Also, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP2 by a signal from the control device, the ECF in the drive path DP2 flows from the second reservoir RV2 toward the second pressure chamber PC2 as shown in Fig. 12(b). As a result, the second elastic film 24 facing the second reservoir RV2 elastically deforms, allowing the movement of the ECF from the first reservoir RV1.

[0105] Due to the flow of the ECF, the internal pressure of the second pressure chamber PC2 increases, causing the second elastic film 24 facing it to deform toward the second valve chamber VC2 and close the outlet port OP. As a result, the outflow of blood through the outlet port OP is blocked.

[0106] When the power supply to the electrode units 16 in the drive paths DP1 and DP2 is stopped, the internal pressures of the pressure chambers PC1 and PC2 decrease. As a result, the second elastic films 24 facing the valve chambers VC1 and VC2 return from elastic deformation, opening the inlet port IP and the outlet port OP. The closing and opening of the inlet port IP and the outlet port OP can be performed independently.

[0107] Next, the expansion and contraction operation of the biological function chip 20 will be described. When no DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the central drive path DPC by a signal from the control device, the internal pressure of the central pressure chamber PCC is equivalent to the atmosphere. Therefore, as shown in Fig. 13(a), the second elastic film 24 facing the central pressure chamber PCC is maintained in the state before deformation.

[0108] On the contrary, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the central drive path DPC by a signal from the control device, the ECF in the central drive path DPC flows from the central pressure chamber PCC toward the central reservoir RVC as shown in Fig. 13(b). By the elastic deformation of the second elastic film 24 facing the central reservoir RVC, the ECF flowing into the central reservoir RVC can be stored, and its volume can be increased.

[0109] At this time, when the electrode units of the drive paths DP1 and DP2 are driven to close the inlet port IP and the outlet port OP as shown in Fig. 12(b), the blood in the internal passage IT does not flow in or out, so the volume remains constant. At that timing, due to the flow of the ECF in the central drive path DPC, the internal pressure of the central pressure chamber PCC decreases, and when the second elastic film 24 facing it elastically deforms downward, as shown in Fig. 13(b), a part of the first elastic film 22, the porous part 22a, also elastically deforms downward, so tensile stress acts on the porous part 22a. Accordingly, the alveolar epithelial cells on the upper surface of the porous part 22a deform and stretch in a bending manner, and the vascular endothelial cells on the lower surface of the porous part 22a also deform and stretch in a bending manner.

[0110] When the power supply to the electrode unit 16 of the central drive path DPC is stopped, the internal pressure of the central pressure chamber PCC returns to its original state. As a result, the second elastic film 24 and the porous part 22a return to their original positions shown in Fig. 13(a) due to the elastic force acting on the film itself, so the alveolar epithelial cells and the vascular endothelial cells also return to their original states.

[0111] According to the third embodiment, while having a compact configuration, it is possible to cause the cell to perform expansion and contraction operations while arbitrarily changing the timing of supplying liquid (or gas) to the cell by applying a DC voltage.

[0112] (Fourth Embodiment) FIG. 14 is a perspective view of the biofunctional chip 30 according to the fourth embodiment, showing the internal structure with dotted lines. FIG. 15 is a perspective view showing the biofunctional chip 30 disassembled. The biofunctional chip 30 of the fourth embodiment is of the recessed double-sided drive type.

[0113] The biofunctional chip 30 is composed of a third membrane member 31, an upper plate 32, a first elastic membrane 33, an intermediate plate 34, a second elastic membrane 35, a lower plate 36, and a pump substrate 37. The upper plate 32 and the lower plate 36 constitute a holding plate.

[0114] In the rectangular third membrane member 31 made of a flexible material, a first inlet hole 31e, a first outlet hole 31f, a second inlet hole 31g, a second outlet hole 31h, a third inlet hole 31a, a third outlet hole 31b, a fourth inlet hole 31c, and a fourth outlet hole 31d are formed.

[0115] In the upper plate 32 having the same outer shape as the third membrane member 31, an intermediate hole 32a is formed corresponding to the third inlet hole 31a, an intermediate hole 32b is formed corresponding to the third outlet hole 31b, an intermediate hole 32c is formed corresponding to the fourth inlet hole 31c, and an intermediate hole 32d is formed corresponding to the fourth outlet hole 31d.

[0116] Furthermore, in the upper plate 32, U-shaped cut grooves 32j and 32k are symmetrically arranged on both sides with the central partition wall (second partition wall) 32i interposed therebetween. The cut grooves 32j and 32k each have straight portions 32m and 32n adjacent to the partition wall 32i.

[0117] One end of the cut groove 32j is a circular end 32e corresponding to the first inlet hole 31e, and the other end of the cut groove 32j is a circular end 32f corresponding to the first outlet hole 31f. Also, one end of the cut groove 32k is a circular end 32g corresponding to the second inlet hole 31g, and the other end of the cut groove 32k is a circular end 32h corresponding to the second outlet hole 31h.

[0118] In the first elastic film 33 having the same outer shape as the upper plate 32, a film hole 33a is formed corresponding to the intermediate hole 32a, a film hole 33b is formed corresponding to the intermediate hole 32b, a film hole 33c is formed corresponding to the intermediate hole 32c, and a film hole 33d is formed corresponding to the intermediate hole 32d.

[0119] Furthermore, in the first elastic film 33, porous portions 33m, 33n are formed corresponding to the straight portions 32m, 32n of the cut grooves 32j, 32k.

[0120] In the intermediate plate 34 having the same outer shape as the first elastic film 33, cut grooves 34j, 34k are symmetrically arranged on both sides with a partition wall (the first partition wall) 34i corresponding to the partition wall 32i interposed therebetween. The cut grooves 34j, 34k have straight portions 34m, 34n corresponding to the straight portions 32m, 32n, but the overall shape is different from that of the cut grooves 32j, 32k.

[0121] One end of the cut groove 34j is a circular end 34a corresponding to the film hole 33a, and the other end of the cut groove 34j is a circular end 34b corresponding to the film hole 33b. Also, one end of the cut groove 34k is a circular end 34c corresponding to the film hole 33c, and the other end of the cut groove 34k is a circular end 34d corresponding to the film hole 33d.

[0122] The second elastic film 35 is in a rectangular shape with a larger area than the intermediate plate 34.

[0123] In the lower plate 36 having the same outer shape as the second elastic film 35, a first rectangular opening 36s is formed corresponding to the straight portions 34m, 34n, and a second rectangular opening 36t is formed at a position protruding from the intermediate plate 34.

[0124] On the upper surface of the pump substrate 37 having the same outer shape as the lower plate 36, a meandering groove 37u is formed. One end of the meandering groove 37u is a rectangular recess 37s disposed at a position corresponding to the first rectangular opening 36s, and the other end is a rectangular recess 37t disposed at a position corresponding to the second rectangular opening 36t.

[0125] In the meandering groove 37u, a plurality of electrode units 16 arranged in series and a power supply wiring (not shown) are formed. The electrode unit 16 is the same as that shown in FIG. 5A.

[0126] The biofunctional chip 30 is formed by laminating and joining the third film member 31, the upper plate 32, the first elastic film 33, the intermediate plate 34, the second elastic film 35, the lower plate 36, and the pump substrate 37.

[0127] When the third film member 31, the upper plate 32, the first elastic film 33, and the intermediate plate 34 are joined, the first inlet hole 31e is connected to the circular end 32e, the first outlet hole 31f is connected to the circular end 32f, the upper and lower ends of the cut groove 32j are shielded, and a first test flow path UP11 having the first inlet hole 31e and the first outlet hole 31f as ends is formed.

[0128] Also, the second inlet hole 31g is connected to the circular end 32g, the second outlet hole 31h is connected to the circular end 32h, the upper and lower ends of the cut groove 32k are shielded, and a second test flow path UP12 having the second inlet hole 31g and the second outlet hole 31h as ends is formed. At this time, the straight portion 32m is located on the porous portion 33m, and the straight portion 32n is located on the porous portion 33n.

[0129] Furthermore, the third inlet hole 31a is connected to the circular end 34a via the intermediate hole 32a and the membrane hole 33a, the third outlet hole 31b is connected to the circular end 34b via the intermediate hole 32b and the membrane hole 33b, the upper and lower ends of the cut groove 34j are shielded, and a third test flow path UP21 having the third inlet hole 31a and the third outlet hole 31b as ends is formed.

[0130] Further, the fourth inlet hole 31c is connected to the circular end 34c via the intermediate hole 32c and the membrane hole 33c, and the fourth outlet hole 31d is connected to the circular end 34d via the intermediate hole 32d and the membrane hole 33d. The upper and lower ends of the cut groove 34k are shielded, and a fourth test flow path UP22 with the fourth inlet hole 31c and the fourth outlet hole 31d as its ends is formed. At this time, the straight portion 34m is located directly below the porous portion 33m, and the straight portion 34n is located directly below the porous portion 33n. Since the lower end of the partition wall 32i and the upper end of the partition wall 34i are joined to the first elastic membrane 33 in opposition, the test flow paths UP11 to UP22 are sealed without fluid leakage.

[0131] Furthermore, when a lower plate 36 with a second elastic membrane 35 adhered to its upper surface is joined to the intermediate plate 34, the open upper end of the first rectangular opening 36s and the second rectangular opening 36t are shielded by the second elastic membrane 35.

[0132] Furthermore, when a pump substrate 37 is joined to the lower plate 36, the first rectangular opening 36s communicates with the rectangular recess 37s, and the second rectangular opening 36t communicates with the rectangular recess 37t. Here, the inside of the first rectangular opening 36s shielded by the second elastic membrane 35 constitutes a pressure chamber PC, and the inside of the second rectangular opening 36t shielded by the second elastic membrane 35 constitutes a reservoir RV.

[0133] Furthermore, by joining the pump substrate 37 to the lower plate 36, the open upper end of the meandering groove 37u is closed, and a drive path DP is formed. The electrode unit 16 will be disposed within the drive path DP.

[0134] (Operation of the biological function chip) FIG. 16 is a schematic cross-sectional view schematically showing the operation of the biological function chip 30 of the fourth embodiment.

[0135] In FIG. 16, although a single electrode unit 16 is shown in the drive path DP, actually a plurality of electrode units 16 are arranged in series. Note that the triangular prism electrode 16b of the electrode unit 16 in the drive path DP is assumed to be arranged on the pressure chamber PC side. Each electrode unit 16 is connected to a DC power supply DC, and its power supply is integrally controlled by a control device (not shown).

[0136] Here, it is assumed that different alveolar epithelial cells are cultured on the upper surfaces of the porous portions 33m and 33n, and different vascular endothelial cells are cultured on their lower surfaces.

[0137] Furthermore, air is injected from the first inlet hole 31e and the second inlet hole 31g, and the injected air enters the first test flow path UP11 and the second test flow path UP12 and touches the alveolar epithelial cells respectively. The surplus air passes through the first test flow path UP11 and the second test flow path UP12 and is discharged through the first outlet hole 31f and the second outlet hole 31h.

[0138] On the other hand, blood is injected from the third inlet hole 31a and the fourth inlet hole 31c, and the injected blood enters the third test flow path UP21 and the fourth test flow path UP22 and touches the vascular endothelial cells respectively. The surplus blood passes through the third test flow path UP21 and the fourth test flow path UP22 and is discharged through the third outlet hole 31b and the fourth outlet hole 31d.

[0139] Next, the expansion and contraction operation of the biological function chip 30 will be described. When a DC voltage is not applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP by a signal from the control device, the internal pressure of the pressure chamber PC is equivalent to the atmosphere. Therefore, as shown in FIG. 16(a), the first elastic membrane 33 and the second elastic membrane 35 are maintained in the state before deformation.

[0140] On the other hand, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP by a signal from the control device, the ECF in the drive path DP flows from the pressure chamber PC toward the reservoir RV as shown in Fig. 16(b). The second elastic membrane 35 facing the reservoir RV elastically deforms, so that the ECF flowing into the reservoir RV can be stored, increasing its volume.

[0141] Due to the flow of the ECF, the internal pressure of the pressure chamber PC decreases, so that the second elastic membrane 35 facing it deforms downward. As a result, the partition walls 34i and 32i shift downward, causing the first elastic membrane 33 and the third membrane member 31 to also deform so as to sink. Accordingly, the porous portions 33m and 33n, which are part of the first elastic membrane 33, also elastically deform downward, and tensile stress acts on the porous portions 33m and 33n. In response to this, the alveolar epithelial cells on the upper surface of the porous portions 33m and 33n are stretched by being pulled left and right, and the vascular endothelial cells on the lower surface of the porous portions 33m and 33n are also stretched by being pulled left and right.

[0142] When the power supply to the electrode unit 16 in the central drive path DPC is stopped, the internal pressure of the pressure chamber PC decreases. As a result, the second elastic membrane 35 and the porous portions 33m and 33n return to their original positions shown in Fig. 16(a) due to the elastic force acting on the membranes themselves, so that the alveolar epithelial cells and the vascular endothelial cells also return to their original states.

[0143] In the fourth embodiment, the test flow paths UP11 to UP22 are provided independently. For example, two types of alveolar epithelial cells and vascular endothelial cells can be evaluated simultaneously under the same conditions, so that the efficiency of, for example, preclinical trials can be improved.

[0144] (Fifth Embodiment) FIG. 17 is a perspective view of the biological function chip 30' according to the fifth embodiment, with the internal structure shown by dotted lines. FIG. 18 is a perspective view showing the biological function chip 30' disassembled. The biological function chip 30' of the fifth embodiment is of the sunken single-sided pump drive type. For the common configurations with respect to the fourth embodiment, the same reference numerals are used and the overlapping descriptions are omitted.

[0145] The biological function chip 30' is formed by a third membrane member 31', an upper plate 32', a first elastic membrane 33', an intermediate plate 34', a second elastic membrane 35, a lower plate 36, and a pump substrate 37, which do not have the structures related to the second test flow path UP12 and the fourth test flow path UP22 of the first embodiment.

[0146] Specifically, the third membrane member 31', the upper plate 32', the first elastic membrane 33', and the intermediate plate 34' have a configuration cut at the intermediate position in the short side direction with respect to the first embodiment. The second elastic membrane 35, the lower plate 36, and the pump substrate 37 have the same configurations as those of the first embodiment.

[0147] (Operation of the biological function chip) FIG. 19 is a schematic cross-sectional view schematically showing the operation of the biological function chip 30' of the fifth embodiment.

[0148] Here, it is assumed that alveolar epithelial cells are cultured on the upper surface of the porous portion 33m, and vascular endothelial cells are cultured on the lower surface thereof.

[0149] Furthermore, air is injected from the first inlet hole 31e, and the injected air enters the first test flow path UP11 and touches the alveolar epithelial cells. The excess air passes through the first test flow path UP11 and is discharged from the first outlet hole 31f.

[0150] On the other hand, blood is injected from the third inlet hole 31a, and the injected blood enters the third test flow path UP21 and touches the vascular endothelial cells. The excess blood passes through the third test flow path UP21 and is discharged through the third outlet hole 31b.

[0151] Next, the expansion and contraction operation of the biological function chip 30' will be described. When a DC voltage is not applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP according to a signal from the control device, as shown in Fig. 19(a), the internal pressure of the pressure chamber PC is equivalent to the atmosphere. Therefore, the first elastic membrane 33' and the second elastic membrane 35 are maintained in the state before deformation.

[0152] On the contrary, when a DC voltage is applied to the slit electrode 16a and the triangular prism electrode 16b of the electrode unit 16 in the drive path DP according to a signal from the control device, the ECF in the drive path DP2 flows from the pressure chamber PC toward the reservoir RV side as shown in Fig. 19(b). When the second elastic membrane 35 facing the reservoir RV elastically deforms, the ECF flowing into the reservoir RV can be stored, and its volume can be increased.

[0153] Due to the flow of the ECF, the internal pressure of the pressure chamber PC decreases, so the second elastic membrane 35 facing it deforms downward. As a result, the partition walls 34i and 32i shift downward, so the first elastic membrane 33' and the third membrane member 31 also deform so as to sink. Thereby, the porous part 33m which is a part of the first elastic membrane 33' also elastically deforms downward, and tensile stress acts on the porous part 33m. In response to this, the alveolar epithelial cells on the upper surface of the porous part 33m are stretched by being pulled left and right, and the vascular endothelial cells on the lower surface of the porous part 33m are also stretched by being pulled left and right.

[0154] When the power supply to the electrode unit 16 of the central drive path DPC is stopped, the internal pressure of the pressure chamber PC decreases. As a result, the second elastic membrane 35 and the porous part 33m return to the original positions shown in Fig. 19(a) due to the elastic force acting on the membrane itself, so the alveolar epithelial cells and the vascular endothelial cells also return to the original state.

[0155] According to the fifth embodiment, the configuration of the biological function chip 30' can be further simplified.

Explanation of symbols

[0156] 10, 10’, 20, 30, 30’ Biological function chips 11, 11’ Upper plates 12, 12’ Elastic membranes 13, 13’ Lower plates 14, 14’ Pump substrates 16 Electrode units 21 Upper plates 22 First elastic membranes 23 Intermediate plates 24 Second elastic membranes 25 Lower plates 25 26 Pump substrates 31, 31’ Third membrane members 32, 32’ Upper plates 33, 33’ First elastic membranes 34, 34’ Intermediate plates 35 Second elastic membranes 36 Lower plates 37 Pump substrates

Claims

1. A first elastic membrane having a surface capable of culturing cells, A holding plate for holding the first elastic membrane, A pressure chamber formed within the holding plate, A drive path connected to the pressure chamber, An operating fluid injected into the pressure chamber and the drive path, An electrode unit disposed within the drive path, and having, When a DC voltage is applied to the electrode unit, the operating fluid moves within the drive path and the pressure in the pressure chamber changes, thereby applying tensile stress to the first elastic membrane. A biofunctional chip characterized by the above.

2. The pressure chamber faces the cells cultured on the first elastic membrane with a partition joined to the first elastic membrane therebetween. The biofunctional chip according to claim 1, characterized by the above.

3. The holding plate is formed to enclose the cells cultured on the first elastic membrane and has a flow path through which fluid can pass. The biofunctional chip according to claim 1 or 2, characterized by the above.

4. Cells can be cultured facing both surfaces of the first elastic membrane, and a pair of the flow paths are arranged so as to enclose the respective cells. The biofunctional chip according to claim 3, characterized by the above.

5. The pressure chamber is disposed on both sides sandwiching the cells cultured on the first elastic membrane, and a pair of the drive paths are each connected to the respective pressure chamber. The biofunctional chip according to any one of claims 1 to 4, characterized by the above.

6. The pressure chamber is disposed on both sides sandwiching the cells cultured on the first elastic membrane, and a single drive path is connected to a pair of the pressure chambers. The biofunctional chip according to any one of claims 1 to 4, characterized by the above.

7. [[ID=2�]]Further having a second elastic membrane parallel to and spaced apart from the surface of the first elastic membrane capable of culturing cells, The pressure chamber is disposed on the side opposite to the first elastic membrane with the second elastic membrane therebetween. The biofunctional chip according to claim 1, characterized by the above.

8. A flow path through which fluid can pass is provided between the first elastic membrane and the second elastic membrane. The biofunctional chip according to claim 7, characterized by the above.

9. Further having a valve mechanism for blocking the inflow of fluid into the flow path and the outflow of fluid from the flow path, The valve mechanism has an operating fluid injected into a valve drive path and an electrode unit disposed within the valve drive path. The biofunctional chip according to claim 8, characterized by the above.

10. It further has, on both sides sandwiching the cell-culturable surface of the first elastic membrane, a spaced-apart second elastic membrane and third elastic membrane. The pressure chamber is disposed on the side opposite to the first elastic membrane with the second elastic membrane therebetween. The biofunctional chip according to claim 1, characterized in that.

11. Flow paths through which fluid can pass are provided between the first elastic membrane and the second elastic membrane and between the first elastic membrane and the third elastic membrane. The biofunctional chip according to claim 10, characterized in that.

12. A first partition wall connecting the first elastic membrane and the second elastic membrane and a second partition wall connecting the first elastic membrane and the third elastic membrane are disposed at opposing positions. The biofunctional chip according to claim 10 or 11, characterized in that.

13. A pair of flow paths through which fluid can pass are provided between the first elastic membrane and the second elastic membrane with the first partition wall therebetween, and a pair of flow paths through which fluid can pass are provided between the first elastic membrane and the third elastic membrane with the second partition wall therebetween. The biofunctional chip according to claim 12, characterized in that.

14. A single flow path through which fluid can pass is provided and surrounded by the first elastic membrane, the second elastic membrane, and the first partition wall, and a single flow path through which fluid can pass is provided and surrounded by the first elastic membrane, the third elastic membrane, and the second partition wall. The biofunctional chip according to claim 12, characterized in that.

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