Cell membrane current measurement device

Abstract

In the present invention, a current related to a cell membrane formed in a well is measured appropriately by a measurement circuit. Specifically, a cell membrane current measurement device 1 comprises a plate-shaped chip 10 and a substrate 76 disposed so as to face the chip 10. A well 20 for forming a cell membrane 64 is provided in the surface 11 of the chip 10 on the opposite side from the substrate 76. An electrode 25 disposed in the well 20 is exposed on a surface 12 of the chip 10 on the substrate 76 side. The substrate 76 is provided with a measurement circuit 100 for measuring a current I related to the cell membrane 64 formed in the well 20. The substrate 76 is provided with a conduction member 70 fixed to the substrate 76 and extending linearly from the substrate 76 toward the chip 10. The electrode 25 and the measurement circuit 100 are electrically connected by bringing the conduction member 70 into contact with the electrode 25.

Description

Cell membrane current measurement device

[0009] ,

[0008] , ,

[0001] The present disclosure relates to a cell membrane current measurement device.

[0002] For example, as shown in Patent Document 1, various techniques regarding cell membranes are disclosed. In Patent Document 1, an artificial cell membrane is formed within a well formed on a plate-shaped chip.

[0003] Japanese Patent Application Laid-Open No. 2007-029911 <*000*008> The chip is provided with a well for forming a cell membrane. The measurement circuit measures the current related to the cell membrane formed in the well.

[0005] When the measurement circuit and the well are disposed far from each other, due to the influence of noise (disturbance, stray capacitance, etc.), the current related to the cell membrane may not be appropriately measured by the measurement circuit.

[0006] An object of the present disclosure is to appropriately measure, by a measurement circuit, the current related to the cell membrane formed in the well. [[ID=*20*]]

[0007] The cell membrane current measurement device according to the present disclosure includes a plate-shaped chip and a substrate disposed to face the chip. On a surface of the chip opposite to the substrate, a well for forming a cell membrane is provided. On a surface of the chip on the substrate side, an electrode disposed in the well is exposed. On the substrate, a measurement circuit for measuring the current related to the cell membrane formed in the well is provided. On the substrate, a conductive member fixed to the substrate and linearly extending from the substrate toward the chip is provided. By the conductive member contacting the electrode, the electrode and the measurement circuit are electrically connected

[0008] The plate-shaped chip and the substrate face each other. The conductive member is fixed to the substrate. The conductive member linearly extends from the substrate toward the chip.

[0009] The electrodes in the wells of the chip and the measurement circuit on the substrate can be brought closer together. When measuring the current related to the cell membrane formed in the wells using the measurement circuit, the influence of noise becomes less significant. The deterioration of the current measurement accuracy by the measurement circuit can be suppressed.

[0010] The current related to the cell membrane formed in the well can be appropriately measured by the measurement circuit.

[0011] In a cell membrane current measuring device according to one embodiment, the measuring circuit has an amplification circuit for amplifying the current, and in a first direction along the substrate, the distance between the conductive member and the amplification circuit is smaller than the thickness of the substrate.

[0012] By bringing the contact pins closer to the amplification circuit, it is possible to suppress the application of noise before amplification in the amplification circuit, which would amplify the noise component and cause the current component related to the cell membrane to be buried in the noise component.

[0013] In a cell membrane current measuring device according to one embodiment, the well includes a first well and a second well, the electrode includes a first electrode disposed in the first well and a second electrode disposed in the second well, the conductive member includes a first conductive member that contacts the first electrode and a second conductive member that contacts the second electrode, the measuring circuit includes a first measuring circuit for measuring a first current as the current relating to the cell membrane formed in the first well and a second measuring circuit for measuring a second current as the current relating to the cell membrane formed in the second well, the first measuring circuit has a first amplification circuit for amplifying the first current and the second measuring circuit has a second amplification circuit for amplifying the second current, the distance between the first conductive member and the first amplification circuit in a first direction along the substrate is smaller than the distance between the first conductive member and the second amplification circuit, and the distance between the second conductive member and the second amplification circuit in the first direction is smaller than the distance between the second conductive member and the first amplification circuit.

[0014] By bringing the contact pins closer to the amplification circuit, it is possible to suppress the application of noise before amplification in the amplification circuit, which would amplify the noise component and cause the current component related to the cell membrane to be buried in the noise component.

[0015] A cell membrane current measuring device according to one embodiment comprises a housing that accommodates the chip, the substrate, and the conductive member.

[0016] It can suppress the intrusion of external noise.

[0017] According to this disclosure, the current related to the cell membrane formed in the well can be appropriately measured by the measurement circuit.

[0018] Figure 1 shows a cross-sectional view of an artificial cell membrane current measuring device. Figure 2 shows a chip for forming an artificial cell membrane. Figure 3 shows an artificial cell membrane. Figure 4 shows a method for forming an artificial cell membrane. Figure 5 shows the top surface of the substrate. Figure 6 shows a circuit block diagram.

[0019] Embodiments of the present disclosure will be described in detail below with reference to the drawings. The following description of preferred embodiments is illustrative in nature and is not intended to limit the present disclosure, its applications, or its uses in any way.

[0020] (Artificial Cell Membrane Current Measuring Device) Figure 1 shows an artificial cell membrane current measuring device 1 as a cell membrane current measuring device, in a cross-sectional view (along line P in Figure 2). The artificial cell membrane current measuring device 1 comprises a chip 10, a support base 50, contact pins 70 as conductive members, a substrate 76, a housing 80, a lid 86, and a support column 99.

[0021] (Artificial Cell Membrane Chip) Figure 2 shows a chip 10 (artificial cell membrane chip) for forming an artificial cell membrane 64 as a cell membrane, viewed from above Za. The chip 10 is plate-shaped. The plate-shaped chip 10 has a thickness in the vertical direction Z and extends horizontally. In this example, the chip 10 is formed in a roughly rectangular shape. The upper surface 11 of the chip 10 includes an outer peripheral portion 13 and a central portion 14. The central portion 14 is located inside the outer peripheral portion 13 in the horizontal direction. The outer peripheral portion 13 is located outside the central portion 14 in the horizontal direction.

[0022] Multiple wells 20 are provided on the upper surface 11 of the chip 10. In this example, 96 wells 20 are arranged on the upper surface 11 of the chip 10, 12 in the front-to-back direction and 8 in the left-to-right direction (some figures are omitted from the illustration). The number of wells 20 in the chip 10 may be 1, 2 to 95, or 97 or more. The wells 20 are there to form an artificial cell membrane 64. The artificial cell membrane 64 is an artificially created cell membrane.

[0023] The well 20 is a recess formed on the upper surface 11 of the chip 10. The well 20 includes a first portion 21 and a second portion 22. The first portion 21 is substantially circular in shape when viewed from above Za. The second portion 22 is substantially circular in shape when viewed from above Za. The first portion 21 and the second portion 22 are connected so as to be adjacent to each other.

[0024] The first part 21 and the second part 22 are separated from each other by a partition wall 23. The partition wall 23 divides (partitions) the first part 21 and the second part 22. The partition wall 23 is provided with a through hole 24 (see Figure 1). The through hole 24 penetrates the partition wall 23. The through hole 24 connects the first part 21 and the second part 22.

[0025] As shown in Figures 1 and 2, electrodes 25 are positioned on the bottom surface of the well 20. The electrodes 25 penetrate the tip 10 in the vertical direction Z. The electrodes 25 are positioned on the bottom surface of the first portion 21 and the bottom surface of the second portion 22, respectively. In other words, there are two electrodes 25 in one well 20. The electrodes 25 are exposed on the bottom surface 12 of the tip 10. The electrodes 25 are made of, for example, metal.

[0026] (Artificial cell membrane) Figure 3 shows the artificial cell membrane 64 as viewed from above (Za). The artificial cell membrane 64 is formed within the well 20. The artificial cell membrane 64 consists of a lipid bilayer. The artificial cell membrane 64 is an artificially formed replica of a living cell membrane.

[0027] Lipid solution 61 and buffer solution 62 are injected into the first portion 21 and the second portion 22 of well 20. The lipid solution 61 is, for example, an organic solvent (oil) in which lipid molecules are dispersed. The buffer solution 62 is, for example, water or an aqueous solution. The buffer solution 62 does not mix with the lipid solution 61.

[0028] In the first section 21 and the second section 22, clumps of buffer solution 62 (e.g., water droplets) are formed. In the first section 21 and the second section 22, a lipid monolayer 63, in which lipid molecules are arranged, spontaneously forms around the clumps of buffer solution 62.

[0029] At the through-holes 24 in the partition wall 23 between the first part 21 and the second part 22, lipid monolayers 63 overlap to form a lipid bilayer, creating an artificial cell membrane 64. Of the first part 21 and the second part 22, one mimics the interior of a living cell, and the other mimics the exterior of a living cell.

[0030] (Ion Channels) Ions and proteins 65 are dispersed in the buffer solution 62. The proteins 65 are precursors to ion channels 66. When the proteins 65 attach to the artificial cell membrane 64, ion channels 66 are formed.

[0031] The ion channel 66 is a passage that penetrates the artificial cell membrane 64. The ion channel 66 connects the buffer solution 62 of the first part 21 and the buffer solution 62 of the second part 22. Ions move between the first part 21 and the second part 22 in the ion channel 66. The ion channel 66 is a passage for ions in the artificial cell membrane 64. Examples of ions include potassium ions and sodium ions. Ions have an electric charge.

[0032] The ion channel 66 opens and closes. When the ion channel 66 opens, ions move between the first part 21 and the second part 22. When the ion channel 66 opens, an ion current I flows due to the movement of ions.

[0033] When the ion channel 66 closes, ions do not move between the first part 21 and the second part 22. When the ion channel 66 closes, a small ion current I flows. This is because even when the ion channel 66 is closed, the ion current I does not become completely zero, but flows a small amount through the ion channel 66 by leaking through the artificial cell membrane 64. The ion current I when the ion channel 66 is closed is smaller than the ion current I when the ion channel 66 is open.

[0034] (Method for forming an artificial cell membrane) Figure 4 shows a method for forming an artificial cell membrane 64. Note that Figure 4 is a cross-sectional view taken along line Q in Figure 2. The method for forming an artificial cell membrane 64 (artificial cell membrane formation method) comprises an injection step S12 (first injection step S1 and second injection step S2).

[0035] In injection step S12, the lipid solution 61 and buffer solution 62 are injected into the wells 20 (first section 21 and second section 22) using a pipette 40. Injection step S12 includes a first injection step S1 and a second injection step S2.

[0036] In the first injection step S1, the lipid solution 61 is injected into the wells 20 (first section 21 and second section 22) using a pipette 40. In the second injection step S2, the buffer solution 62 is injected into the wells 20 (first section 21 and second section 22) using a pipette 40. Note that the buffer solution 62 does not mix with the lipid solution 61.

[0037] When the injection process S12 (first injection process S1 and second injection process S2) is completed, the artificial cell membrane 64 is formed in the well 20. Specifically, the artificial cell membrane 64 is formed as a lipid bilayer in the through-hole 24 of the partition wall 23 between the first portion 21 and the second portion 22 in the well 20.

[0038] The method for forming the artificial cell membrane 64 may be carried out mechanically and automatically by a robot or the like, or it may be carried out manually by a human.

[0039] (Support Base) As shown in FIG. 1, the support base 50 is disposed below the chip 10 in the Zb direction. The support base 50 is plate-shaped. The plate-shaped support base 50 has the vertical direction Z as the thickness direction and extends in the horizontal direction. In this example, the support base 50 has a substantially rectangular shape. The horizontal size of the support base 50 is larger than the horizontal size of the chip 10. The support base 50 supports the chip 10 from below in the Zb direction.

[0040] The support base 50 has holes 51 formed therein. The holes 51 penetrate the support base 50 in the vertical direction Z. The number of the holes 51 is the same as the number of the electrodes 25.

[0041] (Contact Pin) As shown in FIG. 1, the contact pin 70 is disposed below the chip 10 in the Zb direction. Specifically, the contact pin 70 is disposed further below the support base 50 in the Zb direction. The contact pin 70 extends in the vertical direction Z. The number of the contact pins 70 is the same as the number of the electrodes 25. The contact pin 70 has conductivity. The contact pin 70 is formed of, for example, metal. The contact pin 70 extends linearly.

[0042] As described above, the electrodes 25 are disposed on the bottom surfaces of the first portion 21 and the second portion 22 in the well 20, respectively. The electrodes 25 are exposed on the lower surface 12 of the chip 10.

[0043] The contact pin 70 includes a fixed pin 71 and a movable pin 72. The lower end portion of the fixed pin 71 is connected to a substrate 76 described later. A part of the movable pin 72 is accommodated inside the fixed pin 71. The upper end portion of the movable pin 72 projects upward in the Za direction from the hole at the upper end portion of the fixed pin 71 or retracts downward in the Zb direction into the hole at the upper end portion of the fixed pin 71. The projection and retraction of the movable pin 72 with respect to the fixed pin 71 are performed by an actuator (not shown).

[0044] The fixed pin 71 of the contact pin 70 is located below the support base 50 in the Zb direction. The movable pin 72 of the contact pin 70 penetrates the hole 51 of the support base 50 from below in the Zb direction to above in the Za direction.

[0045] The contact pin 70 contacts the electrode 25 from below in the Zb direction. The contact pin 70 contacts the electrode 25 from below in the Zb direction through a hole 51 formed in the support base 50.

[0046] (Substrate) The substrate 76 is, for example, a printed circuit board. The substrate 76 is plate-shaped. The plate-shaped substrate 76 has the vertical direction Z as the thickness direction and extends in the horizontal direction. In this example, the substrate 76 is substantially rectangular. The substrate 76 is formed mainly of resin. Wiring made of copper foil is formed on the substrate 76.

[0047] The substrate 76 is disposed below the contact pin 70 in the Zb direction. The upper surface 76a of the substrate 76 is connected to the lower end of the fixing pin 71 of the contact pin 70.

[0048] The substrate 76 is provided with a measurement circuit 100 and a buffer circuit 110. The measurement circuit 100 and the buffer circuit 110 will be described later.

[0049] (Housing) The housing 80 is box-shaped. The housing 80 is, for example, substantially rectangular parallelepiped. The housing 80 is provided with an opening 81 in the upper Za direction. In this example, the opening 81 is substantially rectangular. The housing 80 houses the chip 10, the substrate 76, and the contact pin 70. Specifically, the housing 80 houses the chip 10 (well 20), the support base 50, the substrate 76, the contact pin 70, and a support column 99 described later.

[0050] (Cover) The cover 86 is plate-shaped. The plate-shaped cover 86 has the vertical direction Z as the thickness direction and extends in the horizontal direction. In this example, the cover 86 is substantially rectangular. The cover 86 covers the opening 81 in the upper Za direction of the housing 80. By the cover 86 covering the opening 81 of the housing 80, intrusion of noise into the housing 80 is prevented. A handle 87 is provided on the upper surface of the cover 86. The handle 87 is grasped by the user.

[0051] Note that noise includes disturbances and stray capacitance.

[0052] (Support Columns) There are four support columns 99. The support columns 99 extend in the vertical direction Z. The support columns 99 pass through the four corners of the support base 50 and the four corners of the base plate 76. The support base 50 and the base plate 76 are fixed to the support columns 99.

[0053] (Relationship between chip, substrate and contact pins) The substrate 76 is positioned below Zb from the chip 10. The chip 10 is positioned above Za from the substrate 76. A support base 50 and contact pins 70 are positioned between the chip 10 and the substrate 76.

[0054] The substrate 76 is positioned to face the chip 10. The chip 10 is positioned to face the substrate 76. Specifically, the chip 10 and the substrate 76 face each other with the support base 50 and contact pins 70 in between.

[0055] The upper surface 11 of the chip 10 is the surface of the chip 10 opposite to the substrate 76. The lower surface 12 of the chip 10 is the surface of the chip 10 facing the substrate 76. The upper surface 76a of the substrate 76 is the surface of the substrate 76 facing the chip 10. The lower surface 76b of the substrate 76 is the surface of the substrate 76 opposite to the chip 10.

[0056] The substrate 76 is provided with contact pins 70. The contact pins 70 are fixed to the substrate 76. Specifically, the lower end of the fixing pin 71 of the contact pin 70 is fixed to the upper surface 76a of the substrate 76.

[0057] The contact pin 70 extends linearly from the substrate 76 toward the chip 10. More specifically, the contact pin 70 extends linearly upward from the upper surface 76a of the substrate 76 toward the electrode 25 exposed on the lower surface 12 of the chip 10. The upper end of the movable pin 72 of the contact pin 70 contacts the electrode 25.

[0058] (Measurement Circuit) Figure 5 shows the upper surface 76a of the substrate 76. Figure 6 shows the circuit block diagram. Circuits provided on the upper surface 76a of the substrate 76 are shown with solid lines, and circuits provided on the lower surface 76b of the substrate 76 are shown with dashed lines.

[0059] The circuit board 76 is provided with measurement circuits 100. There are multiple measurement circuits 100. One measurement circuit 100 is provided for each well 20. The number of measurement circuits 100 is the same as the number of wells 20. In this example, the circuit board 76 is provided with 96 measurement circuits 100 (96 channels). The circuit board 76 is also provided with 96 pairs (2 pins per pair) of contact pins 70.

[0060] The measurement circuit 100 is for measuring the ion current I, which is the current related to the artificial cell membrane 64 formed in the well 20.

[0061] The circuit board 76 is provided with buffer circuits 110. There are multiple buffer circuits 110. One buffer circuit 110 is provided for each well 20. The number of buffer circuits 110 is the same as the number of wells 20. In this example, the circuit board 76 is provided with 96 buffer circuits 110 (96 channels).

[0062] The measurement circuit 100 includes an upstream amplifier circuit 101, a downstream amplifier circuit 102, and a low-pass filter 103, which act as amplification circuits. Here, two (a pair) of electrodes 25 correspond to one well 20.

[0063] The upstream amplification circuit 101 is, for example, a transimpedance amplifier. The upstream amplification circuit 101 is electrically connected to one of the pair of electrodes 25. As an amplifier, the upstream amplification circuit 101 amplifies the ion current I. Also, as a converter, the upstream amplification circuit 101 converts the ion current I into a voltage. Note that "amplifying the ion current I" includes directly amplifying the ion current I, and amplifying the voltage after converting the ion current I into a voltage. One upstream amplification circuit 101 is provided for each measurement circuit 100. The upstream amplification circuit 101 is provided on the lower surface 76b of the substrate 76.

[0064] The downstream amplifier circuit 102 is electrically connected to the upstream amplifier circuit 101. The downstream amplifier circuit 102 amplifies the voltage converted from the ion current I by the upstream amplifier circuit 101. One downstream amplifier circuit 102 is provided for every two measurement circuits 100. The downstream amplifier circuit 102 is provided on the upper surface 76a of the substrate 76.

[0065] The low-pass filter 103 is electrically connected to the downstream amplification circuit 102. The low-pass filter 103 filters the voltage amplified by the downstream amplification circuit 102. Specifically, the low-pass filter 103 allows only low-frequency voltages to pass through and blocks high-frequency voltages. One low-pass filter 103 is provided for every two measurement circuits 100. The low-pass filter 103 is provided on the upper surface 76a of the substrate 76. The low-pass filter 103 may be electrically connected to a computer. The computer, for example, determines the opening probability of the ion channel 66.

[0066] The buffer circuit 110 is electrically connected to the other electrode 25 of the pair of electrodes 25. The buffer circuit 110 is also electrically connected to a power supply (not shown). The buffer circuit 110 distributes the command voltage supplied from the power supply to each well 20. The buffer circuit 110 is located on the lower surface 76b of the substrate 76. The buffer circuit 110 is positioned directly behind the contact pins 70, with the substrate 76 in between.

[0067] When the contact pin 70 contacts the electrode 25, the electrode 25 and the measurement circuit 100 are electrically connected. Similarly, when the contact pin 70 contacts the electrode 25, the electrode 25 and the buffer circuit 110 are electrically connected.

[0068] Specifically, one of the pair of contact pins 70 contacts one of the pair of electrodes 25, and the other of the pair of contact pins 70 contacts the other of the pair of electrodes 25, thereby forming an electrical circuit that includes the pair of electrodes 25, the pair of contact pins 70, the measuring circuit 100, the buffer circuit 110, and the power supply.

[0069] However, if the electrodes 25 of the well 20 in the chip 10 and the measurement circuit 100 on the substrate 76 are located far apart from each other, the measurement of the ion current I related to the artificial cell membrane 64 formed in the well 20 by the measurement circuit 100 becomes susceptible to noise. In this case, the measurement accuracy of the ion current I by the measurement circuit 100 deteriorates.

[0070] In particular, if the distance L between the contact pin 70 and the upstream amplifier circuit 101 is large (i.e., if the contact pin 70 and the upstream amplifier circuit 101 are far apart), noise is applied to the ion current I before it reaches the upstream amplifier circuit 101, and the noise component is amplified by the upstream amplifier circuit 101. Therefore, even if the signal is amplified by the upstream amplifier circuit 101, the ion current I component is buried in the noise component. In other words, the noise negatively affects the upstream amplifier circuit 101. In this case, the measurement accuracy of the ion current I by the measurement circuit 100 deteriorates further.

[0071] In the measurement circuit 100, the distance from the contact pin 70 in the first direction H along the substrate 76 is smallest (closest) in the order of upstream amplifier circuit 101, downstream amplifier circuit 102, and low-pass filter 103. Note that the first direction H along the substrate 76 is the direction in which the substrate 76 extends, and in this example, it is the horizontal direction.

[0072] Therefore, in the first direction H along the substrate 76, the distance L between the contact pin 70 and the upstream amplifier circuit 101 is smaller than the thickness T of the substrate 76.

[0073] (Wells, electrodes, contact pins, measurement circuit) As shown in the second column from the left in Figure 2, well 20 includes a first well 20A, a second well 20B, a third well, and so on.

[0074] As shown in the second column from the left in Figure 2, the electrode 25 includes a first electrode 25A located in the first well 20A, a second electrode 25B located in the second well 20B, a third electrode located in the third well, and so on.

[0075] As shown in Figure 5, the contact pin 70 includes a first contact pin 70A that contacts the first electrode 25A, a second contact pin 70B that contacts the second electrode 25B, a third contact pin that contacts the third electrode, and so on. The first contact pin 70A is an example of a first conductive member. The second contact pin 70B is an example of a second conductive member.

[0076] As shown in Figure 5, the measurement circuit 100 includes a first measurement circuit 100A for measuring a first ion current IA as the ion current I related to the artificial cell membrane 64 formed in the first well 20A, a second measurement circuit 100B for measuring a second ion current IB as the ion current I related to the artificial cell membrane 64 formed in the second well 20B, a third measurement circuit for measuring a third ion current as the ion current I related to the artificial cell membrane 64 formed in the third well, and so on. The first ion current IA is an example of the first current. The second ion current IB is an example of the second current.

[0077] As shown in Figure 5, the first measurement circuit 100A has a first upstream amplifier circuit 101A that amplifies the first ion current IA. The second measurement circuit 100B has a second upstream amplifier circuit 101B that amplifies the second ion current IB. The first upstream amplifier circuit 101A is an example of the first amplifier circuit. The second upstream amplifier circuit 101B is an example of the second amplifier circuit.

[0078] In the first direction H along the substrate 76, the distance LAA between the first contact pin 70A and the first upstream amplifier circuit 101A is smaller than the distance LAB between the first contact pin 70A and the second upstream amplifier circuit 101B.

[0079] In the first direction H along the substrate 76, the distance LBB between the second contact pin 70B and the second upstream amplifier circuit 101B is smaller than the distance LBA between the second contact pin 70B and the first upstream amplifier circuit 101A.

[0080] The measurement circuit 100 with the above configuration is formed to be long in the direction of connection between the first portion 21 and the second portion 22 that form the wells 20 on the chip 10. This makes it possible to set a short spacing between the wells 20.

[0081] Furthermore, in the case of components such as the upstream amplifier circuit 101, where crosstalk may occur between adjacent measurement circuits 100, a GND line is provided between the relevant components of the measurement circuits 100 to prevent crosstalk. On the other hand, in the case of components such as the low-pass filter 103, where there is no concern about crosstalk, the space required for the measurement circuits 100 may be reduced by sharing a set of components among multiple measurement circuits 100.

[0082] (Effects) The plate-shaped chip 10 and the substrate 76 face each other. The contact pins 70 are fixed to the substrate 76. The contact pins 70 extend linearly from the substrate 76 toward the chip 10.

[0083] The electrodes 25 in the well 20 of the chip 10 and the measurement circuit 100 on the substrate 76 can be brought closer together. When measuring the ion current I related to the artificial cell membrane 64 formed in the well 20 using the measurement circuit 100, the influence of noise becomes less pronounced. The deterioration of the measurement accuracy of the ion current I by the measurement circuit 100 can be suppressed.

[0084] The ion current I related to the artificial cell membrane 64 formed in the well 20 can be appropriately measured by the measurement circuit 100.

[0085] Since the contact pin 70 extends in a straight line, it becomes easier to bring the electrode 25 of the well 20 in the chip 10 closer to the measurement circuit 100 on the substrate 76.

[0086] In particular, the proximity of the contact pin 70 and the upstream amplification circuit 101 prevents noise from being applied before amplification in the upstream amplification circuit 101, which would amplify the noise component and cause the ion current I component related to the artificial cell membrane 64 to be buried in the noise component. This suppresses the adverse effects on the upstream amplification circuit 101 caused by noise.

[0087] The housing 80 houses the chip 10, the circuit board 76, and the contact pins 70. This helps to suppress the intrusion of noise from the outside.

[0088] (Other Embodiments) Although the present disclosure has been described above with reference to preferred embodiments, this description is not limiting, and of course, various modifications, substitutions, or combinations are possible.

[0089] Well 20 may contain a cell membrane made of living tissue (biological cell membrane). In this case, it becomes a biological cell membrane current measuring device.

[0090] The well 20 may have any shape. The first portion 21, the second portion 22, the partition wall 23, and the through hole 24 are not required in the well 20.

[0091] The chip 10 is not limited to a roughly rectangular shape. For example, the chip 10 may have a polygonal shape other than a roughly rectangular shape, or a circular shape, etc.

[0092] The conductive component does not have to be a contact pin.

[0093] The chip 10 and the substrate 76 may be arranged facing each other horizontally. Alternatively, the chip 10 and the substrate 76 may be arranged upside down compared to the above embodiment.

[0094] This disclosure is extremely useful and has high potential for industrial application because it can be applied to cell membrane current measuring devices.

[0095] 1. Artificial cell membrane current measuring device (cell membrane current measuring device) 10. Chip 11. Top surface 12. Bottom surface 20. Well 20A. First well 20B. Second well 25. Electrode 25A. First electrode 25B. Second electrode 64. Artificial cell membrane (cell membrane) 70. Contact pin (conductive member) 70A. First contact pin (first conductive member) 70B. Second contact pin (second conductive member) 76. Substrate 80. Housing 100. Measurement circuit 100A. First measurement circuit 100B. Second measurement circuit 101. Upstream amplifier circuit (amplifier circuit) 101A. First upstream amplifier circuit (first amplifier circuit) 101B. Second upstream amplifier circuit (second amplifier circuit)

Claims

1. A cell membrane current measuring device comprising: a plate-shaped chip; a substrate positioned facing the chip; a well for forming a cell membrane provided on the surface of the chip opposite to the substrate; electrodes positioned in the well exposed on the surface of the chip facing the substrate; a measuring circuit for measuring the current related to the cell membrane formed in the well provided on the substrate; a conductive member fixed to the substrate and extending linearly from the substrate toward the chip provided on the substrate; and the electrodes and the measuring circuit being electrically connected by the conductive member contacting the electrodes.

2. The cell membrane current measuring device according to claim 1, wherein the measuring circuit has an amplification circuit for amplifying the current, and in a first direction along the substrate, the distance between the conductive member and the amplification circuit is less than the thickness of the substrate.

3. The well includes a first well and a second well; the electrode includes a first electrode disposed in the first well and a second electrode disposed in the second well; the conductive member includes a first conductive member in contact with the first electrode and a second conductive member in contact with the second electrode; the measuring circuit includes a first measuring circuit for measuring a first current as the current relating to the cell membrane formed in the first well and a second measuring circuit for measuring a second current as the current relating to the cell membrane formed in the second well; the first measuring circuit has a first amplification circuit for amplifying the first current; the second measuring circuit has a second amplification circuit for amplifying the second current; in a first direction along the substrate, the distance between the first conductive member and the first amplification circuit is smaller than the distance between the first conductive member and the second amplification circuit. The cell membrane current measuring device according to claim 1 or 2, wherein in the first direction, the distance between the second conductive member and the second amplification circuit is smaller than the distance between the second conductive member and the first amplification circuit.

4. The cell membrane current measuring device according to claim 1 or 2, comprising a housing for housing the chip, the substrate, and the conductive member.

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