Ion current measurement system

Abstract

Provided is an ion current measurement system capable of easily identifying whether an artificial cell membrane chip is to be used for the first time or has already been used. Specifically, the ion current measurement system measures an ion current flowing through an ion channel formed in an artificial cell membrane, using an ion current measurement device for an artificial cell membrane chip including at least one well forming the artificial cell membrane. The artificial cell membrane chip includes a display section at a predetermined site. The ion current measurement device includes an identification means. The identification means recognizes the display section to identify whether the artificial cell membrane chip is to be used for the first time or has already been used.

Description

Ion current measurement system

[0001] The present invention relates to an ion current measurement system.

[0002] Cells that make up organisms, mitochondria, Golgi bodies, endoplasmic reticulum, etc. that exist inside cells are covered by a biological membrane on the outside, and this biological membrane is basically composed of a lipid bilayer. And various proteins with physiological activities are held on the lipid bilayer in a form that penetrates this lipid bilayer, and such proteins are called transmembrane proteins. These transmembrane proteins play important roles in living organisms.

[0003] One type of such transmembrane protein is an ion channel. An ion channel is a general term for proteins that pass ions passively. In addition to maintaining and changing the membrane potential of cells, it also allows the inflow and outflow of ions in cells. It is involved in the generation of action potentials in electrically excitable cells such as nerve cells, the generation of receptor potentials in sensory cells, and the maintenance of the resting membrane potential in cells.

[0004] When the ion channel opens, ions permeate through it, and when it closes, the permeation of ions stops. Therefore, due to the opening and closing of the ion channel, the flow of ions passing through the lipid bilayer changes, and the ion current changes.

[0005] In recent years, as described in Patent Documents 1 to 3, an artificial lipid bilayer is formed, an ion channel is introduced therein, and the effects of various pharmaceuticals are confirmed to develop pharmaceuticals.

[0006] Japanese Patent Publication No. 2010 - 513332, Japanese Unexamined Patent Application Publication No. 2012 - 81405, Japanese Unexamined Patent Application Publication No. 2017 - 158464

[0007] As described in Patent Document 2, an artificial cell membrane is prepared by adding a lipid bilayer-forming lipid solution to two recesses separated by a partition wall having a through-hole. Specifically, two adjacent and connected recesses are provided on a substrate (for example, a plastic plate), and a partition wall is placed in the connected part.

[0008] An artificial cell membrane is created by adding a lipid bilayer-forming lipid solution to a substrate (artificial cell membrane chip) with such recesses, and this is used to measure ion currents and test to confirm the effects of various pharmaceuticals. When testing pharmaceuticals, reagents are adsorbed onto the septum surface and well surface of the artificial cell membrane chip, resulting in the artificial cell membrane chip being contaminated with the reagents.

[0009] Artificial cell membrane chips contaminated with reagents could not be completely cleaned to remove the reagents for reuse, and the adsorbed reagents affected the results of subsequent tests.

[0010] While it would be ideal to always use new artificial cell membrane chips for testing without washing and reusing them, there is a risk of unintentionally reusing the same chip or washing and reusing used chips to reduce costs. In such cases, it may be impossible to distinguish between used and new artificial cell membrane chips.

[0011] The present invention has been made in view of the above, and its objective is to provide an ion current measurement system that can easily identify whether an artificial cell membrane chip is being used for the first time or has been used before.

[0012] The present invention relates to an ion current measurement system that measures the ion current flowing through ion channels formed in an artificial cell membrane using an ion current measuring device, with respect to an artificial cell membrane chip having at least one well for forming an artificial cell membrane, wherein the artificial cell membrane chip is provided with a display unit at a predetermined location, and the ion current measuring device is provided with an identification means, the identification means is characterized in that it identifies whether the artificial cell membrane chip is being used for the first time or has been used by recognizing the display unit.

[0013] A used artificial cell membrane chip means that it has been used to form an artificial cell membrane and measure ion current using an ion current measuring device at least once.

[0014] The display unit may be a part on which an optically or electrically readable identification mark is displayed.

[0015] Once the artificial cell membrane chip has been used, information indicating that it has been used may be added to the identification information obtainable by reading the identification mark on the artificial cell membrane chip.

[0016] The display unit has memory, and information indicating that it is in use may be assigned to this memory.

[0017] The display unit may be a part whose structure changes physically.

[0018] The change in the structure of the display unit may be irreversible.

[0019] The ion current measuring device may be configured to measure the ion current when the identification means identifies that the artificial cell membrane chip is being used for the first time, and not measure the ion current when the identification means identifies that the artificial cell membrane chip has been used.

[0020] According to the ion current measurement system of the present invention, it is possible to easily identify whether an artificial cell membrane chip is being used for the first time or has been used before, and the effects of contamination of the well due to previous use can be avoided in the measurement and analysis of ion current.

[0021] Figure 1 is a schematic diagram showing the configuration of an artificial cell membrane chip according to an embodiment. Figure 2 is a schematic diagram showing the configuration for measuring ion current according to an embodiment.

[0022] Embodiments of the present invention will be described in detail below with reference to the drawings. The following description of preferred embodiments is essentially illustrative and is not intended to limit the present invention, its applications, or its uses.

[0023] (Embodiment 1) Figure 1 shows an artificial cell membrane chip according to Embodiment 1. The artificial cell membrane chip 1 is provided with four wells 10, and an artificial cell membrane is formed in these wells 10. The wells 10 are formed by providing two adjacent recesses (a first recess 3 and a second recess 4) on a substrate 2 made of plastic, and separating the communicating portion between the first recess 3 and the second recess 4 via a partition wall 5 having a through hole. A display unit 50 is provided on the substrate 2. Details of the display unit 50 will be described later.

[0024] Next, we will explain the measurement of artificial cell membranes and ion currents. As shown in Figure 2, an artificial cell membrane 15 consisting of a lipid bilayer is formed in well 10. The artificial cell membrane 15 is modeled after the cell membrane of a living organism.

[0025] The method for forming the artificial cell membrane 15 is as follows, for example. First, an organic solvent (oil) in which lipid molecules are dispersed is placed into two recesses. The two recesses are separated by a partition wall having through-pores. Next, water containing ions is dropped into the two recesses. As a result, lipid molecules are arranged around the water mass 14, and a lipid monolayer 12 is spontaneously formed. Then, at the through-pores where the liquids of the two recesses come into contact, the lipid monolayers 12 overlap to form a lipid bilayer, and the artificial cell membrane 15 is formed. One of the two recesses mimics the inside of a living cell, and the other mimics the outside of a living cell.

[0026] In addition to ions, the water mass 14 contains dispersed proteins 13 that serve as precursors to ion channels 11. When the proteins 13 attach to the artificial cell membrane 15, ion channels 11 are formed.

[0027] The ion channel 11 serves as a passage that penetrates the artificial cell membrane 15, connecting the two water masses 14, 14 located in the two recesses. Ions move from one water mass 14 to the other through the ion channel 11. The ion channel 11 is an ion passage in the artificial cell membrane 15. Examples of ions include potassium ions and sodium ions.

[0028] The ion channel 11 opens and closes. When the ion channel 11 opens, ions move between the two water masses 14, and since ions have an electric charge, an ionic current I flows due to this movement.

[0029] The ion current analysis system of this embodiment obtains analysis results by the ion current analysis method described below.

[0030] The ion current measuring device 20 comprises a measuring unit 22, a processing unit 24, and an identification means (described later). The measuring unit 22 is an ammeter, and a known ammeter can be used. The measuring unit 22 is connected in series to both ends of the ion channel 11 (one water mass 14 side and the other water mass 14 side) and measures the ion current I flowing through the ion channel 11. The measuring unit 22 also has a function to apply a command voltage to the ion channel 11.

[0031] The artificial cell membrane chip 1, on which the artificial cell membrane 15 has been formed, is placed in the measurement area of ​​the ion current measuring device 20, and the ion current I is measured by the measurement unit 22.

[0032] The processing unit 24 is connected to the measurement unit 22, is built into the main body of the ion current measuring device 20, and includes a computer. The computer in the processing unit 24 includes, for example, a processor mounted on a circuit board, a memory device for storing software to operate the processor, and a data storage unit for storing current data.

[0033] The processing unit 24 processes the ion current I measured by the measurement unit 22 by amplifying, removing noise, and converting it to digital data to make it suitable for analysis, and stores this current data in the data storage unit. Using the stored current data, the processing unit 24 analyzes the open / closed state of the ion channel 11.

[0034] <Display Unit and Identification Means> As shown in Figure 1, the artificial cell membrane chip 1 according to Embodiment 1 has a display unit 50 provided at the corner of the rectangular substrate 2. The display unit 50 in this embodiment is an optically readable display, such as a barcode, QR code (registered trademark), serial number, or symbol. Each artificial cell membrane chip 1 is given individual identification information by the display unit 50. When the artificial cell membrane chip 1 is installed and fixed in the ion current measuring device 20, the display unit 50 is recognized and its information is read by the display reading unit (part of the identification means) provided in the ion current measuring device 20.

[0035] The information read is transmitted from the ion current measuring device 20 to the server via the internet. The server uses the transmitted information to refer to the artificial cell membrane chip information data library stored on the server to determine whether this artificial cell membrane chip 1 is being used for the first time or has been used before (used). If this artificial cell membrane chip 1 is being used for the first time, data indicating that this artificial cell membrane chip 1 has been used is written to the artificial cell membrane chip information data library.

[0036] Next, the above-mentioned discrimination data regarding the use of the artificial cell membrane chip 1 is transmitted from the server to the ion current measuring device 20 via the internet. The ion current measuring device 20 receives the discrimination data, and a discrimination data identification unit (part of the identification means) within the ion current measuring device 20 identifies whether this artificial cell membrane chip 1 is being used for the first time or whether it has been used before (used).

[0037] The ion current measuring device 20 receives discrimination data and, if it identifies that the artificial cell membrane chip 1 is being used for the first time, measures the ion current I and analyzes the open / closed state of the ion channel 11 based on that measurement. On the other hand, if it identifies that the artificial cell membrane chip 1 has already been used, it does not measure the ion current I and instead sends a notification signal to inform the user that it has been used. The user confirms the notification signal and replaces the artificial cell membrane chip 1 set in the ion current measuring device 20 with another artificial cell membrane chip 1 that is being used for the first time.

[0038] In this embodiment, the ion current measurement system is equipped with a display unit 50 on the artificial cell membrane chip 1 that displays an optically readable identification mark. When the artificial cell membrane chip 1 is placed in the device, the ion current measurement device 20 recognizes the display unit 50 and identifies whether the artificial cell membrane chip 1 is being used for the first time or has already been used. This allows the device to select the artificial cell membrane chip 1 to be used for the first time and measure the ion current. Used artificial cell membrane chips 1 are highly likely to have their wells 10 contaminated with previously used drugs, etc., and if they are contaminated in this way, accurate ion current measurement data cannot be obtained. Therefore, in this embodiment, used artificial cell membrane chips 1 are identified and not used, and the ion current is measured using an artificial cell membrane chip 1 that is being used for the first time, making it possible to measure accurate ion current data.

[0039] Each artificial cell membrane chip 1 is equipped with unique identification information via a display unit 50. By linking the measurement data of the ion current I with the identification information on the display unit 50, traceability of the measurement data can be achieved. Similarly, if multiple people measure the ion current and each uses an artificial cell membrane chip to test reagents, the measurement data of each person measuring the ion current I can be linked to apply appropriate analysis conditions.

[0040] (Embodiment 2) The ion current measurement system according to Embodiment 2 differs from Embodiment 1 in its display unit and identification means, while the other configurations and structures are the same as those of Embodiment 1. Therefore, the differences between Embodiment 2 and Embodiment 1 will be explained below.

[0041] The display unit 50 in Embodiment 2 is an electrically readable display, such as an IC tag or an RFID (registered trademark) tag. Each artificial cell membrane chip 1 is assigned individual identification information. When the artificial cell membrane chip 1 is installed and fixed in the ion current measuring device 20, the display unit 50 is recognized and its information is read by the data reading unit (part of the identification means) provided in the ion current measuring device 20.

[0042] After that, discrimination data may be received through communication with the server in the same manner as in Embodiment 1. Also, when the information of the display unit 50 can be rewritten by the data reading unit with respect to the data of, for example, an RFID (registered trademark) tag provided with a memory, information "unused" may be written in advance in the display unit 50 of the unused artificial cell membrane chip 1. When the artificial cell membrane chip 1 is installed in the ion current measuring device 20, the data reading unit reads the information, and when the ion current I is measured, the data reading unit can write information "used" in the display unit 50. Thus, even without an artificial cell membrane chip information data library, it can be determined whether it is used for the first time or already used only by reading the data of the display unit 50.

[0043] The ion current measurement system according to Embodiment 2 also has the same effect as that of Embodiment 1.

[0044] (Embodiment 3) The ion current measurement system according to Embodiment 3 is different from Embodiment 1 in the display unit and the discrimination means, and the other configurations and structures are the same as those in Embodiment 1. Therefore, the differences from Embodiment 1 in Embodiment 3 will be described below.

[0045] The display unit 50 according to Embodiment 3 is a part where the shape changes and the structure physically changes. For example, the display unit 50 is a protruding, hooked, or claw-shaped part, a thin-walled part, or a part that can be bent or folded by a cut line. When the artificial cell membrane chip 1 is installed and fixed in the ion current measuring device 20, irreversible changes such as bending, breaking, or perforating occur. The ion current measuring device 20 is provided with discrimination means for recognizing the state of the display unit 50, and discriminates whether the display unit 50 is in the same state as at the time of manufacture or physically changed (bent, broken, perforated, etc.). As the discrimination means, for example, an image sensor for discriminating the shape or the position of the display unit 50 can be used.

[0046] It is possible for the measurer to physically change the structure of the display unit 50 from its state during manufacturing. However, in order to prevent the measurer from forgetting to make the change, when installing the ion current measuring device 20, it is preferable that a physical change is made by a structure deformation part provided in the ion current measuring device 20. Thus, when the ion current measuring device 20 is provided with a structure deformation part, the time when the identification means identifies the state of the display unit 50 is the time before the structure of the display unit 50 is changed by the structure deformation part.

[0047] In the present embodiment, since the identification means of the ion current measuring device 20 can identify whether the artificial cell membrane chip 1 is being used for the first time or has been used by recognizing the state of the display unit 50 of the artificial cell membrane chip 1, there is no need to transmit data to the server as in Embodiment 1. However, for the purpose of the server grasping and managing the usage status of a large number of artificial cell membrane chips 1, it is also possible to transmit the identified data to the server.

[0048] The ion current measurement system according to Embodiment 3 also has the same effects as those of Embodiment 1.

[0049] (Other Embodiments) The above-described embodiments are examples of the present invention, and the present invention is not limited to these examples. Well-known techniques, conventional techniques, and known techniques may be combined with or partially replaced in these examples. Also, modified inventions that can be easily conceived by those skilled in the art are also included in the present invention.

[0050] The shape of the substrate is not particularly limited, and any shape such as rectangular, circular, strip-shaped, elliptical, etc. may be used.

[0051] The position where the display unit is provided in the artificial cell membrane chip is not particularly limited. As shown in FIG. 1, it may be provided at a corner portion (one of the four corners) of a rectangular substrate, a part of a side, or the central portion. Alternatively, it may be provided on the side surface or the back surface of the substrate.

[0052] In Embodiment 3, the display unit may be a switch structure part provided with a slide mechanism. In this case, the identification means may be means for identifying the position of the switch, or means for identifying that the shape changes as the switch slides, etc.

[0053] Two or more display units may be provided on a single artificial cell membrane chip, and if there are two or more, they may be of different types (for example, an optically readable display and a display whose structure physically changes). If two or more different types of display units are provided on a single artificial cell membrane chip, it is preferable that the ion current measuring device is equipped with multiple types of identification means corresponding to the multiple display units.

[0054] The information from the display unit recognized by the identification means may be sent to a server or another computer via the internet as described above, sent via a wired connection, or written to a storage means within the ion current measuring device. When writing the information from the display unit to a storage means within the ion current measuring device, the data written to that storage means and the information from the display unit are compared to determine whether this artificial cell membrane chip equipped with the display unit is being used for the first time or has already been used.

[0055] After determining that the artificial cell membrane chip equipped with the identification means is used, the ion current measuring device may be configured to either not measure the ion current or to perform the measurement.

[0056] In the above embodiment, the identification means is a means for non-contact identification of the display unit, but it may also be a means for identification that makes contact with the unit.

[0057] The display unit is located in a predetermined area of ​​the substrate and may have the same configuration as the rest of the substrate. For example, if the identification means is a means for recognizing the optical characteristics of the display unit (color, reflectivity, etc.), then by changing the optical characteristics of the display unit (e.g., coloring means, roughening means, etc.) after using an artificial cell membrane chip, it is possible to distinguish whether an artificial cell membrane chip is unused or used by changing the optical characteristics of the display unit after using an unused artificial cell membrane chip. Alternatively, the display unit may be physically ground or recessed using a laser or the like to indicate that it is used.

[0058] 1 Artificial cell membrane chip 10 wells 11 ion channels 15 artificial cell membrane 20 ion current measuring device 50 display unit I ion current

Claims

1. An ion current measurement system for measuring the ion current flowing through ion channels formed in an artificial cell membrane, using an ion current measuring device, for an artificial cell membrane chip having at least one well for forming an artificial cell membrane, wherein the artificial cell membrane chip is equipped with a display unit at a predetermined location, and the ion current measuring device is equipped with an identification means, the identification means identifying whether the artificial cell membrane chip is being used for the first time or has been used by recognizing the display unit.

2. The ion current measurement system according to claim 1, wherein the display unit is a part on which an optically or electrically readable identification mark is displayed.

3. The ion current measurement system according to claim 2, wherein when the artificial cell membrane chip is used, information indicating that it has been used is added to the identification information obtainable by reading the identification mark on the artificial cell membrane chip.

4. The ion current measurement system according to claim 3, wherein the display unit has a memory and assigns information to the memory indicating that it is in use.

5. The ion current measuring system according to claim 1, wherein the display unit is a part whose structure physically changes.

6. The ion current measurement system according to claim 5, wherein the change in the structure of the display unit is irreversible.

7. The ion current measuring system according to claim 1, wherein the ion current measuring device measures the ion current when the identification means identifies that the artificial cell membrane chip is being used for the first time, and does not measure the ion current when the identification means identifies that the artificial cell membrane chip has been used.

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