Signal measurement device for measuring signals of plurality of organoids and control method for controlling signal measurement device

Abstract

Disclosed are a signal measurement device for measuring signals of a plurality of organoids, and a control method for controlling the signal measurement device. The signal measurement device may comprise: a well plate in which chambers accommodating organoids are disposed; a probe array including probes in which electrodes are disposed; a cover in which the probe array is disposed; a gap adjustment unit for adjusting a gap between the well plate and the probe array; and a control unit for controlling the gap adjustment unit to adjust the gap between the well plate and the probe array on the basis of changes in an electrical signal measured by the electrodes.

Description

A signal measuring device for measuring signals of multiple organoids and a control method for controlling the signal measuring device

[0001] The following disclosure relates to a signal measuring device for measuring signals of a plurality of organoids and a control method for controlling the signal measuring device.

[0002] Neural organoids have a structure similar to brain or spinal cord cells and can be applied in drug screening, personalized drug selection, and organ transplantation. To perform functional analysis of neural organoids, electrodes can be inserted into the organoid to measure neural signals. When inserting electrodes into organoids, the probes are typically inserted under a microscope to ensure proper placement.

[0003] A signal measuring device for measuring signals of a plurality of organoids according to one embodiment may include a well plate having chambers for accommodating the organoids arranged therein, a probe array including probes having electrodes arranged therein, a cover having the probe array arranged therein, a gap adjusting unit for adjusting a gap between the well plate and the probe array, and a control unit for controlling the gap adjusting unit to adjust a gap between the well plate and the probe array based on a change in an electric signal measured by the electrodes.

[0004] The control unit can control the gap adjustment unit to reduce the gap between the well plate and the probe array in response to receiving a trigger signal for executing a signal measurement operation by the signal measurement device.

[0005] The control unit may control the gap adjustment unit so that the gap between the well plate and the probe array becomes a reference gap at a first time point, and may control the gap adjustment unit so that the gap between the well plate and the probe array becomes smaller than the reference gap at a second time point after the first time point.

[0006] Each of the above probes includes a plurality of electrodes arranged at intervals from each other to measure changes in electrical signals, and the control unit can control to adjust the interval between the well plate and the probe array based on changes in electrical signals measured at each of the electrodes.

[0007] The control unit can control the operation of the gap adjustment unit based on a change in an electric signal measured from electrodes included in one or more probes when the gap between the well plate and the probe array is reduced.

[0008] The control unit may control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when a change in an electric signal is detected from the electrode closest to the cover among the electrodes.

[0009] The signal measuring device further includes a deformation detection sensor that measures deformation information of the probe, and the control unit can determine whether to control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing based on the deformation information when the gap between the well plate and the probe array is decreasing.

[0010] The above deformation detection sensor is a strain sensor, and the deformation detection sensor may be arranged on one or a plurality of probes or may be arranged at the end of one or a plurality of probes.

[0011] The control unit can control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when deformation of the probe is detected by the deformation detection sensor.

[0012] The control unit can control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when the degree of deformation of the probe detected by the deformation detection sensor is greater than a threshold value.

[0013] The above gap adjusting unit may include a first gap adjusting unit and a second gap adjusting unit formed to correspond to the first gap adjusting unit, and the first gap adjusting unit may include a first cover connecting unit connected to one side of the cover, a first well plate connecting unit connected to one side of the well plate, a first rod along which at least one of the first cover connecting unit and the first well plate connecting unit moves, and a first motor for adjusting the gap between the first cover connecting unit and the first well plate connecting unit on the first rod based on a control signal from the control unit, and the second gap adjusting unit may include a second cover connecting unit formed on the other side of the cover, a second well plate connecting unit formed on the other side of the well plate, a second rod along which at least one of the second cover connecting unit and the second well plate connecting unit moves, and a second motor for adjusting the gap between the second cover connecting unit and the second well plate connecting unit on the second rod based on a control signal from the control unit.

[0014] A control method for controlling a gap between a probe array and a culture array included in a signal measuring device according to one embodiment may include an operation of receiving a trigger signal for starting measurement of an electrical signal by the signal measuring device, an operation of controlling a gap control unit of the signal measuring device to reduce a gap between a well plate included in the signal measuring device and the probe array in response to receiving the trigger signal, and an operation of determining whether to stop reducing the gap between the well plate and the probe array based on a change in an electrical signal measured from electrodes included in one or a plurality of probes.

[0015] The operation of controlling the above-mentioned gap adjustment unit may include an operation of controlling the gap adjustment unit so that the gap between the well plate and the probe array becomes a reference gap at a first time point, and an operation of controlling the gap adjustment unit so that the gap between the well plate and the probe array becomes smaller than the reference gap at a second time point after the first time point.

[0016] Each of the above probes includes a plurality of electrodes arranged at intervals from each other to measure changes in electrical signals, and the operation of controlling the interval control unit may include an operation of controlling the interval between the well plate and the probe array to be reduced based on changes in the electrical signals measured at each of the electrodes.

[0017] The operation of controlling the gap adjustment unit may include an operation of controlling the operation of the gap adjustment unit based on a change in an electric signal measured from electrodes included in one or more probes when the gap between the well plate and the probe array is reduced.

[0018] The operation of controlling the gap adjustment unit may include an operation of controlling the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when a change in an electric signal is detected from an electrode closest to the cover of the signal measuring device among the electrodes.

[0019] The above control method may further include an operation of measuring deformation information of the probe by a deformation detection sensor, and the operation of determining whether to stop the gap from decreasing may include an operation of determining whether to control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing based on the deformation information when the gap between the well plate and the probe array is decreasing.

[0020] The operation of determining whether to stop the gap from decreasing may include an operation of controlling the gap control unit to stop the gap between the well plate and the probe array from decreasing when deformation of the probe is detected by the deformation detection sensor.

[0021] The operation of determining whether to stop the gap from decreasing may include an operation of controlling the gap control unit to stop the gap between the well plate and the probe array from decreasing when the degree of deformation of the probe detected by the deformation detection sensor is greater than or equal to a threshold value.

[0022] FIG. 1 is a drawing for explaining a signal measuring device for measuring signals of a plurality of organoids according to one embodiment.

[0023] FIGS. 2A, 2B, and 2C are drawings illustrating a signal measurement device according to one embodiment for controlling insertion of a probe array into a well plate.

[0024] FIG. 3 is a drawing illustrating a signal measurement device according to one embodiment for controlling the gap between a probe and a well plate when inserting a probe with an electrode disposed thereon into an organoid.

[0025] FIG. 4 is a flowchart illustrating operations of a control method for controlling the gap between a probe array and a well plate included in a signal measuring device according to one embodiment.

[0026] Specific structural or functional descriptions of the embodiments are disclosed for illustrative purposes only and may be modified and implemented in various forms. Therefore, the actual implementation is not limited to the specific embodiments disclosed, and the scope of this specification includes modifications, equivalents, or alternatives within the technical concepts described in the embodiments.

[0027] Although terms such as "first" or "second" may be used to describe various components, these terms should be interpreted solely to distinguish one component from another. For example, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component.

[0028] When it is said that a component is "connected" to another component, it should be understood that it may be directly connected or connected to that other component, but there may also be other components in between.

[0029] Singular expressions include plural expressions unless the context clearly dictates otherwise. In this document, phrases such as "A or B", "at least one of A and B", "at least one of A or B", "A, B, or C", "at least one of A, B, and C", and "at least one of A, B, or C" can each include any one of the items listed together in that phrase, or all possible combinations thereof. In this specification, it should be understood that the terms "comprises" or "has" and the like are intended to specify the presence of a described feature, number, step, operation, component, part, or combination thereof, but do not exclude the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0030] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art. Terms defined in commonly used dictionaries should be interpreted to have a meaning consistent with their meaning in the context of the relevant technology, and will not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0031] The term "module" as used herein may include a unit implemented in hardware, software, or firmware, and may be used interchangeably with terms such as logic, logic block, component, or circuit. A module may be an integral component, or a minimum unit or portion of such a component that performs one or more functions. For example, according to one embodiment, a module may be implemented in the form of an application-specific integrated circuit (ASIC).

[0032] The term "~part" as used in this document refers to a software or hardware component such as an FPGA or ASIC, and the "~part" performs certain roles. However, the "~part" is not limited to software or hardware. The "~part" may be configured to reside on an addressable storage medium and may be configured to execute one or more processors. For example, the "~part" may include components such as software components, object-oriented software components, class components, and task components, as well as processes, functions, attributes, procedures, subroutines, segments of program code, drivers, firmware, microcode, circuits, data, databases, data structures, tables, arrays, and variables. The functionality provided within the components and "~parts" may be combined into a smaller number of components and "~parts" or further separated into additional components and "~parts." Furthermore, the components and "~parts" may be implemented to execute one or more CPUs within a device or a secure multimedia card. Additionally, '~bu' may include one or more processors.

[0033] Hereinafter, embodiments will be described in detail with reference to the attached drawings. In the description with reference to the attached drawings, identical components are assigned the same reference numerals regardless of the drawing numbers, and redundant descriptions thereof will be omitted.

[0034]

[0035] FIG. 1 is a drawing for explaining a signal measuring device for measuring signals of a plurality of organoids according to one embodiment.

[0036] Referring to FIG. 1, a signal measuring device (100) is a device that measures signals of a plurality of organoids (134). The signal measuring device (100) may include a well plate (130) in which chambers (or wells) (132) for accommodating organoids (134) are arranged, a probe array (122) including probes on which electrodes are arranged, a cover (120) in which the probe array (122) is arranged, a gap adjusting unit (140, 150) for adjusting the gap between the well plate (130) and the probe array (122), and a control unit (110) for controlling the gap adjusting unit (140, 150) to adjust the gap between the well plate (130) and the probe array (122) based on a change in an electric signal measured by the electrode.

[0037] According to one embodiment, a well plate (130) may have one or more chambers (or wells) (132) for accommodating organoids (134). For example, the well plate (130) may be a 96-well plate having 96 chambers for accommodating 96 organoids. The well plate (130) may accommodate a plurality of organoids in culture or a plurality of cultured organoids.

[0038] According to one embodiment, a cover (120) may have a probe array (122) including a plurality of probes arranged thereon. In one embodiment, the cover (120) may cover a well plate (130). The probe array (122) may, for example, be a two-dimensional array in which a plurality of probes are arranged on the inner surface of the cover (120). If the well plate (130) has N (a natural number greater than or equal to 2) wells (132), the probe array (122) may have N probes. The arrangement of the probes included in the probe array (122) may correspond to the arrangement of the wells (132) included in the well plate (130). Each probe included in the probe array (122) may have one or more electrodes arranged thereon for measuring signals within the organoid (134).

[0039] According to one embodiment, the gap adjusting unit (140, 150) can connect the cover (120) and the well plate (130) and adjust the gap between the cover (120) and the well plate (130). For example, the gap adjusting unit (140, 150) is connected to the cover (120) and the well plate (130), respectively, and adjusts the gap between the cover (120) and the well plate (130) through the motor (148, 158), thereby allowing the probe placed on the cover (120) to be inserted into the organoid (134) accommodated in the well plate (130).

[0040] In one embodiment, the gap adjusting unit (140, 150) may include a first gap adjusting unit (140) and a second gap adjusting unit (150) formed to correspond to the first gap adjusting unit (140). The first gap adjusting unit (140) may include a first cover connecting unit (142) connected to one side of the cover (120), a first well plate connecting unit (146) connected to one side of the well plate (130), a first rod (144) that moves at least one of the first cover connecting unit (142) and the first well plate connecting unit (146), and a first motor (148) for adjusting the gap between the first cover connecting unit (142) and the first well plate connecting unit (146) based on a control signal of the control unit (110). The first cover connecting portion (142) and the first well plate connecting portion (146) may be connected to one side of each of the cover (120) and the well plate (130), respectively. The second gap adjusting portion (150) may include a second cover connecting portion (152) formed on the other side of the cover (120), a second well plate connecting portion (156) formed on the other side of the well plate (130), a second rod (154) on which at least one of the second cover connecting portion (152) and the second well plate connecting portion (156) moves, and a second motor (158) for adjusting the gap between the second cover connecting portion (152) and the second well plate connecting portion (156) on the second rod (154) based on a control signal of the control portion (110). For example, the second gap adjusting portion (150) may be arranged to correspond to the first gap adjusting portion (140) on the signal measuring device (100). The second cover connecting portion (152) and the second well plate connecting portion (156) can be connected to the other side of the cover (120) and the well plate (130), respectively.

[0041] The first cover connecting portion (142), the first well plate connecting portion (146), the first rod (144), the second cover connecting portion (152), the second well plate connecting portion (156), and the second rod (154) may be made of plastic, metal, or other materials. The first motor (148) can adjust the gap between the first cover connecting portion (142) and the first well plate connecting portion (146), and the second motor (158) can adjust the gap between the second cover connecting portion (152) and the second well plate connecting portion (156). The first motor (148) and the second motor (158) may be, for example, an alternating current (AC) motor, a linear motor, a step motor, a brushless direct current (BLDC) motor, or a direct current (DC) spur gear motor. The first load (144) and the second load (154) may be, for example, metal load screws. The first motor (148) may be, for example, a step motor that can adjust the gap between the first cover connection portion (142) and the first well plate connection portion (146) by rotating the first load (144) (e.g., load screw). The second motor (158) may be, for example, a step motor that can adjust the gap between the second cover connection portion (152) and the second well plate connection portion (156) by rotating the second load (154) (e.g., load screw).

[0042] The control unit (110) according to one embodiment may include one or more processors, which are hardware units that execute a program. The processors may include a central processing unit (CPU), a coprocessor, a microprocessor unit (MPU), and a microcontroller unit (MCU). The control unit (110) may control the gap between the cover (120) and the well plate (130) by controlling the gap adjusting units (140, 150).

[0043] The control unit (110) can control the gap adjustment unit (140, 150) based on a change in an electric signal detected by an electrode placed on the probe. The control unit (110) can receive a user trigger signal for operating the signal measurement device (100), and in response to receiving the trigger signal, control the gap adjustment unit (140, 150) to reduce the gap between the well plate (130) and the probe array (122). For example, the control unit (110) can control the gap between the well plate (130) and the probe array (122) to become a reference gap in response to an input user trigger signal, and then control the gap adjustment unit (140, 150) to reduce the gap between the well plate (130) and the probe array (122) so that the probe can be inserted into the organoid. When an electrode is inserted into the organoid (134) and the optimal insertion position is determined based on the electrode signal, the control unit (110) can control the motor (148, 158) to stop its operation so that the relative positional relationship (e.g., spacing) between the cover (120) (or the probe array (122)) and the well plate (30) is fixed. The control unit (110) can control the measurement of a signal within the organoid (134) through the electrode inserted into the organoid (134). When a probe with an electrode disposed according to one embodiment is inserted into the organoid (134), the electrical signal measured by the electrode may change. For example, the control unit (110) can determine that the insertion of the probe is complete when the impedance based on the electrical signal measured from the electrode disposed closest to the cover (120) changes.

[0044] In one embodiment, the control unit (110) can use a deformation detection sensor (not shown) to determine whether the probe is completely inserted into the organoid or has reached the maximum insertion depth. The deformation detection sensor can be placed or connected to the probe to measure whether the probe is deformed or the degree of deformation. The control unit (110) can determine that the probe is completely inserted or has reached the maximum insertion depth when the deformation of the probe caused by the probe touching the bottom surface after the electrode is inserted into the organoid (134) is detected by the deformation detection sensor. For example, the deformation detection sensor can detect deformation information of the probe when deformation occurs when the probe touches the bottom surface of the chamber (132) containing the organoid (134). The control unit (110) can control the gap adjustment unit (140, 150) to stop the gap between the well plate (130) and the probe array (122) from decreasing based on the deformation information of the probe detected by the deformation detection sensor. The control unit (110) can control to measure a signal generated from the organoid (134) through the electrode after the gap between the well plate (130) and the probe array (122) stops decreasing.

[0045]

[0046] FIGS. 2A, 2B, and 2C are drawings illustrating a signal measurement device according to one embodiment for controlling insertion of a probe array into a well plate.

[0047] Referring to FIG. 2A, it is assumed that the well plate (130) and the probe array (122) are spaced apart from each other in an initial state (210) according to one embodiment. When the control unit of the signal measurement device (e.g., the control unit (110) of FIG. 1) receives, for example, a trigger signal (e.g., a start input signal from a user) to insert the probe array (122) into organoids in the well plate (130) or a trigger signal to execute a signal measurement operation by the signal measurement device, the control unit may control the gap adjustment units (140, 150) to reduce the gap between the well plate (130) and the probe array (122). For example, when the control unit receives a trigger signal from a user to execute the signal measurement operation, the control unit may control the first gap adjustment unit (140) and the second gap adjustment unit (150) to control the cover (120) to move toward the well plate (130).

[0048] In one embodiment, when the cover (120) is moved and the probe array (122) is inserted into a plurality of organoids accommodated in the well plate (130), and there is a change in the electric signal detected by the electrode closest to the cover (120) among the electrodes arranged on each of the probe arrays (122), the control unit may control the gap adjusting unit (140, 150) to stop the gap between the well plate (130) and the probe array (122) from decreasing. For example, the control unit may determine the impedance based on the electric signal measured by the electrode closest to the cover (120) among the electrodes arranged on the probe, and when a change in the impedance caused by the insertion of the electrode into the organoid is detected, or when a deformation of the probe is detected by a deformation detection sensor arranged on the probe, the control unit may control the gap between the well plate (130) and the probe array (122) to stop decreasing. State (220) is a state in which the control unit determines that the gap between the well plate (130) and the probe array (122) has reached the optimal gap, and movement of the probe array (122) is stopped.

[0049] Referring to FIG. 2B, the control unit of the signal measurement device according to one embodiment (e.g., the control unit (110) of FIG. 1) can control the cover (120) to move so that the gap between the well plate (130) and the probe array (122) becomes a reference gap, and then reduce the gap. First, in a state (230), the control unit can control the gap adjustment unit (140, 150) so that the gap between the well plate (130) and the probe array (122) becomes the reference gap at a first time point. For example, the control unit can control the gap adjustment unit (140, 150) so that the cover (120) (or the probe array (122)) gradually moves away from the well plate (130) at a first time point after receiving a trigger signal from a user until the gap between the well plate (130) and the probe array (122) becomes the reference gap.

[0050] In state (240), at a second time point after the first time point, the control unit can control the gap adjusting unit (140, 150) to reduce the gap between the well plate (130) and the probe array (122) to a reference gap. For example, at a second time point after the first time point, in order to reduce the gap between the well plate (130) and the probe array (122) to a reference gap, the control unit can control the first gap adjusting unit (140) and the second gap adjusting unit (150) to move the cover (120) toward the well plate (130).

[0051] When the cover (120) is moved and the probe array (122) is inserted into a plurality of organoids accommodated in the well plate (130), and there is a change in the electric signal detected by the electrode closest to the cover (120) among the electrodes disposed on each of the probe arrays (122), the control unit can control to stop the reduction of the gap between the well plate (130) and the probe array (122). For example, the control unit determines the impedance based on the electric signal measured by the electrode closest to the cover (120) among the electrodes disposed on the probe, and when a change in the impedance caused by the insertion of the electrode into the organoid is detected, or when a deformation of the probe is detected by a deformation detection sensor disposed on the probe, the control unit can control to stop the reduction of the gap between the well plate (130) and the probe array (122). State (250) is a state in which the control unit determines that the gap between the well plate (130) and the probe array (122) has reached the optimal gap, and movement of the probe array (122) is stopped.

[0052] Referring to FIG. 2c, a control unit (e.g., control unit (110) of FIG. 1) of a signal measurement device according to one embodiment can control the spacing between a well plate (130) and a probe array (122) to become a reference spacing, and then move the well plate (130) to reduce the spacing. In state (260), the control unit can control the spacing adjustment unit (140, 150) so that the spacing between the well plate (130) and the probe array (122) becomes the reference spacing at the first time point. The description of the control unit controlling the spacing adjustment unit so that the spacing between the well plate (130) and the probe array (122) becomes the reference spacing is the same as the description of state (230) of FIG. 2b, and a detailed description thereof will be omitted.

[0053] In state (270), at a second time point after the first time point, the spacing control unit (140, 150) may be controlled to move the well plate (130) so that the spacing between the well plate (130) and the probe array (122) is reduced to a reference spacing. For example, at a second time point after the first time point, in order to reduce the spacing between the well plate (130) and the probe array (122) to a reference spacing, the control unit may control the first spacing control unit (140) and the second spacing control unit (150) so that the well plate (130) moves toward the cover (120).

[0054] When the well plate (130) is moved and the probe array (122) disposed on the cover (120) is inserted into a plurality of organoids and there is a change in the electric signal detected by the electrode closest to the cover (120) among the electrodes disposed on each of the probe arrays, the control unit can control to stop the gap between the well plate (130) and the probe array (122) from decreasing. For example, the control unit determines the impedance based on the electric signal measured by the electrode closest to the cover (120) among the electrodes disposed on the probe, and when a change in the impedance caused by the insertion of the electrode into the organoid is detected, or when a deformation of the probe is detected by a deformation detection sensor disposed on the probe, the control unit can control to stop the gap between the well plate (130) and the probe array (122) from decreasing. State (280) is a state in which the control unit determines that the gap between the well plate (130) and the probe array (122) has reached the optimal gap, and movement of the probe array (122) is stopped.

[0055] In one embodiment, the control unit may control the gap between the well plate (130) and the probe array (122) to be reduced directly without performing an operation to adjust the gap between the well plate (130) and the probe array (122) to a reference gap. For example, after receiving a trigger signal, the control unit may control the first gap adjusting unit (140) and the second gap adjusting unit (150) to move the well plate (130) toward the cover (120) to reduce the gap between the well plate (130) and the probe array (122). When the well plate (130) moves toward the cover (120) and the optimal insertion position is determined based on the electrode signal, the control unit (110) may control the motors (148, 158) to stop the operation so that the relative positional relationship (e.g., gap) between the cover (120) (or the probe array (122)) and the well plate (30) is fixed.

[0056]

[0057] FIG. 3 is a drawing illustrating a signal measurement device according to one embodiment that controls the gap between a probe and a well plate when inserting a probe with an electrode placed thereon into an organoid.

[0058] Referring to FIG. 3, a signal measuring device (e.g., a signal measuring device (100) of FIG. 1) can insert a probe (312) having electrodes (331, 332, 333, 334, 335, 336, 337, 338) arranged therein to an appropriate depth into an organoid (314) accommodated in a chamber of a well plate (313), and measure a signal within the organoid (314) through at least one of the electrodes (331, 332, 333, 334, 335, 336, 337, 338). The drawing (330) is an enlarged view of the end of the probe (312) having electrodes (331, 332, 333, 334, 335, 336, 337, 338) arranged therein. State (310) shows the state before the signal measurement device inserts the probe (312) into the organoid (314).

[0059] The control unit of the signal measurement device (e.g., the control unit (110) of FIG. 1) controls the probe (312) having electrodes (331, 332, 333, 334, 335, 336, 337, 338) arranged thereon to be inserted into the organoid (314) accommodated in the chamber of the well plate (313), and can control the gap between the well plate (313) and the probe (312). As described above, the control unit can control the gap adjustment unit of the signal measurement device (e.g., the gap adjustment unit (140, 150) of FIG. 1) to control the gap between the well plate (313) and the probe (312). The control unit can control to adjust the gap between the well plate (313) (more specifically, the bottom (316) of the well plate (313)) and the probe (312) based on the change in the electric signal measured from each of the electrodes (331, 332, 333, 334, 335, 336, 337, 338). For example, the control unit can determine whether the gap between the well plate (313) and the probe (312) has reached an optimal gap based on the change in the electric signal measured from the electrodes included in one or more probes when the gap between the well plate (313) and the probe (312) is reduced. If it is determined that the gap between the well plate (313) and the probe (312) has reached the optimal gap, the control unit can stop the gap between the well plate (313) and the probe (312) from decreasing.

[0060] In one embodiment, when the fisherman detects a change in the electrical signal from the electrode (338) closest to the cover (315) among the electrodes (331, 332, 333, 334, 335, 336, 337, 338), the gap adjustment unit of the signal measurement device can control the gap adjustment unit of the signal measurement device to stop the gap between the well plate (313) and the probe (312) from decreasing. For example, when the probe (312) is inserted into the organoid (314), the electrodes (331, 332, 333, 334, 335, 336, 337, 338) can be sequentially inserted into the organoid (314). The control unit can determine that the insertion of the probe (312) is complete or the optimal insertion position has been determined when there is a change in the electric signal detected by the electrode (338) closest to the cover (315), and can control the gap control unit to stop the gap between the well plate (313) and the probe (312) from decreasing.

[0061] The signal measuring device according to one embodiment may further include a deformation detection sensor (311) that measures deformation information of the probe (312). The deformation detection sensor (311) is a sensor that detects physical changes such as tension, bending, or twisting applied to the deformation detection sensor. For example, the deformation detection sensor (311) may be a strain sensor, and the deformation detection sensor (311) may be disposed on one or a plurality of probes or may be disposed at the ends of one or a plurality of probes. The control unit may determine whether to control the gap adjustment unit to stop the gap between the well plate (313) and the probe array from decreasing based on the deformation information measured by the deformation detection sensor (311) in a state where the gap between the well plate (313) and the probe (312) is decreasing. For example, when the probe (312) touches the bottom (316) of the well plate (313) and the deformation detection sensor (311) detects deformation of the probe (312), the control unit can control the gap adjustment unit to stop the gap between the well plate (313) and the probe (312) from decreasing.

[0062] According to one embodiment, the control unit may control the gap adjustment unit to stop the gap between the well plate (313) and the probe (312) from decreasing when the degree of deformation of the probe (312) detected by the deformation detection sensor (311) is greater than or equal to a threshold value. For example, when the threshold value is 1 με (microstrain) and the degree of deformation detected by the deformation detection sensor (311) is 1.2 με, the control unit may control the gap adjustment unit to stop the gap between the well plate (313) and the probe (312) from decreasing.

[0063] According to an embodiment, the control unit may additionally perform control to move the probe (312) (or probe array) upward when deformation of the probe (312) is detected by the deformation detection sensor (311). Through this, the control unit may ensure that the end of the probe (312) is positioned at an appropriate height from the floor (316) of the chamber containing the organoid (314).

[0064]

[0065] FIG. 4 is a flowchart illustrating operations of a control method for controlling the gap between a probe array and a well plate included in a signal measurement device according to one embodiment. The operations of the control method may be performed by a signal measurement device (e.g., the signal measurement device (100) of FIG. 1).

[0066] In operation (410), the signal measurement device can receive a user's trigger signal for executing signal measurement operations. The trigger signal may be, for example, but is not limited to, a signal for turning on or activating the signal measurement device, a signal for commanding the start of signal measurement, or a signal for commanding the insertion of a probe into an organoid. The trigger signal may be input through an operating unit (e.g., a button, a GUI) provided in the signal measurement device, or transmitted from another device (e.g., a user terminal, a server, a dedicated controller) connected to the signal measurement device.

[0067] In operation (420), the signal measurement device can control the gap between the well plate and the probe array to decrease. For example, the signal measurement device can control the gap adjustment unit of the signal measurement device to decrease the gap between the well plate and the probe array in response to receiving a trigger signal. Through this control, the gap between the well plate and the probe array is gradually decreased, and the probe with the electrode disposed thereon can be inserted into the organoid accommodated in the well plate.

[0068] In one embodiment, the signal measurement device can control the gap adjustment unit so that the gap between the well plate and the probe array becomes a reference gap at a first time point before the gap between the well plate and the probe array is reduced. The reference gap is a predefined gap between the well plate and the probe array to ensure that the operation of inserting the probe of the signal measurement device into the organoid can be accurately performed, and the first time point is a time point after the signal measurement device receives a trigger signal. According to one embodiment, the signal measurement device can control the gap adjustment unit so that the gap between the well plate and the probe array becomes less than the reference gap at a second time point after the first time point. The second time point is a time point after the gap between the well plate and the probe array becomes the reference gap.

[0069] In operation (430), the signal measurement device can measure an electrical signal through an electrode disposed on a probe. The probe may be a microprobe having electrodes disposed thereon, which are inserted into an organoid accommodated in a well plate and capable of measuring an electrical signal. The probes may be arranged in an array form, and may be arranged in a two-dimensional array on the cover of the signal measurement device. For example, a two-dimensional probe array disposed on the cover of the signal measurement device can continuously measure an electrical signal through each electrode.

[0070] In operation (440), each of the probes may include a plurality of electrodes spaced apart from each other to measure a change in an electrical signal, and the signal measurement device may control the operation of the gap control unit based on a change in an electrical signal measured from electrodes included in one or more probes when the gap between the well plate and the probe array is reduced. For example, based on a change in an electrical signal measured from electrodes included in one or more probes, the signal measurement device may determine whether to stop the gap between the well plate and the probe array from decreasing.

[0071] In one embodiment, if there is no change in the electrical signal of the electrode closest to the cover of the signal measurement device ('NO' in operation (440)), the signal measurement device can be controlled to continuously reduce the gap between the well plate and the probe array.

[0072] If there is a change in the electric signal of the electrode closest to the cover of the signal measuring device (if 'YES' in operation (440)), the signal measuring device can stop the gap between the well plate and the probe array from decreasing in operation (470). For example, if the signal measuring device detects a change in the electric signal from the electrode closest to the cover of the signal measuring device among the electrodes, the signal measuring device can control the gap control unit to stop the gap between the well plate and the probe array from decreasing.

[0073] In operation (450), the signal measuring device can measure deformation information of the probe by a deformation detection sensor. A deformation detection sensor (e.g., a strain sensor) is a sensor that detects physical changes such as tension, bending, or twisting applied to the sensor. For example, the probe can touch the bottom surface of the well plate after being inserted into the organoid, and the deformation detection sensor can measure deformation information of the probe. The deformation detection sensor can be arranged on one or a plurality of probes or arranged at the end of one or a plurality of probes to measure deformation information of the probe. The deformation information measured by the deformation detection sensor can include whether the probe is deformed or the degree of deformation of the deformed probe.

[0074] In operation (460), the signal measuring device can detect whether the probe is deformed based on deformation information measured from the deformation detection sensor while the gap between the well plate and the probe array is reduced. If the deformation of the probe is not detected by the deformation detection sensor ('NO' in operation (460)), the signal measuring device can control the gap between the well plate and the probe array to continuously decrease.

[0075] If the deformation of the probe is detected by the deformation detection sensor ('YES' in operation (460)), the signal measurement device can control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing in operation (470).

[0076] As described above, the signal measurement device can control the gap control unit to stop the gap between the well plate and the probe array from decreasing based on the deformation information when the gap between the well plate and the probe array is decreasing.

[0077] In one embodiment, the signal measurement device can control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when the degree of deformation of the probe detected by the strain detection sensor is greater than or equal to a threshold value. For example, when the threshold value is 1 με (microstrain) and the degree of deformation detected by the strain detection sensor exceeds 1 με, the signal measurement device can control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing.

[0078] The first judgment operation (430, 440) and the second judgment operation (450, 460) for controlling the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing can be performed in parallel, or only one of the two judgment operations can be performed.

[0079] As described above, the signal measurement device can stop reducing the gap between the well plate and the probe array when it determines that the insertion of the probe into the organoid accommodated in the well plate is complete. For example, if the electrical signal of the electrode closest to the cover changes and / or the deformation detection sensor detects deformation of the probe, the signal measurement device can determine that the insertion of the probe into the organoid accommodated in the well plate is complete and stop reducing the gap between the well plate and the probe array. The signal measurement device can insert the probe into the organoid at an optimal insertion depth by using the deformation detection sensor that detects the electrical signal measured through the probe and / or the deformation of the probe, thereby enabling accurate measurement of the signal within the organoid.

[0080]

[0081] As described above, the signal measurement device for measuring signals of a plurality of organoids described herein can automatically insert electrodes into a plurality of organoids for signal measurement of organoids, which are three-dimensional organ mimics. At this time, the signal measurement device can insert the electrodes into the organoids without damaging the electrodes or the organoids. The signal measurement device can simultaneously measure signals from a plurality of organoids through a probe array. By simultaneously measuring signals from a plurality of organoids through the signal measurement device, a functional analysis of a drug can be performed, and the signal measurement device can be used to evaluate the effect of a drug by comparing signals before and after drug administration to the organoids. In one embodiment, the signal measurement device can be used to monitor the effect of a drug to analyze the function of brain disease organoids and / or screen for brain disease therapeutics. The signal measurement device helps to collect and process a large number of signals in a short period of time, thereby enabling high-throughput screening (HTS).

[0082] The hardware device of the signal measuring device described above may be configured to operate as one or more software modules to perform the operations of the embodiment, and vice versa.

[0083] The embodiments described above may be implemented using hardware components, software components, and / or a combination of hardware components and software components. For example, the devices, methods, and components described in the embodiments may be implemented using a general-purpose computer or a special-purpose computer, such as, for example, a processor, a controller, an arithmetic logic unit (ALU), a digital signal processor, a microcomputer, a field programmable gate array (FPGA), a programmable logic unit (PLU), a microprocessor, or any other device capable of executing instructions and responding to them. The processing device may execute an operating system (OS) and software applications running on the operating system. Furthermore, the processing device may access, store, manipulate, process, and generate data in response to the execution of the software. For ease of understanding, the processing device is sometimes described as being used alone; however, one of ordinary skill in the art will recognize that the processing device may include multiple processing elements and / or multiple types of processing elements. For example, a processing unit may include multiple processors, or a processor and a controller. Other processing configurations, such as parallel processors, are also possible.

[0084] Software may include computer programs, codes, instructions, or a combination of one or more of these, which may configure a processing device to perform a desired operation or may independently or collectively command the processing device. The software and / or data may be permanently or temporarily embodied in any type of machine, component, physical device, virtual equipment, computer storage medium, or device for interpretation by the processing device or for providing instructions or data to the processing device. The software may also be distributed over networked computer systems and stored or executed in a distributed manner. The software and data may be stored on a computer-readable recording medium.

[0085] The method according to the embodiment may be implemented in the form of program commands that can be executed through various computer means and recorded on a computer-readable medium. The computer-readable medium may store program commands, data files, data structures, etc., alone or in combination, and the program commands recorded on the medium may be those specially designed and configured for the embodiment or may be known and available to those skilled in the art of computer software. Examples of the computer-readable recording medium include magnetic media such as hard disks, floppy disks, and magnetic tapes, optical media such as CD-ROMs and DVDs, magneto-optical media such as floptical disks, and hardware devices specially configured to store and execute program commands, such as ROMs, RAMs, and flash memories. Examples of program commands include not only machine language codes such as those generated by a compiler, but also high-level language codes that can be executed by a computer using an interpreter, etc.

[0086] The hardware devices described above may be configured to operate as one or more software modules to perform the operations of the embodiments, and vice versa.

[0087] Although the embodiments described above have been described with limited drawings, those skilled in the art will appreciate that various technical modifications and variations can be applied based on the described embodiments. For example, appropriate results can still be achieved even if the described techniques are performed in a different order than described, and / or components of the described systems, structures, devices, circuits, etc. are combined or combined in a different manner than described, or are replaced or substituted with other components or equivalents.

[0088] Therefore, other implementations, other embodiments, and equivalents to the claims also fall within the scope of the claims described below.

Claims

1. In a signal measuring device for measuring signals of multiple organoids, A well plate having chambers arranged to accommodate the organoids; A probe array comprising probes having electrodes arranged thereon; A cover on which the above probe array is arranged; A gap adjustment unit for adjusting the gap between the well plate and the probe array; and A control unit that controls the gap adjustment unit to adjust the gap between the well plate and the probe array based on the change in the electric signal measured by the electrode. Including Signal measuring device.

2. In paragraph 1, The above control unit, In response to receiving a trigger signal for executing a signal measurement operation by the signal measurement device, the gap control unit controls the gap control unit to reduce the gap between the well plate and the probe array. Signal measuring device.

3. In paragraph 1, The above control unit, At the first point in time, the gap adjustment unit is controlled so that the gap between the well plate and the probe array becomes a reference gap, At a second time point after the first time point, the spacing control unit is controlled so that the spacing between the well plate and the probe array is reduced to less than the reference spacing. Signal measuring device.

4. In paragraph 1, Each of the above probes, It comprises a plurality of electrodes spaced apart from each other and measuring changes in electrical signals, The above control unit, Controlling the spacing between the well plate and the probe array based on the change in the electrical signal measured at each of the electrodes, Signal measuring device.

5. In paragraph 2, The above control unit, Controlling the operation of the gap control unit based on a change in an electric signal measured from electrodes included in one or more probes, in a state where the gap between the well plate and the probe array is reduced. Signal measuring device.

6. In paragraph 5, The above control unit, When a change in an electric signal is detected from the electrode closest to the cover among the electrodes, the gap control unit is controlled to stop the gap between the well plate and the probe array from decreasing. Signal measuring device.

7. In paragraph 1, A deformation detection sensor that measures deformation information of the above probe, Including more The above control unit, In a state where the gap between the well plate and the probe array is reduced, determining whether to control the gap adjustment unit to stop the gap between the well plate and the probe array from being reduced based on the deformation information; Signal measuring device.

8. In paragraph 7, The above deformation detection sensor, It is a strain sensor, The above deformation detection sensor is arranged on one or more probes or is arranged at the end of one or more probes. Signal measuring device.

9. In paragraph 7, The above control unit, When deformation of the probe is detected by the deformation detection sensor, the gap adjustment unit is controlled to stop the gap between the well plate and the probe array from decreasing. Signal measuring device.

10. In paragraph 7, The above control unit, When the degree of deformation of the probe detected by the deformation detection sensor is greater than a threshold value, the gap control unit is controlled to stop the gap between the well plate and the probe array from decreasing. Signal measuring device.

11. In paragraph 1, The above spacing adjustment part, It includes a first gap adjusting unit and a second gap adjusting unit formed to correspond to the first gap adjusting unit, The above first gap adjustment unit is, A first cover connecting portion connected to one side of the above cover; A first well plate connecting portion connected to one side of the above well plate; A first rod through which at least one of the first cover connecting portion and the first well plate connecting portion moves; and A first motor for adjusting the gap between the first cover connecting portion and the first well plate connecting portion on the first load based on a control signal of the control portion, The above second gap adjustment unit, A second cover connecting portion formed on the other side of the above cover; A second well plate connecting portion formed on the other side of the well plate; A second load, wherein at least one of the second cover connecting portion and the second well plate connecting portion moves; and A second motor for adjusting the gap between the second cover connecting portion and the second well plate connecting portion on the second load based on a control signal from the control portion. including, Signal measuring device.

12. A control method for controlling the gap between a probe array and a culture array included in a signal measuring device, An action of receiving a trigger signal to start measuring an electrical signal by the signal measuring device; In response to receiving the trigger signal, an operation of controlling a gap adjustment unit of the signal measurement device to reduce the gap between the well plate included in the signal measurement device and the probe array; and An operation for determining whether to stop the gap between the well plate and the probe array from decreasing based on a change in an electrical signal measured from electrodes included in one or more probes. A control method including:

13. In paragraph 12, The operation of controlling the above gap adjustment unit is: At the first point in time, an operation of controlling the gap adjustment unit so that the gap between the well plate and the probe array becomes a reference gap; and An operation of controlling the gap adjustment unit so that the gap between the well plate and the probe array is reduced to less than the reference gap at a second time point after the first time point. A control method including:

14. In paragraph 12, Each of the above probes, It comprises a plurality of electrodes spaced apart from each other and measuring changes in electrical signals, The operation of controlling the above gap adjustment unit is: An operation for controlling the gap between the well plate and the probe array to be reduced based on the change in the electrical signal measured at each of the electrodes. A control method including:

15. In paragraph 12, The operation of controlling the above gap adjustment unit is: An operation of controlling the operation of the gap control unit based on a change in an electric signal measured from electrodes included in one or more probes, in a state where the gap between the well plate and the probe array is reduced. A control method including:

16. In paragraph 15, The operation of controlling the above gap adjustment unit is: An operation of controlling the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when a change in an electric signal is detected from the electrode closest to the cover of the signal measuring device among the electrodes. A control method including:

17. In paragraph 12, An operation of measuring deformation information of the probe by a deformation detection sensor. Including more, The action that determines whether or not to stop the above gap from decreasing is: An operation of determining whether to control the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing based on the deformation information, in a state where the gap between the well plate and the probe array is decreasing. A control method including:

18. In paragraph 17, The action that determines whether or not to stop the above gap from decreasing is: An operation of controlling the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when the deformation of the probe is detected by the deformation detection sensor. A control method including:

19. In paragraph 17, The action that determines whether or not to stop the above gap from decreasing is: An operation of controlling the gap adjustment unit to stop the gap between the well plate and the probe array from decreasing when the degree of deformation of the probe detected by the deformation detection sensor is greater than a threshold value. A control method including:

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