Micro-fluidic chip system based on dynamic flow channel regulation and control and cell electric signal detection

Abstract

The invention discloses a micro-fluidic chip system based on dynamic flow channel regulation and control and cell electric signal detection, which comprises a micro-fluidic chip, the micro-fluidic chip comprises a main body layer and an electrode layer, the main body layer is internally provided with a deformation detection flow channel and two air pressure cavities, the deformation detection flow channel is configured to generate elastic deformation when the air pressure in the air pressure cavities changes, and the electrode layer is configured to be electrically connected with the deformation detection flow channel; the electrode layer is positioned below the deformation detection flow channel and is suitable for detecting impedance change when cells in the deformation detection flow channel pass through and a friction electric signal generated by friction between the cells and the deformation detection flow channel; the air pressure adjusting device is respectively communicated with the two air pressure cavities; the electric signal analysis device and the electric signal detection device are electrically connected with the electrode layer. According to the micro-fluidic chip system based on dynamic flow channel regulation and control and cell electric signal detection, multi-parameter synchronous detection of cells under controlled mechanical stimulation can be achieved, and the micro-fluidic chip system has the advantages of being high in applicability, high in flux, reliable in result and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic chip manufacturing, and more specifically, to a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection. Background Art

[0002] As a core platform in the field of cell analysis, microfluidic chips are widely used in research on single-cell mechanical properties, detection of disease markers, drug screening, and other directions.

[0003] In the microfluidic chips in the related art, the flow channel size is formed by photolithography or soft lithography processes, and its width and height cannot be adjusted. It can only screen cells of specific sizes and cannot adapt to the detection requirements of different cell types. When facing heterogeneous cell populations, fixed flow channels are likely to cause missed detection of small-sized cells or blockage of large-sized cells, severely limiting the detection reliability.

[0004] In addition, the microfluidic chips in the related art focus on the detection of single cell characteristics and lack the ability of multi-parameter coupling analysis. For example, they can only detect mechanical properties and lack the ability to detect electrical properties, or can only detect electrical properties and lack the ability to detect mechanical properties; this "one-dimensional" detection mode is difficult to reveal the correlation law between mechanical stimuli and cell electrophysiological properties, limiting the application value of microfluidic chips in pathological mechanism research.

[0005] Therefore, in the microfluidic chips in the related art, the dynamic regulation of the flow channel depends on mechanical extrusion of the flow channel by an external fixture, but local stress concentration is likely to cause cell membrane rupture, significantly reducing cell viability, or uses thermoresponsive materials to adjust the flow channel width through temperature changes; however, the heating process will interfere with normal cell metabolism. Both of these methods may change the native state of cells and affect the biological significance of the detection results. Summary of the Invention

[0006] The present invention aims to solve at least one of the technical problems existing in the prior art. For this purpose, the present invention proposes a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection can achieve multi-parameter synchronous detection of cells under controlled mechanical stimuli, and has the advantages of strong applicability, high throughput, reliable results, etc.

[0007] The present invention also proposes a cell detection method using the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection.

[0008] To achieve the above object, an embodiment of the first aspect of the present invention provides a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection includes: a microfluidic chip, which includes a main body layer and an electrode layer. The main body layer has a deformation detection flow channel and two air pressure chambers. The deformation detection flow channel is located between the two air pressure chambers, and the two air pressure chambers are symmetrically arranged on both sides of the deformation detection flow channel. The deformation detection flow channel is adapted for cells to pass through. The deformation detection flow channel is configured to elastically deform when the air pressure in the air pressure chamber changes to adjust the width of the deformation detection flow channel. The electrode layer is located below the deformation detection flow channel and is adapted to detect the impedance change when cells pass through the deformation detection flow channel and the triboelectric signal generated by the friction between the cells and the deformation detection flow channel; an air pressure adjustment device, which is respectively connected to the two air pressure chambers and is adapted to adjust the air pressure in the two air pressure chambers; an electrical signal analysis device, which is electrically connected to the electrode layer and is adapted to analyze the impedance change and the triboelectric signal detected by the electrode layer.

[0009] The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to the embodiment of the present invention can realize the multi-parameter synchronous detection of cells under controlled mechanical stimulation, and has the advantages of strong applicability, high throughput, reliable results, etc.

[0010] In addition, the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to the above embodiment of the present invention may further have the following additional technical features:

[0011] According to an embodiment of the present invention, a cell suspension inlet, a cell suspension outlet and two ventilation ports are provided on the main body layer. The cell suspension inlet is connected to one end of the deformation detection flow channel through an inlet guiding flow channel, and the cell suspension outlet is connected to the other end of the deformation detection flow channel through an outlet guiding flow channel. The two ventilation ports are respectively connected to the two air pressure chambers through air flow channels.

[0012] According to an embodiment of the present invention, an impurity filtering device is connected to the inlet guiding flow channel, and the impurity filtering device is adapted for the cells to pass through.

[0013] According to an embodiment of the present invention, the impurity filtering device includes: a plurality of first filtering columns, the plurality of first filtering columns are arranged at intervals along the width direction of the inlet guiding flow channel, and the interval between every two adjacent first filtering columns is 40 micrometers; a plurality of second filtering columns, the plurality of second filtering columns are arranged at intervals along the width direction of the inlet guiding flow channel, the plurality of second filtering columns are closer to the deformation detection flow channel than the plurality of first filtering columns, and the interval between every two adjacent second filtering columns is 20 micrometers.

[0014] According to an embodiment of the present invention, the main body layer is a polydimethylsiloxane material piece.

[0015] According to an embodiment of the present invention, the height of the deformation detection flow channel in the up-down direction is 20 micrometers, the length of the air pressure cavity in the horizontal direction is 20 - 200 micrometers and the width is 20 - 40 micrometers, the interval between the deformation detection flow channel and the air pressure cavity is 6 - 12 micrometers, the width of the deformation detection flow channel in the horizontal direction under normal pressure is 8 - 16 micrometers, and the maximum value of the width change amount of the deformation detection flow channel is 75% of the width of the deformation detection flow channel in the horizontal direction under normal pressure.

[0016] According to an embodiment of the present invention, the air pressure regulating device at least includes an air pump, the air pump is respectively communicated with the two air pressure cavities and is adapted to simultaneously charge and discharge air to the two air pressure cavities, and the air pressure control precision of the air pressure regulating device is 0.1 kPa.

[0017] According to an embodiment of the present invention, the electrode layer includes a plurality of electrodes, the plurality of electrodes are arranged at intervals along the length direction of the deformation detection flow channel, each electrode at least partially projects and coincides with the projection of the deformation detection flow channel in the horizontal plane, the width of each electrode in the horizontal direction is 15 - 20 micrometers, and the distance between every two adjacent electrodes is 20 - 50 micrometers.

[0018] According to an embodiment of the second aspect of the present invention, a cell detection method is provided. The cell detection method uses the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to the embodiment of the first aspect of the present invention, and includes the following steps:

[0019] Adjust the air pressure in the two air pressure cavities through the air pressure regulating device to adjust the width of the deformation detection flow channel, so that the minimum width of the deformation detection flow channel is less than the diameter of the target cell;

[0020] Inject the cell suspension into one end of the deformation detection flow channel, so that the cells pass through the deformation detection flow channel, and the cells are deformed under extrusion during the process of passing through the deformation detection flow channel;

[0021] The impedance change of cells when passing through the deformation detection flow channel is detected in real time through the electrode layer, and at the same time, the frictional charges generated when the cells pass through are collected;

[0022] The correlation between cell deformation and electrophysiological characteristics is analyzed by an electrical signal analysis device.

[0023] According to the cell detection method of the embodiment of the present invention, by using the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection described in the embodiment of the first aspect of the present invention, multi-parameter synchronous detection of cells under controlled mechanical stimulation can be achieved, which has the advantages of strong applicability, high throughput, and reliable results.

[0024] According to an embodiment of the present invention, the cells are circulating tumor cells, red blood cells or stem cells.

[0025] The additional aspects and advantages of the present invention will be partially given in the following description, partially become obvious from the following description, or be understood through the practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The above and / or additional aspects and advantages of the present invention will become obvious and easy to understand from the description of the embodiments in conjunction with the following drawings, wherein:

[0027] Figure 1 is a schematic structural diagram of a microfluidic chip of a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention.

[0028] Figure 2 is Figure 1 an enlarged view of part A in

[0029] Figure 3 is a schematic partial structural diagram of a microfluidic chip of a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention.

[0030] Figure 4 is a schematic structural diagram of a microfluidic chip of a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention.

[0031] Figure 5 is a schematic partial structural diagram of a microfluidic chip and cells of a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention.

[0032] Figure 6 is a schematic partial structural diagram of a microfluidic chip of a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention, wherein the air pressure cavity is in a pressurized state.

[0033] Figure 7 It is a partial microscopic image of a microfluidic chip of a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention.

[0034] Figure 8 It is a partial microscopic image of a microfluidic chip of a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention, where the air pressure cavity is in a pressurized state.

[0035] Figure 9 It is a flowchart of a cell detection method according to an embodiment of the present invention.

[0036] Reference numerals: microfluidic chip 10, main body layer 100, deformation detection flow channel 110, air pressure cavity 120, cell suspension inlet 130, cell suspension outlet 140, ventilation port 150, inlet guiding flow channel 160, outlet guiding flow channel 170, air flow channel 180, impurity filtering device 190, first filtering column 191, second filtering column 192, electrode layer 200, electrode 210, glass layer 300, cell 2. Detailed Description of the Invention

[0037] Embodiments of the present invention will be described in detail below. Examples of the embodiments are shown in the accompanying drawings, where the same or similar reference numerals indicate the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary only for explaining the present invention and should not be construed as limiting the present invention.

[0038] In the description of the present invention, it should be understood that the orientation or positional relationships indicated by the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc. are based on the orientation or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as limiting the present invention. In addition, features defined as "first" and "second" may explicitly or implicitly include one or more of such features. In the description of the present invention, unless otherwise specified, the meaning of "a plurality" is two or more.

[0039] In the description of the present invention, it should be noted that unless otherwise clearly specified and defined, the terms "installation", "connection", and "coupling" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, and it can be the communication inside two components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0040] The following describes a microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention with reference to the accompanying drawings.

[0041] As Figures 1-9 shown, the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to an embodiment of the present invention includes a microfluidic chip 10, a pneumatic pressure regulating device (not shown in the figure), and an electrical signal analyzing device (not shown in the figure).

[0042] The microfluidic chip 10 includes a main body layer 100 and an electrode layer 200. The main body layer 100 has a deformation detection flow channel 110 and two pneumatic pressure chambers 120. The deformation detection flow channel 110 is located between the two pneumatic pressure chambers 120. The two pneumatic pressure chambers 120 are symmetrically arranged on both sides of the deformation detection flow channel 110. The deformation detection flow channel 110 is adapted for cells 2 to pass through. The deformation detection flow channel 110 is configured to elastically deform when the pneumatic pressure in the pneumatic pressure chamber 120 changes to adjust the width of the deformation detection flow channel 110. The electrode layer 200 is located below the deformation detection flow channel 110 and is adapted to detect the impedance change when the cells 2 pass through the deformation detection flow channel 110 and the triboelectric signal generated by the friction between the cells 2 and the deformation detection flow channel 110 (the up and down direction is as shown by the arrow in the figure).

[0043] The pneumatic pressure regulating device is respectively communicated with the two pneumatic pressure chambers 120 and is adapted to regulate the pneumatic pressure in the two pneumatic pressure chambers 120.

[0044] The electrical signal detection device is electrically connected to the electrode layer 200 and is adapted to analyze the impedance change and the triboelectric signal detected by the electrode layer 200.

[0045] Specifically, the microfluidic chip 10 may further include a glass layer 300. The glass layer 300 is the lowermost layer and can be used as a glass slide.

[0046] The arrangement direction of the two air pressure cavities 120 is perpendicular to the length direction of the deformation detection flow channel 110. The material of the main body layer 100 has a certain elasticity, enabling the material of the main body layer 100 between the deformation detection flow channel 110 and the air pressure cavities 120 to undergo elastic deformation. The air pressure regulating device regulates the air pressure in the air pressure cavities 120 to cause the air pressure cavities 120 to expand and contract, thereby causing the deformation detection flow channel 110 to undergo elastic deformation and changing the width of the deformation detection flow channel 110.

[0047] When detecting cells, first, the air pressure in the two air pressure cavities 120 is regulated by the air pressure regulating device to adjust the width of the deformation detection flow channel 110, making the minimum width of the deformation detection flow channel 110 smaller than the diameter of the target cells. Then, the cell suspension is injected into one end of the deformation detection flow channel 110, allowing the cells to pass through the deformation detection flow channel 110. During the process of passing through the deformation detection flow channel 110, the cells are squeezed and deformed. At the same time, the impedance change of the cells passing through the deformation detection flow channel 110 is detected in real time through the electrode layer 200, and the frictional charges generated when the cells pass through are collected. Finally, the correlation between cell deformation and electrophysiological characteristics is analyzed by an electrical signal analysis device.

[0048] According to the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection of the embodiments of the present invention, by setting the deformation detection flow channel 110, the air pressure cavities 120, and the air pressure regulating device, and regulating the air pressure of the air pressure cavities 120 by the air pressure regulating device, the deformation detection flow channel 110 undergoes elastic deformation, realizing continuous and precise regulation of the width of the deformation detection flow channel 110. It can not only adapt to the detection requirements of different-sized cells, overcome the limitation that traditional fixed flow channel chips cannot adapt to different-sized cells, improve the applicability of the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection, and ensure the detection throughput, but also facilitate applying controlled mechanical stimuli to cells. Compared with the methods of mechanically squeezing with external clamps and regulating the flow channel width with thermoresponsive materials in related technologies, regulating the flow channel width by air pressure can improve the controllability and uniformity of the applied force, avoid excessive local stress causing cell rupture, avoid cell damage, avoid temperature rise affecting the normal metabolism of cells, avoid changing the original state of cells, ensure the biocompatibility of the detection process, and improve the accuracy and reliability of the detection results.

[0049] Moreover, by setting the electrode layer 200 and the electrical signal analysis device, the impedance change when the cells pass through and the frictional electrical signals generated by the friction between the cells and the inner wall of the deformation detection flow channel 110 can be detected by the electrode layer 200, realizing the detection of the electrical characteristic parameters of the cells.

[0050] That is to say, the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection can dynamically regulate the flow channel size and synchronously detect the electrophysiological characteristics of cells, realizing the multi-parameter synchronous detection of cells under controlled mechanical stimuli, realizing the multi-parameter coupling analysis of cell mechanics, impedance, and triboelectric characteristics, and meeting the requirements of clinical-level cell analysis.

[0051] Therefore, the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to the embodiments of the present invention can realize the multi-parameter synchronous detection of cells under controlled mechanical stimuli, and has the advantages of strong applicability, high throughput, and reliable results.

[0052] Next, the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to specific embodiments of the present invention will be described with reference to the accompanying drawings.

[0053] In some specific embodiments of the present invention, as Figures 1-9 shown, the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to the embodiments of the present invention includes a microfluidic chip 10, a pneumatic regulation device, and an electrical signal analysis device.

[0054] Specifically, as Figure 1 shown, a cell suspension inlet 130, a cell suspension outlet 140, and two ventilation ports 150 are provided on the main body layer 100. One end of the deformation detection flow channel 110 is connected to the cell suspension inlet 130 through an inlet guiding flow channel 160, and the other end of the deformation detection flow channel 110 is connected to the cell suspension outlet 140 through an outlet guiding flow channel 170. The two ventilation ports 150 are respectively connected to the two pneumatic cavities 120 through ventilation flow channels 180. Specifically, the length directions of the inlet guiding flow channel 160 and the outlet guiding flow channel 170 are collinear with the length direction of the deformation detection flow channel 110, and the length directions of the two ventilation flow channels 180 are collinear and perpendicular to the length direction of the deformation detection flow channel 110. This can facilitate the guidance of cells and air flow.

[0055] Specifically, as Figure 1 shown, the width of the inlet guiding flow channel 160 gradually decreases from the cell suspension inlet 130 to the deformation detection flow channel 110, and the width of the outlet guiding flow channel 170 gradually decreases from the cell suspension outlet 140 to the deformation detection flow channel 110. Here, it is preferably that the width gradually decreases from 200 microns to 30 microns. This can prevent cells from easily clogging the flow channel.

[0056] Advantageously, as Figure 1As shown, an impurity filtering device 190 is connected to the inlet guiding channel 160, and the impurity filtering device 190 is adapted to allow the passage of cells 2. In this way, the impurity filtering device 190 can filter impurities in the cell suspension, only allowing the passage of cells, preventing impurities from clogging the channel, and avoiding impurities from interfering with the detection process or affecting the detection results.

[0057] Further, as Figure 1 shown, the impurity filtering device 190 includes a plurality of first filtering columns 191 and a plurality of second filtering columns 192. The plurality of first filtering columns 191 are arranged at intervals in the width direction of the inlet guiding channel 160, and the interval between every two adjacent first filtering columns 191 is 40 micrometers. The plurality of second filtering columns 192 are arranged at intervals in the width direction of the inlet guiding channel 160, and the plurality of second filtering columns 192 are closer to the deformation detection channel 110 relative to the plurality of first filtering columns 191, and the interval between every two adjacent second filtering columns 192 is 20 micrometers. In this way, the cell suspension can pass through two-stage filtration successively, fully filtering out impurities therein, improving the filtration effect, and also allowing the cells to disperse and pass through, avoiding cell clogging of the channel.

[0058] More specifically, the main body layer 100 is a polydimethylsiloxane (PDMS) material part. In this way, the main body layer 100 can have good elasticity, light transmittance and hydrophobicity.

[0059] Optionally, the height of the deformation detection channel 110 in the up and down direction is 20 micrometers, the length of the air pressure cavity 120 in the horizontal direction is 20 - 200 micrometers and the width is 20 - 40 micrometers, the interval between the deformation detection channel 110 and the air pressure cavity 120 is 6 - 12 micrometers, the width of the deformation detection channel 110 in the horizontal direction under normal pressure is 8 - 16 micrometers, and the maximum value of the width change amount of the deformation detection channel 110 is 75% of the width of the deformation detection channel in the horizontal direction under normal pressure. For example, it can be 8 micrometers. In this way, the sizes of the deformation detection channel 110 and the air pressure cavity 120 can be more reasonable, facilitating the formation of the deformation detection channel 110 and facilitating the more uniform deformation of the deformation detection channel 110.

[0060] Further, the air pressure regulating device at least includes an air pump, the air pump is respectively communicated with the two air pressure cavities 120 and is adapted to synchronously charge and discharge the two air pressure cavities 120, and the air pressure control accuracy of the air pressure regulating device is 0.1 kPa. Specifically, the air pressure regulating range of the air pressure regulating device can be 0 - 0.1 MPa. The relationship between the air pressure and the channel width can be calibrated before detection. In this way, the precise control of the channel width can be further ensured and the detection accuracy can be improved.

[0061] Further, the electrode layer 200 includes a plurality of electrodes 210, which are arranged at intervals along the length direction of the deformation detection flow channel 110. Each electrode 210 at least partially overlaps with the projection of the deformation detection flow channel 110 in the horizontal plane. The width of each electrode 210 in the horizontal direction is 15-20 microns, and the distance between every two adjacent electrodes 210 is 20-50 microns. Specifically, the length direction of the electrode 210 can be perpendicular to the length direction of the deformation detection flow channel 110. The electrode 210 can be formed by magnetron sputtering chromium and gold onto the glass layer 300 respectively, and the thickness of the electrode 210 can be 50 nanometers. This facilitates the detection of the electrical properties of cells by the electrode 210.

[0062] Specifically, the electrode 210 can be connected to the edge of the microfluidic chip 10 through a gold lead with a width of 100 microns, facilitating the connection of an external circuit to an electrical signal analysis device.

[0063] The microfluidic chip 10 can be encapsulated as a whole by using an oxygen plasma bonding process for the main body layer 100, the electrode layer 200, and the glass layer 300. After encapsulation, the total thickness of the microfluidic chip 10 is 2-3 millimeters, and the size is 25 millimeters × 75 millimeters, which is the size of a standard microscope slide.

[0064] The preparation process of the microfluidic chip 10 according to the embodiment of the present invention is described below.

[0065] 1) The polydimethylsiloxane (PDMS) matrix and the curing agent are uniformly mixed in a ratio of 10:1.

[0066] 2) Take a silicon plate, drop trimethylchlorosilane beside the silicon plate, seal it for a period of time, and perform a modification operation.

[0067] 3) The mixed PDMS is evacuated to remove air bubbles.

[0068] 4) Place the silicon plate in a tin bowl with the same diameter and size, pour PDMS to completely cover the silicon plate, and place it in an 80°C oven for curing for 15 minutes.

[0069] 5) Take out the cured PDMS, cut the required part, perform an oxygen plasma process on it together with the glass slide with electrodes, and then bond them, and place them in an 80°C oven for bonding for 20 minutes; finally, the required microfluidic chip 10 is obtained.

[0070] Taking the detection of red blood cells as an example, the initial width of the deformation detection flow channel 110 under normal pressure is 10 microns, the length of the air pressure cavity 120 is 100 microns and the width is 20 microns, the wall thickness between the deformation detection flow channel 110 and the air pressure cavity 120 is 10 microns, and the height of the deformation detection flow channel 110 is 20μm.

[0071] In this embodiment, the red blood cell suspension is injected into the cell suspension inlet 130 at a flow rate of 0.2 milliliters per hour; the average diameter of the selected red blood cells is 10 micrometers, and the width of the flow channel needs to be adjusted to be less than the cell diameter so that the cells are mechanically deformed when passing through; here, the air pressure is set to 50 kPa and the flow channel width is reduced to 5 micrometers; the cells pass through the deformed flow channel, and the impedance change when the cells pass through is recorded in real time through the electrode layer 200, and at the same time, the frictional charges generated when the cells pass through are collected; finally, a database between red blood cell deformation and electrical signals is established based on the impedance and triboelectric data.

[0072] The following refers to Figures 1-9 Describe the cell detection method according to an embodiment of the present invention. The cell detection method according to an embodiment of the present invention uses the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to the above-mentioned embodiment of the present invention, and includes the following steps:

[0073] Adjust the air pressure in the two air pressure cavities through the air pressure regulating device to adjust the width of the deformation detection flow channel so that the minimum width of the deformation detection flow channel is less than the target cell diameter;

[0074] Inject the cell suspension into one end of the deformation detection flow channel, so that the cells pass through the deformation detection flow channel, and the cells are deformed under extrusion during the process of passing through the deformation detection flow channel;

[0075] Detect the impedance change of the cells in real time through the electrode layer when the cells pass through the deformation detection flow channel, and at the same time collect the frictional charges generated when the cells pass through;

[0076] Analyze the correlation between cell deformation and electrophysiological characteristics through the electrical signal analysis device.

[0077] According to the cell detection method of the embodiment of the present invention, by using the microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to the above-mentioned embodiment of the present invention, multi-parameter synchronous detection of cells under controlled mechanical stimulation can be realized, and it has the advantages of strong applicability, high throughput, and reliable results.

[0078] Optionally, the cells are circulating tumor cells, red blood cells or stem cells. This can make the cell detection method applicable to the mechanical property research and sorting of circulating tumor cells, red blood cells or stem cells.

[0079] The other constitutions and operations of the microfluidic chip system and cell detection method based on dynamic flow channel regulation and cell electrical signal detection according to the embodiment of the present invention are known to those of ordinary skill in the art and will not be described in detail here.

[0080] In the description of this specification, the descriptions referring to terms such as "one embodiment", "some embodiments", "schematic embodiments", "examples", "specific examples", or "some examples", etc. mean that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0081] Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the claims and their equivalents.

Claims

1. A microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection, characterized in that: include: A microfluidic chip, the microfluidic chip comprising a main body layer and an electrode layer, the main body layer having a deformation detection channel and two air pressure cavities, the deformation detection channel being located between the two air pressure cavities, the two air pressure cavities being symmetrically arranged on both sides of the deformation detection channel, the deformation detection channel being suitable for cells to pass through, the deformation detection channel being configured to undergo elastic deformation when the air pressure in the air pressure cavity changes so as to adjust the width of the deformation detection channel, the electrode layer being located below the deformation detection channel and being suitable for detecting impedance changes when cells pass through the deformation detection channel and triboelectric signals generated by friction between the cells and the deformation detection channel; An air pressure regulating device, the air pressure regulating device is respectively connected to the two air pressure cavities and is suitable for regulating the air pressure in the two air pressure cavities; An electrical signal analysis device is electrically connected to the electrode layer and is suitable for analyzing the impedance change and the friction electric signal detected by the electrode layer.

2. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to claim 1, characterized in that: The main body layer is provided with a cell suspension inlet, a cell suspension outlet and two air vents. The cell suspension inlet is connected to one end of the deformation detection channel through an inlet guide channel, and the cell suspension outlet is connected to the other end of the deformation detection channel through an outlet guide channel. The two air vents are connected to the two air pressure cavities through ventilation channels respectively.

3. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to claim 2, characterized in that: The inlet guide flow channel is connected with an impurity filtering device, and the impurity filtering device is suitable for the cells to pass through.

4. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to claim 3, characterized in that: The impurity filtering device comprises: A plurality of first filter columns, wherein the plurality of first filter columns are arranged at intervals along the width direction of the inlet guide channel, and the interval between each two adjacent first filter columns is 40 microns; A plurality of second filter columns are arranged at intervals along the width direction of the inlet guide channel, the plurality of second filter columns are close to the deformation detection channel relative to the plurality of first filter columns, and the interval between each two adjacent second filter columns is 20 microns.

5. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to claim 1, characterized in that: The main body layer is made of polydimethylsiloxane material.

6. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to claim 1, characterized in that: The height of the deformation detection channel in the up and down directions is 20 microns, the length of the air pressure cavity in the horizontal direction is 20-200 microns and the width is 20-40 microns, the interval between the deformation detection channel and the air pressure cavity is 6-12 microns, the width of the deformation detection channel in the horizontal direction under normal pressure is 8-16 microns, and the maximum value of the width change of the deformation detection channel is 75% of the width of the deformation detection channel in the horizontal direction under normal pressure.

7. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to claim 1, characterized in that: The air pressure regulating device at least includes an air pump, which is connected to the two air pressure cavities respectively and is suitable for synchronously inflating and deflating the two air pressure cavities. The air pressure control accuracy of the air pressure regulating device is 0.1 kPa.

8. The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to claim 1, characterized in that: The electrode layer includes a plurality of electrodes, and the plurality of electrodes are spaced apart along the length direction of the deformation detection channel. Each of the electrodes at least partially overlaps with a projection of the deformation detection channel in a horizontal plane. The width of each electrode in the horizontal direction is 15-20 microns, and the spacing between each two adjacent electrodes is 20-50 microns.

9. A cell detection method, characterized in that: The microfluidic chip system based on dynamic flow channel regulation and cell electrical signal detection according to any one of claims 1 to 8 comprises the following steps: The air pressure in the two air pressure chambers is adjusted by the air pressure regulating device to adjust the width of the deformation detection flow channel so that the minimum width of the deformation detection flow channel is smaller than the target cell diameter; Injecting a cell suspension into one end of the deformation detection flow channel, allowing the cells to pass through the deformation detection flow channel, and the cells are squeezed and deformed in the process of passing through the deformation detection flow channel; The electrode layer is used to detect the impedance change of cells when they pass through the deformation detection channel in real time, and at the same time, the friction charge generated when the cells pass through is collected; The correlation between cell deformation and electrophysiological characteristics is analyzed by an electrical signal analysis device.

10. The cell detection method according to claim 9, characterized in that: The cells are circulating tumor cells, red blood cells or stem cells.

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