Single cell capture micro-channel calorimetric chip, preparation method thereof and single cell capture micro-channel calorimetric system

Abstract

The invention provides a single cell capture micro-channel calorimetric chip, a preparation method thereof and a single cell capture micro-channel calorimetric system, and belongs to the technical field of semiconductor devices. The single cell capture micro-channel calorimetric chip comprises a silicon substrate which is provided with a first surface and a second surface which are opposite to each other, and two accommodating grooves which are arranged in the silicon substrate between the first surface and the second surface in parallel at intervals; the protective film layer is deposited on the first surface, the second surface and the inner wall of the accommodating groove, and the protective film layer located in the accommodating groove is encircled to form a micro-channel unit; wherein one end of the micro-channel unit is provided with a micro-channel inlet penetrating through the second surface, the other end of the micro-channel unit is provided with a micro-channel outlet penetrating through the second surface, and the part, located between the micro-channel inlet and the micro-channel outlet, of the micro-channel unit is provided with a cell capturing cavity suitable for capturing cells.

Description

Technical Field

[0001] The present invention belongs to the technical field of semiconductor devices, and in particular relates to a single-cell capture microfluidic channel calorimetry chip and a preparation method thereof, and a single-cell capture microfluidic channel calorimetry system. Background Art

[0002] All biological activities release or consume energy, which is used to maintain the balance of the internal environment and ultimately promote growth and development. Energy balance in organisms plays an important role in maintaining the body's homeostasis. By monitoring the energy balance of these biological activities, information about cell metabolism and biomolecular interactions can be obtained. Cells mainly maintain energy balance in the body through metabolic heat production. The metabolic heat information of cells can explain some basic cell activity processes and also reflect the activity of cells.

[0003] However, since some microorganisms produce or consume very little energy, it is challenging to monitor heat changes during energy balance. Many methods have been adopted to monitor energy balance, measure metabolic heat or temperature changes of organisms. The heat measurement caused by living organisms can be carried out directly or indirectly, and both types of measurement methods include a variety of temperature sensing technologies. Indirect measurement techniques mainly include luminescent material-based temperature measurement and many other cell temperature sensing methods. Luminescent material-based temperature measurement mainly uses the fluorescence properties of luminescent materials to measure the temperature changes of biological samples, but this method is limited by the temperature resolution of luminescent materials and is easily affected by factors such as molecular concentration and cell composition. Direct measurement methods include contact temperature measurement using nanoscale thermal probes and microcalorimetry. Contact temperature measurement using nanoscale thermal probes generally measures the temperature changes inside the cell through thermocouples. However, during the measurement process, the thermal probe will damage the cell membrane, causing the cell stress response and generating additional heat. Microcalorimetry is generally used to monitor the energy balance of organisms and measure the heat changes of organisms. Among these methods, microcalorimetry has become a powerful and indispensable tool for characterizing biological metabolic processes in a label-free, non-invasive, and non-irritating manner. Microcalorimetry provides direct measurement of cellular thermal information, thereby providing a wealth of key information to reveal the underlying mechanisms of cellular metabolism. Microcalorimetry has been widely used for energy balance monitoring and metabolic heat measurement of biological activity processes in cells and organisms.

[0004] Buried channel technology is used to manufacture microstructures for fluid applications, such as microfluidics, connectors, etc. based on silicon substrates. The technology builds microstructures by etching grooves, depositing a capping layer on the sidewalls of the grooves, removing the capping layer at the bottom of the grooves, and etching the main body of the silicon substrate. The microstructure can seal the grooves by depositing an appropriate capping layer. Buried channel technology is a process that can be used to manufacture complete microchannels on a single wafer, requiring only one photolithography mask and processing on one side of the wafer without assembly and bonding. The process can make the substrate surface almost flat and smooth, which is convenient for further processing. Microchannels manufactured using buried channel technology have good sealing properties, but the etching speed is relatively slow when etching large-diameter, nearly circular microchannels. In addition, when it is necessary to etch microchannels of different diameters that are interconnected and conductive, it is even more difficult to operate and the process needs to be repeated many times. Summary of the invention

[0005] In view of the above technical problems, the present invention provides a single-cell capture microfluidic calorimetry chip and a preparation method thereof and a single-cell capture microfluidic calorimetry system, in order to at least partially solve the above technical problems. The specific technical solutions provided by the present invention are as follows.

[0006] As a first aspect of the present invention, a single-cell capture microfluidic calorimetry chip is provided, comprising: a silicon substrate having a first surface and a second surface relative to each other, two receiving grooves being arranged in parallel and spaced apart inside the silicon substrate between the first surface and the second surface; and a protective film layer deposited on the first surface, the second surface and the inner wall of the receiving groove, the protective film layer in the receiving groove surrounds and forms a microfluidic unit; wherein a microfluidic inlet penetrating the second surface is arranged at one end of the microfluidic unit, a microfluidic outlet penetrating the second surface is arranged at the other end of the microfluidic unit, and a cell capture cavity suitable for capturing cells is arranged at a portion of the microfluidic unit between the microfluidic inlet and the microfluidic outlet.

[0007] As a second aspect of the present invention, a method for preparing a single-cell capture microfluidic calorimetry chip is provided, comprising: providing a silicon substrate with protective film layers deposited on relative first and second surfaces; forming a first window on the protective film layer on the second surface of the silicon substrate, forming a slit structure on the protective film layer on the first surface of the silicon substrate, etching the interior of the silicon substrate through the first window and the slit structure to form two receiving grooves with the same structure; depositing a material identical to the protective film layer on the inner wall of the receiving groove of the silicon substrate to form a microfluidic unit, and sealing the slit structure; forming a temperature measuring resistor and a heating resistor on the protective film layer on the first surface of the silicon substrate on which the microfluidic unit is formed; forming a second window on the protective film layer on the first surface of the silicon substrate on which the temperature measuring resistor and the heating resistor are formed, and forming a heat-insulating groove surrounding the middle part of the microfluidic unit inside the silicon substrate through the second window to obtain a single-cell capture microfluidic calorimetry chip.

[0008] As a third aspect of the present invention, a single-cell capture microfluidic calorimetry system is provided, comprising: a single-cell capture microfluidic calorimetry chip, suitable for single-cell capture and single-cell metabolic heat measurement; a fluid driving device, connected to the microfluidic inlet and microfluidic outlet of the single-cell capture microfluidic calorimetry chip, suitable for injecting a cell suspension into the single-cell capture microfluidic calorimetry chip; and a data acquisition device, electrically connected to the single-cell capture microfluidic calorimetry chip, suitable for receiving an electrical signal transmitted by the single-cell capture microfluidic calorimetry chip.

[0009] Based on the above technical solution, a single-cell capture microfluidic calorimetry chip and a preparation method thereof and a single-cell capture microfluidic calorimetry system provided by the present invention have at least one of the following beneficial effects.

[0010] (1) In the embodiment of the present invention, two receiving grooves with the same structure are arranged in parallel inside the silicon substrate, and a protective film layer is deposited on the first and second surfaces of the silicon substrate and the inner wall of the receiving groove. The protective film layer deposited on the inner wall of the receiving groove forms a microfluidic unit. The microfluidic unit is isolated from the external environment to avoid the influence of the external environment on cell metabolism when measuring cell metabolic heat. At the same time, the two microfluidic units form a differential structure to reduce the common mode interference in the process of measuring cell metabolic heat and improve the measurement accuracy.

[0011] (2) In an embodiment of the present invention, a protective film layer is formed on the first and second surfaces opposite to the silicon substrate to protect the silicon substrate during etching, a first window is formed on the protective film layer on the second surface, a slit structure is formed on the protective film layer on the first surface, the interior of the silicon substrate is etched through the first window and the slit structure to form a receiving groove, and then the same material as the protective film layer is deposited on the inner wall of the receiving groove to form a microfluidic unit. By etching the silicon substrate through the slit structure and the first window, the process of chip preparation can be reduced and the structural strength of the microfluidic unit can be improved. The shape and size of the receiving groove can be adjusted by adjusting the shape and size of the first window and the slit structure, and finally the shape and size of the microfluidic unit can be adjusted to adapt to the capture of biological cells of different sizes. The first window and the slit structure are opened on the protective film layers on different surfaces to avoid the collapse of the channel wall of the microfluidic unit caused by the force applied by the external device when the cell suspension is injected into or flows out of the single cell capture microfluidic calorimeter chip through the external device.

[0012] (3) In the embodiments of the present invention, the single-cell capture microfluidic calorimetry system provided by the present invention can realize the capture of cells in a cell suspension and the accurate measurement of the metabolic heat of the captured cells, and has the advantages of high sensitivity, small sample volume, fast response time and wide application. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 Schematic diagram of the overall structure of a single cell capture microfluidic calorimetry chip in an embodiment of the present invention;

[0014] Figure 2 Detailed schematic diagram of a cell capture chamber of a microfluidic unit in an embodiment of the present invention;

[0015] Figure 3 Detailed schematic diagram of the temperature measuring resistor and the heating resistor in the embodiment of the present invention;

[0016] Figure 4 This is a design diagram of a single cell capture microfluidic calorimetry chip in an embodiment of the present invention;

[0017] Figure 5 This is a process flow chart of the preparation of a single cell capture microfluidic calorimetry chip according to an embodiment of the present invention;

[0018] Figure 6 Detailed design diagram of the temperature measuring resistor and the heating resistor in the embodiment of the present invention;

[0019] Figure 7 Schematic diagram of the structure of a microfluidic fixture clamping a single-cell capture microchannel calorimetric chip in an embodiment of the present invention.

[0020] Description of reference numerals:

[0021] 100. Single cell capture microfluidic calorimetry chip;

[0022] 1. Silicon substrate; 11. Microfluidic unit; 111. Cell capture chamber; 112. First microfluidic channel; 113. Second microfluidic channel; 12. Microfluidic channel inlet; 13. Microfluidic channel outlet; 14. Isolation groove; 15. Temperature measuring resistor; 16. Heating resistor;

[0023] 2. A protective film layer on the first surface;

[0024] 3. A protective film layer on the second surface. DETAILED DESCRIPTION

[0025] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings.

[0026] In the prior art, most single-cell capture microfluidic calorimetry chips adopt the method of constructing a microfluidic channel on a silicon substrate or opening an open microfluidic channel on a silicon substrate and covering the silicon substrate with a glass substrate, etc. The preparation process of these chips is relatively cumbersome and complicated, and when measuring the metabolic heat of the cell after capturing a single cell, it is inevitably affected by the external environment. Based on this, the present application provides a single-cell capture microfluidic calorimetry chip and its preparation method and a single-cell capture microfluidic calorimetry system. Among them, the single-cell capture microfluidic calorimetry chip of the present application forms a microfluidic unit inside the silicon substrate, which can realize single-cell capture and accurately measure the metabolic heat of the cell.

[0027] Figure 1 Schematic diagram of the overall structure of the single cell capture microfluidic calorimetry chip in an embodiment of the present invention.

[0028] As a first aspect of the present invention, a single cell capture microfluidic calorimetry chip 100 is provided. Figure 1 As shown, it includes: a silicon substrate 1, having a first surface and a second surface opposite to each other, and two receiving grooves are arranged in parallel and spaced apart inside the silicon substrate between the first surface and the second surface; and a protective film layer, deposited on the first surface, the second surface and the inner wall of the receiving groove, and the protective film layer located in the receiving groove surrounds and forms a microfluidic unit 11; wherein, one end of the microfluidic unit is provided with a microfluidic inlet 12 penetrating the second surface, and the other end of the microfluidic unit is provided with a microfluidic outlet 13 penetrating the second surface, and the part of the microfluidic unit located between the microfluidic inlet and the microfluidic outlet is provided with a cell capture cavity 111 suitable for capturing cells.

[0029] In an embodiment of the present invention, two receiving grooves with the same structure are arranged in parallel inside the silicon substrate, and a protective film layer is deposited on the first and second surfaces opposite to each other of the silicon substrate and the inner wall of the receiving groove, and the protective film layer deposited on the inner wall of the receiving groove forms a microfluidic unit. The microfluidic unit is isolated from the external environment to avoid the influence of the external environment on cell metabolism when measuring cell metabolic heat. At the same time, the two microfluidic units form a differential structure to reduce common mode interference in the process of measuring cell metabolic heat and improve measurement accuracy.

[0030] Figure 2 Detailed schematic diagram of the cell capture chamber of the microfluidic unit in an embodiment of the present invention.

[0031] According to an embodiment of the present invention, Figure 2 As shown, the microfluidic unit 11 includes a first microfluidic channel 112 located between the microfluidic channel inlet 12 and the cell capture chamber 111, and at least two second microfluidic channels 113 located between the cell capture chamber 111 and the microfluidic channel outlet 13; wherein the diameter of the first microfluidic channel 112 is larger than the diameter of the cell, and the diameter of the second microfluidic channel 113 is smaller than the diameter of the cell.

[0032] In the embodiment of the present invention, the cell suspension enters the microfluidic unit 11 from the microfluidic inlet 12. Since the diameter of the first microfluidic channel 112 is larger than the cell diameter and the diameter of the second microfluidic channel 113 is smaller than the cell diameter, when the cell suspension flows from the first microfluidic channel 112 to the second microfluidic channel 113, the cells are captured by the cell capture chamber 111, and the remaining solution flows out through the second microfluidic channel 113, which will not cause blockage of the microfluidic unit 11. The microfluidic channel diameter can be adjusted according to the diameter of the cells in the cell suspension passed in, and the present invention is not limited thereto.

[0033] According to an embodiment of the present invention, Figure 2 As shown, the above-mentioned single cell capture microfluidic calorimetry chip also includes: a heat-insulating groove 14, which is arranged on the outside of the cell capture cavity 111 inside the silicon substrate 1, and is suitable for isolating the cell capture cavity 111 from the silicon substrate 1. Since the heat-insulating groove 14 isolates the cell capture cavity 111 from the silicon substrate 1, when measuring the metabolic heat of the cells captured by the cell capture cavity 111, the influence of the external temperature transmitted by the silicon substrate 1 on the cells can be further avoided, thereby improving the accuracy of the measurement. The size and shape of the isolation groove 14 are not limited here, and it is sufficient that the cell capture cavity 111 can be isolated from the silicon substrate 1 without penetrating the silicon substrate 1.

[0034] Figure 3 Detailed schematic diagram of the temperature measuring resistor and the heating resistor in the embodiment of the present invention.

[0035] According to an embodiment of the present invention, Figure 3 As shown, the above-mentioned single cell capture microfluidic calorimetry chip also includes: a temperature measuring resistor 15, located on the protective film layer 2 on the first surface, suitable for measuring the metabolic heat of the cell and transmitting electrical signals to the outside world. The material of the temperature measuring resistor 15 can be selected from metal titanium and metal platinum, but the present invention is not limited thereto. The temperature measuring resistor 15 is located on the cell capture chamber 111, and can measure the metabolic heat of the cells captured in the cell capture chamber, and transmit electrical signals to the outside world through the circuit.

[0036] According to an embodiment of the present invention, Figure 3 As shown, the above-mentioned single cell capture microfluidic calorimetry chip also includes: a heating resistor 16, which is located on the protective film layer 2 on the first surface and is suitable for providing stable temperature conditions for cells to survive. The material of the heating resistor 16 can be selected from metal titanium and metal platinum, but the present invention is not limited thereto. The heating resistor 16 is located on the cell capture chamber 111, opposite to the temperature measuring resistor, and the cell capture chamber 111 is heated by the heating resistor 16 to provide suitable and stable temperature conditions for the cells in the cell capture chamber 111.

[0037] In an embodiment of the present invention, the temperature measuring resistor 15 and the heating resistor 16 can be set to a serpentine structure to increase the coverage area, so as to facilitate the temperature measurement of the temperature measuring resistor 15 and the heating resistor 16 to heat. The materials of the temperature measuring resistor 15 and the heating resistor 16 can be the same or different. When titanium (the thermal conductivity of titanium is 15W / (m·K) at 25°C and the temperature coefficient of resistance is 0.32% / K) is selected as the temperature measuring resistor 15 and the heating resistor 16, the line width of the temperature measuring resistor 15 is set to be less than half of the line width of the heating resistor 16. Figure 3 As shown, etching is performed on the protective film layer on the first surface and a conductive material is deposited to achieve electrical connection between the temperature measuring resistor 15 and the heating resistor 16 and the external circuit. When the temperature measuring resistor 15 and the heating resistor 16 are made of metal titanium, in order to improve the adhesion of the conductive material to the protective film layer and the conductivity of the conductive material to the metal titanium, a layer of metal titanium can be deposited before depositing the conductive material.

[0038] According to an embodiment of the present invention, the material of the protective film layer is any one of silicon nitride and silicon oxide. Silicon nitride or silicon oxide with low thermal conductivity is used to deposit on two opposite surfaces of the silicon substrate to form a protective film layer, and a microfluidic unit is formed inside the silicon substrate, which can further reduce the thermal conductivity of the single cell capture microfluidic calorimetric chip and reduce measurement errors.

[0039] Figure 4 This is a design diagram of a single cell capture microfluidic calorimetry chip in an embodiment of the present invention; Figure 5 This is a process flow chart of the preparation of a single cell capture microfluidic calorimetry chip according to an embodiment of the present invention; Figure 6 Detailed design diagram of the temperature measuring resistor and the heating resistor in the embodiment of the present invention.

[0040] As a second aspect of the present invention, according to Figure 4 The structure shown in the figure is processed to provide a method for preparing the above-mentioned single cell capture microfluidic calorimetric chip, such as Figure 5 As shown, the method comprises: providing a silicon substrate 1 with a protective film layer deposited on a first surface and a second surface opposite to each other, as shown in FIG. Figure 5 a; a first window is formed on the protective film layer 3 on the second surface of the silicon substrate, a slit structure is formed on the protective film layer 2 on the first surface of the silicon substrate, and the interior of the silicon substrate is etched through the first window and the slit structure to form two receiving grooves with the same structure, such as Figure 5 b-5e; depositing the same material as the protective film layer on the inner wall of the receiving groove of the silicon substrate to form a microchannel unit 11, and sealing the gap structure, such as Figure 5 f; forming a temperature measuring resistor 15 and a heating resistor 16 on the protective film layer 2 of the first surface of the silicon substrate 1 having the microchannel unit 11, such as Figure 5g; forming a second window on the protective film layer 2 of the first surface of the silicon substrate 1 having a temperature measuring resistor 15 and a heating resistor 16, and forming a heat-insulating groove 14 around the middle portion of the microchannel unit 11 inside the silicon substrate 1 through the second window, such as Figure 5 h-5i, obtaining a single cell capture microfluidic calorimetry chip 100.

[0041] In an embodiment of the present invention, a protective film layer is formed on the first and second surfaces opposite to the silicon substrate 1 to protect the silicon substrate 1 during the etching process, a first window is formed on the protective film layer 3 on the second surface, and a slit structure is formed on the protective film layer 2 on the first surface. The interior of the silicon substrate 1 is etched through the first window and the slit structure to form a receiving groove, and then the same material as the protective film layer is deposited on the inner wall of the receiving groove to form a microfluidic unit 11. By etching the silicon substrate 1 through the slit structure and the first window, the process of chip preparation can be reduced and the structural strength of the microfluidic unit 11 can be improved. The shape and size of the receiving groove are adjusted by adjusting the shape and size of the first window and the slit structure, and finally the shape and size of the microfluidic unit 11 are adjusted to adapt to the capture of biological cells of different sizes. The first window and the slit structure are opened on the protective film layers on different surfaces to avoid the collapse of the channel wall of the microfluidic unit caused by the force applied by the external device when the solution containing cells is injected into or out of the single cell capture microfluidic calorimetric chip through the external device.

[0042] In an embodiment of the present invention, when depositing the protective film layer, low pressure chemical vapor deposition can be used, but the present invention is not limited thereto. When forming the first window, the gap structure, the second window, the temperature measuring resistor and the heating resistor, laser direct writing can be used, but the present invention is not limited thereto. Before etching the silicon substrate deposited with the protective film layer, a layer of metal aluminum can be deposited on the surface of the protective film layer to protect the protective film layer. When etching to form the receiving grooves of the microchannel inlet and the microchannel outlet, dry isotropic etching can be used, and when etching to form the receiving grooves and the isolation grooves of the first microchannel and the second microchannel, dry anisotropic etching can be used, but the present invention is not limited thereto. The first window is circular in shape, so as to etch the shape of the microchannel inlet and the microchannel outlet into a circle as much as possible; the second window is rectangular in shape, and can also be adjusted according to the shape of the microchannel, but the present invention is not limited thereto.

[0043] According to an embodiment of the present invention, when forming the first microchannel 112, the slit structure is a structure with 3-7 slits staggered; when forming the second microchannel 113, the slit structure is a structure with 1-3 slits staggered. The internal width of the microchannel unit is controlled by adjusting the parameters of the slit structure such as the slit path, number, etching time, etc., so as to customize the microchannel diameter of a special size.

[0044] For example, when the diameter of the cells in the cell suspension is 90-120 μm, a 400 μm 100 crystal phase 4-inch double-polished silicon wafer is used as the silicon substrate, the diameter of the first microchannel is set to 120-200 μm, the diameter of the second microchannel is set to 20-90 μm, and the diameters of the microchannel inlet and the microchannel outlet are the same, both 200-600 μm. Figure 6 As shown, when etching the receiving groove of the first microchannel, the gap structure is a structure in which 5 gaps are intermittently distributed, and when etching the receiving groove of the second microchannel, the gap structure is a structure in which 1 gap is intermittently distributed. The gap is 1 μm wide and 95 μm long. In the direction parallel to the etching path, the gaps are 5 μm apart, and in the direction perpendicular to the etching path, the gaps are 10 μm apart.

[0045] As a third aspect of the present invention, a single-cell capture microfluidic calorimetry system is provided, comprising: a single-cell capture microfluidic calorimetry chip 100, suitable for single-cell capture and single-cell metabolic heat measurement; a fluid driving device, connected to the microfluidic inlet 12 and the microfluidic outlet 13 of the single-cell capture microfluidic calorimetry chip 100, suitable for injecting a cell suspension into the single-cell capture microfluidic calorimetry chip 100; and a data acquisition device, electrically connected to the single-cell capture microfluidic calorimetry chip 100, suitable for receiving an electrical signal transmitted by the single-cell capture microfluidic calorimetry chip 100.

[0046] In an embodiment of the present invention, the single-cell capture microfluidic calorimetry system provided by the present invention can realize the capture of cells in a cell suspension and the accurate measurement of the metabolic heat of the captured cells, and has the advantages of high sensitivity, small sample volume, fast response time and wide application.

[0047] Figure 7 Schematic diagram of the structure of a microfluidic fixture clamping a single-cell capture microchannel calorimetric chip in an embodiment of the present invention.

[0048] According to an embodiment of the present invention, the single cell capture microfluidic calorimetry system further comprises: a microfluidic fixture for fixing the single cell capture microfluidic calorimetry chip to achieve the connection between the single cell capture microfluidic calorimetry chip and the fluid driving device. Figure 7 As shown, the microfluidic fixture clamps the single-cell capture microfluidic calorimetric chip through the upper and lower structures, and rubber plugs are provided at the microfluidic inlet and microfluidic outlet to connect the microfluidic inlet and microfluidic outlet with the fluid driving device.

[0049] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A single cell capture microfluidic calorimetry chip, comprising: A silicon substrate having a first surface and a second surface opposite to each other, wherein two receiving grooves are arranged in parallel and spaced apart inside the silicon substrate between the first surface and the second surface; as well as A protective film layer is deposited on the first surface, the second surface and the inner wall of the containing groove, and the protective film layer located in the containing groove surrounds and forms a microfluidic unit; One end of the microfluidic unit is provided with a microfluidic inlet penetrating the second surface, the other end of the microfluidic unit is provided with a microfluidic outlet penetrating the second surface, and the portion of the microfluidic unit located between the microfluidic inlet and the microfluidic outlet is provided with a cell capture cavity suitable for capturing cells.

2. The chip according to claim 1, wherein: The microfluidic channel unit includes a first microfluidic channel located between the microfluidic channel inlet and the cell capture chamber, and at least two second microfluidic channels located between the cell capture chamber and the microfluidic channel outlet; The diameter of the first microfluidic channel is larger than the diameter of the cell, and the diameter of the second microfluidic channel is smaller than the diameter of the cell.

3. The chip according to claim 1, further comprising: The heat-insulating groove is arranged on the outer side of the cell-capturing cavity inside the silicon substrate, and is suitable for isolating the cell-capturing cavity from the silicon substrate.

4. The chip according to claim 1, further comprising: The temperature measuring resistor is located on the protective film layer of the first surface and is suitable for measuring the metabolic heat of the cells and transmitting electrical signals to the outside world.

5. The chip according to claim 4, further comprising: The heating resistor is located on the protective film layer of the first surface and is suitable for providing the cells with stable temperature conditions suitable for the survival of the cells.

6. The chip according to any one of claims 1 to 5, wherein: The material of the protective film layer is any one of silicon nitride and silicon oxide.

7. A method for preparing a chip according to any one of claims 1 to 6, comprising: Providing a silicon substrate with a protective film layer deposited on a first surface and a second surface opposite to each other; Forming a first window on the protective film layer on the second surface of the silicon substrate, forming a slit structure on the protective film layer on the first surface of the silicon substrate, and etching the inside of the silicon substrate through the first window and the slit structure to form two receiving grooves with the same structure; Depositing the same material as the protective film layer on the inner wall of the receiving groove of the silicon substrate to form a microchannel unit and seal the gap structure; Forming a temperature measuring resistor and a heating resistor on the protective film layer on the first surface of the silicon substrate where the microfluidic unit is formed; A second window is formed on the protective film layer on the first surface of the silicon substrate on which the temperature measuring resistor and the heating resistor are formed, and a heat-insulating groove surrounding the middle part of the microfluidic unit is formed inside the silicon substrate through the second window to obtain a single-cell capture microfluidic calorimetric chip.

8. The method according to claim 7, wherein: When forming the first microchannel, the slit structure is a structure in which 3 to 7 slits are staggeredly distributed; When the second microchannel is formed, the slit structure is a structure in which 1 to 3 slits are distributed in a staggered manner.

9. A single cell capture microfluidic calorimetry system, comprising: The chip according to any one of claims 1 to 6, suitable for single cell capture and single cell metabolic heat measurement; a fluid driving device, connected to the microfluidic inlet and the microfluidic outlet of the chip, and suitable for injecting a cell suspension into the chip; as well as The data acquisition device is electrically connected to the chip and is suitable for receiving the electrical signal transmitted by the chip.

10. The system according to claim 9, further comprising: A microfluidic fixture is used to fix the chip to achieve communication between the chip and the fluid driving device.

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