Micro-fluidic chip device and method for measuring, sorting and printing elasticity of single cell

Abstract

The invention relates to a micro-fluidic chip device for single cell elasticity measurement, sorting and printing and an operation method thereof, the micro-fluidic chip device comprises an upper cover plate and a lower cover plate, a cell channel and a printing channel are formed between the upper cover plate and the lower cover plate, and the micro-fluidic chip device further comprises a first pressure control device used for injecting detection liquid in a liquid storage tank into the cell channel; the second pressure control device is used for squeezing the cells; and the elasticity measuring and sorting area is provided with an extrusion device. According to the micro-fluidic chip, the structure of the sorting area is designed, the micro-column array is combined, the cell elasticity is accurately calculated while sorting is achieved, and the two functions of cell elasticity measurement and single cell printing output can be achieved only in one chip.

Description

Technical Field

[0001] The invention relates to the field of microfluidic chips, and in particular to a microfluidic chip device and method for single cell elasticity measurement, sorting and printing. Background Art

[0002] In recent years, with the rapid development of biomedical engineering and cell biology, technologies that can simultaneously measure, sort and print the elasticity of cells have received extensive attention. These technologies combine the latest advances in multidisciplinary fields such as mechanical analysis, microfluidics and 3D printing, opening up new avenues for cell research and application.

[0003] Single-cell printing technology is based on the following core principles: First, the elastic properties of cells are evaluated through microfluidics systems or other mechanical measurement methods. Then, cells are sorted according to their elastic properties using microfluidics or other technologies. Finally, single cells that meet the elastic requirements are accurately printed at the specified location through a high-precision positioning system.

[0004] Cell elasticity measurement technology is mainly used to evaluate the mechanical properties of cells, which is of great significance for understanding the physiological and pathological states of cells. Currently commonly used methods for measuring cell elasticity include: atomic force microscopy (AFM), which uses nanoscale probes to contact the cell surface and obtain the elastic information of the cell by measuring the displacement of the probe. Micro-pillar array technology, which measures the force exerted by the cell by placing a micro-pillar array under the cell to calculate its elastic modulus. Optical tweezers technology, which uses laser beams to capture and manipulate cells and measures their mechanical properties by analyzing the displacement of the cell in the laser beam.

[0005] Cell sorting technology is used to separate different types of cells, which is widely used in disease diagnosis, personalized treatment and basic research. It mainly includes: Fluorescence activated cell sorting (FACS) based on the fluorescence characteristics of cell surface markers, which is sorted by flow cytometry. Magnetic cell sorting (MACS) uses magnetic microbeads combined with cell surface markers to achieve cell sorting through magnetic fields. Microfluidic chip technology for efficient cell sorting can be achieved by designing different flow channel structures on microfluidic chips.

[0006] In recent years, researchers have been committed to integrating cell elasticity measurement, sorting and printing technologies into a single platform to improve research efficiency and application potential. At present, the technical means of combining cell elasticity measurement with single-cell sorting and printing mainly include: microfluidic chips combined with elasticity measurement, atomic force microscopy (AFM) combined with microfluidic printing technology, and optical tweezers technology combined with single-cell printing.

[0007] Microfluidic chips combined with elasticity measurement: This method uses microfluidic chips to measure and sort the elasticity of cells. When cells pass through the microfluidic channel, the system measures their elastic modulus in real time and imports cells that meet specific elastic properties into the printing module for printing. For example, a microchannel that is slightly wider than the diameter of the cell is designed. When the fluid flows through the channel, the flow rate in the middle of the channel is different from the flow rate at the edge. When the cell passes through the channel, the pressure near the edge of the channel and the center of the channel is different, which will cause deformation. The cell elasticity is estimated by deformation, and then fluid power or electrodynamics are used to guide the target cells to the printing area.

[0008] AFM combined with microfluidic printing: Atomic force microscopy (AFM) is used to measure the elasticity of individual cells, and the cells that meet the requirements are printed onto the substrate in combination with a microfluidic system. This method can achieve high-precision elasticity measurement and positioning, but due to the slow measurement speed of AFM, it is suitable for research scenarios that require high precision and low throughput.

[0009] Optical tweezers combined with single-cell printing: Optical tweezers can measure and manipulate the elasticity of cells through optical forces without touching the cells. Combined with microfluidics systems, optical tweezers can accurately locate and print single cells that meet elastic requirements. This method can avoid potential damage caused by mechanical contact and is suitable for the study of living cells.

[0010] Cell elasticity measurement printing technology plays a very important role in the fields of tissue engineering, cancer research and personalized medicine. When constructing tissue engineering materials, selecting cells with specific mechanical properties for printing through elasticity measurement can improve the mechanical consistency and functional performance of artificial tissues. For example, in cartilage tissue engineering, selecting highly elastic chondrocytes for printing can construct tissues with mechanical properties closer to natural cartilage. In cancer research, cells with different elasticities may represent different cancer subtypes or different degrees of malignancy. Through single-cell printing technology, researchers can sort and culture cancer cells with different elasticities to study their biological behavior and drug response. According to the mechanical properties of the patient's own cells, appropriate cells are selected for printing, which can be used to construct personalized therapeutic materials and drug screening models to improve treatment effects and drug development efficiency.

[0011] However, the measurement speed of microfluidic chips combined with atomic force microscopy (AFM) is slow and not suitable for high-throughput screening. Atomic force microscopy (AFM) is complex to operate and requires high-level technicians to operate and maintain. At the same time, due to the physical contact between the probe and the cells, it may cause mechanical damage to the cells or affect the measurement results. Optical tweezers system equipment is not only complex and expensive, but also requires a high level of technology and equipment maintenance when used in microfluidic chips. The intensity and position of the laser need to be precisely controlled during operation to avoid thermal damage to the cells. It is also not suitable for high-throughput operation, but is suitable for fine operation and research of single cells or a small number of cells. The existing cell elasticity sorting chips are all sorted based on the relative elasticity of cells, and cannot accurately measure and print out the elasticity of individual cells. Summary of the invention

[0012] The present invention provides a microfluidic chip device and method for single cell elasticity measurement, sorting and printing, aiming to solve at least one of the technical problems existing in the prior art.

[0013] The technical solution of the present invention is a microfluidic chip device for single cell elasticity measurement, sorting and printing, comprising an upper cover plate and a lower cover plate, wherein the upper cover plate covers the upper part of the lower cover plate, and a cell channel and a printing channel are formed between the upper cover plate and the lower cover plate, wherein the front end of the cell channel is connected to a liquid reservoir, the rear end of the cell channel is connected to a waste liquid reservoir through a waste liquid port, and the rear end of the printing channel is connected to an external collection device through a printing port, and the microfluidic chip device for single cell elasticity measurement, sorting and printing further comprises: A first pressure control device, used to inject the detection liquid in the liquid storage tank into the cell channel, and the first pressure control device is arranged at the front end of the cell channel; A second pressure control device, used for squeezing cells, wherein the second pressure control device is arranged at the front end of the printing channel; The elasticity measurement and sorting area is arranged at the intersection of the cell channel and the printing channel, and an extrusion device is arranged on the elasticity measurement and sorting area.

[0014] Furthermore, it also includes a third pressure control device, which is used to collect waste liquid from the cell channel and is arranged at the rear end of the cell channel.

[0015] Furthermore, the extrusion device is a first microarray, and the first microarray is arranged at the rear end of the printing channel of the elasticity measurement and sorting area. The height between the upper cover plate and the lower cover plate is greater than the diameter of the cell, The first microarray is formed by at least one first array block arranged side by side, and a first microarray channel is formed between every two first array blocks and between a single first array block and a printing channel arm. The width and length of each first microarray channel are consistent, and the width of the first microarray channel is less than the diameter of the cell.

[0016] Further, the extrusion device includes a second microarray, a third microarray, a fourth microarray and a fifth microarray, the second microarray is arranged at the rear end of the printing channel of the elastic measurement and sorting area, the third microarray is arranged at the front end of the cell channel of the elastic measurement and sorting area, the fourth microarray is arranged at the front end of the printing channel of the elastic measurement and sorting area, the third microarray and the fourth microarray are used to prevent cells that do not need to be printed from escaping to the printing channel due to too small flow resistance, causing erroneous printing, the fifth microarray is arranged at the rear end of the cell channel of the elastic measurement and sorting area, and the fifth microarray prevents cells that need to be printed from flowing out of the rear end of the cell channel through the waste liquid port to the waste liquid pool before being printed due to too small flow resistance, The height between the upper cover plate and the lower cover plate is greater than the diameter of the cell, The second microarray is formed by at least one second array block arranged side by side, a second microarray channel is formed between every two second array blocks and between a single second array block and the side wall of the printing channel, and the width and length of each second microarray channel are consistent, The third microarray is formed by at least one third array block arranged side by side, a third microarray channel is formed between every two third array blocks and between a single third array block and a cell channel arm, the width and length of each third microarray channel are consistent, and the width of the third microarray channel is less than the diameter of the cell, The fourth microarray is formed by at least one fourth array block arranged side by side, a fourth microarray channel is formed between every two fourth array blocks and between a single fourth array block and the side wall of the printing channel, and the width and length of each fourth microarray channel are consistent, The fifth microarray is formed by at least one fifth array block arranged side by side, a fifth microarray channel is formed between every two fifth array blocks and between a single fifth array block and the side wall of the cell channel, and each fifth microarray channel has the same width and length.

[0017] Furthermore, the height between the upper cover plate and the lower cover plate is less than the diameter of the cells, and the squeezing device is an squeezing platform, and the cells are squeezed when passing through the squeezing platform.

[0018] Furthermore, it also includes a filtering microstructure for filtering out debris, cell debris and flocculent impurities in the test liquid, and the filtering microstructure is arranged between the liquid storage tank and the cell channel; The bottom of the liquid storage tank and the bottom of the cell channel are inclined. The external collection device at least includes a centrifuge tube or a 96-well plate or a combination of one or more thereof.

[0019] Furthermore, it also includes a camera device, which is arranged above the upper cover plate or below the lower cover plate.

[0020] Furthermore, the present invention also discloses an operating method of a microfluidic chip device for single cell elasticity measurement, sorting and printing, which is applied to a microfluidic chip device for single cell elasticity measurement, sorting and printing comprising a first microarray, and the operating method comprises the following steps: S100, the first pressure control device turns on positive pressure, the third pressure control device turns on negative pressure, the detection liquid containing cells flows out from the liquid storage tank along the cell channel, and when the detection liquid passes through the filtering microstructure, PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure; S200, when the detection liquid flows through the first microarray in the elastic detection and sorting area, if no cells pass through, the second pressure control device arranged at the front end of the printing channel is on standby, and the detection liquid is identified as waste liquid and discharged from the rear end of the cell channel through the waste liquid port to the waste liquid pool; S300, when the detection liquid flows through the first microarray in the elastic detection and sorting area, if a cell passes through, the second pressure control device disposed at the front end of the printing channel turns on the positive pressure to push the cell to the edge of the first microarray, and the cell is deformed due to the continuous pressure along the printing channel; S400, measuring the protrusion length of the cell in real time, and calculating the elastic modulus of the cell based on a preset cell elasticity calculation model; S500, if the elastic modulus of the cell measured in the first microarray channel is within the sorting threshold range, the cell flows out from the end of the printing channel through the first microarray channel and is collected by an external collection device; S600: If the elastic modulus of the cells measured in the first microarray channel is not within the sorting threshold range, the pressure of the second pressure control device is stopped, and the cells are discharged from the rear end of the cell channel to the waste liquid pool through the waste liquid port.

[0021] Furthermore, the present invention also discloses an operating method of a microfluidic chip device for single cell elasticity measurement, sorting and printing, which is applied to a microfluidic chip device for single cell elasticity measurement, sorting and printing comprising a second microarray, a third microarray, a fourth microarray and a fifth microarray, and the operating method comprises the following steps: S100, the first pressure control device turns on positive pressure, the third pressure control device turns on negative pressure, the detection liquid containing cells flows out from the liquid storage tank along the cell channel, and when the detection liquid passes through the filtering microstructure, PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure; S200, when the detection liquid flows through the third microarray in the elastic detection and sorting area, the protrusion length of the cell is measured in real time, and the elastic modulus of the cell is calculated based on a preset cell elasticity calculation model; S300, if the elastic modulus of the cell measured in the third microarray channel is not within the sorting threshold range, the second pressure control device disposed at the front end of the printing channel is on standby, and the cell is discharged from the rear end of the cell channel through the fifth microarray channel and the waste liquid port to the waste liquid pool; S400. If the elastic modulus of the cells measured in the third microarray channel is within the sorting threshold range, the second pressure control device disposed at the front end of the printing channel turns on the positive pressure, and the cells flow out from the end of the printing channel through the second microarray channel and are collected by an external collection device.

[0022] Furthermore, the present invention also discloses an operating method of a microfluidic chip device for single cell elasticity measurement, sorting and printing, which is applied to a microfluidic chip device for single cell elasticity measurement, sorting and printing comprising an extrusion platform, and the operating method comprises the following steps: S100, the first pressure control device turns on positive pressure, the third pressure control device turns on negative pressure, the detection liquid containing cells flows out from the liquid storage tank along the cell channel, and when the detection liquid passes through the filtering microstructure, PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure; S200, when the detection liquid flows through the extrusion platform, the cells are squeezed and deformed, the deformation of the cells is measured in real time, and the elastic modulus of the cells is calculated based on a preset cell elasticity calculation model; S300, if the elastic modulus of the cells measured in the extrusion platform is not within the sorting threshold range, the second pressure control device arranged at the front end of the printing channel is on standby, and the cells are discharged from the rear end of the cell channel through the waste liquid port to the waste liquid pool; S400, if the elastic modulus of the cells measured in the extrusion platform is within the sorting threshold range, the second pressure control device set at the front end of the printing channel starts positive pressure, and the cells flow out from the end of the printing channel through the second microarray channel and are collected by an external collection device.

[0023] The beneficial effects of the present invention are: The single-cell elasticity measurement, sorting and printing microfluidic chip device is designed to combine the microcolumn array with the sorting area structure to accurately calculate the cell elasticity while sorting. The two functions of cell elasticity measurement and single-cell printing output can be realized in only one chip. The unique microcolumn array design ensures that when a limited number of cells enter the microcolumn array, the cells in each array channel are subjected to almost the same pressure, ensuring that the obtained elasticity is accurate while achieving high-throughput sorting. The single-cell elasticity measurement, sorting and printing microfluidic chip device is suitable for the use scenarios of different cells by optimizing and changing the internal specific parameters (channel size, channel pressure, microcolumn array specifications, etc.). BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Schematic diagram of the structure of the microfluidic chip in the microfluidic chip device for single cell elasticity measurement, sorting and printing.

[0025] Figure 2 Schematic diagram of the structure of the elasticity measurement and sorting area in scheme 1 of the microfluidic chip device for single-cell elasticity measurement, sorting and printing.

[0026] Figure 3 A three-dimensional schematic diagram of the structure of the elasticity measurement and sorting area in scheme 1 of the microfluidic chip device for single-cell elasticity measurement, sorting and printing.

[0027] Figure 4 Schematic diagram of the real-time extrusion deformation of cells in the elastic measurement and sorting area in scheme 1 of the microfluidic chip device for single-cell elastic measurement, sorting and printing.

[0028] Figure 5 Schematic diagram of the situation in which cells in the elasticity measurement and sorting area in scheme 1 of the microfluidic chip device for single-cell elasticity measurement, sorting and printing do not meet the set elasticity threshold and are not printed.

[0029] Figure 6 Schematic diagram of the structure of the elasticity measurement and sorting area in scheme 2 of the microfluidic chip device for single-cell elasticity measurement, sorting and printing.

[0030] Figure 7 A three-dimensional schematic diagram of the structure of the elasticity measurement and sorting area in scheme 2 of the microfluidic chip device for single-cell elasticity measurement, sorting and printing.

[0031] Figure 8 Schematic diagram of the real-time extrusion deformation of cells in the micropillar array channel in scheme 2 of the microfluidic chip device for single-cell elastic measurement, sorting and printing.

[0032] Fig. 9Top view of the structure of the elasticity measurement and sorting area in scheme 3 of the microfluidic chip device for single-cell elasticity measurement, sorting, and printing.

[0033] Fig.10 A three-dimensional schematic diagram of the structure of the elasticity measurement and sorting area in scheme 3 of the microfluidic chip device for single-cell elasticity measurement, sorting and printing.

[0034] Fig.11 Schematic diagram of the real-time extrusion deformation of cells in the elastic measurement and sorting area in scheme 3 of the microfluidic chip device for single-cell elastic measurement, sorting and printing.

[0035] Fig.12 Scheme 1. Flowchart of the method of operation of the microfluidic chip device for single cell elasticity measurement, sorting and printing.

[0036] Fig.13 Flowchart of Scheme 2 operating methods of the microfluidic chip device for single cell elasticity measurement, sorting, and printing.

[0037] Fig.14 Flowchart of Scheme III operating methods of the microfluidic chip device for single cell elasticity measurement, sorting, and printing.

[0038] Figure numerals, 100, upper cover; 200, lower cover; 300, cell channel; 310, first pressure control device; 320, third pressure control device; 400, printing channel; 410, second pressure control device; 500, liquid reservoir; 510, filtering microstructure; 600, waste liquid reservoir; 700, external collection device; 800, elasticity measurement and sorting area; 810, first microarray; 811, first array block; 812, first microarray channel; 820, second microarray; 821, second array block; 822, second microarray channel; 830, third microarray; 831, third array block; 832, third microarray channel; 840, fourth microarray; 841, fourth array block; 842, fourth microarray channel; 850, fifth microarray; 851, fifth array block; 852, fifth microarray channel; 860, extrusion platform. DETAILED DESCRIPTION

[0039] The following will be combined with the embodiments and drawings to clearly and completely describe the concept, specific structure and technical effects of the present invention, so as to fully understand the purpose, scheme and effect of the present invention. It should be noted that the embodiments and features in the embodiments of this application can be combined with each other without conflict.

[0040] It should be noted that, unless otherwise specified, when a feature is referred to as being "fixed" or "connected" to another feature, it may be directly fixed or connected to the other feature, or it may be indirectly fixed or connected to the other feature. In addition, the descriptions of up, down, left, right, top, bottom, etc. used in the present invention are only relative to the relative positional relationship of the components of the present invention in the drawings.

[0041] In addition, unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art. The terms used in this specification are only for describing specific embodiments, not for limiting the present invention. The term "and / or" used herein includes any combination of one or more related listed items.

[0042] It should be understood that, although the terms first, second, third, etc. may be used to describe various elements in the present disclosure, these elements should not be limited to these terms. These terms are only used to distinguish elements of the same type from each other. For example, without departing from the scope of the present disclosure, the first element may also be referred to as the second element, and similarly, the second element may also be referred to as the first element.

[0043] Reference Figures 1 to 14 In some embodiments, the technical solution of the present invention is a microfluidic chip device for single cell elasticity measurement, sorting and printing, comprising an upper cover plate 100 and a lower cover plate 200, wherein the upper cover plate 100 covers the upper part of the lower cover plate 200, and a cell channel 300 and a printing channel 400 are formed between the upper cover plate 100 and the lower cover plate 200, wherein the front end of the cell channel 300 is connected to a liquid reservoir 500, and the rear end of the cell channel 300 is connected to a waste liquid reservoir 600 through a waste liquid port, and the rear end of the printing channel 400 is connected to an external collection device 700 through a printing port, with reference to Figure 1 , the microfluidic chip device for single cell elasticity measurement, sorting and printing also includes: A first pressure control device 310, used to inject the detection solution in the liquid reservoir 500 into the cell channel 300, and the first pressure control device 310 is arranged at the front end of the cell channel 300; A second pressure control device 410, used for squeezing cells, wherein the second pressure control device 410 is disposed at the front end of the printing channel 400; The elasticity measurement and sorting area 800 is arranged at the intersection of the cell channel 300 and the printing channel 400 , and an extrusion device is arranged on the elasticity measurement and sorting area 800 .

[0044] Specifically, the present invention proposes three implementation schemes of the extrusion device, including the extrusion device being a first microarray 810 , the extrusion device comprising a second microarray 820 , a third microarray 830 , a fourth microarray 840 and a fifth microarray 850 , and the extrusion device being an extrusion platform 860 .

[0045] The beneficial effects of the present invention are: The single-cell elasticity measurement, sorting and printing microfluidic chip device is designed to combine the microcolumn array with the sorting area structure to accurately calculate the cell elasticity while sorting. The two functions of cell elasticity measurement and single-cell printing output can be realized in only one chip. The unique microcolumn array design ensures that when a limited number of cells enter the microcolumn array, the cells in each array channel are subjected to almost the same pressure, ensuring that the obtained elasticity is accurate while achieving high-throughput sorting. The single-cell elasticity measurement, sorting and printing microfluidic chip device is suitable for the use scenarios of different cells by optimizing and changing the internal specific parameters (channel size, channel pressure, microcolumn array specifications, etc.).

[0046] Specifically, the microfluidic chip system for sorting and printing based on the elastic modulus of cells includes: a liquid reservoir 500, a cell channel 300 (horizontal) and a printing channel 400 (vertical), the latter half of the cell channel 300 is a waste liquid channel, the end of which is a waste liquid outlet, the end of the printing channel 400 is a printing outlet, the printing channel 400 is perpendicular to the cell channel 300, and the junction between them is a sorting area. A microcolumn array is arranged horizontally at the intersection of the end of the sorting area and the printing channel 400, as the starting end of the channel through which the cells flow after being sorted.

[0047] Specifically, elasticity is a basic mechanical property of cells, which is closely related to the anatomical structure, function and pathological state of cells and tissues. Cells deform when they are subjected to stress. When the stress is eliminated, the cells return to their initial state. Using this characteristic of cells, we designed an extrusion array channel that is narrower than the diameter of the cell. By measuring the protrusion length of the cell at each moment in the extrusion channel in real time, the elastic modulus of the cell can be calculated. The chip is divided into three parts: a reservoir 500, a cell channel 300 and a printing channel 400. The intersection of the cell channel 300 and the printing channel 400 and the surrounding area are the elasticity measurement and sorting area 800.

[0048] Positive pressure is applied to the cell channel 300 and the printing liquid channel, and negative pressure is applied to the waste liquid channel. The positive pressure of the cell channel 300 ensures that cells can flow out of the liquid reservoir 500 stably. The negative pressure of the waste liquid channel ensures that the liquid flows stably to the waste liquid outlet during the non-printing time, and prevents the cells from escaping from the cell channel 300 and flowing into the printing channel 400 when the non-printing cells flow through.

[0049] The positive pressure of the printing channel 400 is divided into two parts: the maintenance pressure and the printing pressure. The maintenance pressure is the permanent pressure, which ensures that the printing liquid level is always maintained near the sorting area. The printing pressure is the pressure after the single cell is identified and the pressure is increased suddenly. The printing channel 400 outputs liquid to push the cell to the microcolumn array and deform it until it flows out of the printing outlet. By adjusting the size of the printing liquid flow, cells that meet the elasticity requirements can be selectively printed into an external container (such as a well plate). By setting the size range of elasticity to specify the cell printing hole, elasticity-based cell recovery is achieved. The waste liquid outlet is connected to the waste liquid pool 600, and cells that do not meet the printing requirements flow into the waste liquid pool 600 from the waste liquid outlet along with the waste liquid.

[0050] The key points of the technology are: (1) Precision elasticity measurement structure and method. The microcolumn array at the bottom of the cross channel ensures that all pressures are exactly the same when different single cells are captured. On the one hand, it ensures the stability and uniformity of the force applied to the cells during the squeezing process, and on the other hand, it greatly simplifies the calculation method of cell elasticity (only the cell deformation needs to be measured, and there is no need to accurately measure the pressure of squeezing the cells).

[0051] (2) Automated cell identification and printing. After completing the cell elasticity measurement, the single cell is pushed to the print port by the liquid in the vertical printing channel 400 (the liquid is automatically controlled by the hardware) and printed into an external container (such as a well plate). The cell printing hole can be determined according to the size range of elasticity to achieve elasticity-based cell recovery. This method has high throughput and high precision, and the key is that it can achieve single-cell scale sorting.

[0052] Compared with other methods, the microfluidic chip of the present invention designs the sorting area structure and combines the microcolumn array to achieve accurate calculation of cell elasticity during sorting. The two functions of cell elasticity measurement and single cell printout can be achieved in only one chip. The unique microcolumn array design ensures that when a limited number of cells enter the microcolumn array, the cells in each array channel are subjected to almost the same pressure, ensuring that the obtained elasticity is accurate while achieving high-throughput sorting. By optimizing and changing the internal specific parameters (channel size, channel pressure, microcolumn array specifications, etc.), it is suitable for the use scenarios of different cells.

[0053] Existing methods can only accurately measure cell elasticity but cannot sort cells, or can quickly sort cells but cannot accurately measure cell elasticity. The microfluidic chip described in the present invention can not only accurately measure cell elasticity, but also perform high-throughput sorting of cells based on elasticity. The chip described in the present invention is simple to operate, and while achieving the dual functions of cell elasticity measurement and single-cell printing, it does not require users to have high-level experimental skills, and will not cause harm to the user's body. By optimizing the specific parameters of the chip such as pressure input, microcolumn array specifications and chip size, this cell elasticity sorting chip can be applied to different cells.

[0054] Further, refer to Figures 2 to 5 , also includes a third pressure control device 320, wherein the third pressure control device 320 is used to collect waste liquid from the cell channel 300, and the third pressure control device 320 is arranged at the rear end of the cell channel 300.

[0055] Furthermore, the extrusion device is a first microarray 810, and the first microarray 810 is arranged at the rear end of the printing channel 400 of the elasticity measurement and sorting area 800, The height between the upper cover plate 100 and the lower cover plate 200 is greater than the diameter of the cell. The first microarray 810 is composed of at least one first array block 811 arranged side by side, and a first microarray channel 812 is formed between every two first array blocks 811 and between a single first array block 811 and the printing channel 400 arm. The width and length of each first microarray channel 812 are consistent, and the width of the first microarray channel 812 is less than the diameter of the cell.

[0056] Specifically, in the first scheme, when the chip is working, the liquid reservoir 500 opens positive pressure, the waste liquid port opens negative pressure, and the detection liquid containing cells flows out from the liquid reservoir 500 along the cell channel 300. When passing through the filtering microstructure 510, the PDMS fragments, cell debris in the detection liquid and some flocculent impurities in the culture medium will be filtered out. When the detection liquid flows through the elastic detection sorting area, if no cells pass through, the pressure control of the printing channel 400 is on standby, and the detection liquid is identified as waste liquid and flows out from the waste liquid channel; if there are cells passing through, the printing channel 400 opens positive pressure, and the printing liquid pushes the cells to the edge of the micro-column array channel. The cells are deformed due to the continuous force along the extrusion channel and pass through the micro-column array channel, and flow out from the end of the printing channel 400 and are collected by the external collection device 700 (such as a centrifuge tube, a 96-well plate, etc.).

[0057] By measuring the protrusion length of the cell at each moment in the extrusion channel in real time, the elastic modulus of the cell can be finally calculated according to the cell elasticity calculation model. The pressure of the printing channel 400 is adjustable to control the elasticity threshold of the sorted cells. If the elasticity of the cell measured in the micro-pillar array channel is not within the sorting threshold, the pressure of the printing channel 400 is stopped and the cell flows out from the waste liquid channel.

[0058] Further, refer to Figures 6 to 8 The extrusion device includes a second microarray 820, a third microarray 830, a fourth microarray 840 and a fifth microarray 850. The second microarray 820 is arranged at the rear end of the printing channel 400 of the elastic measurement and sorting area 800. The third microarray 830 is arranged at the front end of the cell channel 300 of the elastic measurement and sorting area 800. The third microarray 830 and the fourth microarray 840 are used to prevent cells that do not need to be printed from escaping to the printing channel 400 due to too small flow resistance, causing erroneous printing. The fourth microarray 840 is arranged at the front end of the printing channel 400 of the elastic measurement and sorting area 800. The fifth microarray 850 is arranged at the rear end of the cell channel 300 of the elastic measurement and sorting area 800. The fifth microarray 850 prevents cells that need to be printed from flowing out from the rear end of the cell channel 300 through the waste liquid port to the waste liquid pool 600 before being printed due to too small flow resistance. The height between the upper cover plate 100 and the lower cover plate 200 is greater than the diameter of the cell. The second microarray 820 is formed by at least one second array block 821 arranged side by side, and a second microarray channel 822 is formed between every two second array blocks 821 and between a single second array block 821 and the side wall of the printing channel 400. The width and length of each second microarray channel 822 are consistent. The third microarray 830 is formed by at least one third array block 831 arranged side by side, and a third microarray channel 832 is formed between every two third array blocks 831 and between a single third array block 831 and the cell channel 300 arm. The width and length of each third microarray channel 832 are consistent, and the width of the third microarray channel 832 is less than the diameter of the cell. The fourth microarray 840 is formed by at least one fourth array block 841 arranged side by side, and a fourth microarray channel 842 is formed between every two fourth array blocks 841 and between a single fourth array block 841 and the side wall of the printing channel 400, and each fourth microarray channel 842 has the same width and length. The fifth microarray 850 is formed by at least one fifth array block 851 arranged side by side, and a fifth microarray channel 852 is formed between every two fifth array blocks 851 and between a single fifth array block 851 and the side wall of the cell channel 300, and each fifth microarray channel 852 has the same width and length.

[0059] Specifically, in the second scheme, the micro-column array in the chip sorting area is increased from one channel to four channels evenly distributed with micro-column arrays. The micro-column array channel of the cell channel 300 is called the elastic measurement channel, which is smaller than the cell diameter. When a cell passes through, the cell first passes through the elastic measurement channel, and the elastic modulus of the cell is obtained according to the protrusion length of the cell at each moment. If the cell does not meet the sorting requirements, the printing channel 400 is on pressure standby, and the cell flows out from the waste liquid channel; if the cell meets the sorting requirements, the printing channel 400 opens positive pressure, and the cell is pushed to the second half of the printing channel 400 by the printing liquid, and finally flows out from the end of the printing channel 400 and is collected by the external collection device 700 (such as a centrifuge tube, a 96-well plate, etc.). The micro-column array on the other side of the cell channel 300 prevents the cells that need to be printed from flowing out of the waste liquid channel before being printed due to too small flow resistance. The micro-column array channel of the printing channel 400 is called the booster channel. When the chip is working, it prevents the unprinted cells from escaping to the printing channel 400, causing erroneous printing.

[0060] Further, refer to Figures 9 to 11 The height between the upper cover plate 100 and the lower cover plate 200 is less than the diameter of the cells, and the squeezing device is a squeezing platform 860 , and the cells are squeezed when passing through the squeezing platform 860 .

[0061] Specifically, in scheme three, the microcolumn array in the chip sorting area is changed to an extrusion platform 860, which covers the intersection of the cell channel 300 and the printing channel 400. The height of the area covered by the extrusion platform 860 is less than the cell diameter. When a cell passes through, it is deformed due to extrusion. The cell elastic modulus is calculated by the deformation of the cell when entering the platform. If the cell does not meet the sorting requirements, the printing channel 400 pressure is on standby, and the cell flows out of the waste liquid channel; if the cell meets the sorting requirements, the printing channel 400 opens the positive pressure, and the cell is pushed to the second half of the printing channel 400 by the printing liquid, and finally flows out from the end of the printing channel 400 and is collected by the external collection device 700 (such as a centrifuge tube, 96-well plate, etc.).

[0062] Because the overall height of the extrusion platform 860 is smaller than the cell channel 300, the cells move very slowly after entering the platform. Therefore, the frame rate of the camera for detecting cell deformation and the response time of the printing pressure output are very low. There is no need for a high camera frame rate, and there is no need for a device to provide pressure, which responds very quickly, greatly reducing the hardware requirements.

[0063] Further, refer to Figure 1 , further comprising a filtering microstructure 510 for filtering the fragments, cell debris and flocculent impurities in the detection liquid, wherein the filtering microstructure 510 is disposed between the liquid storage tank 500 and the cell channel 300; The bottom of the liquid storage tank 500 and the bottom of the cell channel 300 are inclined. The external collection device 700 at least includes a centrifuge tube or a 96-well plate or a combination of one or more thereof.

[0064] Specifically, cell sedimentation, or cell sedimentation, refers to the phenomenon that cells gradually sink in liquids (such as blood, cell culture fluid, etc.) due to gravity. In microfluidic experiments, cell sedimentation may lead to a decrease in the number of cells in the suspension, thereby affecting the number of cells entering the microfluidic channel. Since certain types of cells such as cancer cells settle quickly, they may be more likely to gather in the external sample pool rather than smoothly enter the channel. This will affect the accuracy and repeatability of the experiment. The on-chip reservoir 500 and the inclined cell channel 300 solve the above problems well. The bottom of the reservoir 500 is an inclined plane. The chip is placed vertically when in use. The upright reservoir 500 and the inclined bottom can well prevent cells from settling at the bottom of the pool and being unable to enter the channel during the experiment. A filtering microstructure 510 is set at the connection between the reservoir 500 and the cell channel 300 to prevent broken cells or debris from clogging the microcolumn array and interfering with the experiment. The downward-inclined cell channel 300 can also ensure that cells will not settle and adhere to the channel wall when passing through the narrow channel.

[0065] Further, refer to Figure 1 , also includes a camera device, which is arranged above the upper cover plate 100 or below the lower cover plate 200.

[0066] Further, refer to Fig.12 The present invention also discloses an operating method of a microfluidic chip device for single cell elasticity measurement, sorting and printing, which is applied to a microfluidic chip device for single cell elasticity measurement, sorting and printing comprising a first microarray 810, and the operating method comprises the following steps: S100, the first pressure control device 310 turns on positive pressure, the third pressure control device 320 turns on negative pressure, the detection liquid containing cells flows out from the liquid reservoir 500 along the cell channel 300, and when the detection liquid passes through the filtering microstructure 510, PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure 510; S200, when the detection liquid flows through the first microarray 810 of the elastic detection and sorting area, if no cells pass through, the second pressure control device 410 disposed at the front end of the printing channel 400 is on standby, and the detection liquid is identified as waste liquid and discharged from the rear end of the cell channel 300 through the waste liquid port to the waste liquid pool 600; S300, when the detection liquid flows through the first microarray 810 of the elastic detection and sorting area, if a cell passes by, the second pressure control device 410 disposed at the front end of the printing channel 400 turns on the positive pressure to push the cell to the edge of the first microarray 810, and the cell is deformed due to the continuous pressure along the printing channel 400; S400, measuring the protrusion length of the cell in real time, and calculating the elastic modulus of the cell based on a preset cell elasticity calculation model; S500, if the elastic modulus of the cells measured in the first microarray channel 812 is within the sorting threshold range, the cells flow out from the end of the printing channel 400 through the first microarray channel 812 and are collected by the external collection device 700; S600, if the elastic modulus of the cells measured in the first microarray channel 812 is not within the sorting threshold range, the pressure of the second pressure control device 410 is stopped, and the cells are discharged from the rear end of the cell channel 300 through the waste liquid port to the waste liquid pool 600.

[0067] Specifically, refer to Figure 4 and Figure 5 When cells flow from the cell channel 300 through the elastic detection and sorting area (refer to Figure 4 and Figure 5 In step 1, the second pressure control device 410 at the front end of the printing channel 400 starts positive pressure to push the cells to the edge of the first microarray 810 (refer to Figure 4 and Figure 5 In step 2, the cells are pushed to the first microarray channel 812, and the cells continue to be subjected to pressure along the printing channel 400 and begin to deform (refer to Figure 4 and Figure 5 Step 3 of this paper) and continue to calculate the cell elastic modulus (refer to Figure 4 and Figure 5 Step 4), if the elastic modulus of the cell is within the sorting threshold range, the pressure of the printing channel 400 continues to be output (refer to Figure 4 ), the cells are pushed out of the first microarray channel 812 (refer to Figure 4 Step 6), the cells flow out from the end of the printing channel 400 and are collected by the external collection device 700; if the elastic modulus of the cells is not within the sorting threshold range, the printing channel 400 stops the pressure output, and the cells are no longer subjected to the pressure of the printing channel 400 and return to the cell channel 300 (refer to Figure 5 Step 5), discharge from the rear end of the cell channel 300 to the waste liquid pool 600 (refer to Figure 5 Step 6).

[0068] Further, refer to Fig.13The present invention also discloses an operating method of a microfluidic chip device for single cell elasticity measurement, sorting and printing, which is applied to a microfluidic chip device for single cell elasticity measurement, sorting and printing comprising a second microarray 820, a third microarray 830, a fourth microarray 840 and a fifth microarray 850, and the operating method comprises the following steps: S100, the first pressure control device 310 turns on positive pressure, the third pressure control device 320 turns on negative pressure, the detection liquid containing cells flows out from the liquid reservoir 500 along the cell channel 300, and when the detection liquid passes through the filtering microstructure 510, PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure 510; S200, when the detection liquid flows through the third microarray 830 in the elastic detection and sorting area, the protrusion length of the cell is measured in real time, and the elastic modulus of the cell is calculated based on a preset cell elasticity calculation model; S300, if the elastic modulus of the cell measured in the third microarray channel 832 is not within the sorting threshold range, the second pressure control device 410 disposed at the front end of the printing channel 400 is on standby, and the cell is discharged from the rear end of the cell channel 300 through the fifth microarray channel 852 and the waste liquid port to the waste liquid pool 600; S400. If the elastic modulus of the cells measured in the third microarray channel 832 is within the sorting threshold range, the second pressure control device 410 disposed at the front end of the printing channel 400 turns on the positive pressure, and the cells flow out from the end of the printing channel 400 through the second microarray channel 822 and are collected by the external collection device 700.

[0069] Specifically, refer to Figure 8 , cells flow through the cell channel 300 (ref. Figure 8 Step 1) reaches the third micro-pillar array 830 (refer to Figure 8 In step 2, due to the continuous pressure, the cells are squeezed into and through the third microarray channel 832 (refer to Figure 8 From step 3 to step 5, the elastic modulus of the cell is continuously calculated during the process of the cell passing through the third microarray channel 832. When the measured elastic modulus is within the threshold range, the printing channel pressure is turned on and the cell is pushed out of the second microarray 820 (refer to Figure 8 In step 6), the liquid flows out from the end of the printing channel 400 and is collected by the external collecting device 700.

[0070] Further, refer to Fig.14 The present invention also discloses an operating method of a microfluidic chip device for single cell elasticity measurement, sorting and printing, which is applied to a microfluidic chip device for single cell elasticity measurement, sorting and printing comprising an extrusion platform 860. The operating method comprises the following steps: S100, the first pressure control device 310 turns on positive pressure, the third pressure control device 320 turns on negative pressure, the detection liquid containing cells flows out from the liquid reservoir 500 along the cell channel 300, and when the detection liquid passes through the filtering microstructure 510, PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure 510; S200, when the detection liquid flows through the squeezing platform 860, the cells are squeezed and deformed, the deformation of the cells is measured in real time, and the elastic modulus of the cells is calculated based on a preset cell elasticity calculation model; S300, if the elastic modulus of the cell measured in the extrusion platform 860 is not within the sorting threshold range, the second pressure control device 410 disposed at the front end of the printing channel 400 is on standby, and the cell is discharged from the rear end of the cell channel 300 through the waste liquid port to the waste liquid pool 600; S400. If the elastic modulus of the cells measured in the extrusion platform 860 is within the sorting threshold range, the second pressure control device 410 disposed at the front end of the printing channel 400 turns on the positive pressure, and the cells flow out from the end of the printing channel 400 through the second microarray channel 822 and are collected by the external collection device 700.

[0071] Specifically, refer to Fig.11 , the cells reach the extrusion platform 860 through the cell channel 300 (refer to Fig.11 From step 1 to step 2, the cells are squeezed and deformed due to continuous pressure and begin to enter the squeezing platform 860 (refer to Fig.11 3), until all cells enter the extrusion platform 860 (refer to Fig.11 In step 4), the elastic modulus of the cells is calculated. If the elastic modulus is within the threshold range, the second pressure control device 410 starts the positive pressure, and the cells move toward the rear end of the printing channel 400 (refer to Fig.11 5), until it flows out from the end of the printing channel 400 (refer to Fig.11 In step 6), it is collected by an external collection device 700.

[0072] The above is only a preferred embodiment of the present invention. The present invention is not limited to the above implementation. As long as the technical effect of the present invention is achieved by the same means, any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present disclosure shall be included in the scope of protection of the present disclosure. All should belong to the protection scope of the present invention. Within the protection scope of the present invention, its technical scheme and / or implementation method can have various modifications and changes.

Claims

1. A microfluidic chip device for single cell elasticity measurement, sorting and printing, comprising an upper cover plate (100) and a lower cover plate (200), wherein the upper cover plate (100) covers the upper part of the lower cover plate (200), a cell channel (300) and a printing channel (400) are formed between the upper cover plate (100) and the lower cover plate (200), the front end of the cell channel (300) is connected to a liquid reservoir (500), the rear end of the cell channel (300) is connected to a waste liquid reservoir (600) via a waste liquid port, and the rear end of the printing channel (400) is connected to an external collection device (700) via a printing port, characterized in that: The microfluidic chip device for single cell elasticity measurement, sorting and printing also includes: A first pressure control device (310), used for injecting the detection liquid in the liquid storage tank (500) into the cell channel (300), wherein the first pressure control device (310) is arranged at the front end of the cell channel (300); A second pressure control device (410), used for squeezing cells, wherein the second pressure control device (410) is arranged at the front end of the printing channel (400); An elasticity measurement and sorting area (800), wherein the elasticity measurement and sorting area (800) is arranged at the intersection of the cell channel (300) and the printing channel (400), and an extrusion device is arranged on the elasticity measurement and sorting area (800).

2. The microfluidic chip device for single cell elasticity measurement, sorting and printing according to claim 1, characterized in that: It also includes a third pressure control device (320), which is used to collect waste liquid from the cell channel (300). The third pressure control device (320) is arranged at the rear end of the cell channel (300).

3. The microfluidic chip device for single cell elasticity measurement, sorting and printing according to claim 1, characterized in that: The extrusion device is a first microarray (810), and the first microarray (810) is arranged at the rear end of the printing channel (400) of the elasticity measurement and sorting area (800). The height between the upper cover plate (100) and the lower cover plate (200) is greater than the diameter of the cell. The first microarray (810) is formed by at least one first array block (811) arranged side by side, and a first microarray channel (812) is formed between every two first array blocks (811) and between a single first array block (811) and a printing channel (400) arm. The width and length of each first microarray channel (812) are consistent, and the width of the first microarray channel (812) is less than the diameter of the cell.

4. The microfluidic chip device for single cell elasticity measurement, sorting and printing according to claim 1, characterized in that: The extrusion device comprises a second microarray (820), a third microarray (830), a fourth microarray (840) and a fifth microarray (850), wherein the second microarray (820) is arranged at the rear end of the printing channel (400) of the elasticity measurement and sorting area (800), the third microarray (830) is arranged at the front end of the cell channel (300) of the elasticity measurement and sorting area (800), and the fourth microarray (840) is arranged at the front end of the printing channel (300) of the elasticity measurement and sorting area (800). The first microarray (830) and the second microarray (840) are arranged at the front end of the cell channel (400) of the elastic measurement and sorting area (800), the third microarray (830) and the fourth microarray (840) are used to prevent cells that do not need to be printed from escaping into the printing channel (400) due to too small a flow resistance, thereby causing erroneous printing, the fifth microarray (850) is arranged at the rear end of the cell channel (300) of the elastic measurement and sorting area (800), and the fifth microarray (850) prevents cells that need to be printed from flowing out of the rear end of the cell channel (300) through the waste liquid port into the waste liquid pool (600) before being printed due to too small a flow resistance, The height between the upper cover plate (100) and the lower cover plate (200) is greater than the diameter of the cell. The second microarray (820) is formed by at least one second array block (821) arranged side by side, and a second microarray channel (822) is formed between every two second array blocks (821) and between a single second array block (821) and a side wall of the printing channel (400), and each second microarray channel (822) has the same width and length. The third microarray (830) is formed by at least one third array block (831) arranged side by side, and a third microarray channel (832) is formed between every two third array blocks (831) and between a single third array block (831) and a cell channel (300) arm. The width and length of each third microarray channel (832) are consistent, and the width of the third microarray channel (832) is less than the diameter of the cell. The fourth microarray (840) is formed by at least one fourth array block (841) arranged side by side, and a fourth microarray channel (842) is formed between every two fourth array blocks (841) and between a single fourth array block (841) and a side wall of the printing channel (400), and each fourth microarray channel (842) has the same width and length. The fifth microarray (850) is formed by at least one fifth array block (851) arranged side by side, and a fifth microarray channel (852) is formed between every two fifth array blocks (851) and between a single fifth array block (851) and the side wall of the cell channel (300), and each fifth microarray channel (852) has the same width and length.

5. The microfluidic chip device for single cell elasticity measurement, sorting and printing according to claim 1, characterized in that: The height between the upper cover plate (100) and the lower cover plate (200) is less than the diameter of the cells, and the squeezing device is a squeezing platform (860), and the cells are squeezed when passing through the squeezing platform (860).

6. The microfluidic chip device for single cell elasticity measurement, sorting and printing according to claim 1, characterized in that: It also includes a filtering microstructure (510), the filtering microstructure (510) is used to filter out fragments, cell debris and flocculent impurities in the detection liquid, and the filtering microstructure (510) is arranged between the liquid storage tank (500) and the cell channel (300); The bottom of the liquid storage tank (500) and the bottom of the cell channel (300) are arranged at an inclination; The external collection device (700) comprises at least a centrifuge tube or a 96-well plate or a combination of one or more thereof.

7. The microfluidic chip device for single cell elasticity measurement, sorting and printing according to claim 1, characterized in that: It also comprises a camera device, which is arranged above the upper cover plate (100) or below the lower cover plate (200).

8. A method for operating a microfluidic chip device for measuring, sorting and printing single cell elasticity, applied to the microfluidic chip device for measuring, sorting and printing single cell elasticity as claimed in claim 1 or claim 3, characterized in that: The operation method comprises the following steps: S100, the first pressure control device (310) turns on positive pressure, the third pressure control device (320) turns on negative pressure, the detection liquid containing cells flows out from the liquid storage tank (500) along the cell channel (300), and when the detection liquid passes through the filtering microstructure (510), PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure (510); S200, when the detection liquid flows through the first microarray (810) of the elastic detection and sorting area, if no cells pass through, the second pressure control device (410) arranged at the front end of the printing channel (400) is on standby, and the detection liquid is identified as waste liquid and discharged from the rear end of the cell channel (300) through the waste liquid port to the waste liquid pool (600); S300, when the detection liquid flows through the first microarray (810) of the elastic detection and sorting area, if a cell passes by, the second pressure control device (410) disposed at the front end of the printing channel (400) turns on the positive pressure to push the cell to the edge of the first microarray (810), and the cell is deformed due to the continuous pressure along the printing channel (400); S400, measuring the protrusion length of the cell in real time, and calculating the elastic modulus of the cell based on a preset cell elasticity calculation model; S500, if the elastic modulus of the cells measured in the first microarray channel (812) is within the sorting threshold range, the cells flow out from the end of the printing channel (400) through the first microarray channel (812) and are collected by the external collection device (700); S600: If the elastic modulus of the cells measured in the first microarray channel (812) is not within the sorting threshold range, the pressure of the second pressure control device (410) is stopped, and the cells are discharged from the rear end of the cell channel (300) through the waste liquid port into the waste liquid pool (600).

9. A method for operating a microfluidic chip device for measuring, sorting and printing single cell elasticity, applied to the microfluidic chip device for measuring, sorting and printing single cell elasticity as claimed in claim 1 or claim 4, characterized in that: The operation method comprises the following steps: S100, the first pressure control device (310) turns on positive pressure, the third pressure control device (320) turns on negative pressure, the detection liquid containing cells flows out from the liquid storage tank (500) along the cell channel (300), and when the detection liquid passes through the filtering microstructure (510), PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure (510); S200, when the detection liquid flows through the third microarray (830) in the elastic detection and sorting area, the length of the cell protrusions is measured in real time, and the elastic modulus of the cell is calculated based on a preset cell elasticity calculation model; S300, if the elastic modulus of the cell measured in the third microarray channel (832) is not within the sorting threshold range, the second pressure control device (410) disposed at the front end of the printing channel (400) is on standby, and the cell is discharged from the rear end of the cell channel (300) through the fifth microarray channel (852) and the waste liquid port to the waste liquid pool (600); S400. If the elastic modulus of the cells measured in the third microarray channel (832) is within the sorting threshold range, the second pressure control device (410) disposed at the front end of the printing channel (400) turns on the positive pressure, and the cells flow out from the end of the printing channel (400) through the second microarray channel (822) and are collected by the external collection device (700).

10. A method for operating a microfluidic chip device for measuring, sorting and printing single cell elasticity, applied to the microfluidic chip device for measuring, sorting and printing single cell elasticity as claimed in claim 1 or claim 5, characterized in that: The operation method comprises the following steps: S100, the first pressure control device (310) turns on positive pressure, the third pressure control device (320) turns on negative pressure, the detection liquid containing cells flows out from the liquid storage tank (500) along the cell channel (300), and when the detection liquid passes through the filtering microstructure (510), PDMS fragments, cell debris and flocculent impurities are filtered out by the filtering microstructure (510); S200, when the detection liquid flows through the squeezing platform (860), the cells are squeezed and deformed, the deformation of the cells is measured in real time, and the elastic modulus of the cells is calculated based on a preset cell elasticity calculation model; S300, if the elastic modulus of the cell measured in the extrusion platform (860) is not within the sorting threshold range, the second pressure control device (410) disposed at the front end of the printing channel (400) is on standby, and the cell is discharged from the rear end of the cell channel (300) to the waste liquid pool through the waste liquid port; S400, if the elastic modulus of the cells measured in the extrusion platform is within the sorting threshold range, the second pressure control device (410) disposed at the front end of the printing channel (400) turns on the positive pressure, and the cells flow out from the end of the printing channel through the second microarray channel (822) and are collected by an external collection device.

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