CN114939447A - Integrated chip integrating cell human body culture and cell mechanical characteristic measurement - Google Patents
Integrated chip integrating cell human body culture and cell mechanical characteristic measurement Download PDFInfo
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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Abstract
An integrated chip integrating cell human body culture and cell mechanical characteristic measurement is designed on the basis of a dielectrophoresis principle and based on a vascular organ-like chip and a microfluidic signal operation technology, and can integrate the culture, treatment, capture and stretching of the human body-like in the cell chip, effectively restore the microenvironment of blood vessels of a human body and simultaneously measure the mechanical characteristics of a large number of endothelial cells under the condition of in vitro simulation of various physiological and pathological conditions.
Description
[ technical field ] A method for producing a semiconductor device
The invention relates to the field of cell human body chips, in particular to an integrated chip integrating cell human body culture and cell mechanical characteristic measurement.
[ background ] A method for producing a semiconductor device
At present, the analysis of mechanical properties of vascular endothelial cells is of great importance for physiological and pathological studies in biomedicine, but the quantitative description of the mechanical properties of endothelial cells is rarely studied. The existing research is to measure the elastic modulus of endothelial cells by scanning probe microscopy and atomic force microscope indentation, which has high requirements on equipment and operators and low flux. In addition, cell culture processing in a laboratory environment is far from a real human environment, resulting in inaccurate test results and lack of persuasion of experimental data.
[ summary of the invention ]
The invention aims to provide an integrated chip integrating cell human body culture and cell mechanical characteristic measurement, which is designed based on a vascular organ-like chip and a micro-fluidic signal operation technology on the basis of the principle of dielectrophoresis and can integrate the human body culture, treatment, capture and stretching in a cell chip, effectively restore the microenvironment of a human blood vessel and simultaneously measure the mechanical characteristics of endothelial cells in large quantities under the condition of simulating various physiological and pathological conditions in vitro. The integrated chip utilizes the capillary bursting principle to form a hydrogel interface at the bottom of the chip and sow vascular endothelial cells to simulate a vascular microstructure; the function integration of the chip is realized by forming a multilayer structure, the structure of the anthropomorphic blood vessel is reproduced in the chip, the treatment of cells is directly realized in the chip, and the mechanical property measurement is carried out; and the method is convenient for designing an arrayed capture chip, obtaining the optimal capture port parameters of the cells and realizing high-throughput measurement.
The purpose of the invention is realized by the following technical scheme:
an integrated chip integrating cell human body culture and cell mechanical characteristic measurement comprises an ITO glass, a first PDMS layer, a second PDMS layer and a third PDMS layer which are sequentially bonded and laminated from bottom to top,
the ITO glass is etched to form a first electrode and a second electrode; the first electrode is arranged opposite to the second electrode;
a cell capturing and stretching array is formed at the position of the first PDMS layer corresponding to the first electrode and the second electrode; the cell capturing and stretching array comprises a flared micro-trap which is used for capturing cells and stretching the cells under the action of electric fields generated by the first electrode and the second electrode;
a hydrogel cavity is formed in the second PDMS layer, hydrogel is filled in the hydrogel cavity, and is used for planting cells on an interface of the hydrogel to form a simulated vascular structure;
a straight channel and a solution mixing channel which are communicated with each other are formed on the third PDMS layer; one end of the straight channel is provided with a first solution inlet penetrating through the third PDMS layer; one end of the solution mixing channel is provided with a second solution inlet penetrating through the third PDMS layer, and the other end of the solution mixing channel is communicated with the cell capturing and stretching array; the solution mixing channel has an overall meandering shape.
In one embodiment, the first electrode comprises a first electrode main body part and a first comb-shaped electrode part which are connected with each other; the second electrode comprises a second electrode main body part and a second comb-shaped electrode part which are connected with each other; the first comb-shaped electrode part is aligned and arranged above the second comb-shaped electrode part.
In one embodiment, the first comb-shaped electrode part comprises a plurality of first comb-shaped electrode bodies which are spaced in parallel, and the second comb-shaped electrode part comprises second comb-shaped electrode bodies which are spaced in parallel; the first comb-teeth electrode body is aligned and arranged above the second comb-teeth electrode body.
In one embodiment, the first comb-shaped electrode body and the second comb-shaped electrode body are mutually arranged to form an adjacent parallel electrode group; in the adjacent parallel electrode groups, the gap distance between two adjacent electrode bodies is 40 μm.
In one embodiment, the cell capturing and stretching array comprises a Y-shaped channel and a plurality of micro-wells in a bell mouth shape; one end of the Y-shaped channel is communicated with the other end of the solution mixing channel, and the other two ends of the Y-shaped channel are respectively communicated with the micro-well array; edges of the first and second electrodes are aligned with a capture port of the microtrap.
In one embodiment, the first PDMS layer is provided with a plurality of first solution outlets through the first PDMS layer, the second PDMS layer is provided with a second solution outlet aligned to a position corresponding to each first solution outlet, and the second solution outlet is communicated with the Y-shaped channel and the micro-well.
In one embodiment, the width of the upper part of the micro-well is 25 μm, the width of the lower part of the micro-well is 5 μm, and the length of the micro-well is 20 μm; the channel width of the Y-shaped channel is 300 mu m; the height of the integrated chip is 20 μm.
In one embodiment, a hydrogel injection port is arranged in a position, corresponding to the hydrogel cavity, of the third PDMS layer in a penetrating manner, and the hydrogel injection port is communicated with the hydrogel cavity, so that hydrogel is injected into the hydrogel cavity.
In one embodiment, the solution mixing channel has a meandering shape as a whole; the solution mixing channel comprises a first channel part and a second channel part which are communicated with each other; one end of the first channel part is provided with the second solution inlet which is formed by connecting a plurality of first U-shaped bent pipes; the second channel part is formed by connecting a plurality of second U-shaped bent pipes; the inner diameter of the first U-shaped bend is different from the inner diameter of the second U-shaped bend.
In one embodiment, the channel middle region of the first U-shaped bend has a funnel-shaped structure.
Compared with the prior art, the invention has the following beneficial effects:
the application provides a collection cell class human culture and cell mechanical properties measuring's integration chip, it sets out from the dielectrophoresis principle to class vascular organ chip and micro-fluidic signal operation technique are the basis, designs out and to realize that class human culture, processing, capture and tensile chip as an organic whole in the collection cell chip, can effectively restore human blood vessel microenvironment, reaches under the multiple physiopathological condition of external simulation, carries out the measurement of big batch endothelial cell mechanical properties simultaneously. The integrated chip utilizes the capillary bursting principle to form a hydrogel interface at the bottom of the chip and sow vascular endothelial cells to simulate a vascular microstructure; the function integration of the chip is realized by forming a multilayer structure, the structure of the anthropomorphic blood vessel is reproduced in the chip, the treatment of cells is directly realized in the chip, and the mechanical property measurement is carried out; and the method is convenient for designing an arrayed capture chip, obtaining the optimal capture port parameters of the cells and realizing high-throughput measurement.
[ description of the drawings ]
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts. Wherein:
fig. 1 is a schematic overall perspective structure diagram of the integrated chip for cell-like human body culture and cell mechanical property measurement provided by the present application.
FIG. 2 is a schematic exploded view of the integrated chip shown in FIG. 1, which integrates cell-like human body culture and cell mechanical property measurement.
FIG. 3 is a schematic structural diagram of the ITO glass of the integrated chip shown in FIG. 1, which integrates cell-like human body culture and cell mechanical property measurement.
FIG. 4 is a schematic diagram showing the structure of the micro-well of the integrated chip shown in FIG. 1, which integrates the human body culture of cells and the measurement of mechanical properties of cells.
FIG. 5 is a schematic diagram of the micro-trap of the integrated chip shown in FIG. 1 for human body culture and mechanical cell characteristic measurement.
FIG. 6 is a schematic structural diagram of a straight channel and a solution mixing channel of the integrated chip shown in FIG. 1, which integrates cell-like human body culture and cell mechanical property measurement.
Reference numerals: 10. ITO glass; 11. a first electrode main body portion; 12. a first comb-shaped electrode portion; 13. a second electrode main body portion; 14. a second comb-shaped electrode portion; 15. a first comb-tooth electrode body; 16. a second comb-tooth electrode body; 20. a first PDMS layer; 21. cell capture and stretching the array; 22. a micro-well; 23. a Y-shaped channel; 24. a first solution outlet; 30. a second PDMS layer; 31. a hydrogel cavity; 32. a second solution outlet; 40. a third PDMS layer; 41. a straight channel; 42. a solution mixing channel; 43. a first solution inlet; 44. a second solution inlet; 45. a hydrogel injection port; 46. a first U-shaped bend; 47. a second U-shaped bend; 48. a funnel-shaped structure; 49. and a third solution outlet.
[ detailed description ] A
In order to make the aforementioned objects, features and advantages of the present application more comprehensible, embodiments accompanying the present application are described in detail below with reference to the accompanying drawings. It is to be understood that the specific embodiments described herein are merely illustrative of the application and are not limiting of the application. It should be further noted that, for the convenience of description, only some of the structures related to the present application are shown in the drawings, not all of the structures. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
The terms "comprising" and "having," as well as any variations thereof, in this application are intended to cover non-exclusive inclusions. For example, a process, method, system, article, or apparatus that comprises a list of steps or elements is not limited to only those steps or elements listed, but may alternatively include other steps or elements not listed, or inherent to such process, method, article, or apparatus.
Reference herein to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the application. The appearances of the phrase in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. It is explicitly and implicitly understood by one skilled in the art that the embodiments described herein can be combined with other embodiments.
Referring to fig. 1 to 2, an integrated chip for integrating cell-like human body culture and cell mechanical property measurement provided in an embodiment of the present application includes an ITO glass 10, a first PDMS layer 20, a second PDMS layer 30, and a third PDMS layer 40, which are sequentially bonded and stacked from bottom to top. The first PDMS layer 20, the second PDMS layer 30, and the third PDMS layer 40 are formed by performing photolithography on polydimethylsiloxane PDMS to obtain PDMS layers having corresponding pattern distributions, so that the accuracy of arrangement of the internal channel structure of each PDMS layer can be improved. In addition, after the oxygen plasma treatment is performed on the ITO glass 10, the first PDMS layer 20, the second PDMS layer 30, and the third PDMS layer 40, the ITO glass 10, the first PDMS layer 20, the second PDMS layer 30, and the third PDMS layer 40 are sequentially stacked from bottom to top and subjected to a pressing treatment, so that the four components are subjected to an irreversible bonding treatment, the stability of the integral structure of the integrated chip is ensured, and the four components are effectively prevented from being separated.
Specifically, the ITO glass 10 is etched to form a first electrode and a second electrode; the first electrode is arranged opposite to the second electrode. By forming the first electrode and the second electrode with a specific pattern structure on the ITO glass 10 by etching, an electric field can be generated after the first electrode and the second electrode pass through, thereby acting on cells inside the chip.
A cell capture and stretching array 21 is formed at the position of the first PDMS layer 20 corresponding to the first electrode and the second electrode; the cell capturing and stretching array 21 includes a micro-trap 22 in a bell-mouth shape, and the micro-trap 22 is used for capturing the cells and stretching the cells under the action of the electric field generated by the first electrode and the second electrode. The micro-wells 22 of the cell capturing and stretching array 21 have a bell-mouth shape, and when cells cultured inside the chip are transported to the wider opening side of the micro-wells 22 along with the flow of the solution and captured by the narrower opening side of the bell-mouth, the cells are captured and positioned at the narrower opening. After the dielectrophoresis buffer solution is introduced to replace a cell culture medium, the dielectrophoresis buffer solution can generate a tensile acting force on the cells soaked in the dielectrophoresis buffer solution under the action of an electric field generated by the first electrode and the second electrode, so that the measurement of the mechanical properties of the cells is realized.
A hydrogel cavity 31 is formed on the second PDMS layer 30, and hydrogel is filled in the hydrogel cavity 31 and used for implanting cells on a hydrogel interface to form a simulated vascular structure. When hydrogel, such as methacrylated gelatin GelMA, is injected into the hydrogel cavity 31, the hydrogel is cured by ultraviolet light to form a hydrogel interface, and the hydrogel interface can provide a good environment for the subsequent seeding of vascular endothelial cells on the chip. After the seeding of the vascular endothelial cells is completed, the cells are attached to the hydrogel interface, and then a cell culture medium is injected into the chip, so that the cells can proliferate on the hydrogel interface to culture and form a vascular microstructure. Wherein, the seeding of the vascular endothelial cells can be realized by injecting a suspension of human umbilical vein endothelial cells into a hydrogel interface.
In addition, a hydrogel injection port 45 is formed through the third PDMS layer 40 at a position corresponding to the hydrogel cavity 31, and the hydrogel injection port 45 is communicated with the hydrogel cavity 31, so that hydrogel is injected into the hydrogel cavity 31. Hydrogel can be injected into the hydrogel accommodating cavity 31 through the hydrogel injection port 45 at a constant speed by using the micro-flow pump, so that the hydrogel is fully filled in the hydrogel accommodating cavity.
A straight channel 41 and a solution mixing channel 42 which are communicated with each other are formed on the third PDMS layer 40; one end of the straight channel 41 is provided with a first solution inlet 43 penetrating through the third PDMS layer 40; one end of the solution mixing channel 42 is provided with a second solution inlet 44 penetrating through the third PDMS layer 40, and the other end is communicated with the cell capture and stretching array 21; the solution mixing passage 42 has an overall meandering shape. In actual practice, a cell culture medium is injected into the straight channel 41 through the first solution inlet 43, thereby providing nutrients for cell proliferation; in the operation of separating cells, trypsin is injected into the straight channel 41 through the first solution inlet 43, endothelial cells attached to the hydrogel interface are detached, and at the same time, complete medium is injected from the second solution inlet 44 to terminate trypsin. The solution mixing channel 42 enables mixing of different solutions and delivery of endothelial cells to the cell capture and stretching array 21. Preferably, the cell culture medium and trypsin can be injected into the chip using a micro-pump. When the micro-trap 22 is finished capturing the cells, the micro-flow pump may be turned off.
Continuing to refer to fig. 3, a schematic structural diagram of an ITO glass of an integrated chip for cell-like human body culture and cell mechanical property measurement according to an embodiment of the present application is provided. The first electrode comprises a first electrode main body part 11 and a first comb-shaped electrode part 12 which are connected with each other; the second electrode includes a second electrode main body portion 13 and a second comb-tooth-shaped electrode portion 14 connected to each other. The first comb-shaped electrode part 12 comprises a plurality of first comb-shaped electrode bodies 15 which are parallel to each other and spaced, and the second comb-shaped electrode part 14 comprises second comb-shaped electrode bodies 16 which are parallel to each other and spaced; the first comb-teeth electrode body 15 is arranged above the second comb-teeth electrode body 16 in alignment. When the first electrode and the second electrode are both connected to the signal generator, an electric field is generated between the first electrode and the second electrode. The first comb-shaped electrode part and the second comb-shaped electrode part are respectively provided with a plurality of first comb-shaped electrode bodies and a plurality of second comb-shaped electrode bodies, so that the electric field intensity, the field intensity change rate and the electric field frequency generated between the first electrode and the second electrode can be adjusted according to actual measurement needs.
Specifically, the first comb-shaped electrode body and the second comb-shaped electrode body are mutually arranged to form an adjacent parallel electrode group; in adjacent parallel electrode groups, the gap distance between two adjacent electrode bodies is 40 μm, which can improve the electrical characteristics of the electric field between the first electrode and the second electrode.
With reference to fig. 4 to 5, a schematic structural diagram of a micro-well of an integrated chip for integrating human body cell culture and mechanical cell characteristic measurement and a schematic diagram of a micro-well cell capture are shown. The cell capturing and stretching array 21 comprises Y-shaped channels 23 and a plurality of micro-traps 22 in a bell mouth shape; one end of the Y-shaped channel 23 is communicated with the other end of the solution mixing channel 42, and the other two ends of the Y-shaped channel 23 are respectively communicated with the micro-well array; the edges of the first and second electrodes are aligned with the capture ports of the microtrap 22. The first PDMS layer 20 is provided with a plurality of first solution outlets 24 through the first PDMS layer, the second PDMS layer 30 is provided with a second solution outlet 32 aligned with a position corresponding to each first solution outlet 24, and the second solution outlet 32 is communicated with the Y-shaped channel 23 and the micro-well 22. The third PDMS0 is aligned with each of the second solution outlets 32 to form a third solution outlet 49. The other two ends of the Y-shaped channel 23 are respectively communicated with the micro-trap array, and the two convex structures can inject the solution into the micro-trap array from two opposite directions, so that the interior of the micro-trap 22 can be quickly filled with the solution, and the micro-trap 22 can fully capture cells. By providing the first solution outlet 24, the second solution outlet 32, and the third solution outlet 49, the extra cells can be discharged from the two outlets together with the solution, and the flow smoothness of the solution inside the chip can be improved.
Specifically, the width of the upper part of the micro well 22 is 25 μm, the width of the lower part is 5 μm, and the length is 20 μm; the channel width of the Y-shaped channel 23 is 300 μm; the height of the integrated chip is 20 mu m, and the structural parameters are obtained by multiple times of experimental improvement, so that the micro-trap is more favorable for capturing cells, and the capturing efficiency and accuracy of the cells are improved. As can be further understood from fig. 5, based on the hydrodynamic principle, the cells close to the capturing ports of the micro-wells 22 are directly captured by the micro-wells 22, while the cells far away from the capturing ports are captured by the next capturing port under the influence of the water flow generated by the micro-wells 22, and the multiple groups of micro-wells 22 operate simultaneously, so as to capture multiple cells.
In addition, after the micro-trap 22 finishes capturing the cells, a dielectrophoresis buffer solution is injected into the chip, and the captured cells are subjected to dielectrophoresis adsorption stretching by combining with the electric fields generated by the first electrode and the second electrode. Preferably, the edges of the first and second electrodes may be aligned with the micro-wells 22.
Specifically, when the cell is adsorbed, the output voltage of the signal generator is 4Vpp and the frequency is 12MHz, when the cell is stretched, the output voltage of the signal generator is 7Vpp and the frequency is 12MHz, the cell is controlled by controlling the signal generator to apply sinusoidal electric signals to the first electrode and the second electrode, and the length change of the cell is observed under a microscopic device, so that the mechanical property of the cell is measured. For example, the Young's modulus of the cell is calculated by measuring the change in length of the cell before and after stretching. After the cells are captured by the micro-trap 22, the cells are firstly adsorbed near the edge of the electrode under the action of the sinusoidal electric signal emitted by the signal generator, and when the voltage is increased, the cells are stretched under the action of dielectrophoresis force. By changing the voltage, the length change value of the cell can be accurately measured by a microscopic device. Finally, the signal generator may be turned off after the cell stretching experiment is completed.
With reference to fig. 6, a schematic structural diagram of a straight channel and a solution mixing channel of the integrated chip for human body cell culture and mechanical cell characteristic measurement according to an embodiment of the present disclosure is shown. The solution mixing passage 42 has a meandering shape as a whole; the solution mixing passage 42 includes a first passage portion and a second passage portion communicating with each other; one end of the first channel section is provided with a second solution inlet 44 formed by connecting a plurality of first U-shaped bends 46; the second channel part is formed by connecting a plurality of second U-shaped bent pipes 47; the first U-turn 46 has a different inner diameter from the second U-turn 47. By providing the solution mixing passage in a meandering shape including a plurality of U-shaped bends, the fluid is subjected to centrifugal force when passing through the bends of the solution mixing passage 42 to undergo a change in state, so that the contact area between the two fluids is increased, and sufficient uniformity of mixing between the two fluids is improved.
Preferably, the channel middle region of the first U-bend 46 has a funnel-shaped structure 48. Through setting up above-mentioned funnel shape structure 48, not only can increase the centrifugal force effect that the fluid passes through wherein, improve the mixed effect of two kinds of fluids to can also blow away because of the fluid velocity of flow sudden change leads to the cell of conglobation in the passageway inside, be convenient for follow-up microwell 22 catches single cell.
The above is only one embodiment of the present invention, and any other modifications based on the concept of the present invention are considered as the protection scope of the present invention.
Claims (10)
1. The utility model provides an integrated chip that collection cell class human body was cultivateed and cell mechanical properties measures, includes ITO glass, first PDMS layer, second PDMS layer and the third PDMS layer of range upon range of setting by supreme bonding in proper order down, its characterized in that:
the ITO glass is etched to form a first electrode and a second electrode; the first electrode is arranged opposite to the second electrode;
a cell capturing and stretching array is formed at the position of the first PDMS layer corresponding to the first electrode and the second electrode; the cell capturing and stretching array comprises a bell-mouthed micro-trap, the micro-trap is used for capturing cells and stretching the cells under the action of electric fields generated by the first electrode and the second electrode;
a hydrogel cavity is formed in the second PDMS layer, hydrogel is filled in the hydrogel cavity, and is used for planting cells on an interface of the hydrogel to form a simulated vascular structure;
a straight channel and a solution mixing channel which are communicated with each other are formed on the third PDMS layer; one end of the straight channel is provided with a first solution inlet penetrating through the third PDMS layer; one end of the solution mixing channel is provided with a second solution inlet penetrating through the third PDMS layer, and the other end of the solution mixing channel is communicated with the cell capturing and stretching array; the solution mixing channel has an overall meandering shape.
2. The integrated chip for human body culture and mechanical cell characteristic measurement according to claim 1, wherein the first electrode comprises a first electrode body part and a first comb-shaped electrode part which are connected with each other; the second electrode comprises a second electrode main body part and a second comb-shaped electrode part which are connected with each other; the first comb-shaped electrode part is aligned and arranged above the second comb-shaped electrode part.
3. The integrated chip for human body culture and mechanical cell characteristic measurement according to claim 2, wherein the first comb-shaped electrode portion comprises a plurality of first comb-shaped electrode bodies spaced in parallel, and the second comb-shaped electrode portion comprises second comb-shaped electrode bodies spaced in parallel; the first comb-teeth electrode body is aligned and arranged above the second comb-teeth electrode body.
4. The integrated chip for cell-based human body culture and cell mechanical property measurement according to claim 3, wherein the first comb electrode body and the second comb electrode body are mutually arranged to form an adjacent parallel electrode group; in the adjacent parallel electrode groups, the gap distance between two adjacent electrode bodies is 40 μm.
5. The integrated chip for integrated cell-like human body culture and cell mechanical property measurement according to claim 1, wherein the cell capturing and stretching array comprises a Y-shaped channel and a plurality of micro-wells in a bell mouth shape; one end of the Y-shaped channel is communicated with the other end of the solution mixing channel, and the other two ends of the Y-shaped channel are respectively communicated with the micro-well array; edges of the first and second electrodes are aligned with a capture port of the microtrap.
6. The integrated chip for integrated cell type human body culture and cell mechanical property measurement according to claim 5, wherein the first PDMS layer is provided with a plurality of first solution outlets, the second PDMS layer is provided with a second solution outlet aligned with a position corresponding to each first solution outlet, and the second solution outlet is communicated with the Y-shaped channel and the micro-well.
7. The integrated chip for human body culture and mechanical cell characteristic measurement according to claim 5, wherein the width of the upper part of the micro-well is 25 μm, the width of the lower part of the micro-well is 5 μm, and the length of the micro-well is 20 μm; the channel width of the Y-shaped channel is 300 mu m; the height of the integrated chip is 20 μm.
8. The integrated chip for cell-integrated human body culture and cell mechanical property measurement according to claim 1, wherein a hydrogel injection port is formed in a position of the third PDMS layer corresponding to the hydrogel cavity, and the hydrogel injection port is communicated with the hydrogel cavity so as to inject hydrogel into the hydrogel cavity.
9. The integrated chip for integrated human body culture and mechanical cell characteristic measurement according to claim 1, wherein the solution mixing channel has a meandering shape as a whole; the solution mixing channel comprises a first channel part and a second channel part which are communicated with each other; one end of the first channel part is provided with the second solution inlet which is formed by connecting a plurality of first U-shaped bent pipes; the second channel part is formed by connecting a plurality of second U-shaped bent pipes; the inner diameter of the first U-shaped bend is different from the inner diameter of the second U-shaped bend.
10. The integrated chip for integrated cell-like human body culture and cell mechanical property measurement according to claim 9, wherein the channel middle region of the first U-shaped curve has a funnel-shaped structure.
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