CN-121991803-A - In-situ monitoring method, organ chip, manufacturing method and application

Abstract

The application provides an in-situ monitoring method, an organ chip, a manufacturing method and application, wherein the in-situ monitoring method of the organ chip comprises the steps of receiving cells by a culture membrane of the organ chip, integrating stretchable strain electrodes on the culture membrane, culturing the cells in culture chambers on two sides of the culture membrane, controlling the pressure of the culture chambers to change so as to actuate the culture membrane, and collecting electric signal output of the strain electrodes so as to monitor strain of the culture membrane. By using the culture membrane with the strain electrode, the strain electrode can more truly and accurately acquire the strain data of the culture membrane, so that the organ chip can more accurately monitor the strain of the culture membrane. The application relates to the field of organ chips.

Inventors

• ZHAO MENG
• XU XUEQI
• YANG HUIRU
• LIU QIAN
• LU HENG

Assignees

• 广州国家实验室
• 生物岛实验室

Dates

Publication Date

20260508

Application Date

20241101

Claims (20)

1. 1. An in situ monitoring method of an organ chip, comprising: a culture membrane of the organ-chip receives cells, wherein the culture membrane is integrated with a stretchable strain electrode; Culturing the cells in culture chambers on both sides of the culture membrane; Controlling the pressure of the culture chamber to change to actuate the culture membrane; and collecting the electric signal output of the strain electrode so as to monitor the strain of the culture membrane.
2. 2. The in situ monitoring method of claim 1, further comprising calibrating a stress-strain relationship of the culture membrane prior to receiving the cells.
3. 3. The in situ monitoring method of claim 1, wherein the strained electrode has optical transparency.
4. 4. An organ-chip, comprising: a first sheet forming a first chamber; A second sheet forming a second chamber; the culture membrane is positioned between the first sheet body and the second sheet body, the first chamber and the second chamber are separated by the culture membrane, the culture membrane comprises a substrate and a strain electrode, the strain electrode is arranged on the substrate, and the substrate and the strain electrode can be stretched and deformed.
5. 5. The organ-chip of claim 4, wherein the strain electrode comprises a deformation portion, the deformation portion being located within the first chamber.
6. 6. The organ-chip of claim 5, wherein the stiffness of the deformation portion and the stiffness of the substrate deviate by no more than ± 5%.
7. 7. The organ-chip of claim 4, wherein the culture membrane has light transmittance.
8. 8. The organ-chip of claim 7, wherein the strain electrode has a hole structure.
9. 9. The organ-chip of claim 7, wherein the material of the substrate is a transparent material.
10. 10. The organ-chip according to claim 4, wherein said culture membrane further comprises a signal line connected to said strain electrode, said signal line extending out of said substrate, said signal line being for connection to an external terminal.
11. 11. The organ-chip of claim 10, wherein the portion of the signal line connected to the strain electrode is covered with a protective layer.
12. 12. The organ-chip of claim 4, wherein the material of the strained electrode comprises one or more of graphene, carbon nanotubes, carbon fibers, MXene.
13. 13. The organ-chip of claim 4, wherein the material of the substrate comprises one or more of PDMS, a dual-network hydrogel, an elastic gel.
14. 14. The organ-chip of claim 4, wherein the first chamber is for culturing cells and the second chamber is for actuating the culture membrane.
15. 15. The organ-chip of claim 14, wherein the organ-chip comprises a liquid inlet channel and a liquid outlet channel, the liquid inlet channel being in communication with the first chamber, the liquid inlet channel being for inputting culture liquid, the liquid outlet channel being in communication with the first chamber, the liquid outlet channel being for collecting waste liquid.
16. 16. The organ-chip of claim 14, wherein the organ-chip comprises a gas channel in communication with the second chamber, the gas channel for regulating a gas pressure of the second chamber.
17. 17. The organ-chip of claim 14, wherein the strain electrode is located on a side of the culture membrane adjacent to the second chamber.
18. 18. The organ-chip of claim 4, further comprising a third wafer forming a third chamber and an actuation membrane located between the second wafer and the third wafer, the actuation membrane separating the second chamber and the third chamber.
19. 19. A method for producing a culture membrane, comprising: Forming a strained electrode on a carrier; Forming a substrate on the carrier in combination with the strained electrode; and removing the carrier.
20. 20. The method of claim 19, further comprising forming a signal line connected to the strain electrode.

Description

In-situ monitoring method, organ chip, manufacturing method and application Technical Field The application relates to the field of organ chips, in particular to an in-situ monitoring method, an organ chip, a manufacturing method and application. Background An organ chip is a microfluidic chip for simulating tissues and organs in vitro. Compared with the traditional two-dimensional cell culture and animal models, the organ chip technology can more truly simulate pathological and toxicological interactions among different organs or tissues and reflect the synergistic reaction of a plurality of organs to medicines. Continuous monitoring of important quality parameters of an organ-chip by label-free, non-destructive, reliable, high-throughput and multiplex methods is critical for assessing the condition of an organ-chip system. Wherein in situ real-time strain monitoring is of great importance, e.g. monitoring of key mechanical features of the myocardial cell contraction/relaxation process in heart organs (e.g. beat frequency, intensity, regularity of beat pattern, etc.), monitoring of alveolar cell respiration frequency and intensity in alveolar chips, monitoring of muscle tissue, etc. In the related art, olivier T.Gunnat et al constructed a micro-impedance tomography system that could monitor the mechanical changes occurring in the alveolar barrier via impedance coplanar electrodes to achieve in situ monitoring of strain, but the method was limited to specific organ-chip structures and did not have mobility. In addition, this method indirectly reflects strain of the culture membrane by impedance change of the solution in combination with measurement by a microscope, and has a problem of insufficient accuracy. Disclosure of Invention The present application aims to solve at least one of the technical problems existing in the prior art. Therefore, the application provides an in-situ monitoring method, an organ chip, a manufacturing method and application, wherein the in-situ monitoring method can monitor the strain of the culture membrane more accurately. The in-situ monitoring method for the organ chip is characterized by comprising the steps of receiving cells by a culture membrane of the organ chip, wherein a stretchable strain electrode is integrated on the culture membrane, culturing the cells by culture chambers on two sides of the culture membrane, controlling the pressure of the culture chambers to change so as to actuate the culture membrane, and collecting the electric signal output of the strain electrode so as to monitor the strain of the culture membrane. The in-situ monitoring method provided by the application has at least the following technical effects that the strain electrode can more truly and accurately acquire the strain data of the culture membrane by using the culture membrane with the strain electrode, so that the organ chip can more accurately monitor the strain of the culture membrane. According to some embodiments of the application, the in situ monitoring method further comprises calibrating a stress-strain relationship of the culture membrane prior to receiving the cells. According to some embodiments of the application, the strained electrode has optical transparency. The organ chip provided by the application comprises a first sheet body, a second sheet body and a culture membrane, wherein the first sheet body forms a first chamber, the second sheet body forms a second chamber, the culture membrane is positioned between the first sheet body and the second sheet body, the culture membrane separates the first chamber and the second chamber, the culture membrane comprises a substrate and a strain electrode, the strain electrode is arranged on the substrate, and the substrate and the strain electrode can be stretched and deformed. The organ chip provided by the application has the technical effects that the strain electrode capable of stretching and deforming is adopted, and then the strain electrode is integrated on the culture membrane, so that the strain electrode can more truly and accurately acquire the strain data of the culture membrane, and the organ chip can more accurately monitor the strain of the culture membrane. According to some embodiments of the application, the strain electrode comprises a deformation portion, the deformation portion being located within the first chamber. According to some embodiments of the application, the stiffness of the deformation and the stiffness of the substrate deviate by no more than ±5%. According to some embodiments of the application, the culture membrane has light transmittance. According to some embodiments of the application, the strained electrode has a hole structure. According to some embodiments of the application, the material of the substrate is a transparent material. According to some embodiments of the application, the culture membrane further comprises a signal line connected to the strain electrode, the signal line exte