CN101270333A - A microfluidic cell chip - Google Patents

Abstract

The invention provides a microfluidic cell chip, which has several cell culture units, each cell culture unit has a cell culture area, a cell microchannel and a drug microchannel, and the cell culture area has an inlet and an outlet, the cell microchannel communicates with the inlet of the cell culture area to deliver the cell culture solution to the cell culture area, and the drug microchannel communicates with the inlet of the cell culture area to deliver Drug solution to the cell culture area. In the microfluidic cell chip provided by the present invention, the cell culture area has an inlet and an outlet, and both the cell solution and the drug solution are transported through the inlet and the outlet, so that the delivery direction of the cell culture solution and the delivery direction of the drug solution are the same, and the drug solution is avoided. The solution carries away the cells in the cell culture area.

Description

A microfluidic cell chip

technical field

The invention relates to the technical field of biochips, in particular to microfluidic cell chips in the field.

Background technique

The development of modern micro-manufacturing technology has driven a branch of the development of modern biology, which is the field of biochips. Biochip mainly refers to the integration of tens of thousands of densely arranged molecular arrays on a solid-state chip through microprocessing technology and microelectronics technology. The sample passes through the biochip, and the biological information in the sample can be quickly and accurately obtained. The efficiency is traditional. Detection means hundreds of times.

Microfluidic cell chip is a kind of biochip. Cells are pre-cultured on a cell culture unit with a microfluidic channel, and a microvalve is made on the microfluidic channel, which can control nanoliter (10 ^-9 L) or picoliter Liter (10 ^-12 L) level of liquid for flow control. The size of the microchannel is usually between 10-100 μm, which is in the same order of magnitude as the typical mammalian cell size (10-20 μm), and its heat and mass transfer efficiency is better at the microscale, so the microchannel The fluidic cell chip has a cell culture microenvironment similar to the physiological state.

With the development of technology, currently more microfluidic chips are integrated with thousands of repeatable cell culture units, which are distributed in an array, and each cell culture unit has a cell microchip. The flow channel and a drug micro-channel are respectively used to transport the cell culture solution and the sample into the cell culture unit, so that multiple samples can be analyzed simultaneously.

Please refer to FIG. 1 , which is a schematic diagram of a microfluidic cell chip provided by the prior art.

The microfluidic cell chip has several cell culture units 110, the several cell culture units 110 are distributed in an array, each of the several cell culture units 110 has a cell culture area 112, and the cell culture area 112 has A cell inlet 112a, and a drug inlet 112b, the cell culture area 112 also has a cell outlet, which corresponds to the cell inlet 112a, and the cell culture fluid flows from the cell outlet to the adjacent cell culture unit 110 in the same column cell microchannel 114 . The cell culture area 112 also has a drug outlet corresponding to the drug inlet 112b, and the drug solution flows from the drug outlet to the drug microchannel 116 of the adjacent cell culture unit 110 in the same row.

The cell culture unit 110 also has a cell microchannel 114 and a drug microchannel 116, the cell microchannel 114 communicates with the cell inlet 112a of the cell culture area 112 to deliver the cell culture solution to In the cell culture area 112 , the drug microchannel 116 communicates with the drug inlet 112 b of the cell culture area 112 to transport the drug solution into the cell culture area 112 .

The cell microchannel 114 has a cell microvalve 114a to control the flow of the cell culture solution therein, and the drug microchannel 116 has a cell microvalve 116a to control the flow of the drug solution therein.

Two adjacent cell culture units 110 in the same row, wherein the drug microchannel 116 of one cell culture unit 110 is connected to the drug outlet 112d of the other cell culture unit 110 to obtain the delivered drug solution, obviously, the same row The drug solution delivered was the same.

Two adjacent cell culture units 110 in the same row, wherein the cell microchannel 114 of one cell culture unit 110 is connected with the cell outlet 112c of the other cell culture unit 110 to obtain the transported cell culture fluid, obviously, The cell types cultivated in the same column are the same, and the cell culture units 110 in different columns can select different cell types.

For the manufacturing method and working principle of the microfluidic cell chip 10, please refer to the article High-density microgluidic arrays for cellcytotoxicity analysis published by Zhanhui Wang et al. on Lab Chip, Lab Chip, 2007, Vol.7, 740-745.

The microfluidic cell chip shown in Figure 1 has four cell culture units 110, which are arranged in a 2×2 matrix array. During fabrication, all drug microvalves 116a are closed, and all cell microvalves 114a are opened, so that two types of cells can be selected. Types of cell culture fluid I and cell culture fluid II respectively correspond to two rows of cell microchannels 114 and are delivered to each cell culture area 112. The cell culture area 112 is composed of several microsieves 118, and some cells will be absorbed by the cells. The micro-sieve 118 in the culture unit 110 captures, and grows on the wall of the micro-sieve 118 then; When in use, close all cell micro-valve 114a, open all drug micro-valve 116a, can select the drug solution I and drug of two kinds of drug types Solution II, corresponding to two rows of drug microchannels 116, is transported to each cell culture area 112, and the drug reacts with the adherent cells on the microsieve 118, so that the reaction changes are observed to obtain analysis results, four cell culture units 110 Four analysis results were obtained.

The array structure of the microfluidic cell chip has high expansibility. During actual production, M×N cell culture units 110 can be set as required, M and N are both integers greater than 1, and they are arranged in an M×N matrix, and N types of cells can be cultured in N columns of cell culture units during production , when in use, M drugs can be selected corresponding to M rows of cell culture units for cell analysis, then the results of M×N cell analysis can be obtained at the same time.

The cell culture area of the current microfluidic cell chip has several micro-sieves, most of which are designed for adherent cultured cells. This is because the cells are not easily taken away by the flowing liquid after growing on the adherent wall, which is convenient for analysis and research. . But in biomedical research, it is also necessary to study many suspension cultured cells, such as blood cells, hybridoma cells, T cells, etc. For the cell research of this type of suspension culture, when the microfluidic cell chip is in use, the transport direction of the drug solution in the cell culture area 112 is different from the transport direction of the cell culture solution in the cell culture area 112, so that the cell culture area The cells in 112 are easily taken by the drug solution to the cell culture unit 110 that contaminates other cells of different types in the row of other cell culture units.

Obviously, the current microfluidic cell chip cannot meet the requirements of this type of suspension culture cell research.

It can be seen that there are still defects in the prior art and need to be improved and developed.

Contents of the invention

The object of the present invention is to provide a microfluidic cell chip, which is suitable for both adherent cultured cells and suspension cultured cells.

In order to solve the problems of the technologies described above, the technical solution of the present invention is as follows:

A microfluidic cell chip, which has several cell culture units, wherein each cell culture unit has:

a cell culture zone having an inlet and an outlet;

a cell microfluidic channel, which communicates with the inlet of the cell culture area to deliver the cell solution to the cell culture area, and

A drug micro-flow channel communicates with the inlet of the cell culture area to deliver the drug solution to the cell culture area.

The microfluidic cell chip, wherein the cell culture area has several microstructures, and the several microstructures are columnar microstructures, curved channel microstructures, comb-like microstructures, weir-like microstructures, micro-sieve microstructures, etc. and its mix.

The microfluidic cell chip, wherein the several cell culture units are arranged in an array.

The microfluidic cell chip, wherein, the drug microchannel has a drug microvalve to control the flow of the drug solution, and the cell microchannel has a cell microvalve to control the flow of the cell solution.

The microfluidic cell chip, wherein the cell types of the cell culture units in the same row are the same, and the two adjacent cell culture units in the same row are composed of a first cell culture unit and a second cell culture unit, and the first cell The drug microchannel of the culture unit communicates with the outlet of the cell culture area of the second cell culture unit to obtain its drug solution.

In the microfluidic cell chip, the drug solution in the same column is the same, and the two adjacent cell culture units in the same column are the third cell culture unit and the fourth cell culture unit, and the cell microchip of the third cell culture unit The flow channel communicates with the outlet of the cell culture area of the fourth cell culture unit to obtain cell culture fluid.

The invention provides a microfluidic cell chip, which has a unique structural design so that the injection direction of the drug solution is the same as that of the cell culture solution during production, and the cells captured in the microcell culture environment will not be injected by the drug solution. Take to other cell culture units. This new type of microfluidic cell chip is not only highly scalable, but also suitable for both adherent and suspension cultured cells.

Description of drawings

Fig. 1 is a schematic diagram of a microfluidic cell chip in the prior art;

Fig. 2 is a schematic diagram of a microfluidic cell chip provided by an embodiment of the present invention;

Detailed ways

The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments.

Please refer to FIG. 2 , which is a schematic diagram of a microfluidic cell chip provided by an embodiment of the present invention. The microfluidic cell chip is a microfluidic cell chip in which adherent cultured cells and suspension cultured cells coexist.

The microfluidic cell chip has several cell culture units 210 . The several cell culture units 210 are arranged in an array.

Each cell culture unit 210 has a cell culture area 211 , a cell microchannel 212 and a drug microchannel 213 . Each cell microchannel has a cell microvalve 212a, and each drug microchannel 213 has a drug microvalve 213a.

The cell culture zone 220 has an inlet 220a and an outlet 220b.

One end of the cell microchannel 212 communicates with the inlet 220 a of the cell culture area 220 to transport the cell culture solution into the cell culture area 220 .

One end of the drug microchannel 213 is connected to the position of the cell microchannel 212 adjacent to the inlet 220a, so that the drug microchannel 213 communicates with the inlet 220a of the cell culture area 220 to deliver the drug solution to the cell culture area 220 Inside.

Preferably, the cell culture area 220 has several microstructures 218 for culturing cells, and the microstructures 218 may be columnar microstructures, curved channel microstructures, comb microstructures, weir microstructures or micro-sieves. Of course, the microstructure 218 is not limited thereto, as long as cells can be captured in the cell culture area 220 .

The micro-fabrication method of the cell culture area 220 can be realized by the prior art, and will not be repeated here.

The method for culturing cells in the cell culture medium in the cell culture area 220 is a cell culture method in the prior art. For the needs of cell research, cells in suspension culture or cells in adherent culture can be selected. The selection of the cell culture medium is determined by the existing The technology is provided and will not be repeated here.

Two adjacent cell culture units 210 in the same row, wherein the cell microchannel 214 of one cell culture unit 210 communicates with the outlet 212a of the cell culture area 212 of the other cell culture unit 210 to obtain the transported cell culture solution, Clearly, the same cell types were cultured in the same column. The cell culture units 110 in different columns can choose different cell types, and can also be a combination of suspension culture cells and adherent culture cells.

Two adjacent cell culture units 210 in the same row, wherein the drug microchannel 216 of one cell culture unit 210 is connected to the outlet 212b of the cell culture area of the other cell culture unit 210 to obtain the transported drug solution, obviously, The drug solution delivered in the same row is the same.

It can be understood that the unique structural design of the microfluidic cell chip in the embodiment of the present invention makes the delivery direction of the drug solution in the cell culture area 220 consistent with the delivery direction of the cell culture solution in the cell culture area 220 during production. As far as the cultured cells are concerned, the cells are captured by the several microstructures 218 in the transport direction, so that they will not be taken away by the drug solution. , can also be applied to cells in suspension culture, so it has a good inventive effect.

The specific implementation part in the above description is only the preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as above with the preferred embodiment, it is not used to limit the present invention. Any Those skilled in the art, without departing from the scope of the technical solutions of the present invention, may use the methods and technical content disclosed above to make some changes or modify equivalent embodiments with equivalent changes, but all without departing from the present invention For the content of the technical solution, any simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present invention still belong to the scope of the technical solution of the present invention.

Claims (6)

1. A microfluidic cell chip having several cell culture units, characterized in that each cell culture unit has: a cell culture zone having an inlet and an outlet; a cell microfluidic channel, which communicates with the inlet of the cell culture area to deliver the cell solution to the cell culture area, and A drug micro-flow channel communicates with the inlet of the cell culture area to deliver the drug solution to the cell culture area. 2. The microfluidic cell chip according to claim 1, wherein the cell culture area has several microstructures, and the several microstructures are columnar microstructures, curved channel microstructures, and comb-shaped microstructures. , weir-like microstructures, micro-sieves and their mixtures. 3. The microfluidic cell chip according to claim 1, wherein the plurality of cell culture units are arranged in an array. 4. The microfluidic cell chip according to claim 1, wherein the drug microchannel has a drug microvalve to control the flow of the drug solution, and the cell microchannel has a cell microvalve to Control the flow of cell solution. 5. The microfluidic cell chip according to claim 3, wherein the cell types of the cell culture units in the same row are the same, and the two adjacent cell culture units in the same row are the first cell culture unit and the second cell culture unit. The drug microchannel of the first cell culture unit is connected with the outlet of the cell culture area of the second cell culture unit to obtain its drug solution. 6. The microfluidic cell chip according to claim 3, wherein the drug solution in the same column is the same, and the two adjacent cell culture units in the same column are the third cell culture unit and the fourth cell culture unit, and the The cell microchannel of the third cell culture unit communicates with the outlet of the cell culture area of the fourth cell culture unit to obtain cell culture fluid.

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