KR101619167B1 - Microfluidic Chip for Monitoring of Cell Susceptibility to a Sample - Google Patents

Microfluidic Chip for Monitoring of Cell Susceptibility to a Sample Download PDF

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KR101619167B1
KR101619167B1 KR1020150098152A KR20150098152A KR101619167B1 KR 101619167 B1 KR101619167 B1 KR 101619167B1 KR 1020150098152 A KR1020150098152 A KR 1020150098152A KR 20150098152 A KR20150098152 A KR 20150098152A KR 101619167 B1 KR101619167 B1 KR 101619167B1
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cell culture
sample
culture chamber
cell
cells
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KR1020150098152A
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Korean (ko)
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이창수
정성근
진시형
피터 마티아스
이성식
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충남대학교산학협력단
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles

Abstract

The present invention relates to a microfluidic chip capable of accurately measuring sensitivity of cells to a sample by minimizing error when measuring the sensitivity of cells to a sample, and a method for measuring sensitivity of cells to a sample by using the microfluidic chip. More specifically, the microfluidic chip for measuring sensitivity of cells to a sample comprises: two or more fluid inlets; a gradient forming region for distributing each fluid injected through the inlets into a plurality of micro-channels having different concentration gradients; cell culture chambers each connected to the micro-channels, and culturing cells; and an outlet connected to the cell culture chambers. The microfluidic chip further comprises a flow path for bypass formed by branching a flow path between the micro-channels and the cell culture chambers, and is installed with a cell culture chamber upper valve on an upper end of the cell culture chambers, thereby on/off controlling introduction of a fluid to the cell culture chambers.

Description

[0001] The present invention relates to a microfluidic chip for measuring cell susceptibility,

The present invention relates to a microfluidic chip capable of accurate measurement by minimizing errors in measuring sample sensitivity of cells and a method for measuring sample susceptibility of cells using the microfluidic chip.

In order to understand the effect of various substances, environmental substances, new drugs, and natural substances on the cells, stimulation of the cells with the substance at various concentrations and measurement of the response of the cells by stimulation are performed. In order to measure the sample susceptibility of such cells, the reaction of the cells was measured by adding the sample to the well plate containing the medium containing the cells in the concentration of the cells in the prior art (FIG. 4). In this well-plate method, when a sample is applied onto a medium containing cells, it takes a predetermined time to diffuse from the upper layer of the medium to the cells existing at the bottom of the lower layer. Therefore, the exact stimulation time can not be determined because the difference between the injection time and the time given to the cells by the stimulus corresponding to the specific concentration desired by the researcher. In addition, since the cells are gradually stimulated from low concentration by diffusion, it is difficult to see the cell response to the stimulation at a specific concentration in a strict sense.

Recently, a device for measuring a sample sensitivity of a cell using a microfluidic chip in which a concentration gradient is formed has been actively studied. Microfluidic chips can save time in pharmaceutical, biotechnology, and medical fields, which is efficient, economical enough to require a small amount of sample required for experiments, and can improve accuracy and reliability in results.

Since the microfluidic channel of the microfluidic chip has a low Reynolds number, it forms a laminar flow in the flow path, so that a concentration gradient can be formed using the microfluidic channel (FIG. 5). Using this, the sample sensitivity can be efficiently measured by injecting the sample with the concentration gradient formed in the incubation section where the cell is located and measuring the effect on the cell. The present inventors used this principle to firstly form a biofilm of a bacterium in a microchannel, inject a sample having a concentration gradient into a microchannel formed with a biofilm, cultivate the biofilm, and then observe the biofilm, The method and apparatus for measuring sample susceptibility of a biofilm to be measured have been registered as Patent No. 1210590. [

However, the microfluidic chip is also relatively short in time relative to the well-plate, but it takes time to obtain a stable concentration gradient in the microfluidic channel. That is, when cells are injected into the cell culture area for sample susceptibility observation, the cell solution is filled in not only the cell culture area but also the concentration gradient area. When the cells are attached to the cell culture area and then washed with the culture solution Is not a cell solution but exists in a state filled with a culture solution. If a sample of different concentration is injected through a plurality of sample injection ports, the cell solution or culture fluid remaining in the micro flow path is exposed to the cell before the concentration gradient sample is exposed to the cell. Even if the sample is simultaneously injected into a plurality of sample injection ports, there may be an operation time error and a time required for stable injection of the sample. Therefore, it takes a certain time to form a stable concentration gradient. Thus, the microfluidic chip of the prior art can not accurately measure the cellular response to stimulation at a specific concentration, although its effect is less than that of the well-plate method.

In addition, since the microfluidic chip based on the above-mentioned fluid flow can maintain the concentration gradient only by maintaining the continuous flow of the fluid, the following problems are inherent. First, since the cells in the incubation section are continuously exposed to the flow of the sample, the sample accumulates and is subjected to a locally higher concentration environment than the actual concentration. Therefore, it is difficult to accurately measure the sample sensitivity at a desired concentration. Secondly, since the cells are subjected to drag force by the continuous flow of the fluid and the shear stress acts on the edge of the channel more than the center of the flow path, the reaction of the cells with the specific sample concentration It is difficult to distinguish between responses to cognitive drag or shear stress. Third, the concentration gradient of the sample in the culture section is different between the case where the cell is contained and the case where the cell is not contained, and since the concentration gradient at the beginning and end of the culture section may be different, It is difficult to know the concentration.

Japanese Patent No. 1068672 discloses a microfluidic chip in which a plurality of chamber portions in which cells are captured are provided. According to the microfluidic chip, the problem caused by the difference in the concentration gradient due to the imbalance of the concentration gradient or the presence of the cells in the culture needle of the third of the above-mentioned problems can be solved, but the remaining problems remain unremoved .

Patent No. 1210590 Patent No. 1068672

It is an object of the present invention to provide a microfluidic chip capable of measuring sample susceptibility by stimulating cells at a precise gradient concentration without delay in order to overcome the problems of the prior art.

The present invention also provides a microfluidic chip capable of measuring the sensitivity of a sample to a precise sample concentration without the influence of drag and shear stress by solving the problem of a microfluidic chip based on fluid flow according to the prior art. Another purpose is to provide.

It is still another object of the present invention to provide a method for measuring sample susceptibility of cells using the microfluidic chip.

According to an aspect of the present invention, A gradient forming region for separating each fluid injected into the injection port into a plurality of microchannels having different concentration gradients; A cell culture chamber each connected to the microchannel and cell culture is performed; And a discharge port connected to the cell culture chamber, wherein the microfluidic chip further comprises a bypass flow path formed by branching the flow path between the microchannel and the cell culture chamber, And a microfluidic chip for measuring sample susceptibility of cells, characterized in that a cell culture chamber upper valve is provided at the upper end of the cell culture chamber to open and close the inflow of fluid into the cell culture chamber.

(A) opening a top valve of a cell culture chamber and injecting a fluid into one of fluid injection ports to attach cells to the cell culture chamber; (B) changing the flow path to the bypass channel by locking the uppermost cell culture chamber valve; (C) injecting a sample having a different concentration into the two or more fluid injection ports to form a concentration gradient of the sample through the gradient forming region; (D) opening a valve at the upper end of the cell culture chamber to inject a sample having a concentration gradient into the cell culture chamber when the concentration gradient of the sample is stably formed in the microchannel; (E) when a sample having a concentration gradient is injected into the cell culture chamber, closing the upper end of the cell culture chamber and culturing the cells; And (F) measuring the sensitivity of the sample by observing the cell culture chamber.

As described above, according to the present invention, since the sample sensitivity can be measured by stimulating cells without delay at an accurate gradient concentration, the sample sensitivity of the cells can be more accurately measured.

In addition, since the microfluidic chip of the present invention does not need to maintain the fluid flow to maintain the concentration gradient, the cell is not affected by the drag and shear stress, and the sample sensitivity of the cell to the exact sample concentration can be measured.

1 is a schematic diagram of a microfluidic chip according to an embodiment of the present invention;
2 is a schematic view of a microfluidic chip according to an embodiment of the present invention, in which a bypass flow path valve is added;
3 is an enlarged view of a cell culture chamber and a plan view and a cross-sectional view of a trapper installed in the cell culture chamber.
4 is a schematic diagram showing a method for measuring sample susceptibility of cells by a well-plate method according to the prior art.
5 is a schematic diagram showing a concentration gradient in a microfluidic chip according to the prior art.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described in detail with reference to the accompanying drawings. However, these drawings are only for illustrating the contents and scope of the technical idea of the present invention, and the technical scope of the present invention is not limited or changed. It will be apparent to those skilled in the art that various changes and modifications can be made within the scope of the technical idea of the present invention based on these examples.

The microfluidic chip for measuring sample susceptibility of cells according to the present invention comprises at least two fluid inlets (11, 11 '); A gradient forming region (20) for separating each fluid injected into the injection port into a plurality of microchannels (21) having different concentration gradients; A cell culture chamber 31 connected to each of the microchannels and cell culture is performed; And a discharge port (51) connected to the cell culture chamber, wherein the microfluidic channel further comprises a bypass flow path (41) formed by branching the flow path between the microchannel and the cell culture chamber, And a cell culture chamber upper valve (32) is provided at the upper end of the chamber to control the inflow of the fluid into the cell culture chamber.

In the present invention, the term "cell" includes unicellular organisms such as bacteria and bacteria as well as multicellular organism tissue cells.

The cell culture chamber upper valve 32 is a valve that allows or blocks the inflow of fluid to the cell culture chamber 31. Closing of the cell culture chamber upper valve 32 blocks the inflow of the fluid into the cell culture chamber 31 and at the same time the flow of the fluid from the cell culture chamber 31 to the outlet 51 is also stopped. The microfluidic chip of the present invention may further include a cell culture chamber bottom valve 33 at the lower end of the cell culture chamber 31 to more reliably control the outflow of fluid from the cell culture chamber 31. [

In the present invention, the terms "upper" and "lower" refer to the flow of fluid, and the direction in which the fluid flows is referred to as "upper" and the direction in which the fluid flows out is referred to as "lower." The valves should be installed so that they can operate independently only for each cell culture chamber. That is, the cell culture chamber upper valve 32 must be installed after the microchannel 21 is branched from the bypass flow path to control only the flow into the cell culture chamber without preventing the flow of the fluid to the other flow channel . In addition, if there is a confluence point of the channel at the bottom of the cell culture chamber, the cell culture chamber bottom valve must be installed after the confluence point to control only the flow to the cell culture chamber without preventing the flow of the fluid to the other channel Of course.

The microfluidic chip of the present invention may further include a bypass flow path valve (42) for allowing or blocking the inflow of fluid into the bypass flow path (FIG. 2). The bypass flow path valve 42 should also be provided so as to operate independently of the flow to the bypass flow path just like the cell culture chamber upper valve 32 or the cell culture chamber lower valve 33. In FIG. 2, the bypass flow path valves are provided as one pair per flow path, but this is only for convenience, and only one valve may be provided per one flow path.

The valves may be membrane valves whose opening and closing are controlled by air pressure. The membrane valve is formed in the form of a double chip having a driving channel above or below the fluid channel and a portion forming a boundary between the driving channel and the fluid channel is formed of a material which is easy to swell in a flexible material or a solvent . It is possible to open the valve by removing pressure or solvent from the driving channel by injecting gas into the driving channel and flowing the effective solvent to the swelling to block the micro channel of the fluid channel. The structure and the forming method of the membrane valve in the microfluidic chip are well known in the art, and detailed description is omitted.

1 shows a microfluidic chip having two fluid injection ports, it is impossible to form a concentration gradient when there is only one fluid injection port. Therefore, in order to achieve the object of the present invention, two or more fluid injection ports may be sufficient, It is meaningless to do. As the number of fluid injection ports increases, the concentration gradient of the fluid can be complicatedly realized. For example, if a microfluidic chip is used in which a fluid injection port is provided at the left, center, and right sides, and a fluid is injected into the three injection ports and a concentration gradient is formed by the gradient forming region, And the sample sensitivity of the xenogeneic cells to the samples A and B can be simultaneously measured by simultaneously injecting the sample B into the right side. Or even if the same sample is injected, a more complex concentration gradient can be realized by changing the concentration of the sample for each injection port. However, since the structure of the microfluidic chip becomes complicated as the number of fluid injection ports increases, it is theoretically desirable that the number of fluid injection ports is substantially 2 to 4 even though the upper limit of the number is meaningless.

The culture chamber may be formed in the same manner as a conventional channel, but a trapper may be formed so that a single cell layer can be attached by injecting a cell fluid. Since the shape and size of the cells vary depending on the species of the organism, and even the same organism varies depending on the tissue or organ, the microfluidic chip of the present invention can be used to attach a single cell layer according to the size of a cell It is desirable to determine the height of the trapper. A single cell layer can be formed by setting the height of the trapper to be larger than the size of the cell to be measured and smaller than twice the cell size. FIG. 3 shows an enlarged view of a trapper having a height of about 3 .mu.m.

A method for measuring sample sensitivity of cells using the microfluidic chip of the present invention will be described with reference to FIG. FIG. 1 shows a microfluidic chip including a cell culture chamber bottom valve 33. FIG.

First, (A) the upper end of the cell culture chamber uppermost valve 32 is opened and the cell fluid is injected into one of the fluid injection ports to attach the cells to the cell culture chamber. At this time, if the cell culture chamber lower valve 33 is present, it is natural that the cell culture chamber lower valve 33 should also be opened so that the cells can be injected. Once the cells are attached, unattached cells can be washed off if necessary. Alternatively, when the cell is a bacterium capable of forming a biofilm, the attached bacterium may be cultured to form a biofilm, followed by the subsequent step. If the bypass flow path valve 42 is formed in the microfluidic chip, the bypass flow path valve 42 can be closed while the sample is being used.

(B) The cell culture chamber upper valve 32 (and the cell culture chamber lower valve 33) are locked when the cells are attached to the cell culture chamber 31 and ready to measure the sample susceptibility. By such change of the flow path, the fluid in the subsequent step is allowed to pass through only the bypass flow path 41 without flowing into the cell culture chamber 31. If the bypass flow path valve 42 is formed in the microfluidic chip, it is of course necessary to open the bypass flow path valve 42 in this step.

Thereafter, (C) samples having different concentrations are injected into the two or more fluid injection ports (11, 11 ') and passed through a gradient forming region to form a concentration gradient of the sample. In the early stage of this step, the fluid remaining in the flow path of the gradient forming region 20 from the fluid injection ports 11 and 11 'is first discharged through the discharge port. That is, if the cell fluid remains in the flow path, the cell fluid is removed if the cell fluid has been washed with the culture fluid. Thereafter, the sample injected through the fluid injection port is formed into a concentration gradient and discharged to the discharge port.

(D) When the concentration gradient of the sample is stably formed in the microchannel 21 of the gradient forming region 20, the cell culture chamber upper valve 32 (and the cell culture chamber lower valve 33) The formed sample is injected into a cell culture chamber to expose the cells to the sample. Therefore, when the microfluidic chip of the present invention is used, sample sensitivity can be measured more precisely without a problem due to delayed stimulation with a sample having a concentration gradient formed therein.

(E) When a sample having a concentration gradient is injected into the cell culture chamber 31, the cell culture chamber upper valve 32 (and the cell culture chamber lower valve 33) are closed and the cells are cultured. In order to minimize the error in the sample susceptibility measurement, closing the cell culture chamber upper valve 32 (and the cell culture chamber lower valve 33) immediately so that the sample is filled in the cell culture chamber 31 is not influenced by the fluid flow desirable. Since the volume of the cell culture chamber 31 is very small, the time for the cells to be influenced by the flow of the sample is very short, about 1 to 2 seconds, so that the sample sensitivity of the cell can be measured substantially Precise measurement is possible.

(F) After the cell culture chamber is observed, the sample sensitivity can be measured.

In the method of the present invention, this can be done by observing cell culture chambers in real time. Real-time observations can be made simply by measurement using an optical microscope or, if the cells are labeled, by a detection method selected according to the labeling method. The label of the cell may be a labeling substance used in a conventional biotechnology field such as fluorescent dye, magnetic particle, radioactive isotope or quantum dot, and the person skilled in the art can appropriately select it depending on the type of cell used and an appropriate detection method . According to the real-time observation, the influence of the cells from the stimulation point of the sample to the incubation time can be observed simultaneously with time.

If necessary, the cells in the cell culture chamber may be discharged out of the microfluidic chip, and the discharged sample may be analyzed. In FIG. 1, a microfluidic chip having one outlet is shown. However, a microfluidic chip may be designed to have a separate outlet for each cell culture chamber in order to analyze the sample after discharging the sample.

The microfluidic chip of the present invention can be fabricated by wet etching, dry etching, lithography, molding, milling, turning, drilling, punching, laser micromachining, and the like using various kinds of materials such as silicon, glass, metal, ceramic and polymer. And can be manufactured using the same fine processing technology. The micromachining technique is a well-known method, and a detailed description thereof will be omitted herein.

The microfluidic chip of the present invention can be more effectively used when a stimulus is to be given to a cell before or after treatment of a sample having a concentration gradient in the cell. For example, in order to test the efficacy as an anti-inflammatory agent, cells are usually stimulated with LPS (Lipopolysaccharide), then cultured to induce an inflammatory reaction and then treated with an anti-inflammatory agent having a concentration gradient to observe its effect. And then stimulated with LPS to observe the anti-inflammatory effect. According to the microfluidic chip, it is possible to measure not only the effect but also the effective concentration with a small amount of sample, but the microfluidic chip according to the prior art can not avoid the effect of the fluid remaining in the flow channel. According to the present invention, however, whatever kind of fluid remains in the flow path, the bypass flow path is used to remove all the fluid remaining in the flow path, and after a stable flow of the fluid newly injected into the microchannel is maintained, So that more accurate measurement is possible.

Further, the microfluidic chip of the present invention changes the concentration gradient such as the gradient of the concentration gradient or the direction of the same sample even when the sample is the same, and does not gradually change from the gradient before the change to the gradient after the change It is possible to change it immediately, and it is possible to more accurately measure the sensitivity to changes in the sample concentration.

11, 11 'Fluid inlet
20 gradient area
21 Microchannel
31 cell culture chamber
32 Cell culture chamber top valve 33 Cell culture chamber bottom valve
41 bypass flow path 42 bypass flow path valve
51 outlet

Claims (8)

Two or more fluid injection ports; A gradient forming region for separating each fluid injected into the injection port into a plurality of microchannels having different concentration gradients; A cell culture chamber each connected to the microchannel and cell culture is performed; And a discharge port connected to the cell culture chamber, the microfluidic chip for sample susceptibility measurement of cells comprising:
Further comprising a bypass flow path formed by branching the flow path between the microchannel and the cell culture chamber,
Wherein the upper end of the cell culture chamber is provided at the upper end of the cell culture chamber to open and close the inflow of the fluid into the cell culture chamber.
The method according to claim 1,
Wherein a cell culture chamber bottom valve is additionally provided at the bottom of the cell culture chamber.
The method according to claim 1,
And a bypass flow path valve capable of controlling inflow of the fluid into the bypass flow path is additionally provided in the microfluidic chip for measuring the sample susceptibility of the cell.
The method according to claim 1,
Wherein the valves are membrane valves whose opening and closing are controlled by air pressure. The microfluidic chip for measuring sample susceptibility of cells.
The method according to claim 1,
Wherein the height of the trapper is determined according to the size of the cell to be measured for the sample sensitivity so that the single cell layer can be attached to the cell culture chamber.
A method for measuring sample susceptibility of a cell using a microfluidic chip according to any one of claims 1 to 5,
(A) opening a valve at the upper end of the cell culture chamber and injecting a cell solution into one of the fluid injection ports to attach the cells to the cell culture chamber;
(B) changing the flow path to the bypass channel by locking the uppermost cell culture chamber valve;
(C) injecting a sample having a different concentration into the two or more fluid injection ports to form a concentration gradient of the sample through the gradient forming region;
(D) opening a valve at the upper end of the cell culture chamber to inject a sample having a concentration gradient into the cell culture chamber when the concentration gradient of the sample is stably formed in the microchannel;
(E) when a sample having a concentration gradient is injected into the cell culture chamber, closing the upper end of the cell culture chamber and culturing the cells; And
(F) observing the cell culture chamber to measure sample susceptibility;
And measuring the sensitivity of the sample to the sample.
The method according to claim 6,
Wherein the observation of the cell culture area in step (D) is performed in real time.
The method according to claim 6,
The cell is a bacterium,
In the step (A), bacteria are attached to the cell culture chamber,
(a) washing unattached germs;
(b) culturing the attached bacteria to form a biofilm;
, ≪ / RTI >
And measuring the sample susceptibility to the biofilm.

KR1020150098152A 2015-07-10 2015-07-10 Microfluidic Chip for Monitoring of Cell Susceptibility to a Sample KR101619167B1 (en)

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CN114231397A (en) * 2021-12-21 2022-03-25 中国医科大学 High-throughput drug testing centrifugal microfluidic system and use method thereof
CN114231397B (en) * 2021-12-21 2024-02-23 中国医科大学 Centrifugal microfluidic system for high-flux drug testing and application method thereof
KR20230108214A (en) 2022-01-10 2023-07-18 충남대학교산학협력단 Microfluidic Device for Generating Microdroplets with Concentration Gradient and Method for Measuring Susceptibility to Samples Using the Microdroplet
CN114632564A (en) * 2022-04-20 2022-06-17 香港城市大学深圳研究院 Integrated micro-fluidic chip and in-vitro treatment method for primary circulating tumor cells
CN114632564B (en) * 2022-04-20 2024-03-08 香港城市大学深圳研究院 Integrated micro-fluidic chip and primary circulating tumor cell in-vitro treatment method

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