CN213624081U - Circulating tumor cell capturing device based on micro-fluidic chip - Google Patents

Circulating tumor cell capturing device based on micro-fluidic chip Download PDF

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Publication number
CN213624081U
CN213624081U CN202022093311.0U CN202022093311U CN213624081U CN 213624081 U CN213624081 U CN 213624081U CN 202022093311 U CN202022093311 U CN 202022093311U CN 213624081 U CN213624081 U CN 213624081U
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microfluidic chip
tube
waste liquid
sample
circulating tumor
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刘宗彬
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Shenzhen Ruige Biotechnology Co ltd
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Shenzhen Ruige Biotechnology Co ltd
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/04Apparatus for enzymology or microbiology with gas introduction means
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/24Apparatus for enzymology or microbiology tube or bottle type
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/26Inoculator or sampler
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/36Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors

Abstract

The utility model provides a circulating tumor cell capture device based on micro-fluidic chip, for solving Circulating Tumor Cell (CTC) separation and catch the big problem of the degree of difficulty, the utility model provides a technical scheme is: the capture device comprises an operation table, a test tube rack and a microfluidic chip; the capturing device also comprises a control console, an air source device, an air pressure adjusting device and a touch display device; the gas source device and the gas pressure regulator are hermetically connected through a pipeline and a test tube to provide gas pressure for the test tube, so that the sample is driven to flow into the microfluidic chip at a certain flow rate, and therefore separation and capture are performed. The beneficial effects of the utility model reside in that: the blood sample and the buffer solution enter the micro-fluidic chip at a certain flow rate by air pressure driving of the device, and suspension containing circulating tumor cells flows out from an outlet of the enrichment liquid collecting pipe and waste liquid flows out from the other two waste liquid outlets by physical separation of the internal structure of the micro-fluidic chip.

Description

Circulating tumor cell capturing device based on micro-fluidic chip
Technical Field
The utility model relates to a Circulating Tumor Cell (CTC) capture device based on micro-fluidic chip especially relates to a Circulating Tumor Cell (CTC) separation capture device of atmospheric pressure drive control formula.
Background
The current clinical discovery and diagnosis of most tumors still rely on imaging examination, traditional tumor markers and tissue biopsy, and the traditional invasive tissue biopsy requires taking a tissue or cell sample from a patient, and this operation often brings certain risks and pains to the patient, and more importantly, the tissue biopsy is not suitable for repeated extraction and is easy to cause complications, and has the risk of spreading cancer cells.
Circulating Tumor Cell (CTC) detection is a novel liquid biopsy mode and has the advantages of real time, no wound, convenience and the like. Circulating Tumor Cell (CTC) capture devices are diagnostic tools for detecting Circulating Tumor Cells (CTCs) in blood, but because of the extremely low number of CTCs in a patient blood sample, tumor metastasis patients have only 1-10 CTCs per ml of whole blood, making separate detection a great challenge. At present, the CTC enrichment method mainly comprises a biochemical characteristic enrichment method and a physical characteristic enrichment method. The biochemical characteristic method is complex to operate and high in cost and depends on the expression condition of cell surface antigens; the density gradient centrifugation and membrane filtration method in the physical characteristic enrichment method can not overcome the heterogeneity of CTC in physical characteristics, and the membrane filtration method is easy to cause blockage and has low separation flux.
The CTC detection technology based on the microfluidic chip can not only detect the number of CTCs, but also separate living CTC cells so as to carry out subsequent research and analysis. Compared with various CTC enrichment technologies at present, the microfluidic chip technology is the mainstream technology for CTC detection in the future.
SUMMERY OF THE UTILITY MODEL
Big, the complicated problem of operation of the degree of difficulty is caught in order to solve current CTC separation, the utility model provides a circulating tumor cell trapping apparatus based on micro-fluidic chip, the device's technical scheme as follows:
a capture device for circulating tumor cells based on a microfluidic chip comprises an operation table, the microfluidic chip and a test tube rack, wherein the microfluidic chip is arranged on the operation table and used for separating and capturing the circulating tumor cells of a sample, and the test tube rack is used for placing test tubes; the capturing device also comprises a control console, an air source device arranged in the control console, an air pressure adjusting device connected with the air source device and used for controlling the output air pressure and a touch display device used for setting and displaying the output air pressure; the gas source device and the gas pressure regulator are hermetically connected through a pipeline and a test tube to provide gas pressure for the test tube, so that the sample is driven to flow in the microfluidic chip to perform separation and capture.
Furthermore, the test tube including be used for to the micro-fluidic chip provide the sample cell of treating the separation sample, be used for collecting the first waste liquid collecting pipe of the main waste liquid after the micro-fluidic chip separation, be used for to removing the solution pipe that the primary separation sample after the main waste liquid provided secondary treatment solution, be used for collecting the second waste liquid collecting pipe of the secondary waste liquid after the micro-fluidic chip separation and be used for collecting the enrichment liquid collecting pipe of the target cell enrichment liquid that obtains after the micro-fluidic chip separation, sample cell, first waste liquid collecting pipe, solution pipe, second waste liquid collecting pipe and enrichment liquid collecting pipe pass through the pipeline with micro-fluidic chip sealing connection.
Furthermore, the microfluidic chip is respectively provided with a sample inflow port corresponding to the sample tube, a first waste liquid outlet corresponding to the first waste liquid collecting tube, a solution inflow port corresponding to the solution tube, a second waste liquid outlet corresponding to the second waste liquid collecting tube, and an enriched liquid outflow port corresponding to the enriched liquid collecting tube.
Further, the gas source device comprises a micro gas pump, or an external gas steel cylinder.
Further, the air pressure adjusting device is an electric proportional valve.
Further, a transparent shell is arranged on the operating platform; the rear side of the operating platform is provided with 5 air pipe connectors connected from the air pressure adjusting device, one ends of the connectors are respectively connected with the 5 air pressure adjusting devices, and the other ends of the connectors are respectively connected with the sample pipe, the first waste liquid collecting pipe, the solution pipe, the second waste liquid collecting pipe and the enrichment liquid collecting pipe.
The beneficial effects of the utility model reside in that: the cost is low, the practicability is high, and the device is simple to operate as a carrying platform of the microfluidic chip. The blood sample and the buffer solution enter the micro-fluidic chip at a certain flow rate through the air pressure drive of the device, and suspension containing Circulating Tumor Cells (CTC) flows out of the concentrated solution collecting pipe through the physical separation of the internal structure of the chip, and main waste blood and secondary waste blood respectively flow out of the first waste solution collecting pipe and the second waste solution collecting pipe. The obtained CTC cell suspension has high separation activity, can be used for immunofluorescence and FISH staining, can also be applied to downstream analysis such as digital PCR and single cell gene sequencing, and provides accurate detection service for tumor patients.
Drawings
Fig. 1 is a perspective view of the present invention;
fig. 2 is a schematic view of the present invention with the transparent shell removed;
fig. 3 is a schematic view of the internal structure of the present invention.
Detailed Description
The present invention will be further explained with reference to the accompanying drawings.
A capture device for circulating tumor cells based on a microfluidic chip comprises an operation table (1), a microfluidic chip (11) which is arranged on the operation table (1) and used for separating and capturing tumor cells of a sample, and a test tube rack (12) used for placing test tubes (01); the capturing device also comprises a control console (2), an air source device arranged in the control console (2), an air pressure adjusting device connected with the air source device and used for controlling the output air pressure and a touch display device used for setting and displaying the output air pressure, wherein the air source device shown in the attached figure 3 is a micro air pump (21); the displayed air pressure adjusting unit is an electric proportional valve (22), the touch display device is a touch screen (23) capable of human-computer interaction, and the touch screen (23) controls and adjusts the electric proportional valve (22) so as to control and adjust the air pressure value of each test tube (01); the gas source device and the air pressure regulator are hermetically connected with the test tube (01) through a pipeline to provide air pressure for the test tube, so that the sample is driven to flow in the microfluidic chip (11) to be separated; the connection mode is that the air source device is connected with the air pressure adjusting device, the air pressure adjusting device is connected to the test tube (01), and the test tube is connected to the microfluidic chip through a pipeline.
In one embodiment, the test tubes (01) have five test tubes, as shown in fig. 2 and 3, which are respectively a sample tube for providing a sample to be separated to the microfluidic chip (11), a first waste liquid collecting tube for collecting a main waste liquid separated by the microfluidic chip (11), a solution tube for providing a secondary treatment solution to a primary separated sample from which the main waste liquid is removed, a second waste liquid collecting tube for collecting a secondary waste liquid separated by the microfluidic chip (11), and an enriched liquid collecting tube for collecting a target cell enriched liquid separated by the microfluidic chip (11), wherein the sample tube, the first waste liquid collecting tube, the solution tube, the second waste liquid collecting tube, and the enriched liquid collecting tube are hermetically connected with the microfluidic chip (11) through a pipeline (such as a capillary). The air pressure output value of the electric proportional valve (22) is adjusted to respectively give different air pressures to the sample tube, the first waste liquid collecting tube, the solution tube, the second waste liquid collecting tube and the enriched liquid collecting tube, so that pressure difference is formed among different tubes, and the blood sample is promoted to flow in the microfluidic chip; after being processed (such as diluted), a blood sample is placed into a sample tube, enters a sample inflow port of the microfluidic chip (11) under the driving of air pressure, a solution (such as a buffer solution) in the solution tube enters a solution inflow port of the microfluidic chip (11) under the driving of the air pressure, the sample and the solution flow according to a separation path inside the microfluidic chip (11), a main waste liquid flows out from an outflow port of a first waste liquid collecting tube, a secondary waste liquid flows out from an outlet port of a second waste liquid collecting tube, and a target sample flows into an enrichment liquid collecting tube.
Furthermore, the micro-fluidic chip (11) is respectively provided with a sample inflow port (31) which is in butt joint with the sample tube, a first waste liquid outlet (32) which corresponds to the first waste liquid collecting tube, a solution inflow port (34) which corresponds to the solution tube, a second waste liquid outlet (33) which corresponds to the second waste liquid collecting tube and an enrichment liquid outflow port (32) which corresponds to the enrichment liquid collecting tube. The sample tube, the first waste liquid collecting tube, the solution tube, the second waste liquid collecting tube and the concentrated liquid collecting tube can be randomly arranged on the test tube rack (12), but are fixed with a connecting port (31/32/33/34/35) of the microfluidic chip (11), and fig. 2 and 3 only show the connection condition of one tube and the microfluidic chip (11), and the connection can be realized by adopting a capillary tube.
In various embodiments, the air pressure source may be a micro air pump provided in the console, or an external air pump, or an external gas cylinder.
In one embodiment, the air pressure adjusting device is an electric proportional valve (22), as shown in fig. 3, there are five electric proportional valves, which correspond to the sample tube, the first waste liquid collecting tube, the solution tube, the second waste liquid collecting tube and the enrichment liquid collecting tube respectively through pipelines, 5 air pipe connectors (4) are arranged at the rear side of the operating platform (1), one end of each connector is connected with the 5 electric proportional valves (22), and the other end of each connector is connected with the sample tube, the first waste liquid collecting tube, the solution tube, the second waste liquid collecting tube and the enrichment liquid collecting tube respectively.
In one embodiment, a transparent enclosure (14) is also provided on the operator station, the transparent enclosure (14) allowing an operator to view the separation capture process.

Claims (6)

1. A capture device of circulating tumor cells based on a microfluidic chip is characterized by comprising an operation table, the microfluidic chip and a test tube rack, wherein the microfluidic chip is arranged on the operation table and used for separating and capturing the circulating tumor cells of a sample, and the test tube rack is used for placing test tubes; the capturing device also comprises a control console, an air source device arranged in the control console, an air pressure adjusting device connected with the air source device and used for controlling the output air pressure and a touch display device used for setting and displaying the output air pressure; the gas source device and the gas pressure regulator are hermetically connected through a pipeline and a test tube to provide gas pressure for the test tube so as to drive the sample to flow in the microfluidic chip for separation and capture.
2. The microfluidic chip-based circulating tumor cell capturing device according to claim 1, wherein the test tube comprises a sample tube for providing a sample to be separated to the microfluidic chip, a first waste liquid collecting tube for collecting a main waste liquid separated by the microfluidic chip, a solution tube for providing a secondary treatment solution to a primary separated sample after the main waste liquid is removed, a second waste liquid collecting tube for collecting a secondary waste liquid separated by the microfluidic chip, and an enriched liquid collecting tube for collecting a target cell enriched liquid separated by the microfluidic chip, wherein the sample tube, the first waste liquid collecting tube, the solution tube, the second waste liquid collecting tube, and the enriched liquid collecting tube are hermetically connected to the microfluidic chip through a tubular object.
3. The microfluidic chip-based circulating tumor cell capturing device of claim 2, wherein the microfluidic chip is provided with a sample inlet corresponding to the sample tube, a first waste liquid outlet corresponding to the first waste liquid collecting tube, a solution inlet corresponding to the solution tube, a second waste liquid outlet corresponding to the second waste liquid collecting tube, and a concentrated liquid outlet corresponding to the concentrated liquid collecting tube, respectively.
4. The microfluidic chip-based circulating tumor cell capturing device of claim 1, wherein the gas source device comprises a micro gas pump, or an external gas cylinder.
5. The microfluidic chip based device for capturing circulating tumor cells according to claim 1, wherein the air pressure regulating device is an electric proportional valve.
6. The microfluidic chip-based circulating tumor cell capturing device of claim 1, wherein a transparent housing is disposed on the console.
CN202022093311.0U 2020-09-22 2020-09-22 Circulating tumor cell capturing device based on micro-fluidic chip Active CN213624081U (en)

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CN202022093311.0U CN213624081U (en) 2020-09-22 2020-09-22 Circulating tumor cell capturing device based on micro-fluidic chip
PCT/CN2021/117878 WO2022062934A1 (en) 2020-09-22 2021-09-13 Microfluidic chip-based circulating tumor/fusion cell capturing device and method

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