CN115463699A - Microfluidic product plate for screening tumor cells by using immunomagnetic beads - Google Patents

Microfluidic product plate for screening tumor cells by using immunomagnetic beads Download PDF

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Publication number
CN115463699A
CN115463699A CN202211187865.4A CN202211187865A CN115463699A CN 115463699 A CN115463699 A CN 115463699A CN 202211187865 A CN202211187865 A CN 202211187865A CN 115463699 A CN115463699 A CN 115463699A
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pipe
tube
injection
sheath flow
communicated
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熊霞辉
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Suzhou Diketong Biotechnology Co ltd
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Suzhou Diketong 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
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502761Containers 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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/16Microfluidic devices; Capillary tubes
    • 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
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668Trapping microscopic beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0883Serpentine channels
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043Moving fluids with specific forces or mechanical means specific forces magnetic forces

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Abstract

The invention discloses a microfluidic product plate for screening tumor cells by using immunomagnetic beads, which belongs to the technical field of tumor cell screening, and comprises a dust-free injection molding or micro-injection molding product core plate pipeline processing mechanism arranged on a product core plate and used for carrying out target cell screening operation on injected liquid, wherein the pipeline processing mechanism comprises an input pipe, a plurality of conveying pipes, a first connecting pipe, an electromagnetic adsorption unit, a second connecting pipe and an output pipe, the input pipe is communicated and provided with a sample injection pipe, a first sheath flow injection pipe, an immunomagnetic bead injection pipe and a blood cell recovery pipe, and the output pipe is communicated and provided with a second sheath flow injection pipe, a waste liquid recovery pipe and a target cell recovery pipe; the sheath flow injection tube I, the immunomagnetic bead injection tube, the blood cell recovery tube, the electromagnet and the sheath flow injection tube II are matched for use, the separation of impurity cells is completed at the front end of the same product core plate, and the injection and mixing of immunomagnetic beads are completed at the middle end; the back end completes the accurate sorting of the target cells.

Description

Microfluidic product plate for screening tumor cells by using immunomagnetic beads
Technical Field
The invention belongs to the technical field of tumor cell screening, and particularly relates to a microfluidic product plate for screening tumor cells by using immunomagnetic beads.
Background
Microfluidics refers to the science and technology involved in systems that process or manipulate tiny fluids using microchannels, and is an emerging interdiscipline that involves chemical, fluid physics, microelectronics, new materials, biology, and biomedical engineering. Because of the miniaturization, integration, and other features, microfluidic devices are generally called microfluidic chips, also called lab-on-a-chip and micro total analysis systems, and one of the important features of microfluidics is that it has unique fluid properties in a micro-scale environment, such as laminar flow, droplet, and the like. With the aid of these unique fluidic phenomena, microfluidics can realize a series of microfabrication and micromanipulation that are difficult to be completed by conventional methods, and at present, microfluidics is considered to have great development potential and wide application prospects in biomedical research.
At present, the domestic market utilizes immunomagnetic beads to screen tumor cells in a few clinical rapid detection modes; in addition, on the same microfluidic chip, the product which completes magnetic bead injection and magnetic bead mixing and recycling electromagnetic precise separation does not exist.
Compared with a biological electrode screening method commonly used in foreign platforms, a fluorescence accurate positioning method commonly used in laboratories and the like, the method has extremely high process requirements on the manufactured carrier. On the premise of large population base and large use base in China, two problems of time efficiency and cost exist in the aspect of application of clinical examination and in-vitro diagnosis.
For example, the bioelectrode screening method requires vacuum sputtering of a plurality of metal films on a glass substrate; then, displaying an electrode pattern by using a photoetching method; the process is complex, the cost is high, and mass production is not facilitated; for example, the precise fluorescent labeling method requires that a dense array of concave holes are manufactured on a glass substrate by photolithography or laser micro-engraving according to the size of target cells, and is complex in general process, high in cost and not beneficial to large-scale mass production.
Disclosure of Invention
The invention aims to provide a microfluidic product plate for screening tumor cells by using immunomagnetic beads, and aims to solve the problems that the existing bioelectrode screening method and the existing fluorescence accurate positioning method in the background art have complex processes, high cost and difficulty in mass production, and magnetic bead injection and magnetic bead mixing can not be continuously carried out by using electromagnetic accurate sorting.
In order to achieve the purpose, the invention provides the following technical scheme: a microfluidic product plate for screening tumor cells by using immunomagnetic beads comprises a product core plate which is formed by dust-free injection molding or micro injection molding;
the device comprises a product core plate, a pipeline processing mechanism and a control mechanism, wherein the product core plate is provided with a plurality of conveying pipes, a plurality of first connecting pipes, an electromagnetic adsorption unit, a second connecting pipe and an output pipe, the pipeline processing mechanism is arranged on the product core plate and used for carrying out target cell screening operation on injected liquid, the input pipe is communicated and provided with a sample injection pipe, a first sheath flow injection pipe, an immunomagnetic bead injection pipe and a blood cell recovery pipe, the output pipe is communicated and provided with a second sheath flow injection pipe, a waste liquid recovery pipe and a target cell recovery pipe, the input pipe is communicated with the conveying pipe at the foremost side, and the conveying pipe at the last side is communicated with one end of the first connecting pipe;
the protective cover is fixed on the product core plate and covers the electromagnetic adsorption unit, a closed cavity is formed between the protective cover and the product core plate, the closed cavity is respectively communicated with the first connecting pipe and the second connecting pipe, and the other end of the second connecting pipe is communicated with the output pipe.
By adopting the scheme, the sheath flow injection tube I, the immunomagnetic bead injection tube, the blood cell recovery tube, the electromagnet and the sheath flow injection tube II are matched for use, the separation of impurity cells is completed at the front end of the same product core plate, and the injection and mixing of immunomagnetic beads are completed at the middle end; the back end finishes the accurate sorting of target cells, the immunomagnetic bead injection pipes are arranged to be matched for use, the same product core plate can be matched with the electromagnet to realize screening operation corresponding to different target cells as long as different immunomagnetic beads are injected, the traditional dust-free injection molding process and the micro injection molding process are utilized to manufacture the product core plate, the production and packaging of finished products can be finished quickly and in large batch, the cost is low, and the process structure is simple.
In a preferred embodiment, the sample injection tube, the first sheath flow injection tube, the immunomagnetic bead injection tube, and the second sheath flow injection tube are disposed vertically upward, and the blood cell recovery tube, the target cell recovery tube, and the waste liquid recovery tube are disposed vertically downward.
By adopting the scheme, the sample injection pipe arranged upwards is convenient for injecting sample liquid, the sheath flow injection pipe I and the immunomagnetic bead injection pipe are convenient for injecting sheath flow and immunomagnetic beads, the blood cell recovery pipe is arranged downwards and is convenient for rapidly recovering blood cells, and the target cell recovery pipe and the waste liquid recovery pipe are convenient for recovering target cells and waste liquid.
As a preferred embodiment, the conveying pipes are arranged in a serpentine shape, and a plurality of conveying pipes arranged in a serpentine shape are communicated with one another end to end.
Adopt above-mentioned scheme, utilize the conveyer pipe that snakelike laid, and a plurality of conveyer pipes cooperation end to end connection, the abundant transport of the liquid of being convenient for mixes.
As a preferred embodiment, the electromagnetic adsorption unit includes an electromagnet, and the electromagnet is installed on the product core board and is electrically connected to an external power supply.
Adopt above-mentioned scheme, utilize the electro-magnet cooperation to use, can utilize electro-magnet adsorption effort cooperation immunomagnetic bead to use, immunomagnetic bead carries out the motion under the electro-magnet magnetic action and does directional removal to reach the purpose of separation viral factor.
In a preferred embodiment, the first sheath flow injection tube and the immunomagnetic bead injection tube are respectively located on the front side and the rear side of the blood cell recovery tube.
By adopting the scheme, the blood cell recovery tube is arranged between the sheath flow injection tube I and the immunomagnetic bead injection tube, so that the separation of impurity cells, the injection and the mixing of the immunomagnetic beads at the middle end can be completed at the front end of the same product core plate.
In a preferred embodiment, the protective cover is filled with nitric oxide gas.
Adopt above-mentioned scheme, utilize the nitric oxide gas to fill in the protection casing, can avoid outside gas to enter into the protection casing inside, played fine isolated protective effect.
Compared with the prior art, the invention has the beneficial effects that:
the microfluidic product board for screening tumor cells by using immunomagnetic beads is characterized in that a sheath flow injection tube I, an immunomagnetic bead injection tube, a blood cell recovery tube, an electromagnet and a sheath flow injection tube II are matched for use, so that impurity cells are separated at the front end of the same product core board, and immunomagnetic beads are injected and mixed at the middle end of the same product core board; the back end completes the accurate sorting of the target cells.
The microfluidic product board for screening tumor cells by using the immunomagnetic beads is matched with an immunomagnetic bead injection tube for use, and the same product core board can be matched with an electromagnet to realize screening operation corresponding to different target cells as long as different immunomagnetic beads are injected;
the microfluidic product plate for screening tumor cells by using the immunomagnetic beads is used for manufacturing the product core plates by using the traditional dust-free injection molding process and the micro injection molding process, can be used for rapidly completing the production and packaging of finished products in large batch, and has low cost and simple process structure.
Drawings
FIG. 1 is a schematic structural view of the present invention;
FIG. 2 is a schematic view of another embodiment of the present invention;
FIG. 3 is a schematic view of the structure of the shield of the present invention;
fig. 4 is a schematic structural view of the pipe treatment mechanism of the present invention.
In the figure: 1. a product core board; 2. a pipeline processing mechanism; 3. a protective cover; 4. an input tube; 5. a sample injection tube; 6. a sheath flow injection tube I; 7. an immunomagnetic bead injection tube; 8. a blood cell recovery tube; 9. a delivery pipe; 10. a first connecting pipe; 11. an electromagnet; 12. a second connecting pipe; 13. an output pipe; 14. a sheath flow injection tube II; 15. a target cell recovery tube; 16. a waste liquid recovery pipe.
Detailed Description
Referring to fig. 1-4, the present invention provides a microfluidic product plate for screening tumor cells using immunomagnetic beads, which includes a dust-free injection molded or micro-injection molded product core plate 1.
Pipeline processing mechanism 2, set up on product core 1, be used for carrying out target cell screening operation to the liquid of pouring into, pipeline processing mechanism 2 includes input tube 4, a plurality of conveyer pipe 9, connecting pipe one 10, the electromagnetism adsorbs the unit, connecting pipe two 12 and output tube 13, sample injection tube 5, sheath flow injection tube one 6, immunomagnetic bead injection tube 7 and sheath flow injection tube two 14 are all laid vertically upwards, blood cell recovery tube 8, target cell recovery tube 15 and waste liquid recovery tube 16 all lay vertically downwards, the sample injection tube 5 of laying upwards is convenient for pour into sample liquid into, sheath flow injection tube one 6 and immunomagnetic bead injection tube 7 are convenient for pour into sheath flow and immunomagnetic bead into, blood cell recovery tube 8 lays downwards and is convenient for retrieve the blood cell fast, target cell recovery tube 15 and waste liquid recovery tube 16 are convenient for retrieve target cell and waste liquid.
The electromagnetism adsorbs the unit and includes electro-magnet 11, and electro-magnet 11 is installed on product core board 1 and electro-magnet 11 and external power electric connection, uses the cooperation of electro-magnet 11 to use, can use the cooperation immunomagnetic bead of electromagnetism adsorption effort cooperation to use, and the immunomagnetic bead carries out the motion under 11 magnetic actions of electro-magnet and is directional removal to reach the purpose of separating the viral factor.
Sheath flow injection pipe 6 and immunomagnetic bead injection pipe 7 are located the front and back both sides of blood cell recovery pipe 8 respectively, through set up blood cell recovery pipe 8 between sheath flow injection pipe 6 and immunomagnetic bead injection pipe 7, can accomplish the separation of impurity cell at the front end on same product core board 1, the injection and the mixing of the immunomagnetic bead of middle-end.
The input tube 4 is communicated with and provided with a sample injection tube 5, a sheath flow injection tube I6, an immunomagnetic bead injection tube 7 and a blood cell recovery tube 8, the output tube 13 is communicated with and provided with a sheath flow injection tube II 14, a waste liquid recovery tube 16 and a target cell recovery tube 15, the input tube 4 is communicated with the delivery tube 9 at the forefront side, and the delivery tube 9 at the rearmost side is communicated with one end of the connecting tube I10.
Conveyer pipe 9 specifically becomes snakelike laying, and the end to end intercommunication each other between the conveyer pipe 9 that a plurality of was snakelike laying, utilizes the conveyer pipe 9 that snakelike laying, and a plurality of conveyer pipes 9 cooperation end to end connection, and the abundant transport of the liquid of being convenient for mixes.
The protection casing 3, fix on product core 1 and cover the outside of establishing at the electromagnetic adsorption unit, form an airtight cavity between protection casing 3 and the product core 1, and airtight cavity is linked together with connecting pipe one 10 and connecting pipe two 12 respectively, and the other end and the output tube 13 of connecting pipe two 12 are linked together, and the 3 intussuseptions of protection casing are filled with the nitric oxide gas, utilize the nitric oxide gas to fill in protection casing 3, can avoid outside gas to enter into inside protection casing 3, have played fine isolated protecting effect.
When the device is used, liquid to be screened is injected through the sample injection pipe 5, after injection, sheath liquid is added from the sheath flow injection pipe 6, blood cells are discharged from the blood cell recovery pipe 8, required immunomagnetic beads are added from the immunomagnetic bead injection pipe 7, the required immunomagnetic beads are conveyed to the conveying pipe 9 through the input pipe 4, then the required immunomagnetic beads are conveyed to the interior of the protective cover 3 through the conveying pipe 9 and the connecting pipe one 10, the magnetic acting force is generated by the work of the electromagnet 11, the immunomagnetic beads are driven to move, screening operation is achieved, conveying is carried again through the connecting pipes two 12 and the output pipe 13, the sheath liquid is injected again through the sheath flow injection pipe two 14, waste liquid is discharged through the waste liquid recovery pipe 16, and target cells are discharged through the target cell recovery pipe 15.

Claims (6)

1. A microfluidic product plate for screening tumor cells by using immunomagnetic beads is characterized in that: comprises a product core plate (1) formed by dust-free injection molding or micro injection molding;
the device comprises a product core plate (1), a pipeline processing mechanism (2) and a control unit, wherein the pipeline processing mechanism (2) is arranged on the product core plate (1) and used for performing target cell screening operation on injected liquid, the pipeline processing mechanism (2) comprises an input pipe (4), a plurality of conveying pipes (9), a first connecting pipe (10), an electromagnetic adsorption unit, a second connecting pipe (12) and an output pipe (13), a sample injection pipe (5), a first sheath flow injection pipe (6), an immunomagnetic bead injection pipe (7) and a blood cell recovery pipe (8) are communicated and installed on the input pipe (4), a second sheath flow injection pipe (14), a waste liquid recovery pipe (16) and a target cell recovery pipe (15) are communicated and installed on the output pipe (13), the input pipe (4) is communicated with the conveying pipe (9) at the front side, and the conveying pipe (9) at the rear side is communicated with one end of the first connecting pipe (10);
the protective cover (3) is fixed on the product core plate (1) and covers the outer part of the electromagnetic adsorption unit, a closed cavity is formed between the protective cover (3) and the product core plate (1), the closed cavity is communicated with the first connecting pipe (10) and the second connecting pipe (12) respectively, and the other end of the second connecting pipe (12) is communicated with the output pipe (13).
2. The microfluidic product plate for screening tumor cells using immunomagnetic beads according to claim 1, wherein: the sample injection tube (5), the sheath flow injection tube I (6), the immunomagnetic bead injection tube (7) and the sheath flow injection tube II (14) are all vertically arranged upwards, and the blood cell recovery tube (8), the target cell recovery tube (15) and the waste liquid recovery tube (16) are all vertically arranged downwards.
3. The microfluidic product plate for screening tumor cells using immunomagnetic beads according to claim 1, wherein: the conveying pipes (9) are distributed in a snake shape, and the conveying pipes (9) distributed in the snake shape are communicated end to end.
4. The microfluidic product plate for screening tumor cells using immunomagnetic beads according to claim 1, wherein: the electromagnetic adsorption unit comprises an electromagnet (11), wherein the electromagnet (11) is installed on the product core plate (1), and the electromagnet (11) is electrically connected with an external power supply.
5. The microfluidic product plate for screening tumor cells using immunomagnetic beads according to claim 1, wherein: the sheath flow injection tube I (6) and the immunomagnetic bead injection tube (7) are respectively positioned at the front side and the rear side of the blood cell recovery tube (8).
6. The microfluidic product plate for screening tumor cells using immunomagnetic beads according to claim 1, wherein: and the protective cover (3) is filled with nitric oxide gas.
CN202211187865.4A 2022-09-28 2022-09-28 Microfluidic product plate for screening tumor cells by using immunomagnetic beads Pending CN115463699A (en)

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CN202211187865.4A CN115463699A (en) 2022-09-28 2022-09-28 Microfluidic product plate for screening tumor cells by using immunomagnetic beads

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211187865.4A CN115463699A (en) 2022-09-28 2022-09-28 Microfluidic product plate for screening tumor cells by using immunomagnetic beads

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CN115463699A true CN115463699A (en) 2022-12-13

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