CN112280667A - Single cell extraction method - Google Patents
Single cell extraction method Download PDFInfo
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- CN112280667A CN112280667A CN202011125195.4A CN202011125195A CN112280667A CN 112280667 A CN112280667 A CN 112280667A CN 202011125195 A CN202011125195 A CN 202011125195A CN 112280667 A CN112280667 A CN 112280667A
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- 238000000605 extraction Methods 0.000 title claims abstract description 30
- 238000000926 separation method Methods 0.000 claims abstract description 39
- 230000007480 spreading Effects 0.000 claims abstract description 4
- 238000003892 spreading Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 12
- 230000007246 mechanism Effects 0.000 claims description 8
- 230000009471 action Effects 0.000 claims description 6
- 230000002209 hydrophobic effect Effects 0.000 claims description 6
- 238000007789 sealing Methods 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 2
- 230000004807 localization Effects 0.000 claims description 2
- 238000003234 fluorescent labeling method Methods 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 5
- 238000001514 detection method Methods 0.000 abstract description 4
- 238000004458 analytical method Methods 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 126
- 238000003825 pressing Methods 0.000 description 8
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 7
- 229910052710 silicon Inorganic materials 0.000 description 7
- 239000010703 silicon Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000007847 digital PCR Methods 0.000 description 2
- 230000005489 elastic deformation Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 238000001215 fluorescent labelling Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 210000003701 histiocyte Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000003698 laser cutting Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/04—Cell isolation or sorting
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- 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
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
- B01L3/0213—Accessories for glass pipettes; Gun-type pipettes, e.g. safety devices, pumps
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Wood Science & Technology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
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- Sustainable Development (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention discloses a single cell extraction method, which specifically comprises the following steps: firstly, dripping a cell solution with labeled cells onto a cell separation chip, and automatically spreading the cell solution on the cell separation chip to form a solution film; and then positioning the target cells in a fluorescence system, and finally, operating the cell separation gun head to a specific position to suck the target cells under the control of the control system. By the extraction method, the impurities in the cell extracting solution are less, and the cell extracting solution with higher purity is obtained, so that the subsequent detection and analysis are facilitated.
Description
Technical Field
The invention relates to biomedical detection, in particular to a single cell extraction method.
Background
At present, the extraction of the calibrated histiocyte is mostly carried out by adopting a laser cutting method, namely, the histiocyte is coated on a glass slide at first, then a cell membrane layer is dried, and finally, a required calibration target is cut by utilizing laser. The cell extract obtained by the method has a lot of impurities, and living cells are damaged in the process of baking cell membranes, so that an extraction method capable of accurately extracting labeled cells needs to be researched to improve the purity of the cell extract.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a single cell extraction method, so that impurities in a cell extraction solution are reduced, and the subsequent detection and analysis are facilitated.
In order to achieve the purpose, the technical scheme adopted by the invention is a single cell extraction method, which comprises the following steps:
dripping the cell solution with the marked cells onto a cell separation chip, and automatically spreading the cell solution on the cell separation chip to form a solution film;
locating the target cell;
under the control of the control system, the cell separation gun head runs to a target position and sucks out target cells.
In an embodiment of the present invention, the method further includes the steps of: the control system controls the cell separation gun head to be positioned to a certain target cell, sucks the corresponding target cell, and then releases the sucked target cell; positioning the cell separation gun head to another target cell through the control system again, sucking the corresponding target cell, and releasing the sucked target cell; and circulating the steps until the extraction requirement is met.
In one embodiment of the invention, cells are labeled using fluorescent labeling.
In one embodiment of the present invention, the labeled cells exhibit fluorescence under the action of the fluorescence system, thereby achieving the localization of the cells.
In an embodiment of the present invention, the cell separation chip is provided with a solution film forming region, the solution film forming region is recessed toward the cell separation chip, and the cell solution is automatically spread in the solution film forming region to form a cell solution film.
In an embodiment of the present invention, the cell separation chip further includes an edge region, the edge region continuously surrounds the periphery of the solution film formation region, the solution film formation region is provided with a cell groove, the cell groove is composed of a plurality of cell anchor grooves which are closely arranged, and the cells in the tiled cell solution film are spread into the single cell anchor groove.
In an embodiment of the invention, the cell separation gun head is provided with a pressure cavity, and the target cell is sucked into the capillary tube of the cell separation gun head by changing the air pressure in the pressure cavity. The concrete realization mode for changing the pressure inside and outside the pressure cavity is as follows: the method comprises the steps of firstly extruding the cavity wall of the pressure cavity through external force to deform the cavity wall, extruding partial air in the pressure cavity, and then releasing the external force.
In an embodiment of the invention, the cell separation gun head includes:
a fixed mount;
the pressure pipe is fixedly connected with the fixing frame, and one end of the pressure pipe is opened;
the capillary tube is fixedly connected with the pressure tube in a sealing mode and is communicated with the pressure tube;
the pipe sleeve is hermetically sleeved on the pressure pipe and forms a pressure cavity with the pressure pipe; and
and the pressure mechanism is matched with the pipe sleeve to change the air pressure in the pressure cavity.
In an embodiment of the invention, one end of the pressure tube is open, the other end of the pressure tube is connected with the capillary tube, the tube sleeve is hermetically sleeved at one end of the opening of the pressure tube, and the capillary tube is subjected to hydrophobic treatment.
In an embodiment of the present invention, the pressure mechanism includes a pressing frame and a convex pressing head, the pressing frame is fixedly connected to the convex pressing head, the pressing frame is mounted on the fixing frame, and the convex pressing head is located above the pipe sleeve.
The technical scheme has the following beneficial effects:
the cell solution with the marked cells is spread on the cell separation chip to form a film, so that the cells in the cell solution can be independently dispersed in the cell anchor groove on the cell separation chip, and the extraction of single cells becomes possible; furthermore, the marked cells can be clearly and accurately found in a fluorescence system, and the target marked cells are respectively extracted by the cell separation gun head under the action of the control system, so that the high-purity cell extracting solution is obtained. The extraction method has high extraction accuracy, high safety and efficiency, and no damage to cell activity.
Drawings
FIG. 1 is a schematic structural view of a cell separation lance head according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a cell separation chip according to an embodiment of the present invention;
FIG. 3 is an enlarged view of the invention at A in FIG. 2;
FIG. 4 is a schematic cross-sectional view of a cell separation chip according to an embodiment of the present invention;
fig. 5 is an enlarged view of the invention at B in fig. 4.
Description of reference numerals: the device comprises a fixed frame 1, a pressure pipe 2, a capillary 3, a pipe sleeve 4, a pressure elastic sheet 5, a convex pressure head 6, a screw 7, a silicon substrate 8, a solution film forming area 81, an edge area 82, a cell anchor groove 9 and a pressure cavity 10.
Detailed Description
The invention will now be further described with reference to the following examples and figures 1 to 5.
The cell extraction system comprises a hardware device, a digital PCR cell separation chip (hereinafter referred to as a cell separation chip or a chip), a digital PCR cell separation gun head (hereinafter referred to as a cell separation gun head or a gun head), and a control system, wherein the control system is used for controlling the gun head to be positioned to a target cell and extracting the target cell through the gun head. The specific method for extracting the single cell comprises the following steps: firstly, dripping a cell solution with labeled cells onto a cell separation chip, and automatically spreading the cell solution on the cell separation chip to form a solution film; and then positioning the target cells in a fluorescence system, and finally, operating the cell separation gun head to a specific position to suck the target cells under the control of the control system. Thereby obtaining the cell extract with less impurities and being more beneficial to the subsequent detection and analysis.
As shown in fig. 1, the cell separation gun head comprises a fixed frame 1, a pressure tube 2, a capillary tube 3, a tube sleeve 4 and a pressure mechanism, wherein the pressure tube 2, the capillary tube 3 and the tube sleeve 4 are connected together and fixed on the fixed frame 1, and the pressure mechanism is also installed on the fixed frame 1.
One end of the pressure pipe 2 is open, the other end is closed, and the open end of the pressure pipe 2 is sleeved with a sealing pipe sleeve 4, so that a pressure cavity 10 is formed between the sealing pipe sleeve 4 and the pressure pipe 2. The sleeve 4 is a deformable material having sealing performance, and thus the pressure chamber 10 is changed in volume by deformation of the sleeve. Under the action of external force, the pipe sleeve 4 deforms, the volume of the pressure chamber 10 becomes smaller, namely, air in the pressure chamber 10 is extruded out partially; when the external force disappears, the elastic deformation of the sleeve 4 disappears and the volume of the pressure chamber 10 returns to the original size. In this embodiment, the pipe sleeve 4 is a silica gel sealing ring.
The other end of pressure pipe 2 is sealed to be installed a capillary 3, capillary 3 is a superfine both ends open-ended pipe, capillary 3 with pressure pipe 2 inside hollow portion is linked together, promptly the one end of capillary 3 with pressure chamber 10 is linked together, and both constitute the linker. It can be further understood that when the pressure chamber 10 is squeezed, air in the pressure chamber 10 is discharged through the capillary tube 3, and when the external force disappears, the pressure chamber 10 returns to the initial state, and at this time, the air pressure in the pressure chamber 10 is lower than the atmospheric pressure, and the atmospheric pressure presses the cells at the tube opening of the capillary tube 3 into the capillary tube 3, in other words, when the external force disappears, the gun head sucks the target cells into the capillary tube 3, thereby realizing the extraction of the target labeled cells.
What deforms the sleeve 4 is the pressure means. The pressure mechanism comprises a pressure frame and a convex pressure head 6, the convex pressure head 6 is fixedly connected with the pressure frame, and one end of the pressure frame is fixedly arranged on the fixed frame 1 through a screw 7. The pressing frame is a pressure spring piece 55, and the pressure spring piece 5 can automatically rebound when the external force disappears. The convex pressure head 6 is arranged at the other end of the pressure spring piece 5. The convex pressure head 6 is arranged above the pipe sleeve 4, and the pipe sleeve 4 can be deformed by applying pressure to the pipe sleeve 4 through the convex pressure head 6, so that the pressure cavity 10 positioned below the pipe sleeve 4 is extruded. The control system controls external force to be applied to the pressure spring piece 5, the pressure spring piece 5 deforms to enable the convex pressure head 6 to abut against the pipe sleeve 4, the external force is transmitted to the pipe sleeve 4 through the convex pressure head 6, the pipe sleeve 4 is extruded to deform, and therefore air in the pressure cavity 10 is discharged.
The end of the male crimp 6 intended to contact the socket 4 is rounded so that the pinch damage to the socket 4 can be minimized. By controlling the degree of depression of the ram 6, the amount of deformation of the sleeve 4 can be controlled, and thus the amount of air discharged from the pressure chamber 10 can be controlled, as desired. The part of the pressure spring 5 close to the pipe sleeve 4 is positioned above the pipe sleeve 4 in parallel to form a cantilever, and the downward bending angle of the cantilever is different according to the external pressure, so that the deformation of the pipe sleeve 4 is different. In this implementation, the circular arc end of the protruding pressure head 6 with the mouth of pipe of pressure pipe 2 cooperatees, under the effect of outside pressure, pressure shell fragment 5 bends down, and protruding pressure head 6 just in time presses on the pipe box 4 of 2 openings of pressure pipe, thereby makes pipe box 4 realizes elastic deformation smoothly, and after outside pressure disappeared, pressure shell fragment 5 lifted, and pipe box 4 reverted original shape. In this embodiment, the pressure spring 5 is provided with the arc-shaped bend, and the arc-shaped bend improves the service performance of the pressure spring 5 in order to reduce the internal stress of the pressure spring 5 in the process of bending downwards and springing upwards.
The external force applied to the pipe sleeve 4 is controlled by a control system, and the air pressure in the pressure cavity 10 is changed through the cooperation between the pressure mechanism and the pipe sleeve 4, so that an air pressure difference is formed between the inside and the outside of the pressure cavity 10, and the cell liquid at the pipe orifice of the capillary 3 is sucked into the capillary 3 when the external force is eliminated. The specific implementation manner for changing the pressure inside and outside the pressure chamber 10 is as follows: the tube sleeve 4, the cavity wall of the pressure cavity 10, is extruded by external force, the cavity wall is deformed, part of air in the pressure cavity 10 is extruded, then the external force is released, when the external force disappears, the deformation of the cavity wall disappears, the pressure cavity 10 recovers to the original state, at the moment, the air pressure in the pressure cavity 10 becomes lower than the atmospheric pressure, the target cell fluid at the orifice of the capillary tube 3 is pressed into the capillary tube 3 by the atmospheric pressure, and the extraction of single target cell is realized.
The pressure tube 2 and the capillary tube 3 are made of stainless steel or quartz, and the inner diameter of the capillary tube 3 is 1-50 mu m. In order to avoid the phenomenon of siphoning when the target cell sap is sucked, the inner and outer surfaces of the capillary 3 need to be subjected to hydrophobic treatment, specifically, the inner and outer surfaces of the capillary 3 can be coated with hydrophobic coatings, so that the siphoning phenomenon is eliminated, and under the condition of pressure difference between the inside and the outside of the capillary 3, only cell substances pointed by the pipe orifice of the capillary 3 are allowed to be sucked into the capillary 3, namely, other substances except for the labeled cells are sucked as little as possible.
When the gun head is used for extracting the single marked cells paved on the chip, the adopted principle is as follows: the external pressure presses the tube sleeve 4, thereby squeezing out a part of the air in the pressure chamber 10; with the disappearance of the external pressure, the deformation of the tube sleeve 4 disappears, at this time, the air pressure in the pressure chamber 10 is smaller than the atmospheric pressure, and the target cell at the orifice of the capillary tube 3 is sucked into the capillary tube 3 by the difference between the internal air pressure and the external air pressure.
The way to achieve "as little as possible uptake of other substances than labeled cells" is by special design of the structure of the chip. The specific structure of the chip is shown in fig. 2-5, the main structure of the chip is a silicon substrate 8, a solution film forming region 81 and a marginal region 82 are arranged on the silicon substrate 8, the marginal region 82 is located around the solution film forming region 81, and the solution film forming region 81 is recessed in the silicon substrate 8. The solution film forming region 81 is a concave region photo-etched on the silicon substrate 8 having a flat surface, and the depth of the concave region is smaller than the thickness of a single cell film. The solution film forming region 81 is photo-etched with a cell groove, and the cell groove is composed of a plurality of cell anchor grooves 9 which are closely arranged. The solution-film forming region 81 is subjected to hydrophilic treatment, i.e., each surface of the cell anchor groove 9 located in the solution-film forming region 81 is coated with a hydrophilic coating. The edge region 82 is coated with a hydrophobic coating to ensure that the cell solution dropped on the chip is spread only in the solution film forming region 81.
The cell anchor groove 9 is a hexagonal or pentagonal or quadrangular or circular groove. In this embodiment, the cell anchor grooves 9 are arranged in a honeycomb structure, and this arrangement can better spread the cell solution from the fluid mechanics angle, and can better fix the spread single cell, thereby being more beneficial to the suction of the gun head. The depth of the cell anchor groove 9 is 2-15 μm, preferably 2-5 μm, so as to avoid overlapping of a plurality of cells after the membrane in the unfolded cell liquid membrane is too thick, which is not beneficial to the extraction of single labeled cells. The diameter of the inscribed circle of the cell anchor groove 9 is 2-10 mu m, which is convenient for better realizing the fixation of each cell after being spread.
When the chip is prepared, the silicon substrate 8 with regular shape and smooth surface is selected to be firstly subjected to surface hydrophobic treatment, a shallow groove is etched on the silicon substrate 8 and is a solution film forming area 81, and annular steps are arranged around the shallow groove, so that the cell solution dropped into the shallow groove is prevented from overflowing the area; then, the cell anchor grooves 9 with a certain depth are photo-etched in the shallow grooves in a close arrangement, and finally, the solution film forming region 81 is subjected to hydrophilic treatment, so that each surface of the cell anchor grooves 9 is coated with a hydrophilic coating.
When single cell extraction is carried out by utilizing the cooperation of the gun head and the chip, the specific method comprises the following steps:
step 1: delivering a certain amount of cell solution after fluorescent labeling to the solution film forming area 81, wherein the cell solution can be diffused into a layer of cell liquid film under the action of surface tension and evenly and flatly paved on the solution film forming area 81, and cells contained in the cell liquid film can be respectively fixed in each cell anchor groove 9;
step 2: the marked cells in the fluorescence system emit fluorescence to realize the positioning of the marked cells;
and step 3: the control system controls the gun head to move to a target position on the chip, the orifice of the capillary 3 of the gun head is aligned with the marked cell, a certain external force is applied to the pressure spring 5 through the control system, the pressure spring 5 is pressed down onto the pipe sleeve 4, and the pipe sleeve 4 deforms, so that part of air in the pressure cavity 10 is extruded out through the orifice of the capillary 3; then, the external force is cancelled, and the marked cells at the opening of the capillary 3 are sucked into the capillary 3;
and 4, step 4: moving the gun head away from the chip under the control of the control system, and releasing the cells sucked into the capillary 3 into the collection container;
and 5: and (4) repeating the steps 1-4 until all target marker cells on the chip are extracted.
By adopting the extraction equipment and the extraction method, the activity of cells cannot be influenced in the whole extraction process, meanwhile, the precise extraction of the marked cells is realized through the specific design of the chip and the structure of the gun head, the automatic extraction of the single marked cell is realized under the action of a control system, and the obtained cell extracting solution has fewer impurities and higher purity.
The above-described embodiments are intended to illustrate rather than to limit the invention, and any changes and alterations made without inventive step within the spirit and scope of the claims are intended to fall within the scope of the invention.
Claims (10)
1. A single cell extraction method, comprising the steps of:
dripping the cell solution with the marked cells onto a cell separation chip, and automatically spreading the cell solution on the cell separation chip to form a solution film;
locating the target cell;
under the control of the control system, the cell separation gun head runs to a target position and sucks target cells.
2. The single cell extraction method of claim 1, further comprising the steps of: the control system controls the cell separation gun head to be positioned to a certain target cell, sucks the corresponding target cell, and then releases the sucked target cell; and positioning the cell separation gun head to another target cell through the control system again, sucking the corresponding target cell, releasing the sucked target cell, and circulating the steps.
3. The method for extracting single cells according to claim 1, wherein the cells are labeled by a fluorescent labeling method.
4. The method for extracting single cells according to claim 1, wherein the labeled cells exhibit fluorescence under the action of a fluorescence system, thereby realizing the localization of the cells.
5. The method for extracting single cell according to claim 1, wherein the cell separation chip is provided with a solution film forming region which is recessed toward the cell separation chip, and the cell solution is automatically spread in the solution film forming region to form a cell solution film.
6. The single cell extraction method according to claim 5, wherein the cell separation chip further comprises an edge region, the edge region continuously surrounds the solution film formation region, the solution film formation region is provided with a cell recess, the cell recess is composed of a plurality of cell anchor grooves which are closely arranged, and the cells in the tiled cell solution film are spread into the single cell anchor grooves.
7. The method for extracting the single cell according to claim 1, wherein the cell separation gun head is provided with a pressure cavity, and the target cell is sucked into the capillary tube of the cell separation gun head by changing the air pressure in the pressure cavity.
8. The single cell extraction process of claim 1, wherein the cell separation tip comprises:
a fixed mount;
the pressure pipe is fixedly connected with the fixing frame, and one end of the pressure pipe is opened;
the capillary tube is fixedly connected with the pressure tube in a sealing mode and is communicated with the pressure tube;
the pipe sleeve is hermetically sleeved on the pressure pipe and forms a pressure cavity with the pressure pipe; and
and the pressure mechanism is matched with the pipe sleeve to change the air pressure in the pressure cavity.
9. The single cell extraction method as claimed in claim 8, wherein the pressure tube is open at one end and connected to the capillary tube at the other end, the tube housing is sealed at one end of the opening of the pressure tube, and the capillary tube is hydrophobic-treated.
10. The single cell extraction method according to claim 8, wherein the pressure mechanism comprises a pressure frame and a convex pressure head, the pressure frame is fixedly connected with the convex pressure head, the pressure frame is mounted on the fixed frame, and the convex pressure head is positioned above the pipe sleeve.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202011125195.4A CN112280667A (en) | 2020-10-20 | 2020-10-20 | Single cell extraction method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202011125195.4A CN112280667A (en) | 2020-10-20 | 2020-10-20 | Single cell extraction method |
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| CN112280667A true CN112280667A (en) | 2021-01-29 |
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| CN1369698A (en) * | 2001-01-31 | 2002-09-18 | 株式会社岛津制作所 | Liquid transfer system and reacting vessel |
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| US20070048857A1 (en) * | 2005-08-05 | 2007-03-01 | Fujitsu Limited | Automatic macroinjection apparatus and cell trapping plate |
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-
2020
- 2020-10-20 CN CN202011125195.4A patent/CN112280667A/en active Pending
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| US20030022268A1 (en) * | 2000-07-31 | 2003-01-30 | Albrecht Lepple-Wienhues | Method and apparatus for patch-clamp measurements on cells |
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| US20070048857A1 (en) * | 2005-08-05 | 2007-03-01 | Fujitsu Limited | Automatic macroinjection apparatus and cell trapping plate |
| CN107389642A (en) * | 2017-08-01 | 2017-11-24 | 北京科技大学 | Unicellular efficient capture, the imaging of high intension and full transcriptome analysis apparatus and method |
| CN109270262A (en) * | 2018-10-08 | 2019-01-25 | 宁波美晶医疗技术有限公司 | A kind of unicellular extracting method of laser based on micro-fluidic technologies |
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| Title |
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