CN108330065A - Cell screening device and cell screening method based on cell printing nozzle array - Google Patents
Cell screening device and cell screening method based on cell printing nozzle array Download PDFInfo
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- CN108330065A CN108330065A CN201710041720.6A CN201710041720A CN108330065A CN 108330065 A CN108330065 A CN 108330065A CN 201710041720 A CN201710041720 A CN 201710041720A CN 108330065 A CN108330065 A CN 108330065A
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- 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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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
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- C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
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Abstract
The application provides a cell screening device and screening method based on cell printing nozzle array for screening different cells, the cell screening device has: the cell printing nozzle array is formed by arranging a plurality of cell printing nozzles in an array, and the spray hole of each cell printing nozzle can hold and spray cells; a detector that detects the type of cell held in each of the nozzle holes; a controller that controls the cell print head array to cause the nozzle holes holding a predetermined kind of cells to eject the predetermined kind of cells, based on a result of detection of the kind of cells held by each of the nozzle holes by the detector; and a collector that collects the predetermined kind of cells ejected from the ejection holes of the cell-printing ejection head. According to the method and the device, the cell screening process and the cell screening device can be simplified, the efficiency is improved, and the damage degree to the cells is reduced.
Description
Technical field
This application involves biomedicine technical field more particularly to a kind of cell screenings based on cell printing jet array
Device and cell screening method.
Background technology
Flow cytometer (Flow Cetometry) is a kind of device for being automatically analyzed and being screened to cell, and principle is
With the fluorescein stain of the specificity of the biomarker-specific object (bio-marker) for target cell, target cell is dyed
Afterwards, fluoroscopic examination is carried out to individual cells via fluid channel, and then filters out target cell, be allowed to the skill detached with other cells
Art.Wherein, which for example can be the albumen or antibody on cell membrane.Fig. 1 is using fluorescein stain to mesh
The schematic diagram that mark cell is dyed, as shown in Figure 1,100 surface of target cell has biomarker-specific object (bio-
Marker) 101, fluorescein stain molecule 102 can be combined with biomarker-specific object 101, to be dyed to target cell 100.
Fig. 2 is a schematic diagram of existing cell sorting system.Existing cell sorting system generally uses excess sound pressure
Crystal and high-voltage electrostatic field, for example, by excess sound pressure crystal unit on cell flow chamber, excess sound pressure crystal generates high frequency after energization
Rate is vibrated, and makes to generate microlayer model 201 in cell flow chamber 200, a drop includes a cell 202 to be detected.Laser
203 irradiate laser to drop 201 shows if detecting that drop sends out fluorescence corresponding with fluorescein stain by fluorescence analyser 204
Show that the cell contains target biomarker, then give drop charge, by when deflecting plates 205 under the traction of high-voltage electrostatic field it is thin
Cytosol drop can turn left or fall toward right avertence, drop down onto in target container and collected;Conversely, for without target biomarker
Cell will not give and charge, drop directly drops down onto at intermediate waste collection.
Hot note formula cell printing nozzle is to make the stream of micro volume using the micro-heater heating flow surface in fluid channel
Body moment is heated to gasification, generates the substance in bubble propulsion fluid or fluid.The nozzle possesses quick rapid advantage, often
Second can print the fine droplet of 1,000,000 drops or more, and jet size can be realized in 20-60 microns to individual cells
Printing.In addition, the nozzle can border town, can be precisely controlled with controller printing process obtain better quality at
Product.
It should be noted that above to the introduction of technical background be intended merely to it is convenient to the technical solution of the application carry out it is clear,
Complete explanation, and facilitate the understanding of those skilled in the art and illustrate.Cannot merely because these schemes the application's
Background technology part is expounded and thinks that above-mentioned technical proposal is known to those skilled in the art.
Invention content
The inventors of the present application found that traditional charging and electrostatic field cell sorting methods flow is complicated, time-consuming and efficiency
It is low, also, drop charge containing cell may be caused to damage to cell in its assorting room, or cause cell interior
Variation.
The application provides a kind of cell sorting devices and cell screening method based on cell printing jet array, according to thin
The type for the cell that each nozzle of born of the same parents' printing head array is kept, drives corresponding nozzle printing to go out the cell of predetermined kind,
Thereby, it is possible to simplify the flow and device of cell screening, efficiency is improved, and reduce the degree of injury to cell.
According to the one side of the embodiment of the present application, a kind of cell sieve based on cell printing jet array is provided and is chosen to install
It sets, for being screened to different types of cell, which is characterized in that the cell sorting devices have:
Cell printing jet array is arranged by multiple cell printing nozzles by array, each cell printing
The spray orifice of nozzle can be kept and be sprayed to cell;
Detector detects the type for the cell that each spray orifice is kept;
Controller, the testing result of the type for the cell that each spray orifice is kept according to the detector, control
The cell printing jet array, makes the spray orifice for the cell for maintaining predetermined kind spray the cell of the predetermined kind;And
Collector collects the cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle.
According to the one side of the embodiment of the present application, wherein at least one of the detector and the collector
It is removable.
According to the one side of the embodiment of the present application, wherein kept thin detecting each spray orifice using detector
In the case of the type of born of the same parents, the detector is moved adjacent to described thin from the position far from the cell printing jet array
The position of born of the same parents' printing head array, in the case where terminating to detect the type for the cell that each spray orifice is kept, the detection
Device is moved away from the position of the cell printing jet array from the position of the close cell printing jet array.
According to the one side of the embodiment of the present application, wherein collected by the cell printing nozzle using collector
In the case of the cell for the predetermined kind that spray orifice is sprayed, the collector by from far from the cell printing jet array position
The position for being moved adjacent to the cell printing jet array is set, is sprayed by the spray orifice of the cell printing nozzle terminating to collect
In the case of the cell of the predetermined kind gone out, the collector is moved to from the position close to the cell printing jet array
Position far from the cell printing jet array.
According to the one side of the embodiment of the present application, wherein the controller controls the spray orifice sequentially will be described predetermined
The cell of type sprays, and simultaneously sprays the cell of the predetermined kind alternatively, the controller controls the spray orifice.
According to the one side of the embodiment of the present application, wherein the cell sorting devices also have:
Cell solution reservoir is used to accommodate solution containing cell, and the solution is injected into the cell printing
Jet array.
According to the one side of the embodiment of the present application, a kind of cell screening side based on cell printing jet array is provided
Method, for being screened to different types of cell, which is characterized in that the cell screening method has:
Cell is maintained in the spray orifice of cell printing nozzle, wherein multiple cell printing nozzles are arranged by array
Cell printing jet array;
The type for the cell that each spray orifice is kept is detected using detector;
According to the testing result of the type of the cell kept to each spray orifice, the cell printing nozzle battle array is controlled
Row, make the spray orifice for the cell for maintaining predetermined kind spray the cell of the predetermined kind;And
The cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle is collected using collector.
According to the one side of the embodiment of the present application, wherein kept thin detecting each spray orifice using detector
In the step of type of born of the same parents, the detector is moved adjacent to described thin from the position far from the cell printing jet array
The position of born of the same parents' printing head array, in the case where terminating to detect the type for the cell that each spray orifice is kept, the detection
Device is moved away from the position of the cell printing jet array from the position of the close cell printing jet array.
According to the one side of the embodiment of the present application, wherein collected by the cell printing nozzle using collector
In the step of cell for the predetermined kind that spray orifice is sprayed, the collector by from far from the cell printing jet array position
The position for being moved adjacent to the cell printing jet array is set, is sprayed by the spray orifice of the cell printing nozzle terminating to collect
In the case of the cell of the predetermined kind gone out, the collector is moved to from the position close to the cell printing jet array
Position far from the cell printing jet array.
According to the one side of the embodiment of the present application, wherein the spray orifice is controlled as the predetermined kind sequentially
Cell sprays, and is sprayed alternatively, the spray orifice is controlled as the cell by the predetermined kind simultaneously.
The advantageous effect of the application is:The flow and device of cell screening can be simplified, improve efficiency, and reduction pair
The degree of injury of cell.
With reference to following description and accompanying drawings, the particular implementation of the application is disclosed in detail, specifies the original of the application
Reason can be in a manner of adopted.It should be understood that presently filed embodiment is not so limited in range.In appended power
In the range of the spirit and terms that profit requires, presently filed embodiment includes many changes, modifications and is equal.
The feature for describing and/or showing for a kind of embodiment can be in a manner of same or similar one or more
It is used in a other embodiment, it is combined with the feature in other embodiment, or substitute the feature in other embodiment.
It should be emphasized that term "comprises/comprising" refers to the presence of feature, one integral piece, step or component when being used herein, but simultaneously
It is not excluded for the presence or additional of one or more other features, one integral piece, step or component.
Description of the drawings
Included attached drawing is used for providing being further understood from the embodiment of the present application, and which constitute one of specification
Point, for illustrating presently filed embodiment, and with verbal description come together to illustrate the principle of the application.Under it should be evident that
Attached drawing in the description of face is only some embodiments of the present application, for those of ordinary skill in the art, is not paying wound
Under the premise of the property made is laborious, other drawings may also be obtained based on these drawings.In the accompanying drawings:
Fig. 1 is the schematic diagram dyed to target cell using fluorescein stain;
Fig. 2 is a schematic diagram of existing cell sorting system;
Fig. 3 is a schematic diagram of the cell sorting devices of the embodiment of the present application;
Fig. 4-Fig. 7 is the schematic diagram for each step that the cell sorting devices of the embodiment of the present application are screened.
Specific implementation mode
With reference to attached drawing, by following specification, the aforementioned and other feature of the application will be apparent.In specification
In attached drawing, the particular implementation of the application is specifically disclosed, which show the portions for the principle that the application wherein may be used
Divide embodiment, it will thus be appreciated that the application is not limited to described embodiment, on the contrary, the application includes falling into appended power
Whole modifications, modification and equivalent in the range of profit requirement.
Embodiment 1
The embodiment of the present application 1 provides a kind of cell sorting devices based on cell printing jet array, for not of the same race
The cell of class is screened.
Fig. 3 is a schematic diagram of the cell sorting devices 300.As shown in figure 3, the cell sorting devices 300 have:Carefully
Born of the same parents' printing head array 301, detector 302, controller (not shown) and collector 303.
In the present embodiment, cell printing jet array 301 is arranged by multiple cell printing nozzles 3011 by array,
The spray orifice 3012 of each cell printing nozzle 3011 can be kept and be sprayed to cell;Detector 302 detects each spray orifice
The type of 3012 cells kept;The inspection of the type for the cell that controller can keep each spray orifice according to detector 302
It surveys as a result, the described cell printing jet array of control, so that the spray orifice for the cell for maintaining predetermined kind is sprayed institute, this determines type
Cell;Collector 303 can collect the cell of the predetermined kind sprayed by the spray orifice 3012 of cell printing nozzle.
The cell sorting devices of the present embodiment are simple in structure, make simple, print speed of the cell printing nozzle to cell
Far above traditional screening technique so that cell screening process is rapid, also, can be to thin in multiple spray orifices using detector
The type of born of the same parents is detected, and improves the efficiency of cell detection, in addition, cell printing nozzle is carrying out cell to spray printing
It is very small to the injury of cell itself in the process.
In the present embodiment, the cell printing nozzle 3011 in cell printing jet array 301 for example can be hot note formula
(thermal ink jet) cell printing nozzle.In the present embodiment, the size of cell printing nozzle 3011 can be 20-60
Micron, can realize the printing to individual cells.In addition, cell printing nozzle 3011 can pass through MEMS (MEMS)
Manufacturing process manufactures.About the structure and principle of cell printing nozzle 3011, the prior art can be referred to.
In the present embodiment, detector 302 can detect the type of cell based on the characteristic of cell, for example, detector
302 can detect the type of cell based on image, for example, the luminescence unit of detector 302 can be mixed to fluorescent molecular
The exciting light of cell irradiation specific band afterwards, the photosensitive unit of detector 302 can detect cell whether send out it is specific glimmering
Light.
In the present embodiment, cell sorting devices 300 can store the result detected by detector 302, with
It is controlled convenient for the controller.
In the present embodiment, which can be to each cell printing nozzle in cell printing jet array 301
3011 are controlled, and printing head is made to carry out ejection printing to particular kind of cell as a result,.
In the present embodiment, which can control the sequence that the spray orifice 3012 of each printing head 3011 is printed,
Sequentially the cell of predetermined kind is sprayed for example, the controller can control each spray orifice, alternatively, the controller can control holding
There is each spray orifice of the cell of the predetermined kind simultaneously to spray the cell of the predetermined kind.
In the present embodiment, the cell that collector 303 can spray a spout is collected, the number of collector 303
Amount can be corresponding to the type with cell, for example, in figure 3, collector 303 may include that the first collector 3031 and second is received
Storage 3032, wherein the first collector 3031 can collect the cell of the first type, and the second collector 3032 can collect second
The cell of type, the cell of the first type for example can be the cells that specific fluorescent can be sent out after being mixed with fluorescent molecular, the
The cell of two types for example can be the cell that cannot send out the specific fluorescent.
In the present embodiment, at least one of detector 302 and collector 303 are removable, wherein detector 302
And/or collector 303 can be connect with mechanical arm, and moved under the driving of the mechanical arm, which can be in needs
Direction is moved, such as can be moved up and down.
For example, in the case where detecting the type for the cell that each spray orifice is kept using detector, the detector
It is moved adjacent to the position of the cell printing jet array from the position far from the cell printing jet array, is being terminated
In the case of the type for detecting the cell that each spray orifice is kept, the detector is by from close to the cell printing nozzle battle array
The position of row moves away from the position of the cell printing jet array;In addition it is also possible to be collected by institute using collector
In the case of the cell for stating the predetermined kind that the spray orifice of cell printing nozzle is sprayed, the collector is by from far from the cell
The position of printing head array is moved adjacent to the position of the cell printing jet array, is beaten by the cell terminating to collect
In the case of the cell for the predetermined kind that the spray orifice of print nozzle is sprayed, the collector is by from close to the cell printing nozzle
The position of array moves away from the position of the cell printing jet array.
In the present embodiment, as shown in figure 3, the cell sorting devices 300 can also have cell solution reservoir 304,
It is used to accommodate solution containing cell, and the solution is injected into the cell printing jet array.Wherein, this contains cell
Solution for example can be by cell solution (cell solution) and the mixed solution of fluorescent molecular.
In the following, illustrate the operation principle of the cell sorting devices 300 of the application with an example, Fig. 4-Fig. 7 be with carefully
The corresponding schematic diagram of each step of born of the same parents' screening plant 300.
1, cell solution and fluorescent molecular solution are mixed to form solution containing cell, can be started after appropriate reaction
Carry out cell screening;
2, the solution containing cell that step 1 obtains cell is injected by uppermost cell solution reservoir 304 to beat
Print jet array 301;
3, individual cells rest on a spray orifice, as shown in Figure 3;
Whether 4, detector 302 rises, be target cell based on each cell of fluoroscopic examination, as shown in Figure 4;
5, after detector 302 detects specific fluorescent, the information of spray orifice corresponding with the position for sending out specific fluorescent is stored up
It deposits;
6, the detection of detector 302 finishes, and and then mechanical arm declines together, and the first collector 3031 and second of side is collected
Device 3032 moves to immediately below cell printing jet array 301, as shown in Figure 5;
7, controller pair with send out corresponding to the position of specific fluorescent to spray orifice drive, by these spray orifices
It generates bubble BU the target cell A in these spray orifices is sequentially printed upon in each collecting region 3031a of the first collector 3031,
Cell B in remaining spray orifice continues to be maintained in spray orifice, as shown in (A) and (B) of Fig. 6, wherein by target cell A sequentially
During printing in each collecting region 3031a of the first collector 3031, the first collector 3031 can be made to move, to use
It is corresponding with the spray orifice of target cell A to be sprayed in the collecting region 3031a of reception;
8, after all target cell A are printed, the first collector 3031 is removed to side, on the second collector 3032
It is raised to the position of 3031 script of the first collector;
9, controller drives remaining all spray orifices, and cell B is sprayed simultaneously and is printed upon in the second collector 3032, such as
Shown in (C) of Fig. 6;
10, the second collector 3032 is removed to side, and target cell A and untargeted cells B screenings are completed, and the selection result is such as
Shown in Fig. 7;
11, it to continue to screen, then repeats the above steps after the collector more renewed.
The cell sorting devices of the present embodiment are simple in structure, make simple, print speed of the cell printing nozzle to cell
Far above traditional screening technique so that cell screening process is rapid, also, can be to thin in multiple spray orifices using detector
The type of born of the same parents is detected, and improves the efficiency of cell detection;In addition, cell printing nozzle is carrying out cell to spray printing
It is very small to the injury of cell itself in the process;In addition, untargeted cells can discharge simultaneously, the classification of screening one by one is subtracted significantly
Time;In addition, the cell in all spray orifices of photosensitive unit single pass can be used, the position of target cell is rapidly found out with image
It sets, improves the efficiency of screening.
According to the embodiment of the present application, also provide a kind of cell screening method, this method using Fig. 3 cell sorting devices into
Row cell screening.
The cell screening method may include:
Cell is maintained in the spray orifice of cell printing nozzle by step 801, wherein multiple cell printing nozzles are pressed
Array arranging cells printing head array;
Step 802, the type that the cell that each spray orifice is kept is detected using detector;
Step 803, the testing result according to the type of the cell kept to each spray orifice, control the cell printing
Jet array makes the spray orifice for the cell for maintaining predetermined kind spray the cell of the predetermined kind;And
Step 804 collects the predetermined kind sprayed by the spray orifice of the cell printing nozzle using collector
Cell.
In the present embodiment, in the step of detecting the type for the cell that each spray orifice is kept using detector, institute
State the position that detector is moved adjacent to the cell printing jet array from the position far from the cell printing jet array
It sets, in the case where terminating to detect the type for the cell that each spray orifice is kept, the detector is by from close to the cell
The position of printing head array moves away from the position of the cell printing jet array.
In the present embodiment, the predetermined kind sprayed by the spray orifice of the cell printing nozzle is being collected using collector
Cell the step of in, the collector is moved adjacent to the cell from far from the position of the cell printing jet array
The position of printing head array collects the cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle in end
In the case of, the collector is moved away from the cell printing nozzle from the position close to the cell printing jet array
The position of array.
In the present embodiment, the spray orifice is controlled as the sequentially cell ejection by the predetermined kind, alternatively, the spray
Hole is controlled as the cell by the predetermined kind simultaneously and sprays.
The application is described above in association with specific embodiment, it will be appreciated by those skilled in the art that this
A little descriptions are all exemplary, and are not the limitation to the application protection domain.Those skilled in the art can be according to the application
Spirit and principle various variants and modifications are made to the application, these variants and modifications are also within the scope of application.
Claims (10)
1. a kind of cell sorting devices, for being screened to different types of cell, which is characterized in that the cell sorting devices
Have:
Cell printing jet array is arranged by multiple cell printing nozzles by array, each cell printing nozzle
Spray orifice cell can be kept and be sprayed;
Detector detects the type for the cell that each spray orifice is kept;
Controller, the testing result of the type for the cell that each spray orifice is kept according to the detector, described in control
Cell printing jet array makes the spray orifice for the cell for maintaining predetermined kind spray the cell of the predetermined kind;And
Collector collects the cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle.
2. cell sorting devices as described in claim 1, which is characterized in that
At least one of the detector and the collector are removable.
3. cell sorting devices as claimed in claim 2, which is characterized in that
In the case where detecting the type for the cell that each spray orifice is kept using detector, the detector is by from far from institute
The position for stating cell printing jet array is moved adjacent to the position of the cell printing jet array,
In the case where terminating to detect the type for the cell that each spray orifice is kept, the detector is by from close to the cell
The position of printing head array moves away from the position of the cell printing jet array.
4. cell sorting devices as claimed in claim 2, which is characterized in that
In the case where collecting the cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle using collector, institute
State the position that collector is moved adjacent to the cell printing jet array from the position far from the cell printing jet array
It sets,
In the case where terminating to collect the cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle, the collection
Device is moved away from the position of the cell printing jet array from the position of the close cell printing jet array.
5. cell sorting devices as described in claim 1, which is characterized in that
The controller controls the spray orifice and sequentially sprays the cell of the predetermined kind,
Or
The controller controls the spray orifice and simultaneously sprays the cell of the predetermined kind.
6. cell sorting devices as described in claim 1, which is characterized in that the cell sorting devices also have:
Cell solution reservoir is used to accommodate solution containing cell, and the solution is injected into the cell printing nozzle
Array.
7. a kind of cell screening method, for being screened to different types of cell, which is characterized in that the cell screening method
Have:
Cell is maintained in the spray orifice of cell printing nozzle, wherein multiple cell printing nozzles press array arranging cells
Printing head array;
The type for the cell that each spray orifice is kept is detected using detector;
According to the testing result of the type of the cell kept to each spray orifice, the cell printing jet array is controlled, is made
The spray orifice for maintaining the cell of predetermined kind sprays the cell of the predetermined kind;And
The cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle is collected using collector.
8. cell screening method as claimed in claim 7, which is characterized in that
In the step of detecting the type for the cell that each spray orifice is kept using detector, the detector is by from far from institute
The position for stating cell printing jet array is moved adjacent to the position of the cell printing jet array,
In the case where terminating to detect the type for the cell that each spray orifice is kept, the detector is by from close to the cell
The position of printing head array moves away from the position of the cell printing jet array.
9. cell screening method as claimed in claim 7, which is characterized in that
In the step of collecting the cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle using collector, institute
State the position that collector is moved adjacent to the cell printing jet array from the position far from the cell printing jet array
It sets,
In the case where terminating to collect the cell of the predetermined kind sprayed by the spray orifice of the cell printing nozzle, the collection
Device is moved away from the position of the cell printing jet array from the position of the close cell printing jet array.
10. cell screening method as claimed in claim 7, which is characterized in that
The spray orifice is controlled as the sequentially cell by the predetermined kind and sprays,
Or
The spray orifice is controlled as the cell by the predetermined kind simultaneously and sprays.
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CN201710041720.6A CN108330065A (en) | 2017-01-20 | 2017-01-20 | Cell screening device and cell screening method based on cell printing nozzle array |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN112574851A (en) * | 2019-09-30 | 2021-03-30 | 上海傲睿科技有限公司 | Single cell screener, screening assembly, screening method and application |
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