CN105400679A - Micro-fluidic chip device used for cell separation - Google Patents
Micro-fluidic chip device used for cell separation Download PDFInfo
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- CN105400679A CN105400679A CN201410457958.3A CN201410457958A CN105400679A CN 105400679 A CN105400679 A CN 105400679A CN 201410457958 A CN201410457958 A CN 201410457958A CN 105400679 A CN105400679 A CN 105400679A
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Abstract
The invention discloses a micro-fluidic chip device used for cell separation. The device comprises a centrifugal rotor, chip structures, and chip covers. The centrifugal rotor is provided with at least one chip placement groove and at least two liquid storage tanks, wherein the liquid storage tanks communicate with through-holes formed in the chip placement groove. Each chip structure comprises two chips bonded into one body and a filter screen arranged between the two chips, wherein the inner chip is provided with fluid inlets which communicate with microfluid channels, and the outer chip is provided with a fluid outlet A, which communicate with microfluid channels in the inner chip, and a fluid outlet B, which communicate with microfluid channels in the outer chip. The chip structures are fixed in the chip placement groove. The fluid inlet communicates with the liquid storage tanks through through-holes, and the fluid outlet A and the fluid outlet B communicate with outlets arranged in the chip covers, respectively. A centrifugation method is used in the micro-fluidic chip device used for cell separation, and cell separation is performed through two-layer chips together with a filter screen. The device has advantages of low prices and easy operation.
Description
Technical field
The present invention relates to a kind of micro flow control chip device for cellular segregation, belong to micro-fluidic field.
Background technology
Fetal nucleated red blood (fetalnucleatedredbloodcell, FNRBC) is the red corpuscle of the fetal origin existed in the middle of maternal blood.Compared with the cell of other the fetal origin existed in maternal blood, FNRBC is had complete Fetal genome, has multiple Specific marker to be convenient to be separated, easily recognized by form or foetal haemoglobin, namely get rid of from parent disappearance in pregnancy duration sustainable existence, one month postpartum the impact of gestation last time, so, FNRBC better in antenatal diagnosis, thus can determine the healthy state of fetus.With traditional methods for prenatal diagnosis as fine hair biopsy, amniocentesis, compared with skin Umbilical blood art etc., utilize FNRBC to carry out diagnosis only to take a morsel peripheral blood from pregnant woman, this is a kind of detection method of Noninvasive, the complication such as the infection of traditional method, miscarriage can be avoided, the detrimentally affect to pregnant woman and fetus can be reduced to greatest extent, so be a kind of methods for prenatal diagnosis having very much using value.But FNRBC is comparatively small amt in pregnant woman blood, usually only have tens in every milliliter of blood.So be separated very difficult.
At present, the detection of FNRBC will first be carried out enrichment by density gradient centrifugation, Fluorescence-activated cell sorting, magnetic field activating cells separating method, micrurgy partition method or selecting cell culture method etc. and analyzes.These method complex operations, easily make mistakes, are difficult at clinical application.Therefore, need to provide that a kind of cost is low, simple operation, reaction is fast, integrated level is high cell separation apparatus.
Summary of the invention
The object of this invention is to provide a kind of micro flow control chip device for cellular segregation, can be used for cellular segregation and follow-up immunization analysis, its structure is simple, simple operation, high relative to traditional cell separation technology level of automation, good reliability.
Micro flow control chip device for cellular segregation provided by the present invention, comprises centrifugal rotor, chip structure and chip lid;
Described centrifugal rotor is provided with at least one chip standing groove and at least two liquid storage tanks; Described liquid storage tank is connected with the through hole that described chip standing groove is arranged by passage;
The filter screen that described chip structure comprises laminating all-in-one-piece two panels chip and is arranged in two panels chip, chip described in a slice is designated as inner side chip, and chip described in another sheet is designated as outside chip, and the binding face of chip described in two panels is equipped with microfluidic channel; Described inner side chip is provided with the fluid intake be connected with described microfluidic channel, described outside chip is provided with fluid outlet A and fluid outlet B, described fluid outlet A is connected with the microfluidic channel on the chip of described inner side, and described fluid outlet B is connected with the microfluidic channel on the chip of described outside;
By described chip lid, described chip structure is fixed in described chip standing groove; Described fluid intake is connected with described liquid storage tank by described through hole, and the outlet that described fluid outlet A covers setting with described chip respectively with described fluid outlet B is connected.
In above-mentioned micro flow control chip device, described centrifugal rotor is provided with several symmetrically arranged described chip standing grooves;
Each described chip standing groove side arranges two described liquid storage tanks.
In above-mentioned micro flow control chip device, described centrifugal rotor is provided with two symmetrically arranged described chip standing grooves.
In above-mentioned micro flow control chip device, described chip is perspex layer, and the microfluidic channel that it is arranged obtains by the mode of laser sculpture;
Described filter screen is photoresist material dry film, and the micropore on it can set according to specific needs;
The degree of depth of described microfluidic channel is 100 ~ 1000 μm.
In above-mentioned micro flow control chip device, the shape of the microfluidic channel on chip described in two panels is identical, thus forms through fluid channel time two panels perspex layer is fitted mutually.
In above-mentioned micro flow control chip device, be threaded connection and described chip lid and described chip structure are fixed in described chip standing groove, namely through hole is set in the corresponding position, position of described chip lid and described chip structure, and the corresponding position, position on described chip standing groove arranges threaded hole, just described chip lid and chip structure can be fixed on described centrifugal rotor by screw.
In above-mentioned micro flow control chip device, the outlet that described chip covers setting is groove-like, and its centrifuge tube that can connect corresponding capacity can receive the liquid of outflow, and can arrange rubber cradle on groove, to strengthen stopping property.
When the present invention is used for the micro flow control chip device work of cellular segregation, be fixed on whizzer by described centrifugal rotor, liquid injects described liquid storage tank, flows through described chip structure, and the outlet covering setting from described chip flows into centrifuge tube.When using of the present invention, use centrifugal force as motivating force, filter screen described in the cell permeable making diameter little flows out from the described fluid outlet B the chip of outside, the cell that diameter is large then cannot through described filter screen, flow out from the described fluid outlet A the chip of outside, thus realize the object of cellular segregation.
The invention provides the device that a kind of novel mode utilizing continuous flow centrifugation to filter carrys out isolating fetal erythroblast.The core of this device is micro-fluidic chip.Microfluidic chip technology utilizes micro-machined method, biological, chemistry, medical analysis process the elementary operation such as sample preparation, reaction, separation, detection is integrated on the chip of one piece of micro-meter scale, has that cost is low, simple operation, reaction are fast, integrated level advantages of higher.General micro-fluidic chip is in the plane by realizing object to the manipulation of fluid.And sensu lato micro-fluidic chip can have three-dimensional structure, use different microtube structures at different layers, for the thinking realizing cellular segregation and can provide more wide.
The present invention is used for the micro flow control chip device of cellular segregation, can use centrifugal method, add the mode isolated cell of filter screen, have the advantages such as cheap and easy operation with double-layer chip; Meanwhile, apparatus of the present invention eliminate a lot of manual operations, are easy to integrated with subsequent biochemical detection chip.The present invention to promoting the facilitation of cellular segregation and detection, further genralrlization application tool is of great significance.
Accompanying drawing explanation
Fig. 1 is the side-view of the present invention for the micro flow control chip device of cellular segregation.
Fig. 2 is the schematic diagram of the present invention for the micro flow control chip device chips lid of cellular segregation.
Fig. 3 is the schematic diagram of the present invention for centrifugal rotor in the micro flow control chip device of cellular segregation.
Fig. 4 is the schematic diagram of the present invention for the micro flow control chip device chips structure of cellular segregation.
Fig. 5 is that the present invention is for the flow direction schematic diagram in the micro flow control chip device of cellular segregation.
Fig. 6 is the microfluidic channel schematic diagram of the present invention in the micro flow control chip device chips of cellular segregation.
Fig. 7 is the sectional view of the present invention for the micro flow control chip device chips structure of cellular segregation.
In figure, each mark is as follows:
Chip, 8 photoresist material dry films, 9 fluid intakes, 10 fluid outlet A, 11 fluid outlet B, 12 through holes, 13 threaded holes, 14 outlets outside chip, 7 inside 1 centrifugal rotor, 2 chip structures, 3 chip lids, 4 chip standing grooves, 5 liquid storage tanks, 6.
Embodiment
Below in conjunction with accompanying drawing, the present invention will be further described, but the present invention is not limited to following examples.
As shown in Figure 1, for the present invention is used for the micro flow control chip device of cellular segregation, it comprises centrifugal rotor 1, chip structure 2 and chip lid 3.In the present invention, as shown in Figure 3, centrifugal rotor 1 is provided with 2 symmetrical chip standing grooves 4, and each chip standing groove 4 side arranges 2 liquid storage tanks 5, and each liquid storage tank 5 is all connected with the through hole that chip standing groove 4 is arranged by passage.As shown in figs. 4 and 7, chip structure 2 in the present invention comprises inner side chip 6 and the outside chip 7 of laminating all-in-one-piece perspex layer material, and the photoresist material dry film 8 be arranged between inner side chip 6 and outside 7, the thickness of inner side chip 6 and outside chip 7 is 2mm, inner side chip 6 and outside chip 7 are all carved as microfluidic channel by the mode of laser sculpture, its shape is identical, and as shown in Figure 6, the degree of depth is 100 ~ 1000 μm; In the present invention, the thickness of photoresist material dry film 8 is 100 μm, is formed with diameter and is about 10 microns after overexposure and development operation, and spacing is the microwell array of 20 microns.As shown in Figure 6, inner side chip 6 is provided with the fluid intake 9 be connected with microfluidic channel, and outside chip 7 is provided with the fluid outlet A10 communicated with the microfluidic channel on inner side the chip 6 and fluid outlet B11 be connected with the microfluidic channel on outside chip 7.Chip structure 2 is fixed in chip standing groove 4 by chip lid 3 by the present invention, connect particular by such as under type: the corresponding position, position of chip lid 3 and chip structure 2 arranges through hole 12, as shown in Figure 2 and Figure 6, and the corresponding position, position on chip standing groove 4 arranges threaded hole 13, just chip lid 3 and chip structure 2 can be fixed on centrifugal rotor 1 by screw.After chip structure 2 being connected on chip standing groove 4, fluid intake 9 on the chip 6 of inner side is connected with liquid storage tank 5, fluid outlet A10 and fluid outlet B11 are connected with the outlet 14 that chip lid 3 is arranged respectively, and groove-like is arranged in outlet 14, its centrifuge tube that can connect corresponding capacity can receive the liquid of outflow, rubber cradle can be set on groove, to strengthen stopping property.
When using above-mentioned micro flow control chip device isolating fetal erythroblast, the fetus whole blood diluent for centrifugation and phosphoric acid buffer is added respectively in 2 liquid storage tanks 5 be connected with a chip standing groove 4, also fetus whole blood diluent and phosphoric acid buffer is added respectively in symmetrical liquid storage tank 5, then chip structure is loaded on centrifugal rotor, and connect centrifuge tube in the exit of chip lid 3.After centrifugal rotor is fixed on whizzer rotating shaft, carry out centrifugal under the rotating speed of 1000 revs/min, the liquid now in liquid storage tank 5 is entered in chip structure 2 by connecting passage under the action of the centrifugal.Wherein, fetus whole blood diluent enters near centrifugal rotor passage, and phosphoric acid buffer enters outer passage.Originally, two strands of liquid can not contact under the separation of photoresist material dry film 8, but under the influence of centrifugal force, cell againsts photoresist material dry film 8 and flows, when flowing to the local time of micropore, the cell (as white corpuscle, erythroblast) that diameter is larger will be stopped to be continued to flow along inner channel, finally flows out from the left side outlet fluid outlet A10 of outside chip 7.And finally flow out from the right-side outlet fluid outlet B11 below outside chip 7 in the less cell of diameter just enters into outside passage by micropore.Need further to be screened by modes such as fluorescent marks to obtain erythroblast finally by the fetal nucleated red blood of screening and the larger cell of white corpuscle equal diameter.
The structure that the present invention is used for the micro flow control chip device of cellular segregation is simple, have cheap, be easy to the advantages such as processing and operation.Meanwhile, the micro flow control chip device that the present invention is used for cellular segregation also can be used in circulating tumor cell initial stage separation etc., is of great significance at biologic medical context of detection tool promotion micro-total analysis system.
Claims (7)
1. for the micro flow control chip device of cellular segregation, it is characterized in that: it comprises centrifugal rotor, chip structure and chip lid;
Described centrifugal rotor is provided with at least one chip standing groove and at least two liquid storage tanks; Described liquid storage tank is connected with the through hole that described chip standing groove is arranged by passage;
The filter screen that described chip structure comprises laminating all-in-one-piece two panels chip and is arranged in two panels chip, the binding face of chip described in two panels is equipped with microfluidic channel; Chip described in a slice is designated as inner side chip, chip described in another sheet is designated as outside chip, described inner side chip is provided with the fluid intake be connected with described microfluidic channel, described outside chip is provided with fluid outlet A and fluid outlet B, described fluid outlet A is connected with the microfluidic channel on the chip of described inner side, and described fluid outlet B is connected with the microfluidic channel on the chip of described outside;
By described chip lid, described chip structure is fixed in described chip standing groove; Described fluid intake is connected with described liquid storage tank by described through hole, and the outlet that described fluid outlet A covers setting with described chip respectively with described fluid outlet B is connected.
2. micro flow control chip device according to claim 1, is characterized in that: described centrifugal rotor is provided with several symmetrically arranged described chip standing grooves;
Each described chip standing groove side arranges two described liquid storage tanks.
3. micro flow control chip device according to claim 2, is characterized in that: described centrifugal rotor is provided with two symmetrically arranged described chip standing grooves.
4. the micro flow control chip device according to any one of claim 1-3, is characterized in that: described chip is perspex layer;
Described filter screen is photoresist material dry film;
The degree of depth of described microfluidic channel is 100 ~ 1000 μm.
5. the micro flow control chip device according to any one of claim 1-4, is characterized in that: the shape of the microfluidic channel on chip described in two panels is identical.
6. the micro flow control chip device according to any one of claim 1-5, is characterized in that: be threaded connection and described chip lid and described chip structure be fixed in described chip standing groove.
7. the micro flow control chip device according to any one of claim 1-6, is characterized in that: the outlet that described chip covers setting is groove-like.
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| CN201410457958.3A CN105400679B (en) | 2014-09-10 | 2014-09-10 | A kind of micro flow control chip device for cell separation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021120288A1 (en) * | 2019-12-20 | 2021-06-24 | 苏州昊通仪器科技有限公司 | Micro-total analysis chip, chip assembly, and method for preparing single cell sample |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2021120288A1 (en) * | 2019-12-20 | 2021-06-24 | 苏州昊通仪器科技有限公司 | Micro-total analysis chip, chip assembly, and method for preparing single cell sample |
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| CN105400679B (en) | 2017-10-31 |
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