CN204824901U - A mix dynamic electricity micro -fluidic chip device for declining size target is controlled - Google Patents
A mix dynamic electricity micro -fluidic chip device for declining size target is controlled Download PDFInfo
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- CN204824901U CN204824901U CN201520237286.5U CN201520237286U CN204824901U CN 204824901 U CN204824901 U CN 204824901U CN 201520237286 U CN201520237286 U CN 201520237286U CN 204824901 U CN204824901 U CN 204824901U
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Abstract
The utility model provides a mix dynamic electricity micro -fluidic chip device for declining size target is controlled, characterized by include micro -fluidic chip (1), micro -injection pump (2), function waveform generator (3), microscope (4), CCD (5), computer (6). Characterized by is through changing the contained angles between the different reposition of redundant personnel microchannels of micro -fluidic chip, the length width of business turn over appearance microchannel and the separation enrichment that not unidimensional little target was accomplished to the degree of depth, and this device is applicable to mark separation, the enrichment of not unidimensional little target or catches etc. And controls, can be the in succession swift not unidimensional separation enrichment of target a little of realization.
Description
Technical field:
The utility model relates to the dynamic electricity manipulation of micro-dimension target, and particularly electric micro flow control chip device is moved in a kind of mixing for manipulating micro-dimension target.
Background technology:
To the manipulation of micro-dimension target, especially to the catching of target cell in physiological fluid, enrichment or separation etc., the early diagnosis and therapy of disease or the design of medicine and side effect are controlled all have potential significance.Such as from the research of (as blood, urine etc.) Direct Acquisition cancer cells clinical sample, because in peripheral blood, the number of circulating tumor cell is less, usually need to catch or be further analyzed again after enrichment.
In the research that current employing direct method is carried out, a large amount of research report is the CellSearch (Veridex of application commercialization, LLC) draw, it is a kind of circulating tumor cell concentrating platforms based on affinity, by being loaded with the ferrofluid enrichment cycles tumour cell of anti-signal transduction factor (EpCAM) antibody.CellSearch platform has 5 significantly deficiencies: 1. instrument and expensive reagents; 2. the consuming time and complicated operation of sample preparation; 3. sample is fixed in small test tube, hinders the in-vivo analysis of circulating tumor cell; 4. depend on EpCAM to express, can false negative result be caused: namely EpCAM expression of results is variable in epithelium tumor; 5. because Benign Epithelial cell expressing EpCAM is also captured, thus cause false positive results.Recently, the circulating tumor cell enriching method based on EpCAM affinity is combined with micro-fluidic chip by people, develops a class circulating tumor cell and catches chip.Although this platform can catch circulating tumor cell alive, its inefficiency (~ 1 hour/sample), and the inevitable equally limitation based on EpCAM method.People there was reported a kind of based on size instead of the circulating tumor cell capture platform based on EpCAM affinity, and it as strainer with parylene-C microporous membrane, is different from other hemocytes according to the size of circulating tumor cell thus is caught.But this millipore filter has 4 obvious shortcomings: 1. it depends on sample and fixes, hinder the research to circulating tumor cell of living; 2. fixing microwell array cannot regulate in real time according to the density of different blood sample and viscosity, affects the screening to different sample; 3., owing to there being the close white corpuscle of part size to be captured simultaneously, cause unnecessary background, and make enrichment result undesirable; 4. process a large amount of sample may result in blockage, therefore dilution or Centrifuge A sample is needed before filtering, to reduce sample volume and cell concentration, research on DEP chip mainly concentrates on the effect of dielectrophoretic force to cell, such as, Becker etc. determine the dielectricity of metastatic breast cancer cell in rotating electric field, achieve the separation of breast cancer cell in serum; Li and Doh etc. utilize parallel pole array, achieve viable yeast bacterium and are separated with extremely saccharomycetic; Cheung etc. devise the dielectrophoresis chip with three-diemsnional electrode, are separated the red corpuscle through different treatment; Xu Yi etc. propose a kind of array of two-dimensional electrode structure to electrode DEP chip, adopt go forward one by one spacing to electrod-array, increase positive dielectrophoresis force effective range in the duct, achieve the separation to cell sample in current system and enrichment.But play the effect of dielectrophoretic force, require that experiment is carried out in low conductivity medium.And there is the level of conductivity higher (~ 1S/m) of most of physiological fluids (comprising blood, white corpuscle liquid, urine etc.) of circulating tumor cell, this just needs to carry out pre-treatment to sample, regulates specific conductivity to lower level (~ 0.01S/m).The Common advantages of these methods is without the need to carrying out surperficial immune modification and fluorescent mark to target cell; Weak point is, on the one hand the process of sample is likely caused to loss or the dilution of target cell, reduces detection sensitivity; Be difficult to the feature playing other galvanic action on the one hand, limit the use range of method.
Therefore for the deficiencies in the prior art, need to invent a kind of mixing that can be used in the manipulation of micro-dimension target and move electric micro flow control chip device.
Summary of the invention:
In order to overcome the consuming time and shortcomings such as complicated operation of the instrument of existing micro-dimension target tripping device and expensive reagents, sample preparation, improve separation efficiency and experiment circulation ratio, simplify apparatus, the utility model provides a kind of mixing for the manipulation of micro-dimension target to move electric micro flow control chip device.
Technical solution of the present utility model is as follows:
An electric micro flow control chip device is moved in mixing for the manipulation of micro-dimension target, it is characterized in that comprising micro-fluidic chip (1), micro-injection pump (2), function waveform generator (3), microscope (4), CCD (5), computer (6).Wherein, function waveform generator (3) is connected with micro-fluidic chip (1); Micro-injection pump (2) is connected with micro-fluidic chip (1); Micro-fluidic chip (1) is placed in (4) on microscope; Microscope is connected with CCD (5); CCD (5) is connected with computer (6).
(1) micro-fluidic chip (1) comprises the glass substrate (101) having deposited microelectrode and the PDMS substrate (102) preparing microchannel, injection port (103), shunting microchannel (104 ~ 106), sample introduction microchannel (110) and outlet (111 ~ 113) are all on the PDMS substrate (102) preparing microchannel, and the glass substrate having deposited microelectrode and the PDMS substrate bonding preparing microchannel are integrally.
(2) function waveform generator one end is connected with microelectrodes point (108); The other end is connected with microelectrodes point (109), voltage range 2V ~ 20V, range of frequency 100kHz ~ 20MHz, bias range-1V ~ 1V.
(3) flow velocity of micro-injection pump (2) is 0.01 μ Lmin
-1~ 1 μ Lmin
-1, microsyringe is connected with injection port (103) by rubber hose.
Preferably, Ti-Au-Ti (107) the three-layer sandwich type structure that Ti (1071), the Au (1072) of described microelectrode to be each layer thickness be 10nm ~ 50nm, Ti (1073) form; It is of a size of: electrode length is 0.5mm ~ 10mm, and electrode width is 20 μm ~ 200 μm, and adjacent electrode gap width is 20 μm ~ 200 μm.
Preferably, described micro-fluidic chip shunts the angle of microchannel (104) and shunting microchannel (105) and shunting microchannel (106) and the variable angle scope 1 ° ~ 90 ° shunting microchannel (105).
Preferably, sample introduction microchannel (110) length of described micro-fluidic chip can be 10mm ~ 40mm, the degree of depth can reach 20 μm ~ 1000 μm, width can be 20 μm ~ 10000 μm, (104,106) length can be 1mm ~ 30mm in shunting microchannel, the degree of depth can be 10 μm ~ 1000 μm, width can be 10 μm ~ 10000 μm, and microchannel (105) length can be 1mm ~ 30mm, the degree of depth can reach 10 μm ~ 1000 μm and width can reach 10 μm ~ 10000 μm in shunting.
Preferably, described microelectrode utilizes electron beam transpiration legal system standby, can in high-conductivity solution long-term steady operation.
Accompanying drawing illustrates:
Fig. 1 is that electric micro flow control chip device structured flowchart is moved in the mixing of the utility model micro-dimension target manipulation;
Fig. 2 is the utility model microfluidic chip structure vertical view;
Fig. 3 is Ti-Au-Ti sandwich microelectrode sectional view;
Fig. 4 is micro-dimension target mixing dynamic electricity manipulation schematic diagram;
Fig. 5 is the dynamic electric manipulation result schematic diagram of micro-dimension target mixing.
101: the glass substrate 102 having deposited microelectrode: the PDMS substrate 103 preparing microchannel: injection port 104 ~ 106: shunting microchannel 107:Ti-Au-Ti sandwich electrode 108,109: microelectrodes point 110: sample introduction microchannel 111 ~ 113: outlet
2: micro-injection pump 3: function waveform generator 4: microscope 5:CCD6: computer
1071: metal Ti 1072: metal A u1073: metal Ti
Embodiment:
Below in conjunction with embodiment and accompanying drawing, the utility model is described in further detail, but should not limit protection domain of the present utility model with this.
Embodiment 1
Consult Fig. 1 and Fig. 2, the utility model is that electric micro flow control chip device is moved in a kind of mixing for the manipulation of micro-dimension target, and its formation comprises: micro-fluidic chip (1), micro-injection pump (2), function waveform generator (3), microscope (4), CCD (5), computer (6).Wherein, function waveform generator (3) is connected with micro-fluidic chip (1); Micro-injection pump (2) is connected with micro-fluidic chip (1); Micro-fluidic chip (1) is placed on microscope; Microscope (4) is connected with CCD (5); CCD (5) is connected with computer (6).
(1) micro-fluidic chip (1) comprises the glass substrate (101) having deposited microelectrode and the PDMS substrate (102) preparing microchannel, injection port (103), shunting microchannel (104 ~ 106), sample introduction microchannel (110) and outlet (111 ~ 113) are all on the PDMS substrate (102) preparing microchannel, and the glass substrate having deposited microelectrode and the PDMS substrate bonding preparing microchannel are integrally.
(2) function waveform generator (being set to square wave) one end is connected with microelectrodes point (108); The other end is connected with microelectrodes point (109).
(3) flow velocity of micro-injection pump (2) is 0.1 μ Lmin
-1, microsyringe is connected with injection port (103) by rubber hose.
Described micro-fluidic chip sample introduction microchannel (110) length, the degree of depth, width be respectively 35mm, 100 μm, 1000 μm, outlet microchannel (104,106) length, the degree of depth and width be respectively 20mm, 100 μm, 800 μm, outlet microchannel (105) length, the degree of depth and width be respectively 25mm, 100 μm, 300 μm.
The angle of described micro-fluidic chip shunting microchannel (104) and shunting microchannel (105) is all 40 ° with the angle angle shunted microchannel (106) and shunt microchannel (105).
Described microelectrode is Ti-Au-Ti three-layer sandwich type structure, and it is of a size of: electrode length 2.5mm, upper/lower electrode width 100 μm, central electrode width 50 μm, and Ti-Au-Ti layer is 30nm, and adjacent electrode gap width is 125 μm.Refer to Fig. 3.
Working process of the present utility model comprises:
1. open micro-injection pump (2), flow velocity is 0.1 μ Lmin
-1, open function waveform generator (3), be set to square wave, apply voltage 14V, frequency 100kHz, bias voltage 0.3V, open computer (6) etc.
2. micro-fluidic chip (1) is placed in microscope (4), regulates focusing knob to computer to occur clear picture.
3. inject 10 μm and 25 μm of polystyrene microsphere suspensions, function waveform generator (3) applies electric field, after 15s, substantially the separation of two kinds of microballoons can be realized, 25 μm of microballoons are captured on the medullary ray of central electrode (Fig. 5, because electrode blocks therefore invisible), flow out from shunting microchannel (105), 10 μm of polystyrene microspheres are captured in electrode gap and flow out from shunting microchannel (104,106), thus reach separation and concentration.Refer to Fig. 4,5.
Embodiment 2
The other the same as in Example 1, difference is, the angle that micro-fluidic chip goes out sample microchannel (104) and goes out sample microchannel (105) is 60 ° with the angle going out sample microchannel (106) and go out sample microchannel (105), electrode length 3.5mm.
Claims (4)
1. an electric micro flow control chip device is moved in the mixing for the manipulation of micro-dimension target, it is characterized in that comprising micro-fluidic chip (1), micro-injection pump (2), function waveform generator (3), microscope (4), CCD (5), computer (6); Wherein, function waveform generator (3) is connected with micro-fluidic chip (1); Micro-injection pump (2) is connected with micro-fluidic chip (1); Micro-fluidic chip (1) is placed in (4) on microscope; Microscope is connected with CCD (5); CCD (5) is connected with computer (6);
(1) micro-fluidic chip (1) comprises the glass substrate (101) having deposited microelectrode and the PDMS substrate (102) preparing microchannel, injection port (103), shunting microchannel (104 ~ 106), sample introduction microchannel (110) and outlet (111 ~ 113) are all on the PDMS substrate (102) preparing microchannel, and the glass substrate having deposited microelectrode and the PDMS substrate bonding preparing microchannel are integrally;
(2) function waveform generator one end is connected with microelectrodes point (108); The other end is connected with microelectrodes point (109), voltage range 2V ~ 20V, range of frequency 100kHz ~ 20MHz, bias range-1V ~ 1V;
(3) flow velocity of micro-injection pump (2) is 0.01 μ Lmin
-1~ 1 μ Lmin
-1, microsyringe is connected with injection port (103) by rubber hose.
2. electric micro flow control chip device is moved in the mixing for the manipulation of micro-dimension target according to claim 1, it is characterized in that, Ti-Au-Ti (107) the three-layer sandwich type structure that Ti (1071), the Au (1072) of microelectrode to be each layer thickness be 10nm ~ 50nm, Ti (1073) form, it is of a size of: electrode length is 0.5mm ~ 10mm, electrode width is 20 μm ~ 200 μm, and adjacent electrode gap width is 20 μm ~ 200 μm.
3. electric micro flow control chip device is moved in the mixing for the manipulation of micro-dimension target according to claim 1, it is characterized in that, sample introduction microchannel (110) length of micro-fluidic chip can be 10mm ~ 40mm, the degree of depth can reach 20 μm ~ 1000 μm, width can be 20 μm ~ 10000 μm, shunting microchannel (104, 106) length can be 1mm ~ 30mm, the degree of depth can be 10 μm ~ 1000 μm, width can be 10 μm ~ 10000 μm, shunting microchannel (105) length can be 1mm ~ 30mm, the degree of depth can reach 10 μm ~ 1000 μm and width can reach 10 μm ~ 10000 μm.
4. electric micro flow control chip device is moved in the mixing for the manipulation of micro-dimension target according to claim 1, it is characterized in that, angle and shunting microchannel (106) and the variable angle scope 1 ° ~ 90 ° shunting microchannel (105) of micro-fluidic chip shunting microchannel (104) and shunting microchannel (105).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106881160A (en) * | 2017-05-03 | 2017-06-23 | 山东大学 | A kind of candida albicans bacterium micro-fluidic chip |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106881160A (en) * | 2017-05-03 | 2017-06-23 | 山东大学 | A kind of candida albicans bacterium micro-fluidic chip |
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