CN102350379A - Micro fluid control whole blood preprocessing chip based on naturally-deposited filling column - Google Patents
Micro fluid control whole blood preprocessing chip based on naturally-deposited filling column Download PDFInfo
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- CN102350379A CN102350379A CN2011101854763A CN201110185476A CN102350379A CN 102350379 A CN102350379 A CN 102350379A CN 2011101854763 A CN2011101854763 A CN 2011101854763A CN 201110185476 A CN201110185476 A CN 201110185476A CN 102350379 A CN102350379 A CN 102350379A
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Abstract
The invention provides a micro fluid control whole blood preprocessing chip based on a naturally-deposited filling column. The chip consists of an upper layer and a lower layer, wherein the upper layer is a cover sheet with a microstructure, the lower layer is a flat substrate, and the upper layer and the lower layer are in butt joint to form a fluid channel or a cavity chamber. micro-beads are deposited in the channel naturally by the evaporation of a solution in bead plasma to form a filling column. The naturally-deposited filling column is used as a sieving medium for whole blood preprocessing, when whole blood passes through the filling column, blood cells are intercepted, but blood plasma penetrates through the filling column to realize simple and quick whole blood preprocessing, and the acting force of capillaries provides driving force for fluid. The chip is easy to assemble, operate and carry, and has an application prospect in real-time inspection.
Description
Technical field
The present invention relates on micro-fluidic chip, carry out the whole blood preliminary treatment based on the packed column that deposits naturally; With the driving force of capillary force, realize simply, the catching of the extraction of the separation of blood plasma, whole blood amplifying nucleic acid and specific haemocyte in the whole blood apace as fluid.
Background technology
Comprise a large amount of biological informations in the blood, can reflect health status and the change of illness state of organism directly or indirectly, important significance arranged clinical.A large amount of interfering materials can influence the result of blood testing in the blood, and the whole blood preliminary treatment is the successful key of blood analysis.Yet traditional whole blood preliminary treatment is to need special devices, and by professional person operation, the result of detection needs the time of several hours and even several days to obtain.
Microflow control technique is as a kind of novel technology, has that amount of samples is few, analysis time short, different operating unit integrated characteristics flexibly.Some research groups begin exploration and utilize microflow control technique to realize whole blood preliminary treatment such as separating plasma, nucleic acid extraction etc.Landers research group utilizes the structure in cofferdam or photopolymerisable method that the nucleic acid extraction medium is fixed in the microchannel, carries out the extraction of whole blood amplifying nucleic acid.Heath research group copy blood in vivo the Zweifach-Fung principle of Capillary Flow made up micro-fluidic separating plasma platform.Ahn research group pours into microballon the packed column that is used for separation of whole blood in advance with preparation in the microchannel of little dam qualification.It is complicated that but the limitation of these methods is facture of microchip, and cost is high, needs the professional to operate.
The present invention has designed a kind of micro-fluidic whole blood preprocessed chip based on the packed column that deposits naturally.It is packed column with deposition naturally as the pretreated sieving media of whole blood, capillary force is as the driving force of fluid, avoided external syringe pump to be connected with complicated stream, realization simply, whole blood preliminary treatment fast.The assembling of this chip is simple, easy operating, portable characteristics have shown the potentiality that it is used in real-time test.
Summary of the invention
The invention provides a kind ofly based on the micro-fluidic whole blood preprocessed chip of packed column of deposition naturally, this chip is by two-layer composition up and down, and the upper strata is the cover plate with micro-structural, and lower floor is a flat plate substrate, two-layerly up and down forms fluid passage or chamber through sealing-in.Naturally the packed column of deposition is formed in the micro-structural, and packed column is the evaporation that relies on the solvent in the pearl slurry, and microballon is deposited in the passage naturally.The microballon material of packed column is silica, polystyrene, hydrogel.The said packed column of deposition naturally, pre-configured pearl slurry concentration is 50%-300% (wt/vol), microballon is of a size of 0.5-20 μ m.The length of packed column depends on the volume that adds the pearl slurry, and its length is 1-10mm.
The preparation method of micro-fluidic chip micro-structural is dry etching method, wet etching method, photoetch method.
The material of micro-fluidic chip is glass, polymer, silicon materials, metal.
The flat plate substrate material is glass, polymer, silicon materials, metal.
Capillary force is as the driving force of fluid, and the cover plate or the substrate of micro-fluidic chip need hydrophilicity-imparting treatment.
The method of the cover plate of micro-fluidic chip or substrate hydrophilicity-imparting treatment is chemical modification, UV/ ozone, oxygen plasma.
Micro-fluidic whole blood preprocessed chip based on the packed column that deposits naturally provided by the invention, the packed column of deposition can be tackled the haemocyte in the whole blood naturally, and blood plasma can see through packed column, thus realize the extraction of blood plasma in the whole blood.
Provided by the invention it not only can be used for the separation of whole blood blood plasma based on the micro-fluidic whole blood preprocessed chip of packed column of deposition naturally, and can be used for the extraction of whole blood amplifying nucleic acid and catching of specific haemocyte.
Description of drawings
Fig. 1 analyzes sketch map based on the micro-fluidic whole blood preprocessed chip of the packed column that deposits naturally.
Among the figure: 1 cover plate; 2 substrates, 3 whole bloods; 4 naturally the deposition packed column; The blood plasma of 5 separation.
Fig. 2 extracts figure as a result based on the micro-fluidic whole blood preprocessed chip blood plasma of the packed column that deposits naturally.The tool microscope that is equipped with CCD has write down the blood plasma leaching process.Length of the scale is 500 μ m among the figure.
The specific embodiment
Following embodiment will further explain the present invention, but therefore not limit the present invention.
Embodiment
Chip is by two-layer composition up and down: cover plate and substrate with micro-structural.The making of micro-structural is to utilize optical lithography to make the SU-8 template earlier on the cover plate, then polymer is cast in polymerization forming on the template, has the polymer of micro-structural to peel off from mould the marking at last.Substrate is a plate glass.Cover plate or substrate are used oxygen plasma treatment, make it hydrophilic.Last cover plate and reversible the sealing of substrate form microfluidic channel.The microballon dry powder (silica, polystyrene, hydrogel) of unlike material is scattered in the solvent, is configured to the pearl slurry, its concentration is 50%-300% (wt/vol).Then the pearl slurry of abundant mixing is loaded on the injection port place of microchannel, under the effect of capillary force, siphon gets into microfluidic channel.The introducing amount of pearl slurry has determined the length of the packed column of final making.Leave standstill the solvent evaporation that makes in the pearl slurry afterwards.Along with the evaporation of solvent, microballon is deposited on and forms closely knit packed column in the passage.The droplets of whole blood of 10 μ l is added on injection port, and under the effect of capillary force, blood gets into packed column, and wherein haemocyte is tackled, and blood plasma penetrates packed column.The blood plasma clarification that separates is faint yellow, and showing does not have haemolysis to take place, and does not receive the pollution of microballon.
Claims (6)
1. one kind based on the micro-fluidic whole blood preprocessed chip of packed column of deposition naturally, it is characterized in that: this chip is by two-layer composition up and down, and the upper strata is the cover plate with micro-structural, and lower floor is a flat plate substrate, two-layerly up and down forms fluid passage or chamber through sealing-in.Naturally the packed column of deposition is formed in the micro-structural.Naturally the packed column that deposits, microballon is of a size of 0.5-20 μ m, and pearl slurry concentration is 50%-300% (wt/vol), and its length is 1-10mm.Cover plate or substrate that micro-fluidic chip has micro-structural need hydrophilicity-imparting treatment.
2. according to the said micro-fluidic whole blood preprocessed chip based on the packed column that deposits naturally of claim 1, it is characterized in that: said cover plate with micro-structural is glass, polymer, silicon materials, metal.
3. according to the said micro-fluidic whole blood preprocessed chip based on the packed column that deposits naturally of claim 1, it is characterized in that: said flat plate substrate is glass, polymer, silicon materials, metal.
4. according to the said micro-fluidic whole blood preprocessed chip based on the packed column that deposits naturally of claim 1, it is characterized in that: the microballon material is silica, polystyrene, hydrogel.
5. according to claim 1,2,3 or 4 said micro-fluidic whole blood preprocessed chips based on the packed column that deposits naturally, it is characterized in that: method of hydrophilizing is chemical modification, UV/ ozone, oxygen plasma.
6. according to claim 1,2,3 or 4 said micro-fluidic whole blood preprocessed chips based on the packed column that deposits naturally, it is characterized in that: the micro-structural preparation method on the said cover plate is dry etching method, wet etching method, photoetch method.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011101854763A CN102350379A (en) | 2011-07-04 | 2011-07-04 | Micro fluid control whole blood preprocessing chip based on naturally-deposited filling column |
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| CN2011101854763A CN102350379A (en) | 2011-07-04 | 2011-07-04 | Micro fluid control whole blood preprocessing chip based on naturally-deposited filling column |
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| CN102350379A true CN102350379A (en) | 2012-02-15 |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102773122A (en) * | 2012-08-06 | 2012-11-14 | 苏州汶颢芯片科技有限公司 | Centrifugal microfluidic serum separation chip and preparation method thereof |
| CN103285949A (en) * | 2013-05-27 | 2013-09-11 | 苏州扬清芯片科技有限公司 | Micro-fluidic serum extracting chip |
| CN106483276A (en) * | 2016-09-29 | 2017-03-08 | 大连理工大学 | A kind of optofluidic blood cell micro imaging system based on smart mobile phone |
| CN106574883A (en) * | 2014-03-05 | 2017-04-19 | 赛拉诺斯股份有限公司 | Methods and devices for sample collection and sample separation |
| CN106841591A (en) * | 2017-02-27 | 2017-06-13 | 同昕生物技术（北京）有限公司 | The test card that a kind of capillary force drives |
| CN107362840A (en) * | 2016-05-13 | 2017-11-21 | 李榕生 | Using the micro flow control chip device of PDMS material substrates |
| CN107362841A (en) * | 2016-05-13 | 2017-11-21 | 李榕生 | Easily-disassembled hypotype swine flu multi-channel testing device comprising electromagnetism auxiliary part |
| CN109012773A (en) * | 2018-08-06 | 2018-12-18 | 西北工业大学 | A kind of micro-flow control chip preparation method and functional method of photoinduction infiltration |
| CN109647554A (en) * | 2019-01-11 | 2019-04-19 | 邓治杨 | Hemostasis examination chip and hemostasis examination method |
| CN112098388A (en) * | 2020-08-18 | 2020-12-18 | 上海交通大学 | Preparation method and application for constructing micro-fluidic chip based on silver microsphere monolithic column |
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|---|---|---|---|---|
| CN102773122A (en) * | 2012-08-06 | 2012-11-14 | 苏州汶颢芯片科技有限公司 | Centrifugal microfluidic serum separation chip and preparation method thereof |
| CN103285949A (en) * | 2013-05-27 | 2013-09-11 | 苏州扬清芯片科技有限公司 | Micro-fluidic serum extracting chip |
| CN106574883A (en) * | 2014-03-05 | 2017-04-19 | 赛拉诺斯股份有限公司 | Methods and devices for sample collection and sample separation |
| CN113796860A (en) * | 2014-03-05 | 2021-12-17 | 赛拉诺斯知识产权有限责任公司 | Method and apparatus for sample collection and sample separation |
| CN107362840A (en) * | 2016-05-13 | 2017-11-21 | 李榕生 | Using the micro flow control chip device of PDMS material substrates |
| CN107362841A (en) * | 2016-05-13 | 2017-11-21 | 李榕生 | Easily-disassembled hypotype swine flu multi-channel testing device comprising electromagnetism auxiliary part |
| CN106483276A (en) * | 2016-09-29 | 2017-03-08 | 大连理工大学 | A kind of optofluidic blood cell micro imaging system based on smart mobile phone |
| CN106841591A (en) * | 2017-02-27 | 2017-06-13 | 同昕生物技术（北京）有限公司 | The test card that a kind of capillary force drives |
| CN109012773A (en) * | 2018-08-06 | 2018-12-18 | 西北工业大学 | A kind of micro-flow control chip preparation method and functional method of photoinduction infiltration |
| CN109012773B (en) * | 2018-08-06 | 2021-01-05 | 西北工业大学 | Preparation method and functionalization method of micro-fluidic chip for photoinduced infiltration |
| CN109647554A (en) * | 2019-01-11 | 2019-04-19 | 邓治杨 | Hemostasis examination chip and hemostasis examination method |
| CN112098388A (en) * | 2020-08-18 | 2020-12-18 | 上海交通大学 | Preparation method and application for constructing micro-fluidic chip based on silver microsphere monolithic column |
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Application publication date: 20120215 |