CN103805504A - Membrane type separating chip - Google Patents
Membrane type separating chip Download PDFInfo
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- CN103805504A CN103805504A CN201210460005.3A CN201210460005A CN103805504A CN 103805504 A CN103805504 A CN 103805504A CN 201210460005 A CN201210460005 A CN 201210460005A CN 103805504 A CN103805504 A CN 103805504A
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- membrane
- type separating
- membrane type
- separating chips
- collection channel
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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
- C12M45/00—Means for pre-treatment of biological substances
Abstract
The invention discloses a membrane type separating chip. The membrane type separating chip comprises a cover sheet, a substrate and a separating membrane, wherein at least one liquid storing tank and a collecting tank are formed on the cover sheet; a collecting channel is arranged on the substrate; at least one separating member is arranged between the cover sheet and the substrate; the cover sheet, the separating membrane and the substrate are of a sandwich structure; the liquid storing tank is communicated with the collecting channel through the separating membrane; and the collecting channel is communicated with the collecting tank. According to the membrane type separating chip, the cover sheet, the substrate and the separating membrane effectively improve the separating efficiency, and the problems of easy blocking and poor selectivity can be solved.
Description
Technical field
The present invention relates to medical skill, relate in particular to a kind of membrane type separating chips for cellular segregation.
Background technology
Blood, urine and other sample liquid detect the information obtaining and contribute to analysing patient's condition, observe the curative effect, judging prognosis, for preventing disease provides foundation, instruct clinical application and carry out clinic study.Although adopt existing semi-automatic or full automatic analyser to detect in certain degree, but perfect along with the raising of living standards of the people and medical care system, people have had new requirement to it, sooner, more accurate, sample size still less, cost is lower.In order to adapt to people's demand, arise at the historic moment take microelectronic processing technique as the chip lab concept of relying on, it is thought that by scientific circles and industrial community 21 century most important, forefront is one of scientific and technological, in a new revolution of the field guiding such as medical science, chemistry, biology, engineering science.
At present generally adopt centrifugation to realize the cellular segregation in blood, urine and other biological specimens that contains cell, utilize centrifugation isolated cell to need the strict centrifugal speed of controlling, even need under freezing conditions centrifugal for special sample, necessary equipment whizzer or the refrigerated centrifuge price of cellular segregation experiment are simultaneously more expensive, and the shearing force that high speed centrifugation produces easily causes cell rupture.The inapplicable any occasion of tradition centrifugation mode, the open air experiment detect as fast bed is other, field operations equal samples needing fast processing, investigator has proposed the new-type separation method based on chip lab.Based on the micro-filtration structure of chip lab platform processing, as pectination, dam shape or twine shape, separation efficiency, separated volume are limited; Cross flow filter, be difficult for blocking up, but separation efficiency is low, and blood plasma/clear amount is few; Loading microballon filters, and easily stifled, separation efficiency is low, and whole blood needs dilution; Difference effect is filtered, and is difficult for blocking up, and selectivity is good, but blood plasma/clear separation efficiency is low.
Chip lab system, Sample Pretreatment Technique Used is as integral part indispensable in this system, develops relatively slowly, become the bottleneck of whole evolution, restricting the development of biochemical analysis.Existing Sample Pretreatment Technique Used is often realized outward at sheet, mostly exist time-consuming, labour intensity large, be difficult to realize that automatization, precision are poor, sample and the shortcoming such as other biochemical reagents consumptions are large, and be often the major cause of error at measurment.Traditional Sample Pretreatment Technique Used can not meet the needs of chip lab, is necessary to develop a kind of new micro-isolation technique.The microminiaturized biological sample pretreater that utilizes micro-processing technology to make, have that analysis efficiency is high, sample and reagent consumption less, many advantages such as energy consumption is low, integrated level is high.Microminiaturized biological sample preprocessed chip all obtains applying very widely at aspects such as biochemistry detection, drugs evaluation, DNA analysis, cellular segregation and enrichment, medicine preparation and drug conveying, becomes the focus of micro-total analysis system research.
Membrane separation technique utilizes the effects such as selective permeation, pressure difference, concentration difference, potential difference, pore size to realize the separation of fluid or gaseous mixture, reach separation, concentrated, purifying and refining function, there are efficient, energy-saving and environmental protection, molecular level filters and filtration procedure is simple, be easy to the features such as control, therefore membrane separation technique, as the important component part of development Micro biochemical analysis system, has broad application prospects with chemical analysis field biomedical.Design a kind of simple in structure, volume is little, be convenient to integrated tiny segregator, not only there is higher precision, also there is very high reliability, the complete processing of exploitation separating chips and each assembly of microfluid drive system, and system integration technology is by the work that is a challenging meaning.
Summary of the invention
In view of this, be necessary to provide the separation membrane type that a kind of separation efficiency is high, cost is low separating chips.
Membrane type separating chips provided by the invention, comprises cover plate, substrate and separatory membrane.Wherein, cover plate is provided with at least one liquid storage tank and collecting tank; Substrate is provided with collection channel; At least one separatory membrane is arranged between described cover plate and described substrate, wherein, described cover plate, described separatory membrane and described substrate are sandwich structure, and described liquid storage tank is communicated with described collection channel through described separatory membrane, and described collection channel is communicated with described collecting tank.
The present invention also provides a kind of membrane type separating chips, comprises cover plate and substrate, and wherein, cover plate is provided with collecting tank; And substrate is provided with collection channel, separatory membrane and absorbent pad, wherein, described absorbent pad is arranged between described collection channel and described separatory membrane, and described collection channel is communicated with described collecting tank.
Membrane type separating chips in embodiment of the present invention effectively raises separation efficiency by cover plate, substrate and separatory membrane, has solved easily stifled, the bad problem of selectivity.
Accompanying drawing explanation
Fig. 1 is the structure iron of membrane type separating chips in first embodiment of the invention;
Fig. 2 is the structure iron of membrane type separating chips in second embodiment of the invention;
Fig. 3 is the structure iron of membrane type separating chips in third embodiment of the invention;
Fig. 4 is the structure iron of membrane type separating chips in four embodiment of the invention.
Embodiment
Describe embodiments of the invention below in detail, the example of described embodiment is shown in the drawings, and wherein same or similar label represents same or similar element or has the element of identical or similar functions from start to finish.Be exemplary below by the embodiment being described with reference to the drawings, only for explaining the present invention, and can not be interpreted as limitation of the present invention.
In description of the invention, term " interior ", " outward ", " longitudinally ", " laterally ", " on ", orientation or the position relationship of the indication such as D score, " top ", " end " be based on orientation shown in the drawings or position relationship, be only the present invention for convenience of description rather than require the present invention with specific orientation structure and operation, therefore can not be interpreted as limitation of the present invention.
Refer to Fig. 1, Figure 1 shows that the structure iron of membrane type separating chips in first embodiment of the invention.
In the present embodiment, membrane type separating chips, comprising: cover plate 10, substrate 20 and separatory membrane 30.
In the present embodiment, cover plate 10 is provided with liquid storage tank 110 and collecting tank 120, and substrate 20 is provided with collection channel.
In the present embodiment, separatory membrane 30 is arranged between described cover plate 10 and described substrate 20, and wherein, described cover plate 10, described separatory membrane 30 and described substrate 20 are sandwich structure.In the present embodiment, take the multiple sealing means such as mechanical pressing (as screw fixed chip periphery), adhesive seal (as separatory membrane peripheral point glue), lamination sealing (as sealing element), folder thing mould (as high molecular film material hot pressing) to prevent separatory membrane 30 edge seepage hemocytes.
In the present embodiment, described liquid storage tank 110 is communicated with described collection channel through described separatory membrane 30, and described collection channel is communicated with described collecting tank 120.
In the present embodiment, the groove aperture of liquid storage tank 110 bottoms is slightly large, for fixedly separated film 110.
In the present embodiment, described collection channel comprises multiple capillary channels 210 and flow-guiding channel 220.
In the present embodiment, described separatory membrane 30 is arranged between multiple capillary channels 210 of described liquid storage tank 110 and described collection channel.
In the present embodiment, separatory membrane 30 can be monofilm or the combination of multiple film, can be symmetric membrane, asymmetric membrane or composite membrane, can be single-component film or hybrid films, can be natural polymer or synthetic polymer, for example, have cellulose family (as Cellulose diacetate, cellulosetri-acetate, nitrocellulose, cellulose mixture, regenerated cellulose, cellulose acetate propionate, cellulose acetate butyrate, ethyl cellulose, cellulose mixed esters etc.), polyamide-based (as aromatic polyamides class, nylon, aromatic polyamides hydrazides, Polyphenylene Sulfone paraphenylene terephthalamide, polysulfonamides, fluorinated polyimide, polyacrylamide etc.), aromatic heterocycle class (polybenzimidazole, polybenzimidazole ketone, polypiperazine-amide, polyimide etc.), polysulfones is (as polysulfones, polyethersulfone, polyether sulphone, Poly-s 179, polyarylsulphone, SPSF, polysulfonamides etc.), polyolefins is (as polyvinyl alcohol, polyethylene, polypropylene, polystyrene, polyacrylonitrile, polyacrylic acid, poly-tetramethyl-amylene, polyvinylpyrrolidone etc.), silicone rubber kinds is (as polydimethylsiloxane, poly-trimethylammonium silica propine, polyvinyl trimethyl silane etc.), fluoro containing polymers is (as poly-perfluorinated sulfonic acid, polyvinylidene difluoride (PVDF), tetrafluoroethylene etc.), other are (as terylene, polycarbonate, polyelectrolyte complex compound etc.), mineral membrane is (as ceramic membrane, metallic membrane, metal oxide film, glass, glass, zeolite, inorganic macromolecule material etc.).
In the present embodiment, described separatory membrane 30 is provided with multiple fenestra (not shown), as cell barrier film, by blood, urine and other biological specimens that contains cell be separated into can see through fenestra material (as blood plasma/clear, urine, sample liquid) and can not be through the material (as cell) of fenestra, prevent that the blood plasma that caused by cell/clear, urine, sample liquid from polluting, isolated blood plasma/clear, urine, sample liquid can be used for biochemical indicator detection, antibody test, hormone test etc., and isolated cell can be used for detection of nucleic acids, protein detection etc.
In the present embodiment, the relation of the maximum diameter of hole dc of described fenestra and the volume V of required entrapped cell, the long-pending A of cell surface is: d
c=(4V/A) { 1+ (16 π/3) V
2/ A
3+ ..., the relation of the aperture d of sample flow Q and described fenestra is: Q ∝ d
4.
In the present embodiment, separatory membrane aperture should consider according to required entrapped cell size, flow velocity, separating effect etc.Calculating according to formula the minimum-value aperture that HRBC can pass through is 2.5 microns, so blood, urine RBC separatory membrane aperture are in 0.05-2.5 micrometer range, if be less than 0.05 micron, protein, mixtinite and similar substance in blood, urine are likely blocking microporous, if and be greater than 2.5 microns, red corpuscle deformation behavior can make its by separate fenestra do not reach separating effect; When membrane type separating chips is used for other cells, calculate according to formula the minimum-value aperture that cell can pass through, determine applicable separatory membrane pore diameter range, select optimum aperture in conjunction with flow velocity, separating effect etc., as separating blood, Urinary White Blood Cell, as separated suspension after insect gonad cell SF9 (mean diameter is about 18.3 microns) cell cultures, as separated the suspension after Human umbilical vein endothelial cells HUVEC (mean diameter is about 17 microns) cell cultures, separatory membrane aperture extends to 10 microns or larger.
In the present embodiment, the described flow-guiding channel 220 on described collection channel is communicated with described collecting tank 120.
Refer to Fig. 2, Figure 2 shows that the structure iron of membrane type separating chips in second embodiment of the invention.
In the present embodiment, for fear of the Pore Blocking on separatory membrane 30, further improve separation efficiency, reduce sample size, on cover plate 10, increased a liquid storage tank 110, and a corresponding separatory membrane 30.
In the present embodiment, two liquid storage tanks 30 are communicated with by connecting passage 140.
In the present embodiment, stepped the arranging of multiple capillary channels 210 realized and the contacting of separatory membrane 30 maximum areas as far as possible.
Refer to Fig. 3, Figure 3 shows that the structure iron of membrane type separating chips in third embodiment of the invention.
In the present embodiment, comprise liquid storage tank 110 and waste liquid pool 130 on cover plate 10, wherein, described waste liquid pool 130 is communicated with described liquid storage tank 110 by connecting passage 140.
In the present embodiment, separatory membrane 30 is positioned at liquid storage tank 110 and waste liquid pool 130 belows.
Therefore, when sample separation liquid to be separated flows, produce shearing force on separatory membrane 30 surfaces, reduced the accumulation of cake layer or gel coat, filtration velocity is stable.
Refer to Fig. 4, Figure 4 shows that the structure iron of membrane type separating chips in four embodiment of the invention.
In the present embodiment, membrane type separating chips comprises: cover plate 10 and substrate 20.
In the present embodiment, cover plate 10 is provided with collecting tank 120.
In the present embodiment, substrate 20 is provided with collection channel, separatory membrane 240 and absorbent pad 230, and wherein, described absorbent pad 230 is arranged between described collection channel and described separatory membrane 240, and described collection channel is communicated with described collecting tank 120.
In the present embodiment, described separatory membrane 240 is vesicular structure.
Described collection channel comprises multiple capillary channels 210 and flow-guiding channel 220.
In the present embodiment, described separatory membrane 240 sees through described absorbent pad 230 and is communicated with described multiple capillary channels 210, and described flow-guiding channel 220 is communicated with described collecting tank 120.
Membrane type separating chips in embodiment of the present invention effectively raises separation efficiency by cover plate 10, substrate 20 and separatory membrane 30, has solved easily stifled, the bad problem of selectivity.
Although the present invention is described with reference to current preferred embodiments; but those skilled in the art will be understood that; above-mentioned preferred embodiments is only used for illustrating the present invention; not be used for limiting protection scope of the present invention; any within the spirit and principles in the present invention scope; any modification of doing, equivalent replacement, improvement etc., within all should being included in the scope of the present invention.
Claims (11)
1. a membrane type separating chips, comprising:
Cover plate, is provided with at least one liquid storage tank and collecting tank;
Substrate, is provided with collection channel;
At least one separatory membrane, be arranged between described cover plate and described substrate, wherein, described cover plate, described separatory membrane and described substrate are sandwich structure, described liquid storage tank is communicated with described collection channel through described separatory membrane, and described collection channel is communicated with described collecting tank.
2. membrane type separating chips as claimed in claim 1, is characterized in that, described collection channel comprises multiple capillary channels and flow-guiding channel.
3. membrane type separating chips as claimed in claim 2, is characterized in that, described separatory membrane is arranged between described liquid storage tank and described collection channel.
4. membrane type separating chips as claimed in claim 3, is characterized in that, described separatory membrane is porous medium, comprises multiple fenestras.
5. membrane type separating chips as claimed in claim 4, is characterized in that, the maximum diameter of hole d of described fenestra
cwith the volume V of required entrapped cell, the relation of the long-pending A of cell surface be: d
c=(4V/A) { 1+ (16 π/3) V
2/ A
3+ ..., the relation of the aperture d of sample flow Q and described fenestra is: Q ∝ d
4.
6. membrane type separating chips as claimed in claim 2, is characterized in that, the described flow-guiding channel on described collection channel is communicated with described collecting tank.
7. membrane type separating chips as claimed in claim 1, is characterized in that, also comprises waste liquid pool and connecting passage, and wherein, described waste liquid pool is communicated with described liquid storage tank by connecting passage.
8. a membrane type separating chips, comprising:
Cover plate, is provided with collecting tank; And
Substrate, is provided with collection channel, separatory membrane and absorbent pad, and wherein, described absorbent pad is arranged between described collection channel and described separatory membrane, and described collection channel is communicated with described collecting tank.
9. membrane type separating chips as claimed in claim 8, is characterized in that, described separatory membrane is vesicular structure.
10. membrane type separating chips as claimed in claim 8, is characterized in that, described collection channel comprises multiple capillary channels and flow-guiding channel.
11. membrane type separating chips as claimed in claim 10, is characterized in that, described separatory membrane sees through described absorbent pad and is communicated with described multiple capillary channels, and described flow-guiding channel is communicated with described collecting tank.
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CN201210460005.3A CN103805504B (en) | 2012-11-15 | 2012-11-15 | Membrane type separating chips |
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CN201210460005.3A CN103805504B (en) | 2012-11-15 | 2012-11-15 | Membrane type separating chips |
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CN103805504A true CN103805504A (en) | 2014-05-21 |
CN103805504B CN103805504B (en) | 2016-01-20 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105994250A (en) * | 2016-05-19 | 2016-10-12 | 电子科技大学 | Method for adding or removing low-temperature protective agent for cells on basis of microfluidic and membrane separation techniques |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2010009415A1 (en) * | 2008-07-18 | 2010-01-21 | Canon U.S. Life Sciences, Inc. | Methods and systems for microfluidic dna sample preparation |
WO2011112023A2 (en) * | 2010-03-12 | 2011-09-15 | 주식회사 나노엔텍 | Chip for separating blood cells |
CN102375055A (en) * | 2010-08-19 | 2012-03-14 | 中国人民解放军军事医学科学院微生物流行病研究所 | Multiplex detection immune chromatography chip |
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2012
- 2012-11-15 CN CN201210460005.3A patent/CN103805504B/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010009415A1 (en) * | 2008-07-18 | 2010-01-21 | Canon U.S. Life Sciences, Inc. | Methods and systems for microfluidic dna sample preparation |
WO2011112023A2 (en) * | 2010-03-12 | 2011-09-15 | 주식회사 나노엔텍 | Chip for separating blood cells |
CN102375055A (en) * | 2010-08-19 | 2012-03-14 | 中国人民解放军军事医学科学院微生物流行病研究所 | Multiplex detection immune chromatography chip |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105994250A (en) * | 2016-05-19 | 2016-10-12 | 电子科技大学 | Method for adding or removing low-temperature protective agent for cells on basis of microfluidic and membrane separation techniques |
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Granted publication date: 20160120 Termination date: 20171115 |