CN103805504B - Membrane type separating chips - Google Patents
Membrane type separating chips Download PDFInfo
- Publication number
- CN103805504B CN103805504B CN201210460005.3A CN201210460005A CN103805504B CN 103805504 B CN103805504 B CN 103805504B CN 201210460005 A CN201210460005 A CN 201210460005A CN 103805504 B CN103805504 B CN 103805504B
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- membrane
- separatory membrane
- collection channel
- cover plate
- type separating
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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
A kind of membrane type separating chips, 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.Membrane type separating chips in the present invention effectively raises separation efficiency by cover plate, substrate and separatory membrane, solves easily stifled, problem that selectivity is bad.
Description
Technical field
The present invention relates to medical skill, particularly relate to a kind of membrane type separating chips for cellular segregation.
Background technology
Blood, urine and other sample liquid detect the information obtained 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 can detect in certain degree, but along with the raising of living standards of the people and the perfect of medical care system, people have had new requirement to it, and sooner, more accurate, sample size less, cost is lower.In order to adapt to the demand of people, be that the chip lab concept of relying on is arisen at the historic moment with microelectronic processing technique, by scientific circles and industrial community, it is thought that 21 century most important, forefront is one of scientific and technological, guide the revolution that new in fields such as medical science, chemistry, biology, engineering sciences.
Generally adopt at present centrifugation realize blood, urine and other contain cellular segregation in the biological specimen of cell, utilize centrifugation isolated cell strictly need control centrifugal speed, special sample is even needed under freezing conditions centrifugal, 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 conventional centrifugal separate mode, detection as other in fast bed, field operations equal samples need the open air experiment of fast processing, and investigator proposes 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, not easily blocks up, but separation efficiency is low, and blood plasma/clear amount is few; Loading microballon filters, and easily block up, separation efficiency is low, and whole blood needs dilution; Difference effect is filtered, and not easily block up, selectivity is good, but blood plasma/clear separation efficiency is low.
Array experiment chamber system, Sample Pretreatment Technique Used is as integral part indispensable in this system, and development is relatively slow, has become the bottleneck of whole evolution, has govern the development of biochemical analysis.Existing Sample Pretreatment Technique Used often realizes 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 separation technique.The microminiaturized biological sample pretreater utilizing 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 prepares at biochemistry detection, drugs qualification, DNA analysis, cellular segregation and enrichment, medicine and all obtains applying very widely in drug conveying etc., becomes the focus that micro-total analysis system is studied.
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 is as the important component part of development Micro biochemical analysis system, has broad application prospects with chemical analysis field biomedical.Design that a kind of structure is simple, 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 micro fluid dynamcis system, and the work that system integration technology will be a challenging meaning.
Summary of the invention
In view of this, be necessary to provide the separation membrane type separating chips that a kind of separation efficiency is high, cost is low.
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, solves easily stifled, problem that selectivity is bad.
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
Be described below in detail embodiments of the invention, the example of described embodiment is shown in the drawings, and wherein same or similar label represents same or similar element or has element that is identical or similar functions from start to finish.Being exemplary below by the embodiment be described with reference to the drawings, only for explaining the present invention, and can not limitation of the present invention being interpreted as.
In describing the invention, term " interior ", " outward ", " longitudinal direction ", " transverse direction ", " on ", D score, " top ", the orientation of the instruction such as " end " or position relationship be based on orientation shown in the drawings or position relationship, be only the present invention for convenience of description instead of require that the present invention with specific azimuth configuration and operation, therefore must 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 is in sandwich structure.In the present embodiment, take mechanical press (as screw fixed chip periphery), adhesive seal (as separatory membrane peripheral point glue), lamination to seal the multiple sealing means such as (as sealing element), insert mould (as high molecular film material hot pressing) and prevent separatory membrane 30 edge seepage hemocyte.
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 bottom liquid storage tank 110 is slightly large, for fixedly separated film 110.
In the present embodiment, described collection channel comprises multiple capillary channel 210 and flow-guiding channel 220.
In the present embodiment, described separatory membrane 30 is arranged between described liquid storage tank 110 and multiple capillary channels 210 of 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, such as, 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 heterocyclic (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, blood, urine and other biological specimens containing cell being separated into can through the material of fenestra (as blood plasma/clear, urine, sample liquid) and can not through the material of fenestra (as cell), prevent blood plasma/clear, urine, the sample liquid pollution caused by cell, 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 volume V of the maximum diameter of hole dc of described fenestra and required entrapped cell, cell surface amass the relation of A and are: 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.Show that the minimum-value aperture that HRBC can be passed through is 2.5 microns according to formulae discovery, so blood, urine RBC separatory membrane aperture is in 0.05-2.5 micrometer range, if be less than 0.05 micron, protein in blood, urine, mixtinite and similar substance are likely blocking microporous, if and be greater than 2.5 microns, red corpuscle deformation behavior can make it pass through to be separated fenestra and do not reach separating effect; When membrane type separating chips is used for other cells, according to the minimum-value aperture that formulae discovery cell can pass through, determine the separatory membrane pore diameter range be suitable for, optimum aperture is selected in conjunction with flow velocity, separating effect etc., as separating blood, Urinary White Blood Cell, as being separated the suspension after insect gonad cell SF9 (mean diameter is about 18.3 microns) cell cultures, as the suspension after separation 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, the Pore Blocking on separatory membrane 30, improves separation efficiency further, reduces sample size, cover plate 10 adds 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, the stepped arrangement of multiple capillary channels 210, realizes the contact with separatory membrane 30 maximum area 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, cover plate 10 comprises liquid storage tank 110 and waste liquid pool 130, 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 below liquid storage tank 110 and waste liquid pool 130.
Therefore, produce shearing force on separatory membrane 30 surface when sample separation liquid to be separated flows, decrease the accumulation of cake layer or gel coat, filtration velocity is stablized.
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 channel 210 and flow-guiding channel 220.
In the present embodiment, described separatory membrane 240 is communicated with described multiple capillary channel 210 through described absorbent pad 230, 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, solves easily stifled, problem that selectivity is bad.
Although the present invention is described with reference to current better embodiment; but those skilled in the art will be understood that; above-mentioned better embodiment is only used for the present invention is described; 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, equivalence replacement, improvement etc., all should be included within the scope of the present invention.
Claims (7)
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, described collection channel is directly communicated with described collecting tank, and described collection channel comprises multiple capillary channel and flow-guiding channel, and the described flow-guiding channel on described collection channel is communicated with described collecting tank;
Take the sealing means of the sealing of mechanical press, adhesive seal, lamination or insert mould by described cover plate and the sealing of described separatory membrane, prevent separatory membrane edge seepage hemocyte.
2. membrane type separating chips as claimed in claim 1, it is characterized in that, described separatory membrane is arranged between described liquid storage tank and described collection channel.
3. membrane type separating chips as claimed in claim 2, it is characterized in that, described separatory membrane is porous medium, comprises multiple fenestra.
4. membrane type separating chips as claimed in claim 3, is characterized in that, the maximum diameter of hole d of described fenestra
cthe relation amassing A with the volume V of required entrapped cell, 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.
5. membrane type separating chips as claimed in claim 1, it is characterized in that, also comprise waste liquid pool and connecting passage, wherein, described waste liquid pool is communicated with described liquid storage tank by connecting passage.
6. a membrane type separating chips, comprising:
Cover plate, is provided with collecting tank; And
Substrate, be provided with collection channel, separatory membrane and absorbent pad, wherein, described absorbent pad is arranged between described collection channel and described separatory membrane, described collection channel is directly communicated with described collecting tank, described collection channel comprises multiple capillary channel and flow-guiding channel, and described separatory membrane is communicated with described multiple capillary channel through described absorbent pad, and described flow-guiding channel is communicated with described collecting tank.
7. membrane type separating chips as claimed in claim 6, it is characterized in that, described separatory membrane is vesicular structure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210460005.3A CN103805504B (en) | 2012-11-15 | 2012-11-15 | Membrane type separating chips |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210460005.3A CN103805504B (en) | 2012-11-15 | 2012-11-15 | Membrane type separating chips |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103805504A CN103805504A (en) | 2014-05-21 |
| CN103805504B true CN103805504B (en) | 2016-01-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210460005.3A Expired - Fee Related CN103805504B (en) | 2012-11-15 | 2012-11-15 | Membrane type separating chips |
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Families Citing this family (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 |
|---|---|---|---|---|
| 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 |
-
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 |
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| CN103805504A (en) | 2014-05-21 |
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