CN102965276A - Biochip for screening rare cells in blood - Google Patents
Biochip for screening rare cells in blood Download PDFInfo
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- CN102965276A CN102965276A CN2012104772435A CN201210477243A CN102965276A CN 102965276 A CN102965276 A CN 102965276A CN 2012104772435 A CN2012104772435 A CN 2012104772435A CN 201210477243 A CN201210477243 A CN 201210477243A CN 102965276 A CN102965276 A CN 102965276A
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- thin slice
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- 239000008280 blood Substances 0.000 title claims abstract description 40
- 210000004369 blood Anatomy 0.000 title claims abstract description 40
- 238000000018 DNA microarray Methods 0.000 title claims abstract description 25
- 238000012216 screening Methods 0.000 title claims abstract description 18
- 239000011521 glass Substances 0.000 claims abstract description 37
- 239000000463 material Substances 0.000 claims description 10
- 239000012530 fluid Substances 0.000 claims description 9
- 229920002943 EPDM rubber Polymers 0.000 claims description 8
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 5
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- -1 polydimethylsiloxane Polymers 0.000 claims description 3
- 239000012780 transparent material Substances 0.000 claims description 3
- 239000002122 magnetic nanoparticle Substances 0.000 abstract description 6
- 238000004458 analytical method Methods 0.000 abstract description 4
- 239000007788 liquid Substances 0.000 abstract 2
- 230000008105 immune reaction Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 22
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 11
- 230000000694 effects Effects 0.000 description 4
- 210000005266 circulating tumour cell Anatomy 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
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- 229920001971 elastomer Polymers 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
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- 230000001771 impaired effect Effects 0.000 description 1
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- 239000003550 marker Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
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Abstract
The invention discloses a biochip for screening rare cells in blood. The biochip comprises a thin slice and a glass slide, wherein the thin slice is provided with a groove which faces the glass slide and enable the thin slice to be clung to the glass slide so that a closed microfluid passage is formed between the thin slice and the glass slide; and a liquid outlet hole and a liquid inlet hole, which are communicated with the microfluid passage are formed in the thin slice. The biochip has the advantages that magnetic nano-particles are put into a blood sample, the surfaces of the magnetic nano-particles are provided with antibodies which are adsorbed on target cells through immune reaction, then the blood sample in which the rare cells are marked flows through the microfluid passage, and the rare cells to which the magnetic nano-particles are attached in the blood sample are placed in and guided by a gradient magnetic field generated by a magnet below the biochip, and then are collected on the glass slide. Because the thin slice is detachably connected with the glass slide, after collection, the glass slide is separated from the thin slice, and the rare cells on the glass slide are subjected to subsequent analysis. The biochip is simple in structure, and is very convenient to operate.
Description
Technical field
The present invention relates to a kind of blood testing biochip, especially relate to a kind of biochip for screening blood rare cell.
Background technology
The blood testing biochip is the diagnostic tool of future generation that detects rare cell in the blood relevant with major disease, and rare cell comprises cell with specified protein mark of circulating tumor cell (CTC), pernicious stem cell and the pathology of circulation in blood sample etc.Relevant studies confirm that the circulating tumor cell quantity that occurs in patient's the blood sample and patient's early diagnosis and survival rate have very strong dependency.Therefore, be the key that improves tumor disease early discovery rate and personalized treatment to the rare cell determination and analysis of patient's blood sample.
Because the CTCs quantity of patient blood sample is very little, CTC is detected have very large challenge.The flow cytometer detection method is a kind of CTC detection method of the most generally using, and CTC is larger than general cell space, and the caryoplasm ratio is high, the endochylema no particulate matter is few, expression specificity antigen, its characteristic to scattering of light and immunofluorescence identification of flow cytometry is separated CTC from total cell.Present up-to-date flow cytometer BD FACSAria is the new breakthrough of streaming high speed cell sorting, but its defective that is difficult to overcome is: instantaneous laser hits will bring damage to cell, the sorting poor activity; Because the intersection that exists between spectrum is easily sneaked into false-positive cell; The required compensation of fluorescent signal is difficult to allotment; Tend to occur the agglomerating phenomenon of cytoadherence, the obstruction of efferent tract happens occasionally; The filtration cell of having no progeny in the sorting again prepares sample, and this has increased the probability of polluting, and cytoactive is greatly impaired.Still deposit dispute with the method for the CTC in the Flow cytometry tumour patient merely; Other form fractionation method, the quantity of isolated CTCs and density are smaller from white corpuscle, can stay simultaneously a large amount of similar and be not enough to be considered as the cell of CTC with the CTC form, such as the same little acyclic tumour cell with white corpuscle.Also have immunologic detection method, because CTCs has the high special effect property of separating, can utilize specific marker, target CTC is carried out mark, but need the extra immunofluorescence dyeing screening step that increases.
So, be necessary to provide a kind of simple in structure, easy to operate blood testing biochip from the patient blood sample, to separate the specific protein cell plastid of rare cell and/or pathology.
Summary of the invention
Technical problem to be solved by this invention provides a kind of simple in structure, easy to operate biochip that is used for screening blood rare cell.
The present invention solves the problems of the technologies described above the technical scheme that adopts: a kind of biochip for screening blood rare cell, comprise the reeded thin slice of tool and slide glass, groove on the thin slice is close on the described slide glass towards slide glass and with thin slice, makes and forms an airtight microfluidic channel between thin slice and the slide glass; Offer the fluid hole and the inlet opening that are communicated with described microfluidic channel on the described thin slice.
Comprise that also described thin slice and slide glass are positioned at described housing by upper enclosing cover and the lower outside shell that covers, the medial surface of described upper enclosing cover is pressed on the upper surface of thin slice, and the medial surface of described lower enclosing cover is pressed on the lower surface of slide glass.Shell plays the effect of protection thin slice and slide glass; the simultaneously interaction by upper enclosing cover and lower enclosing cover; thin slice and slide glass are fitted tightly and interfix; form airtight microfluidic channel; behind disassembling shell; can easily thin slice be separated with slide glass, slide glass is used for subsequent analysis to be processed.
Described lower enclosing cover offers the empty avoiding window that can embed magnetic substance, described empty avoiding window be positioned at microfluidic channel under.The magnet that is used to form gradient magnetic is placed on the below of slide glass, and offering of empty avoiding window can avoid shell to stop magnetic field, make magnetic field more useful effect in the blood sample of the microfluidic channel of flowing through.
Described thin slice is made by transparent material, and described upper enclosing cover offers the viewing window that can watch liquid-flow in the microfluidic channel.
Be connected with the first pipe joint element on the described fluid hole, be connected with the second pipe joint element on the described inlet opening, described the first pipe joint element and the second pipe joint element are bonded on the described thin slice.Blood. reservoir is communicated with the first pipe joint element by pipe connecting, the second pipe joint element is communicated with liquor pump by pipe connecting, under the suction of liquor pump, blood sample in the storer is in the first pipe joint element flows into microfluidic channel, blood sample in the microfluidic channel flows to liquor pump through the second pipe joint element, and blood sample is with a certain suitable speed runoff microfluidic channel.
Described thin slice is made by polydimethylsiloxane (PDMS) or ethylene propylene diene monomer (EPDM) material (EPDM).
The cross section of microfluidic channel is hexagon.Hexagonal cross section can be under the prerequisite that guarantees capture rate, and it is wide that the rare cell that captures is distributed.
Pass through buckle or gemel connection between upper enclosing cover and the lower enclosing cover.Make things convenient for dismounting and the assembling of shell, behind the disassembling shell, the taking-up of convenient-loading slide.
Described shell adopts PE or PP material to make.
The thickness of described thin slice is 8-12mm, and the degree of depth of described groove is 0.4mm-0.6mm, and the diameter of bore of described inlet opening and fluid hole is 1.5mm-1.7mm.
Compared with prior art, advantage of the present invention is to put into first magnetic nano-particle in blood sample, the magnetic nano-particle surface is with antibody, be adsorbed on the target cell by immune response, then the blood sample that rare cell has been labeled the microfluidic channel of flowing through, the rare cell that is attached with magnetic nano-particle in the blood sample is placed on the gradient magnetic guiding that the magnetic substance below the biochip sends, and then be collected on the slide glass, since between thin slice and the slide glass for removably connecting, after finishing Deng collecting work, the user can take out slide glass easily with slide glass and slice separates, and the rare cell on the slide glass is carried out subsequent analysis.The present invention is relatively simple for structure, and it is very convenient to operate.
Description of drawings
Fig. 1 is three-dimensional structure diagram of the present invention;
Fig. 2 is exploded view of the present invention (one);
Fig. 3 is exploded view of the present invention (two);
Fig. 4 is the stereographic map of thin slice of the present invention;
Fig. 5 is the front elevation of thin slice of the present invention.
Embodiment
Embodiment is described in further detail the present invention below in conjunction with accompanying drawing.
A kind of biochip for screening blood rare cell, comprise thin slice 1 and slide glass 2 with groove 11, groove 11 on the thin slice 1 is close on the slide glass 2 towards slide glass 2 and with thin slice 1, makes and forms an airtight microfluidic channel between thin slice 1 and the slide glass 2; Offer the fluid hole 12 and the inlet opening 13 that are communicated with microfluidic channel on the thin slice 1.The cross section of microfluidic channel is hexagon.Thin slice 1 is made by polydimethylsiloxane (PDMS) or terpolymer EP rubber (EPDM) material.EPDM material and EPDM material have good thermoplasticity and elasticity.Thin slice also can adopt 40 DURO TRANSLUCENT SILICONE RUBBER materials.That above-mentioned materials is is transparent, be insoluble to acetone, and has elasticity, has good sealing property under middle pressure, guarantees that blood sample can not ooze out in microfluidic channel.Wave carrier piece can adopt pathology level slide glass.
The shell 3 that upper enclosing cover 31 and lower enclosing cover 32 synthesize, thin slice 1 and slide glass 2 are positioned at housing 3, and the medial surface of upper enclosing cover 31 is pressed on the upper surface of thin slice 1, and the medial surface of lower enclosing cover 32 is pressed on the lower surface of slide glass 2.By buckle or gemel connection, shell adopts PE or PP material to make between upper enclosing cover 31 and the lower enclosing cover 32.Lower enclosing cover 32 offers the empty avoiding window 321 that can embed magnetic substance, empty avoiding window 321 be positioned at microfluidic channel under.Thin slice 1 is made by transparent material, and upper enclosing cover 31 offers the viewing window 311 that can watch liquid-flow in the microfluidic channel.Be connected with the first pipe joint element 14 on the fluid hole 12, be connected with the second pipe joint element 15, the first pipe joint elements 14 and the second pipe joint element 15 on the inlet opening 13 and be bonded on the thin slice 1.Pipe joint element and thin slice adopt tackiness agent, and requirement is to produce any impact to blood sample, guarantees simultaneously the stopping property of system, prevent the blood sample leakage.The thickness of thin slice 1 is 8mm or 10mm or 12mm, and the degree of depth of groove 11 is 0.4mm or 0.5mm or 0.6mm, and the diameter of bore of inlet opening 13 and fluid hole 12 is 1.5mm or 1.58mm or 1.7mm.
Claims (10)
1. biochip that is used for screening blood rare cell, it is characterized in that comprising the reeded thin slice of tool and slide glass, groove on the thin slice is close on the described slide glass towards slide glass and with thin slice, makes and forms an airtight microfluidic channel between thin slice and the slide glass; Offer the fluid hole and the inlet opening that are communicated with described microfluidic channel on the described thin slice.
2. a kind of biochip for screening blood rare cell according to claim 1, characterized by further comprising by upper enclosing cover and the lower outside shell that covers, described thin slice and slide glass are positioned at described housing, the medial surface of described upper enclosing cover is pressed on the upper surface of thin slice, and the medial surface of described lower enclosing cover is pressed on the lower surface of slide glass.
3. a kind of biochip for screening blood rare cell according to claim 2 is characterized in that described lower enclosing cover offers the empty avoiding window that can embed magnetic substance, described empty avoiding window be positioned at microfluidic channel under.
4. a kind of biochip for screening blood rare cell according to claim 2 is characterized in that described thin slice made by transparent material, and described upper enclosing cover offers the viewing window that can watch liquid-flow in the microfluidic channel.
5. a kind of biochip for screening blood rare cell according to claim 1, it is characterized in that being connected with on the described fluid hole the first pipe joint element, be connected with the second pipe joint element on the described inlet opening, described the first pipe joint element and the second pipe joint element are bonded on the described thin slice.
6. a kind of biochip for screening blood rare cell according to claim 1 is characterized in that described thin slice made by polydimethylsiloxane or ethylene propylene diene monomer (EPDM) material.
7. a kind of biochip for screening blood rare cell according to claim 1, the cross section that it is characterized in that microfluidic channel is hexagon.
8. a kind of biochip for screening blood rare cell according to claim 2 is characterized in that between enclosing cover and the lower enclosing cover by buckle or gemel connection.
9. a kind of biochip for screening blood rare cell according to claim 2 is characterized in that described shell adopts PE or PP material to make.
10. a kind of biochip for screening blood rare cell according to claim 1, the thickness that it is characterized in that described thin slice is 8-12mm, the degree of depth of described groove is 0.4mm-0.6mm, and the diameter of bore of described inlet opening and fluid hole is 1.5mm-1.7mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104772435A CN102965276A (en) | 2012-11-20 | 2012-11-20 | Biochip for screening rare cells in blood |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104772435A CN102965276A (en) | 2012-11-20 | 2012-11-20 | Biochip for screening rare cells in blood |
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| CN102965276A true CN102965276A (en) | 2013-03-13 |
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| CN2012104772435A Pending CN102965276A (en) | 2012-11-20 | 2012-11-20 | Biochip for screening rare cells in blood |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103255055A (en) * | 2013-04-24 | 2013-08-21 | 宁波美晶医疗技术有限公司 | Buckle type biological chip |
| CN103255056A (en) * | 2013-04-24 | 2013-08-21 | 宁波美晶医疗技术有限公司 | Easy-pull type detachable biological chip |
| CN103255054A (en) * | 2013-04-24 | 2013-08-21 | 宁波美晶医疗技术有限公司 | Slide block closed type biological chip |
| CN103305416A (en) * | 2013-05-17 | 2013-09-18 | 宁波美晶医疗技术有限公司 | Adjustable magnetic field based tumor cell immunoscreening system |
| CN107058081A (en) * | 2017-04-11 | 2017-08-18 | 宁波美晶医疗技术有限公司 | A kind of biochip for being used to screen rare cell in positioning and detection blood |
| CN107233941A (en) * | 2017-04-24 | 2017-10-10 | 深圳无微华斯生物科技有限公司 | A kind of multiple near-infrared fluorescent enhancing biochip screening circulating tumor cell method |
| CN109270262A (en) * | 2018-10-08 | 2019-01-25 | 宁波美晶医疗技术有限公司 | A kind of unicellular extracting method of laser based on micro-fluidic technologies |
| CN112041425A (en) * | 2018-04-27 | 2020-12-04 | 离子通道与转运研究公司 | Method for measuring intracellular potential by capacitive potential measuring device |
| WO2022068648A1 (en) * | 2020-09-30 | 2022-04-07 | 苏州莱博睿思生物科技有限公司 | Microfluidic chip cartridge |
| CN114414435A (en) * | 2022-02-25 | 2022-04-29 | 苏州市独墅湖医院(苏州大学附属独墅湖医院) | A parallel plate device for detecting platelet adhesion in mobile phase |
| WO2024087107A1 (en) * | 2022-10-27 | 2024-05-02 | 深圳华大生命科学研究院 | Biochip container and methods for preparation and use thereof |
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| CN102732415A (en) * | 2012-04-24 | 2012-10-17 | 武汉介观生物科技有限责任公司 | High-efficiency rare-cell-capturing integrated chip, manufacturing method thereof, and application thereof |
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2012
- 2012-11-20 CN CN2012104772435A patent/CN102965276A/en active Pending
Patent Citations (3)
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| US4710472A (en) * | 1985-09-25 | 1987-12-01 | The United States Of America As Represented By The Secretary Of The Navy | Magnetic separation device |
| CN101576523A (en) * | 2009-06-11 | 2009-11-11 | 上海交通大学 | Method for detecting tumour cells by adopting microelectrode array impedance biosensor chip |
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103255055A (en) * | 2013-04-24 | 2013-08-21 | 宁波美晶医疗技术有限公司 | Buckle type biological chip |
| CN103255056A (en) * | 2013-04-24 | 2013-08-21 | 宁波美晶医疗技术有限公司 | Easy-pull type detachable biological chip |
| CN103255054A (en) * | 2013-04-24 | 2013-08-21 | 宁波美晶医疗技术有限公司 | Slide block closed type biological chip |
| CN103255054B (en) * | 2013-04-24 | 2014-08-06 | 宁波美晶医疗技术有限公司 | A slider closed biochip |
| CN103305416A (en) * | 2013-05-17 | 2013-09-18 | 宁波美晶医疗技术有限公司 | Adjustable magnetic field based tumor cell immunoscreening system |
| CN107058081A (en) * | 2017-04-11 | 2017-08-18 | 宁波美晶医疗技术有限公司 | A kind of biochip for being used to screen rare cell in positioning and detection blood |
| CN107233941A (en) * | 2017-04-24 | 2017-10-10 | 深圳无微华斯生物科技有限公司 | A kind of multiple near-infrared fluorescent enhancing biochip screening circulating tumor cell method |
| CN112041425A (en) * | 2018-04-27 | 2020-12-04 | 离子通道与转运研究公司 | Method for measuring intracellular potential by capacitive potential measuring device |
| CN112041425B (en) * | 2018-04-27 | 2024-04-16 | 离子通道与转运研究公司 | Method for measuring intracellular potential by capacitive potential measuring device |
| CN109270262A (en) * | 2018-10-08 | 2019-01-25 | 宁波美晶医疗技术有限公司 | A kind of unicellular extracting method of laser based on micro-fluidic technologies |
| CN109270262B (en) * | 2018-10-08 | 2022-05-20 | 宁波美晶医疗技术有限公司 | Laser single cell extraction method based on microfluid technology |
| WO2022068648A1 (en) * | 2020-09-30 | 2022-04-07 | 苏州莱博睿思生物科技有限公司 | Microfluidic chip cartridge |
| CN114414435A (en) * | 2022-02-25 | 2022-04-29 | 苏州市独墅湖医院(苏州大学附属独墅湖医院) | A parallel plate device for detecting platelet adhesion in mobile phase |
| WO2024087107A1 (en) * | 2022-10-27 | 2024-05-02 | 深圳华大生命科学研究院 | Biochip container and methods for preparation and use thereof |
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Application publication date: 20130313 |