CN107338184A - A kind of capture sieve and device for being used to capture biomolecule in cell or solution - Google Patents
A kind of capture sieve and device for being used to capture biomolecule in cell or solution Download PDFInfo
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- CN107338184A CN107338184A CN201710650815.8A CN201710650815A CN107338184A CN 107338184 A CN107338184 A CN 107338184A CN 201710650815 A CN201710650815 A CN 201710650815A CN 107338184 A CN107338184 A CN 107338184A
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Abstract
The invention discloses a kind of capture sieve and device for being used to capture biomolecule in cell or solution.The capture sieve, including reticulated matrix and the trapping layer that is formed on the reticulated matrix, the trapping layer include the catches that can be specifically bound with target cell or biomolecule.The capture sieve and device of the present invention has high specific and high flux, and suitable for the biomolecule in the molecule trapping cell by being expressed by cell or capture solution, particularly suitable for capturing and sorting circulating tumor cell.
Description
Technical field
The present invention relates to the dress for capturing biomolecule in cell or capture solution by the molecule expressed by cell
Put, it is more particularly to a kind of to be used to capture target cell by the biomolecule expressed by target cell（Such as, circulating tumor is thin
Born of the same parents）Or the capture sieve of target biological molecules and the device with this capture sieve in capture solution.
Background technology
Circulating tumor cell is sanguimotor tumour cell, and there is great pass the problems such as being considered as the far-end transfer with tumour
System.Only 1-10 circulating tumor cell in the 10ml blood of general cancer patient, its acquisition speed is slow or poor specificity is fast
Speed detection patient's blood sample problem in the urgent need to address.
For example traditional immunological magnetic bead sorting method of present method for separating is reproducible, high sensitivity, the good, Ke Yiding of specificity
Amount analysis circulating tumor cell, but service speed is slow, flux is small.Although membrane micropore filtering technique and Percoll gradient centrifugation behaviour
Make simply, cytoactive is preferable after separation, but specificity is low and false positive rate is high.Microflow control technique is simple to operate, required antibody
Amount is few, but cost is higher, false negative rate is high.And microflow control technique company primarily now for scientific research client, it is necessary to mix in advance
Plurality of reagents is closed, excessively relies on old-fashioned chip, industrialization is difficult, therefore it is difficult to enter in-vitro diagnosis field.Other such as U.S.
Cell Search system sensitivities are high, specificity is high, but hematozemia amount is big, required amount of antibody is big, cost is high, can not realize work
Cell capture, circulating tumor cell can not be collected and be further cultured for, therefore DNA sequencing can only be done can not but to do RNA sequencings, no
Medication guide can be used as.
The content of the invention
An object of the present invention is to provide a kind of capture sieve for being used to capture biomolecule in cell or solution, and it has
High specific and high flux, and the biomolecule being suitable in the molecule trapping cell by being expressed by cell or capture solution, especially
Suitable for capturing and sorting circulating tumor cell.
To reach above-mentioned purpose one, the technical solution adopted by the present invention is：
A kind of capture sieve for being used to capture biomolecule in cell or solution, including reticulated matrix and it is formed at the reticulated matrix
On trapping layer, the trapping layer includes the catches that can be combined with target cell or molecular specificity.
Preferably, the biomolecule is protein that is in solution or being expressed by cell, oligonucleotides（DNA and/or
RNA）, enzyme or their any combination.
Preferably, the catches is selected from antibody（Including nano antibody）, oligonucleotides（Including aptamer
（aptamer））And molecularly imprinted polymer（molecularly imprinted polymers）In one or more groups
Close.
Preferably, the catches is bonded on the reticulated matrix by physical absorption and/or chemical bonded refractory.
It is highly preferred that the chemical bonds pass through mercaptan molecules of salt, traut ' s reagents, salinization
（silanisation）Or click chemistry（click chemistry）Realize.
It is highly preferred that the catches is antibody, the antibody is by using traut ' s reagents or with biotin-parent
It is connected to the mercaptan molecules of salt of element on the reticulated matrix.
Further, the biomolecule is signal transduction factor, and the target cell is circulating tumor cell, institute
State antibody for can with by circulating tumor cell surface expression signal transduction factor specific binding anti-epithelium it is thin
Born of the same parents' adhesion molecule antibodies.
Preferably, the size of the reticulated matrix is 1-100 mm × 1-100 mm, and the hole of the sieve is 2 μm of -800 μ
m.It is highly preferred that the size of the reticulated matrix is 2-10 mm × 2-10 mm, the hole of the sieve is 20 μm -100 μm.
Preferably, the material of the reticulated matrix is gold or other noble metals, stainless steel or the combination of the two.
Preferably, the reticulated matrix includes：
Body of stainless steel；And
It is formed at the protective layer on the body of stainless steel surface；
Wherein, the protective layer is by noble metal or its alloy（Such as AuPd）It is made, the catches is connected to the protective layer.
It is highly preferred that the protective layer passes through physical coating（Such as, magnetron sputtering）Or chemical deposition forms.
The second object of the present invention is to provide a kind of device for being used to capture biomolecule in cell or solution, and it has high special
Property and high flux, and suitable for by the biomolecule in the molecule trapping cell expressed by cell or capture solution, particularly suitable for catching
Obtain and sort circulating tumor cell.
To reach above-mentioned purpose two, the technical solution adopted by the present invention is：
A kind of device for being used to capture biomolecule in cell or solution, including capture mechanism, the capture mechanism are included at least
Capture sieve described in one.
Preferably, the capture mechanism includes the capture sieve of multiple stackings.
Preferably, described device further comprises going out with entrance, first outlet and positioned at the entrance and described first
The main body of cavity between mouthful, the capture mechanism is fixed in the cavity, the entrance and the first outlet and described
Cavity connects.The main body is preferably manufactured using existing manufacturing technology such as injection molded technology.The material of main body should be compatible
Solvent.For example, PEEK meets above-mentioned condition.
It is highly preferred that the cavity is divided into two parts of the first cavity and the second cavity by the capture mechanism.
Further, the capture sieve is horizontally disposed, and the entrance is located at the top of the capture mechanism and with described the
One cavity communicates, and the first outlet is located at the lower section of the capture mechanism and communicated with second cavity.
Further, the entrance and the central axis of the first outlet are in the residing plane of the capture sieve.
Preferably, the main body further has a second outlet, in the main body formed with the cavity and described
The microfluidic channel for being used to collect captured cell or biomolecule that second outlet communicates.
Preferably, described device further comprises being used for captured cell or life in the microfluidic channel
The counting mechanism that thing molecule is counted.
It is highly preferred that the counting mechanism includes impedance measurement electrode.
It is highly preferred that the cavity is divided into two parts of the first cavity and the second cavity by the capture mechanism, it is described
Entrance communicates with first cavity, and the microfluidic channel communicates with second cavity.
The present invention uses above scheme, has the following advantages that compared with prior art：
It is easy to functionalization and there is higher flux；The risk of blocking is low；Higher specificity；Higher efficiency；Device is set
It is calculated as that conventional fabrication processes can be used（Such as injection molded）Manufacture；Existing counting technology can be combined；Can be after experiment by cell
Collect.
Brief description of the drawings
In order to illustrate more clearly of technical scheme, the required accompanying drawing used in being described below to embodiment
It is briefly described, it should be apparent that, drawings in the following description are only some embodiments of the present invention, general for this area
For logical technical staff, on the premise of not paying creative work, other accompanying drawings can also be obtained according to these accompanying drawings.
Fig. 1 is to be used to capture circulation cancer cell according to one kind of the present invention（Abbreviation CTCs）Device schematic diagram；
Fig. 2 is the schematic diagram sieved according to a kind of capture with captured circulating tumor cell of the present invention；
Fig. 3 is the sectional view sieved according to a kind of capture of the present invention；
Fig. 4 a are the flow charts for capturing circulating tumor cell；
Fig. 4 b show that a kind of device using shown in Fig. 1 captures the typical process of circulating tumor cell；
Fig. 5 a and 5b are respectively the circulating tumor cell for two kinds of expression target acquistion molecules for showing that captured sieve is captured
Photo.
In above-mentioned accompanying drawing,
1st, main body；10th, cavity；101st, upper cavity；102nd, lower chamber；11st, entrance；12nd, first outlet；13rd, microfluidic channel；
14th, second outlet；
2nd, capture mechanism；20th, sieve；201st, body of stainless steel；202nd, protective layer；21st, antibody；
3rd, counting mechanism；30th, electrode；
4th, circulating tumor cell；5th, blood cell.
Embodiment
Presently preferred embodiments of the present invention is described in detail below in conjunction with the accompanying drawings, so that advantages and features of the invention energy
It is easier to be understood by the person skilled in the art.Herein it should be noted that being used to help for the explanation of these embodiments
Understand the present invention, but do not form limitation of the invention.It is in addition, involved in each embodiment of invention described below
As long as and to technical characteristic each other do not form conflict can be combined with each other.
Device disclosed by the invention is combining macroscopic view/small-fluid means dependent on one or more capture sieves（Shown in Fig. 1）
Middle capture circulating tumor cell（CTCs）." macroscopic view " is partly used to reduce test period simultaneously to optimize by increasing capture area
Capture." small " is partly used to detecting and collecting circulating tumor cell.
Fig. 1 shows one embodiment of the fluid means for capturing circulating tumor cell.The device includes：
Inside has the main body 1 of a cavity 10, and goes out with an entrance 11 and a first outlet 12 and one second
Mouth 14；
Capture mechanism 2, including at least one capture sieve 20；And
Counting mechanism；
Wherein, main body 1 is manufactured using existing manufacturing technology such as injection molded technology.The material of main body also should be compatible solvent
Material.For example, PEEK（Polyether-ether-ketone, polyetheretherketone）All conditions can be met.Preferably, main body 1 is adopted
Manufactured with injection molding and form the cavity 10.Capture mechanism 2 is in cavity 10.Entrance 11 and first outlet 12 are distinguished
Positioned at the opposite end of cavity, capture mechanism 2 is located in cavity 10 and between entrance 11 and first outlet 12.More specifically
Ground, entrance 11 are opened in 1 upper surface of main body, and first outlet is opened in the lower surface of main body 1, that is to say, that entrance 11 is higher than
Capture mechanism 2 and first outlet 12 is less than capture mechanism 2.The mechanism 2 that is captured of cavity 10 is divided into two parts, i.e. upper cavity
101（First cavity）With lower chamber 102（Second cavity）.Upper cavity 101 and lower chamber 102 all substantially cuboids, and on
The section in the horizontal direction of cavity 101（Refer specifically to area）More than the section in the horizontal direction of lower chamber 102.Capture mechanism
2 include the capture sieve 20 of one or more stackings, and capture sieve 20 includes reticulated matrix and the trapping layer being formed on reticulated matrix,
Trapping layer contains the catches that can be specifically bound with target cell or biomolecule.The capture sieve 20 of capture mechanism 2 is made
It is standby be with catches, the catches can use any technology based on compatibility specifically with target cell or solution
By the molecule of cell expression or it is expressed in molecule on cell membrane surface.In medium, especially solution（Such as undressed blood
Liquid）In target cell or biomolecule upper cavity 101 can be conducted to via entrance, flow through afterwards arresting structure 2 reach cavity of resorption
In body 102, and finally flow out main body 1 via first outlet 12.In this process, target cell or biomolecule are captured
Mechanism 2 captures, and the other parts of blood by capture mechanism 2 without captured.The advantages of capture sieve is high surface area-body
Product ratio, it is allowed to which the processing of a large amount of samples reduces blocking risk again simultaneously.Binding specificity antibody technique have devised antibody and catch
Sieve is obtained, using epitope screening, ensure that hypersensitivity, specificity, cytoactive.Once target cell or biomolecule quilt
Capture, they can be released（Such as, chemistry, thermodynamics, electrical method）, for further analysis.Typically, the cell quilt
Count, and be collected for further analyzing afterwards.Sieve can capture any target cell or biomolecule, and these molecules
Can float over solution（Biofluid is other）In or be attached on cell（In this case, it will be that capture is thin
Born of the same parents）.Capture mechanism 2 may include multiple stackings capture sieve 20, can be directly be mutually stacked in or adjacent two layers between have interval.
In one embodiment, as shown in Fig. 2 the antibody 21 that can capture the molecule on circulating tumor cell surface is connected
To each sieve 20.Preferably, antibody 21 is anti-epithelial cell adhesion molecule antibody（anti - epithelial cell
Adhesion molecule antibodies, abbreviation anti-EpCAM）.Anti- epithelial cell adhesion molecule antibody can with molecule,
Particularly epithelial cell adhesion molecule (EpCAM) specific binding of circulating tumor cell, the circulating tumor cell so expressed
It can be captured.From such as 2 as can be seen that circulating tumor cell 4 is incorporated in on the antibody 21 on sieve 20, and other blood cells 5
Do not influenceed by sieve 20 then.
The material of sieve 20 can select golden or other noble metals and be coated with the stainless steel of golden or other noble metals.It is preferred that
Ground, as shown in figure 3, capture sieve includes：Body of stainless steel 201 and the protective layer 202 on body of stainless steel 201.
The material of protective layer 202 is gold or billon（Such as, AuPd）, and antibody 21 is connected on protective layer 202.Protection
Layer 202 is the AuPd layers being deposited on using magnetron sputtering or chemical method on body of stainless steel 201.Anti- epithelial cell adhesion molecule
Antibody passes through traut ' s reagents（Te Laote reagent）It is connected on sieve 20, the mercaptan molecules of salt with biotin-avidin can
Replace traut ' s reagents.
Also in main body 1, it is connected microfluidic channel 13 with the lower chamber of cavity 10, by the circulating tumor of the capture of sieve 20
Cell can be collected after being separated by cell dissociating buffer from sieve 20 by microfluidic channel 13.The counting mechanism 3 is set
Counted with the circulating tumor cell to capture in the microfluidic channel 13.Counting mechanism 3 includes impedance measurement electrode 30.The
Two outlets 14 are opened in the upper surface of main body 1, are connected with microfluidic channel 13, flow out master for the circulating tumor cell for capture
Body 1.
A kind of method for capturing circulating tumor cell, as shown in fig. 4 a, including step：
（I）Undressed blood is injected in described device；
（II）Undressed blood is set to flow through capture mechanism, so that CTCs is incorporated on capture mechanism；
（III）Remove the unwanted uncombined debris that may not be specifically interacted with the capture mechanism, thin
Born of the same parents or molecule；
（IV）Cell dissociating buffer is injected so that CTCs separates from capture mechanism；
（V）Collect CTCs and CTCs is counted.
As shown in Figure 4 b, specifically, step（I）In, undressed blood is injected by cavity via entrance 11 using pump
In 10；Step（II）In, undressed blood pump is gone down to sieve 20 by capturing, so that CTCs is incorporated in capture sieve 20
On, the operation direction of conversion pump makes blood multipass capture sieve 20, and to improve Percentage bound, while useless blood is via first outlet 12
Outflow；Step（III）In, it is all uncombined to be removed via first outlet 12 with water or other gentle solvent washing capture sieves 20
Debris, cell or molecule；Step（IV）In, close first outlet 12 and inject cell dissociating buffer（Such as contain tryptose
The buffer solution of enzyme）, so as to be departed from by the CTCs of the capture of sieve 20 from sieving 20；And in step（V）In, received by microfluidic channel 13
Collect CTCs, and the CTCs flowed through is counted by the impedance measurement electrode in microfluidic channel.It is described after counting
CTCs flows out via second outlet 14.
Example 1
Here, give a kind of preparation method for the capture sieve for being used to sort CTCs.The preparation method includes：
（I）The selection of sieve；
Gold sieve：The hole of selection gold sieve（Such as, 64 μm or 40 μm）To maximize the time of contact with tumour cell, at the same it is pre- anti-blocking
Fill in risk.The size of gold sieve used is 2 × 2mm in once testing2.According to the size that concrete operations are preferably larger.
Stainless steel and gold sieve：Select 51 μm of holes and using magnetron sputtering cladding AuPd.This sieve is less expensive and than gold
High mechanical strength, therefore this sieve is more suitable for integrating in a device.
（II）Pre- functionalization；
Various cleaning method is employed before functionalization come prepare sieve, including autoclaving, oxygen plasma cleaning with
And be cleaned by ultrasonic in a variety of solution, including Piranha solution（piranha solutions）.For example, for 64 μm of gold sieve
Best result be included in detergent and be ultrasonically treated 15 minutes, rinse, be ultrasonically treated 15 minutes in 70% ethanol solution, punching
Wash, high purity water 5 minutes.Using more other volumes（Such as, Piranha solution）Processing time can be shortened.
（III）Antibody；
Typically, 10 μ l antibody are taken and are freezed, prepare reactant mixture with it thereafter（That is, antibody+PBS with EDTA）, foot
Enough 2 × 50 μ l（50 μ l are 2 mm of submergence2Gold sieve minimum volume）.
（IV）Traut ' s reagents；
Quick freeze after purchase.The ratio of Traut ' s reagents and antibody is 4:1.Other methods, including with biotin-affine
Alternative Traut ' the s reagents of mercaptan molecules of salt of element are sieved to be connected to sieve with forming the capture.
（V）The incubation time of Traut ' s reagents with antibody；
Optimum reacting time is 1 hour.The time can be shortened under suitable conditions.
（VI）The incubation of above-mentioned solution with sieve；
Test different incubation times（Between 10 minutes to 12 hours）And different condition（4 DEG C, room temperature and 37 DEG C）.Preferably
1 hour at room temperature（It is that small improvement can be observed in longer incubation time but is not highly significant）.
Example 2
Experiment has been carried out to confirm that sieve is captured by the EpCAM of tumor cells expression efficiency.In this case, sieve aperture is 51 μm.
Cell selects --- there is the cell of high expression level to EpCAM albumen（Such as CaCo2 and MCF7 cells）Used.
Cell growth --- grown in 37 DEG C of DMEM buffer solutions.
Cell prepares and the incubation of sieve --- CaCo2 with MCF7 cell differentiations are into 1:2.Test 37 DEG C in a rotation
Carried out in heating dish.After separation, cell dilutes 1 in DMEM buffer solutions:10,0.5ml are used to be incubated the capture sieve, during incubation
Between be 1 hour.
The flushing of the cell of non-specific binding, the sieve use pure water rinsing, are incubated 2 minutes in pure water solution, so
Rinsed again before microexamination afterwards.
The cell being captured using microscopic evaluation：The photo of microscope photographing sieve（Fig. 5 a and 5b）.Fig. 5 a are shown
The CaCo2 cells for the expression target acquistion molecule being trapped in after being incubated 1 hour on capture sieve, Fig. 5 b quilts after being incubated 1 hour
Capture the MCF7 cells of the expression target acquistion molecule on capture sieve.The EpCAM due to cell is can be seen that from Fig. 5 a and 5b
With the combination of the anti-EpCAM antibody on sieve, multiple CaCo2 and MCF7 cells by it is described sieve capture, at the same time, sieve not by
Block.It should be noted that the mesh that device according to the present invention and methods described can be used in capture various concentrations solution
Mark biomolecule.
Capture sieve according to the present invention allows to contact with the time on the cell in blood while reduce blocking risk.It is logical
Cross using the sieve with bigger serface, it is possible that a large amount of samples are handled within a few minutes.
The above embodiments merely illustrate the technical concept and features of the present invention, is a kind of preferred embodiment, and its purpose exists
It can understand present disclosure in person skilled in the art and implement according to this, the protection of the present invention can not be limited with this
Scope.The equivalent transformation or modification that all principles according to the present invention are made, should all be included within the scope of the present invention.
Claims (11)
- A kind of 1. capture sieve for being used to capture biomolecule in cell or solution, it is characterised in that：Including reticulated matrix and formation Trapping layer on the reticulated matrix, the trapping layer include the capture that can be combined with target cell or molecular specificity Thing.
- 2. capture sieve according to claim 1, it is characterised in that：The biomolecule is in solution or expressed by cell Protein, oligonucleotides, enzyme or their any combination；The catches is selected from antibody, oligonucleotides and molecular engram One or more combinations in polymer；The catches is bonded to the netted base by physical absorption and/or chemical bonded refractory On body.
- 3. capture sieve according to claim 2, it is characterised in that：The biomolecule is signal transduction factor, institute It is circulating tumor cell to state target cell, and the antibody is can be with being sticked by the epithelial cell in circulating tumor cell surface expression The anti-signal transduction factor antibody of attached molecule specific binding.
- 4. capture sieve according to claim 3, it is characterised in that：The antibody is by using traut ' s reagents or carries The mercaptan molecules of salt of biotin-avidin is connected on the reticulated matrix.
- 5. capture sieve according to claim 1, it is characterised in that：The size of the reticulated matrix is 1-100 mm × 1- 100 mm, the hole of the sieve is 2 μm -800 μm.
- 6. capture sieve according to claim 5, it is characterised in that：The size of the reticulated matrix is 2-10 mm × 2-10 Mm, the hole of the sieve is 20 μm -100 μm.
- 7. capture sieve according to claim 1, it is characterised in that：The material of the reticulated matrix is noble metal；OrThe reticulated matrix includes：Body of stainless steel；AndIt is formed at the protective layer on the body of stainless steel surface；Wherein, the protective layer is made up of noble metal or its alloy, and the catches is connected to the protective layer.
- A kind of 8. device for being used to capture biomolecule in cell or solution, it is characterised in that：Including capture mechanism, the capture Mechanism includes the sieve of the capture as described in claim any one of 1-7 of at least one or more stacking, and described device is further wrapped Include the main body with entrance, first outlet and the cavity between the entrance and the first outlet, the capture mechanism It is fixed in the cavity, the entrance connects with the first outlet with the cavity.
- 9. device according to claim 8, it is characterised in that：The cavity is divided into the first cavity by the capture mechanism With two parts of the second cavity, the central axis of the entrance and the first outlet is in the residing plane of the capture sieve.
- 10. device according to claim 9, it is characterised in that：The capture sieve is horizontally disposed, and the entrance is positioned at described The top of capture mechanism simultaneously communicates with first cavity, the first outlet be located at the lower section of the capture mechanism and with it is described Second cavity communicates.
- 11. device according to claim 8, it is characterised in that：The main body further has second outlet, the main body It is interior formed with communicated with the cavity and the second outlet be used for collect captured cell or the miniflow of biomolecule Body passage, described device further comprise being used to enter captured cell or biomolecule in the microfluidic channel The counting mechanism that row counts.
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| CN108761080A (en) * | 2018-08-16 | 2018-11-06 | 中国科学院合肥物质科学研究院 | One specific cells in body captures box |
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| CN109694809A (en) * | 2018-11-19 | 2019-04-30 | 昆山汇先医药技术有限公司 | For capturing biomolecule, cell or the capture of bacterium sieve and preparation method thereof |
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| CN110361536A (en) * | 2019-07-04 | 2019-10-22 | 昆山汇先医药技术有限公司 | A kind of detection method of tumor cell surface marker molecule PD-L1 |
| WO2019223214A1 (en) | 2018-05-25 | 2019-11-28 | 昆山汇先医药技术有限公司 | Apparatus for enriching and screening target object such as cell, bacteria or biomolecule from sample |
| WO2020093374A1 (en) * | 2018-11-09 | 2020-05-14 | 清华大学 | Cell electrofusion culture chip and device, and cell electrofusion method |
| CN113124650A (en) * | 2019-12-31 | 2021-07-16 | 苏州博福生物医药科技有限公司 | Freeze-drying method of capture screen |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0246760A2 (en) * | 1986-04-24 | 1987-11-25 | E-Y Laboratories, Inc. | Variable volume assay device and method |
| US5556598A (en) * | 1992-09-18 | 1996-09-17 | Amersham International Plc. | Device and method for affinity separation |
| US20060292680A1 (en) * | 2005-06-09 | 2006-12-28 | Barbari Timothy A | Affinity membrane for capture of a target biomolecule and formation thereof by site-directed immobilization of a capture biomolecule |
| US20080318203A1 (en) * | 2004-07-09 | 2008-12-25 | Phuong-Lan Tran | Novel Microfluidic System and Method for Capturing Cells |
| WO2009115938A1 (en) * | 2008-03-18 | 2009-09-24 | Koninklijke Philips Electronics N.V. | Membranes suited for immobilizing biomolecules |
| CN103937658A (en) * | 2014-03-28 | 2014-07-23 | 武汉介观生物科技有限责任公司 | Rare cell detection chip and application thereof |
| WO2014181896A1 (en) * | 2013-05-06 | 2014-11-13 | (주)실리콘화일 | Organic substance analysis apparatus including membrane based multiple tubes |
| US20150041398A1 (en) * | 2013-08-06 | 2015-02-12 | Viatar LLC | Extracorpereal fluidic device for collecting circulating tumor cells and method of use thereof |
| CN207276608U (en) * | 2017-08-02 | 2018-04-27 | 苏州博福生物医药科技有限公司 | A kind of capture sieve for being used to capture biomolecule in cell or solution |
-
2017
- 2017-08-02 CN CN201710650815.8A patent/CN107338184A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0246760A2 (en) * | 1986-04-24 | 1987-11-25 | E-Y Laboratories, Inc. | Variable volume assay device and method |
| US5556598A (en) * | 1992-09-18 | 1996-09-17 | Amersham International Plc. | Device and method for affinity separation |
| US20080318203A1 (en) * | 2004-07-09 | 2008-12-25 | Phuong-Lan Tran | Novel Microfluidic System and Method for Capturing Cells |
| US20060292680A1 (en) * | 2005-06-09 | 2006-12-28 | Barbari Timothy A | Affinity membrane for capture of a target biomolecule and formation thereof by site-directed immobilization of a capture biomolecule |
| WO2009115938A1 (en) * | 2008-03-18 | 2009-09-24 | Koninklijke Philips Electronics N.V. | Membranes suited for immobilizing biomolecules |
| WO2014181896A1 (en) * | 2013-05-06 | 2014-11-13 | (주)실리콘화일 | Organic substance analysis apparatus including membrane based multiple tubes |
| US20150041398A1 (en) * | 2013-08-06 | 2015-02-12 | Viatar LLC | Extracorpereal fluidic device for collecting circulating tumor cells and method of use thereof |
| CN103937658A (en) * | 2014-03-28 | 2014-07-23 | 武汉介观生物科技有限责任公司 | Rare cell detection chip and application thereof |
| CN207276608U (en) * | 2017-08-02 | 2018-04-27 | 苏州博福生物医药科技有限公司 | A kind of capture sieve for being used to capture biomolecule in cell or solution |
Non-Patent Citations (1)
| Title |
|---|
| JEFFREY D. MCBRIDE等: "Screening Autoantibody Profiles in Systemic Rheumatic Disease with a Diagnostic Protein Microarray That Uses a Filtration-Assisted Nanodot Array Luminometric Immunoassay (NALIA)" * |
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