CN109136087A - Separating chips and separation method - Google Patents

Separating chips and separation method Download PDF

Info

Publication number
CN109136087A
CN109136087A CN201811057775.7A CN201811057775A CN109136087A CN 109136087 A CN109136087 A CN 109136087A CN 201811057775 A CN201811057775 A CN 201811057775A CN 109136087 A CN109136087 A CN 109136087A
Authority
CN
China
Prior art keywords
electrode
separating chips
layer
adsorbent material
separating
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201811057775.7A
Other languages
Chinese (zh)
Inventor
毛德丰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BOE Technology Group Co Ltd
Beijing BOE Technology Development Co Ltd
Original Assignee
BOE Technology Group Co Ltd
Beijing BOE Technology Development Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BOE Technology Group Co Ltd, Beijing BOE Technology Development Co Ltd filed Critical BOE Technology Group Co Ltd
Priority to CN201811057775.7A priority Critical patent/CN109136087A/en
Publication of CN109136087A publication Critical patent/CN109136087A/en
Pending legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/10Separation or concentration of fermentation products

Abstract

Present disclose provides a kind of separating chips and separators, belong to biochip technology field.The separating chips are set to the underlay substrate for separating target substance, including underlay substrate, electrode layer and cover board, electrode layer, have at least one electrode;The electrode is configured to that adsorbent material is adsorbed to the electrode when power is off, and adsorbent material is made to be detached from the electrode when being powered, and the adsorbent material can be specifically bound with the target substance;Cover board is set to side of the electrode layer far from the underlay substrate, and a cavity is formed between the electrode layer;The cavity covers the electrode;The through-hole of at least two connection cavity of setting on the cover board.The separating chips can sort from fluid to be separated and obtain target substance.

Description

Separating chips and separation method
Technical field
This disclosure relates to biochip technology field more particularly to a kind of separating chips and separation method.
Background technique
The detection and separation of bioactive substance have great importance for the diagnosis of disease.With the development of technology, The biochip of detection for bioactive substance is in clinical and scientific research using increasingly extensive.
Existing biochip mainly includes microflow controlled biochip and dielectrophoresis biochip etc..However, micro-fluidic life Object chip and dielectrophoresis biochip can only sub-elect a kind of bioactive substance every time and detect its content, and technical staff can not It obtains the bioactive substance sub-elected and conducts further research research.Above- mentioned information disclosed in the background technology part are only used In understanding of the reinforcement to the background of the disclosure, therefore it may include not constituting to known to persons of ordinary skill in the art existing The information of technology.
Summary of the invention
The disclosure is designed to provide a kind of separating chips and separation method, can sort and obtain target substance.
For achieving the above object, the disclosure adopts the following technical scheme that
According to the first aspect of the disclosure, a kind of separating chips are provided, for separating target substance;The separating chips Include:
Underlay substrate;
Electrode layer is set to the underlay substrate, has at least one electrode;The electrode is configured to inhale when power is off Enclosure material is adsorbed to the electrode, so that adsorbent material is detached from the electrode when being powered, the adsorbent material can be with the mesh Mark substance specific binding
Cover board, the side set on the electrode layer far from the underlay substrate, and formed between the electrode layer Chamber;The cavity covers the electrode;The through-hole of at least two connection cavity of setting on the cover board.
In a kind of exemplary embodiment of the disclosure, the separating chips further include:
Drive circuit layer is set between the underlay substrate and the electrode layer;The drive circuit layer includes at least one A switching device, the switching device connect one to one with the electrode.
In a kind of exemplary embodiment of the disclosure, the separating chips further include:
Planarization layer is set between the drive circuit layer and the electrode layer;At least one is arranged in the planarization layer Via hole, the switching device are connected one to one by the via hole and the electrode.
In a kind of exemplary embodiment of the disclosure, the switching device is thin film transistor (TFT), the thin film transistor (TFT) Drain electrode connect with the electrode, the source electrode of the thin film transistor (TFT) with a power supply for connecting, the grid of the thin film transistor (TFT) Pole with a control circuit for connecting.
In a kind of exemplary embodiment of the disclosure, the electrode layer further include:
Insulation division, the region except the electrode on the electrode layer, and the insulation division is far from underlay substrate Side is flushed with the electrode far from the side of the underlay substrate.
In a kind of exemplary embodiment of the disclosure, the quantity of the electrode is exhausted between multiple and two neighboring electrode Edge;The separating chips further include the adsorbent material,
The type of the adsorbent material is not more than the quantity of the electrode, and every kind of adsorbent material is adsorbed at least one The electrode and a kind of adsorbent material of each electrode adsorption.
In a kind of exemplary embodiment of the disclosure, the material of the cover board is transparent material.
In a kind of exemplary embodiment of the disclosure, the separating chips further include:
Shielded layer is covered in the cover board close to the surface of the electrode layer, or is covered in the cover board far from the electricity The surface of pole layer;The material of the shielded layer is transparent material.
In a kind of exemplary embodiment of the disclosure, the adsorbent material is the antibody of antibody or chemical modification.
In a kind of exemplary embodiment of the disclosure, the antibody is EpCAM and its antibody, CK and its antibody and CD45 And its at least one of antibody.
In a kind of exemplary embodiment of the disclosure, the separating chips further include at least one conducting wire, each described Conducting wire connects one to one with the electrode, for powering to the electrode.
According to the second aspect of the disclosure, a kind of separation method is provided, for separating institute by above-mentioned separating chips State target substance;The separation method includes:
Under outage condition, the adsorbent material is adsorbed in the electrode;
Under the conditions of electrode power off, the fluid to be separated containing the target substance is made to flow through the cavity;
Under electrode power on condition, extraction fluid is made to flow through the cavity;
Obtain the extraction fluid for flowing out the cavity.
The separating chips of the disclosure are provided with the electrode for having adsorbed adsorbent material, under the conditions of electrode power off, can will inhale Enclosure material is adsorbed on electrode;Under outage condition, when the fluid to be separated containing target substance flows through cavity, target substance It will be adsorbed on the electrode in conjunction with adsorbent material;After fluid to be separated all outflow cavitys, it can be imported into cavity It extracts fluid and coordination electrode is powered, adsorbent material and its target substance combined are detached from electrode and are distributed to extraction fluid at this time In, the target substance isolated from fluid to be separated can be obtained by exporting the extraction fluid.The separation that the disclosure provides Target substance can not only be sorted out from fluid to be separated, and can export the target substance sub-elected by chip Separating chips allow a technician to obtain target substance, are further analyzed and study convenient for technical staff.
Detailed description of the invention
Its example embodiment is described in detail by referring to accompanying drawing, the above and other feature and advantage of the disclosure will become It is more obvious.
Fig. 1 is the schematic perspective view of one embodiment of separating chips of the disclosure.
Fig. 2 is the schematic diagram of the section structure of one embodiment of separating chips of the disclosure.
Fig. 3 is the schematic diagram of the section structure of one embodiment of separating chips of the disclosure.
Fig. 4 is the distribution of electrodes schematic diagram of one embodiment of separating chips of the disclosure.
Fig. 5 is the adsorption control units electrical block diagram of one embodiment of separating chips of the disclosure.
Fig. 6 is the adsorption control units array distribution schematic diagram of one embodiment of separating chips of the disclosure.
Fig. 7 is the passive control circuit structural schematic diagram of one embodiment of separating chips of the disclosure.
The reference numerals are as follows for main element in figure:
1, underlay substrate;2, electrode layer;21, electrode;22, insulation division;3, cover board;31, through-hole;32, conduit;41, it seals Portion;42, cavity;5, drive circuit layer;51, switching device;6, planarization layer;61, via hole;7, shielded layer;8, conductive array;9, Conducting wire.
Specific embodiment
Example embodiment is described more fully with reference to the drawings.However, example embodiment can be real in a variety of forms It applies, and is not understood as limited to example set forth herein;On the contrary, these embodiments are provided so that the disclosure will more comprehensively and Completely, and by the design of example embodiment comprehensively it is communicated to those skilled in the art.Described feature, structure or characteristic It can be incorporated in any suitable manner in one or more embodiments.In the following description, many details are provided Embodiment of the disclosure is fully understood to provide.
In the figure for clarity, may be exaggerated the thickness of region and layer.Identical appended drawing reference indicates identical in figure Or similar structure, thus the detailed description that them will be omitted.
Described feature, structure or characteristic can be incorporated in any suitable manner in one or more embodiments. In the following description, many details are provided to provide and fully understand to embodiment of the disclosure.However, this field Technical staff will realize can with technical solution of the disclosure without one or more in the specific detail, or Person can be using other methods, constituent element, material etc..In other cases, be not shown in detail or describe known features, material or The major technique intention that person operates to avoid the fuzzy disclosure.
When certain structure is at other structures "upper", it is possible to refer to that certain structural integrity is formed in other structures, or refer to certain Structure is " direct " to be arranged in other structures, or refers to that certain structure is arranged in other structures by the way that another structure is " indirect ".
Term "one", " one ", " described " to indicate there are one or more elements/component part/etc.;Term " packet Include " and " having " to indicate the open meaning being included and refer to that the element/component part/in addition to listing waits it Outside also may be present other element/component part/etc..Term " first " and " second " etc. are only used as label, are not to it The quantity of object limits.
Disclosure embodiment provides a kind of separating chips, for separating target substance.Wherein, target substance can make a living Active substances, including but not limited to various protein, polysaccharide, polypeptide, cell fragment, organelle or cell etc. have biology living Small molecule compound, monomeric substance or the complex etc. of property.Technical staff it is clear that the target substance can be one it is single Compound or certain a kind of compound, be also possible to the more of the functional group that can be specifically bound with same adsorbent material The different types of substance of kind or complex.
As depicted in figs. 1 and 2, which includes underlay substrate 1, electrode layer 2, adsorbent material and cover board 3;Electrode layer 2 are set to underlay substrate 1, have at least one electrode 21;Electrode 21 is configured to that adsorbent material is adsorbed to electrode when power is off 21, so that adsorbent material is detached from electrode 21 when being powered, adsorbent material can be specifically bound with target substance;Cover board 3 is set to electricity Pole 2 side far from underlay substrate 1 of layer, and a cavity 42 is formed between electrode layer 2;Cavity 42 covers electrode 21;On cover board 3 The through-hole 31 of at least two connection cavitys 42 is set.
Under the conditions of electrode power off, adsorbent material can be adsorbed on electrode 21;Under outage condition, when containing target When the fluid to be separated of substance flows through cavity 42, target substance will be attracted on electrode 21 in conjunction with adsorbent material;When to After separating fluid whole outflow cavity 42, it can be imported into cavity 42 and extract fluid and the energization of coordination electrode 21, adsorbed at this time Material and its target substance combined, which are detached from electrode 21 and are distributed to, to be extracted in fluid, can be obtained by exporting the extraction fluid The target substance isolated from fluid to be separated.The separating chips that the disclosure provides, can not only be by target substance from wait divide From sorting out in fluid, and the target substance sub-elected can be exported separating chips, allow a technician to obtain Target substance is further analyzed and is studied convenient for technical staff.
Each component of the separating chips provided with reference to the accompanying drawing disclosure embodiment is described in detail:
Underlay substrate 1 can be unorganic glass substrate, pmma substrate, metal substrate etc., and technical staff can basis The requirement of separating chips selects corresponding underlay substrate 1.The size of underlay substrate 1 can be not less than electrode layer 2, can be realized Subject to the support of electrode layer 2.In one embodiment, when carrying out the preparation of separating chips, it can choose and separated with one The underlay substrate 1 that chip size matches, and electrode layer 2 and cover board 3 are prepared on underlay substrate 1.In another embodiment, Can choose a size can accommodate the substrate plate of multiple separating chips, and multiple electricity of array distribution are prepared on substrate plate Pole layer 2 obtains multiple underlay substrates 1 for carrying electrode layer 2 by cutting.
Electrode 21 can choose the conductive materials such as metal material, alloy material or tin indium oxide.For example, electrode 21 Gold be can choose as material, in order to the firm covalent bond of the formation such as electrode 21 and protein, polypeptide.The thickness of electrode 21 with Realization is capable of providing subject to electric field or thermal field, electric field or thermal field is generated when electrode 21 is powered, so that being adsorbed on electrode 21 Adsorbent material is detached from electrode 21 under electric field or thermal field effect.For example, the thickness of electrode 21 can be 10nm.Electrode 21 can To be prepared by the methods of deposition or plating, such as can be prepared by the method for physical vapour deposition (PVD).
Electrode 21 can be prepared into the various shape of needs, such as can be circle, rectangle, irregular polygon etc.. In order to facilitate the preparation of electrode 21, in one embodiment, as shown in figure 4, electrode 21 can prepare it is rectangular.
When multiple electrodes 21 are set on electrode layer 2, mutually insulated between each electrode 21, to guarantee each electrode 21 It can independent control.For example, it is mutually not attached between each electrode 21 and there are gap, so between each electrode 21 mutually absolutely Edge.It is real one in order to reduce turbulent flow when fluid flows through 2 surface of electrode layer since the presence in gap leads to 2 out-of-flatness of electrode layer It applies in mode, insulation division 22 can be set in the region except 2 top electrode 21 of electrode layer, as shown in figure 3, insulation division 22 is far from lining The side of substrate 1 is flushed with electrode 21 far from the side of underlay substrate 1.
The competitive adsorption for detecting substance is treated in order to which the insulation division 22 guaranteed between electrode 21 divides, in an embodiment In, it can be between electrode 21 partially with the material modification for being able to suppress substance absorption to be detected.
The quantity of electrode 21 is not more than the type of adsorbent material, so that at most only adsorbing a kind of absorption on each electrode 21 Material and every kind of adsorbent material are adsorbed at least one electrode 21.For example, in one embodiment, the quantity of electrode 21 is more In the type of adsorbent material, then a kind of adsorbent material is only set, and can set on multiple and different electrodes 21 on each electrode 21 Set same adsorbent material.In this way, one kind included in the fluid to be separated be difficult in conjunction with corresponding adsorbent material or When the low-down target substance of content, it can be improved by adsorbing corresponding adsorbent material in multiple electrodes 21 to the target The separation rate of substance.
In another embodiment, the quantity of electrode 21 can be identical as the number of species of adsorbent material, so various types of Adsorbent material is adsorbed in electrode 21 correspondingly.
Adsorbent material can for hydrogel, the silica gel of chemical modification, protein or the protein of chemical modification, nucleotide and Its chemical modification object, phosphatide and its peptide modified object, polysaccharide and its peptide modified object etc., are also possible to the mixing of above-mentioned material Object or other materials with similar functions.
In one embodiment, above-mentioned adsorbent material can be antibody, and antibody can directly adsorb on electrode, can also be with By being adsorbed on electrode after chemical modification, it can also be adsorbed or be constrained in framework material and as framework material is adsorbed onto On electrode, or it is adsorbed on electrode by other means.According to the type of target substance, technical staff can choose suitable Antibody or antibody combination, or antibody is modified by chemical method.For example, antibody can be CK (cell factor) And its in antibody, CD45 (leukocyte common antigen) and its antibody and EpCAM (epithelial cell adhesion molecule) and its antibody extremely Few one kind.
In another embodiment, the adsorbent material can be gel, such as can be for adsorb adenosine, glycoprotein, The P (NIPAAm-co-AAPBA) of the substances such as enzyme is also possible to the P (NIPAAm-co-VPBA) for adsorbed proteins, both Hydrogel can adsorb on the electrode, and be detached from electrode as electrode energization generates thermal field.
In one embodiment, adsorbent material can be adsorbed in advance on electrode 21, so when using the separating chips, Detached job personnel are not necessarily to the step be adsorbed onto adsorbent material on electrode 21, improve the simplicity of separating chips application Property.Meanwhile the problem being accurately adsorbed onto adsorbent material on corresponding electrode 21 is difficult to this also avoids detached job personnel, it protects Adsorbent material precision corresponding with the position of electrode 21 is demonstrate,proved.In another embodiment, which can not include the suction Enclosure material, detached job personnel can obtain adsorbent material matched with the separating chips or be adsorbed by other approach Material, before carrying out detached job, which is adsorbed on corresponding electrode by detached job personnel, then separates target Substance.In this way, detached job personnel not only more flexible selection adsorbent material and can carry out detached job, but also can keep away Exempt from the problem of adsorbent material is adsorbed onto the preservation inconvenience that may cause on electrode in advance or is easy failure.
When the quantity of adsorbent material is multiple, the separating chips of the disclosure can sub-elect multiple target substances simultaneously, And can take out the multiple target substances sub-elected from separating chips one by one, it avoids providing the mixing of multiple target substances Object.For example, when the type of adsorbent material is three, when fluid to be separated flows through 21 surface of electrode of separating chips, then Three kinds of adsorbent materials adsorb a kind of target substance respectively, adsorb while realization to three kinds of target substances.Exporting stream to be separated Body and after importing and extracting fluid, controls the corresponding electrode 21 of the first adsorbent material and is powered, then the first adsorbent material is in electric field Or thermal field effect under from be detached from corresponding electrode 21 and be distributed to extract fluid in;Meanwhile the corresponding electricity of other adsorbent materials Pole 21 remains powered off, other adsorbent materials are still adsorbed on corresponding electrode 21;In this way, only including first in the extraction fluid Adsorbent material and corresponding target substance can obtain the target substance by exporting the extraction fluid.It so repeats, successively obtains Obtain other two kinds of target substances.
Adsorbent material can be adsorbed on electrode 21 by various ways.For example, when the suction of separating chips It, can be by importing the buffer solution containing the adsorbent material in the cavity 42 to the separating chips when enclosure material type is a kind of And electrode 21 is kept to power off, so that the adsorbent material is adsorbed on electrode 21.Of course, electricity can also be covered on cover board 3 Before on pole layer 2, the buffer solution containing the adsorbent material is added drop-wise to the position of corresponding electrode 21 by way of dropping liquid, So that adsorbent material is adsorbed on electrode 21.In order to realize that single adsorption material is adsorbed on the electrode 21 of separating chips, technology Personnel are also an option that other feasible modes, in this regard, disclosure embodiment will not enumerate.
When adsorbent material type is multiple, adsorbent material can be adsorbed before cover board 3 is covered on electrode layer 2 Onto corresponding electrode 21.For example, in one embodiment, the buffer solution containing the first adsorbent material can be dripped It adds on corresponding electrode 21, and the buffer solution is made not enter other 21 corresponding regions of electrode, when the first adsorbent material After being adsorbed on corresponding electrode 21, the buffer solution is removed.Then, in the method successively by other kinds of adsorbent material It is adsorbed on corresponding electrode 21.In another embodiment, each adsorbent material is prepared into a kind of buffer solution, Duo Zhonghuan It rushes solution to be added drop-wise to respectively on corresponding electrode 21, and each buffer solution is made not enter other corresponding areas of electrode 21 Domain removes each buffer solution after adsorbent material is adsorbed on corresponding electrode 21.In this way, various types of adsorption material can be made Expect while being adsorbed on corresponding electrode 21, saves the preparation time of separating chips.Of course, technical staff is also an option that it His feasible mode, so that a variety of adsorbent materials are adsorbed onto respectively on corresponding electrode 21.
Cover board 3 can be connect by joint filling material with electrode layer 2.The joint filling material can be sealing compound, metal, alloy etc. Material, technical staff, which can according to need, to be selected.When cover board 3 is connect with electrode layer 2, joint filling material can be coated in The edge of electrode layer 2 or the edge of cover board 3 are bonded after being then directed at cover board 3 with electrode layer 2.As shown in Figure 2 and Figure 4, when After cover board 3 is bonded with electrode layer 2, joint filling material is clipped between electrode layer 2 and cover board 3, forms surrounding electric poles layer 2 and 3 side of cover board The mouth-sealed portion 41 of edge.
The material of cover board 3 can be transparent material, such as glass, plastics, resin.In this way, can be seen by optical device The target substance adsorbed on electrode 21 is examined, so that the separating chips are provided simultaneously with the function of analysis detection.
31 quantity of through-hole on cover board 3 can be two or more.For example, as shown in Fig. 2, implementing one In mode, two through-holes 31 of first through hole and the second through-hole can be set on cover board 3, first through hole enters as the fluid of cavity 42 Mouthful, fluid outlet of second through-hole as cavity 42.Both ends or phase in cover board 3 can be set in first through hole and the second through-hole Pair two corners, so as to make fluid in cavity 42 flow through area maximize.It in another embodiment, can be on cover board 3 Two groups of through-holes 31 are set, and every group of through-hole 31 includes multiple through-holes 31, and one group of through-hole 31 is linearly distributed in cover board 3 to arrangement One end, another group of through-hole 31 are linearly distributed in arrangement the other end of cover board 3;One group of two groups of through-holes 31 can be used as cavity 42 fluid inlet, another group of fluid outlet that can be used as cavity 42.The distribution of through-hole 31 of two groups of straight lines arrangement is used as feed liquor Mouth and liquid outlet, can make the flowing of fluid each position in cavity 42 more uniform, that is, facilitate to reduce fluid flowing Dead angle, and make stroke of the fluid each section in cavity 42 more uniform, so that the fluid environment that each electrode 21 faces It is more uniform.
As shown in Figures 2 and 3, cavity 42 is surrounded jointly by mouth-sealed portion 41, electrode layer 2 and cover board 3 and is formed.Cavity 42 needs With certain thickness, allow fluid to flow in cavity 42.In order to realize making full use of to electrode 21, cavity 42 can To cover all electrodes 21 on electrode layer 2.
As shown in figure 3, the separating chips that the disclosure provides can also include drive circuit layer 5, drive circuit layer 5 is set to lining Between substrate 1 and electrode layer 2;Drive circuit layer 5 includes at least one switching device 51, and switching device 51 and electrode 21 are one by one It is correspondingly arranged and connects.In this way, can by switching device 51 come coordination electrode 21 energization whether.
As shown in Figure 1, the separating chips can also be in drive circuit layer 5 in order to realize the control to switching device 51 Edge prepares conductive array 8, and conductive array 8 is for control switch device 51 and has golden finger structure, so as to as separating core The external line interface of piece.The conductive array 8 can be realized by the methods of depositing, being electroplated.
As shown in figure 3, the separating chips that the disclosure provides can also include planarization layer 6, planarization layer 6 is set to driving electricity Between road floor 5 and electrode layer 2;At least one via hole 61 is arranged in planarization layer 6, and switching device 51 passes through via hole 61 and electrode 21 1 One is correspondingly connected with.
For example, as shown in figure 5, the switching device 51 can be thin film transistor (TFT), thin film transistor (TFT) and via hole 61, electricity Pole 21 is arranged in a one-to-one correspondence, and the drain electrode of each thin film transistor (TFT) is connected by corresponding via hole 61 with corresponding electrode 21, so One thin film transistor (TFT) and corresponding electrode 21 form an adsorption control units.The source electrode and grid of each thin film transistor (TFT) point It is not connect with conductive array 8, the source electrode of thin film transistor (TFT) can be connect by conductive array 8 with a power supply, in thin film transistor (TFT) When conducting, which can power to electrode;The grid of thin film transistor (TFT) can be connected by conductive array 8 and a control circuit It connects, which can export control signal, and then the conducting between the drain electrode and source electrode of control thin film transistor (TFT) to grid With disconnection, and then energization and power-off to electrode is controlled, the final control realized to the electric field or thermal field of electrode.As shown in fig. 6, When target substance is a variety of, which can be arranged multiple adsorption control units in array, and can pass through active control The mode of system realizes the independent control to each adsorption control units.
Planarization layer 6 can provide a flat plane for electrode layer 2, convenient for the arrangement of electrode 21.Planarization layer 6 can To select insulating materials, such as SiN, SiO2Or PI (polyimides) etc., so that being isolated between electrode layer 2 and drive circuit layer 5 And it insulate.
There are many modes that electrode layer 2 is arranged on planarization layer 6, and technical staff can select according to production status It selects.For example, in one embodiment, a metal layer can be formed far from the side of underlay substrate 1 in planarization layer 6, so Afterwards by semiconductor technologies such as gluing, exposure, development, etchings, by the metallic layer graphic, the metal layer part of reservation is as electricity Pole 21.In order to enable 2 surfacing of electrode layer, it can also be in one layer of 6 region overlay of planarization layer insulation of non-electrode 21 covering Layer is used as insulation division 22, and the thickness of insulation division 22 and the thickness of metal layer are identical.
In another embodiment, groove can be etched on planarization layer 6, then by the non-recessed portion of planarization layer 6 Divide and protect with photoresist, then forms one layer of metal layer in whole surface, the thickness of the metal layer and the depth of groove are identical.Stripping From photoresist, then the metal layer in groove maintains an equal level as electrode 21 with the surface of planarization layer 6.In this embodiment, flat Change layer 6 a part and 2 same layer of electrode layer far from underlay substrate 1 to be arranged.
As shown in Figure 1 and Figure 7, in the other embodiments of the disclosure, conductive array is can be set in the edge of electrode layer 2 8, conductive array 8 connects corresponding electrode 21 by conducting wire 9;Conducting wire 9 can be arranged with electrode 21 with same layer, to supply to electrode 21 Electricity.In this way, whether the energization of each electrode 21 being controlled by way of Passive Shape Control (passive manage).
As shown in Figures 2 and 3, separating chips can also include shielded layer 7, which covers cover board 3, and can set In cover board 3 close to the side of underlay substrate 1, side of the cover board 3 far from underlay substrate 1 can also be set to.Shielded layer 7 selects conduction Material generates interference to chip to avoid separating chips external charge.For the ease of the mesh adsorbed on electrode 21 from cover board 3 The case where marking substance, which can choose transparent material.For example, which can choose ITO (indium oxide Tin), graphene, CNT (carbon nanotube), IGO (indium gallium oxide) or IGZO (indium gallium zinc oxide) etc..
As shown in Figures 2 and 3, which can also include at least two conduits 32, and conduit 32 can correspond Connect with through-hole 31.Conduit 32 can be used for the connection with external equipment, so that external equipment is to the cavity 42 of separating chips Injection fluid exports fluid from cavity 42.In one embodiment, which selects flexible material, such conduit 32 can bend, when conduit 32 is connect with external equipment, will not result in separating chips displacement, bear excessive stresses or It damages.In another embodiment, which may include metal tube and rubber tube, and metal tube directly connects with through-hole 31 It connects, rubber tube is connect with metal tube.
Need to illustrate when, prepare disclosure embodiment separating chips when, both can preparation one by one individually divide Off-chip piece can also first prepare the overall structure that array distribution has the separating chips, then be formed by way of cutting single Separating chips.The array distribution has in the overall structure of the separating chips, and the underlay substrate 1 of each separating chips can be one A part of monolith substrate plate, and the cover board 3 of each separating chips can be a part of 3 plate of a monolith cover board, in base Electrode layer 2 and cavity 42 corresponding with electrode layer 2 are distributed in array between 3 plate of plate plate and cover board.
Disclosure embodiment also provides a kind of separator comprising above-mentioned separating chips.The separator is used for The work of separating chips is controlled, realization separates target substance from fluid to be separated.
In one embodiment, which further includes controller, liquid pump and liquid trap, controller and the separating core Whether piece connects and is used for the energization of coordination electrode 21, the through-hole 31 of liquid pump connection separating chips simultaneously controls fluid flow into cavity 42 and outflow cavity 42;Liquid trap connect with liquid pump and is used to collect extraction fluid flowing out from cavity 42, needing to retain.
In another embodiment, which may include multiple separating chips, to improve separation dress The efficiency and speed for the extraction target substance set.
Point in the embodiment of separating chips and above-mentioned separating chips that the separator of disclosure embodiment uses Off-chip piece is identical, and therefore, beneficial effect having the same, details are not described herein.
It should be appreciated that the disclosure is not limited in its application to the detailed construction and arrangement of the component of this specification proposition Mode.The disclosure can have other embodiments, and can realize and execute in many ways.Aforesaid deformation form and Modification is fallen within the scope of this disclosure.It should be appreciated that this disclosure and the disclosure of restriction extend in text And/or it is mentioned in attached drawing or all alternative combinations of two or more apparent independent features.It is all these different Combination constitutes multiple alternative aspects of the disclosure.Embodiment described in this specification illustrates to become known for realizing the disclosure Best mode, and those skilled in the art will be enable using the disclosure.

Claims (12)

1. a kind of separating chips, for separating target substance, which is characterized in that the separating chips include:
Underlay substrate;
Electrode layer is set to the underlay substrate, has at least one electrode;The electrode is configured to adsorption material when power is off Material is adsorbed to the electrode, so that adsorbent material is detached from the electrode when being powered, the adsorbent material can be with the object Matter specific binding;
Cover board, the side set on the electrode layer far from the underlay substrate, and a cavity is formed between the electrode layer;Institute It states cavity and covers the electrode;The through-hole of at least two connection cavity of setting on the cover board.
2. separating chips according to claim 1, which is characterized in that the separating chips further include:
Drive circuit layer is set between the underlay substrate and the electrode layer;The drive circuit layer includes that at least one is opened Device is closed, the switching device connects one to one with the electrode.
3. separating chips according to claim 2, which is characterized in that the separating chips further include:
Planarization layer is set between the drive circuit layer and the electrode layer;At least one via hole is arranged in the planarization layer, The switching device is connected one to one by the via hole and the electrode.
4. separating chips according to claim 2, which is characterized in that the switching device is thin film transistor (TFT), described thin The drain electrode of film transistor is connect with the electrode, and for the source electrode of the thin film transistor (TFT) for connecting with a power supply, the film is brilliant The grid of body pipe with a control circuit for connecting.
5. separating chips according to claim 1, which is characterized in that the electrode layer further include:
Insulation division, the region except the electrode on the electrode layer, and side of the insulation division far from underlay substrate It is flushed with the electrode far from the side of the underlay substrate.
6. separating chips according to claim 1, which is characterized in that the quantity of the electrode is multiple and two neighboring electricity It insulate between pole;
The separating chips further include the adsorbent material, and the type of the adsorbent material is not more than the quantity of the electrode;Often The kind adsorbent material is adsorbed at least one described electrode and a kind of adsorbent material of each electrode adsorption.
7. separating chips according to claim 1, which is characterized in that the material of the cover board is transparent material.
8. separating chips according to claim 1, which is characterized in that the separating chips further include:
Shielded layer is covered in the cover board close to the surface of the electrode layer, or is covered in the cover board far from the electrode layer Surface;The material of the shielded layer is transparent material.
9. separating chips according to claim 1, which is characterized in that the adsorbent material is the anti-of antibody or chemical modification Body.
10. separating chips according to claim 9, which is characterized in that the antibody be EpCAM and its antibody, CK and its Antibody and one of CD45 and its antibody or a variety of.
11. separating chips according to claim 1, which is characterized in that the separating chips further include at least one conducting wire, Each conducting wire connects one to one with the electrode, for powering to the electrode.
12. a kind of separation method, for separating the object by the described in any item separating chips of claim 1~11 Matter, which is characterized in that the separation method includes:
Under outage condition, the adsorbent material is adsorbed in the electrode;
Under the conditions of electrode power off, the fluid to be separated containing the target substance is made to flow through the cavity;
Under electrode power on condition, extraction fluid is made to flow through the cavity;
Obtain the extraction fluid for flowing out the cavity.
CN201811057775.7A 2018-09-11 2018-09-11 Separating chips and separation method Pending CN109136087A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201811057775.7A CN109136087A (en) 2018-09-11 2018-09-11 Separating chips and separation method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811057775.7A CN109136087A (en) 2018-09-11 2018-09-11 Separating chips and separation method

Publications (1)

Publication Number Publication Date
CN109136087A true CN109136087A (en) 2019-01-04

Family

ID=64824540

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201811057775.7A Pending CN109136087A (en) 2018-09-11 2018-09-11 Separating chips and separation method

Country Status (1)

Country Link
CN (1) CN109136087A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109234158A (en) * 2018-10-08 2019-01-18 北京京东方技术开发有限公司 Biochip and its manufacturing method, operating method, biological detection system
CN110064449A (en) * 2019-05-17 2019-07-30 北京京东方传感技术有限公司 A kind of biology drop detection substrate and preparation method thereof and detection device
WO2022184093A1 (en) * 2021-03-03 2022-09-09 华联生物科技股份有限公司 Bioelectronic system for rare cell separation and application thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1337580A (en) * 2000-08-08 2002-02-27 清华大学 Solid molecule operating method in microfluid system
CN1865959A (en) * 2006-06-01 2006-11-22 复旦大学 Electrode array microchip sensor, preparation method and application therefor
CN101201350A (en) * 2007-08-29 2008-06-18 刘文韬 Biochip system capable of rapidly hybridization and detection of biomolecule with high sensibility and method thereof
WO2010124227A2 (en) * 2009-04-24 2010-10-28 The Board Of Trustees Of The University Of Illinois Methods and devices for capturing circulating tumor cells
CN103998932A (en) * 2011-06-29 2014-08-20 中央研究院 Capture, purification and release of biological substance using a surface coating

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1337580A (en) * 2000-08-08 2002-02-27 清华大学 Solid molecule operating method in microfluid system
CN1865959A (en) * 2006-06-01 2006-11-22 复旦大学 Electrode array microchip sensor, preparation method and application therefor
CN101201350A (en) * 2007-08-29 2008-06-18 刘文韬 Biochip system capable of rapidly hybridization and detection of biomolecule with high sensibility and method thereof
WO2010124227A2 (en) * 2009-04-24 2010-10-28 The Board Of Trustees Of The University Of Illinois Methods and devices for capturing circulating tumor cells
CN103998932A (en) * 2011-06-29 2014-08-20 中央研究院 Capture, purification and release of biological substance using a surface coating

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109234158A (en) * 2018-10-08 2019-01-18 北京京东方技术开发有限公司 Biochip and its manufacturing method, operating method, biological detection system
CN110064449A (en) * 2019-05-17 2019-07-30 北京京东方传感技术有限公司 A kind of biology drop detection substrate and preparation method thereof and detection device
CN110064449B (en) * 2019-05-17 2021-09-03 北京京东方传感技术有限公司 Biological liquid drop detection substrate, preparation method thereof and detection device
WO2022184093A1 (en) * 2021-03-03 2022-09-09 华联生物科技股份有限公司 Bioelectronic system for rare cell separation and application thereof

Similar Documents

Publication Publication Date Title
CN109136087A (en) Separating chips and separation method
US10967387B2 (en) Continuous whole-chip 3-dimensional DEP cell sorter and related fabrication method
CN101250483B (en) Combined splint microelectrode type micro-fluidic dielectrophoresis cell separation and enrichment chip
Li et al. Continuous dielectrophoretic cell separation microfluidic device
Wu et al. A planar dielectrophoresis-based chip for high-throughput cell pairing
US7189359B2 (en) Electrowetting electrode device with electromagnetic field for actuation of magnetic-bead biochemical detection system
CN103170383B (en) Nano-material electrode modification based electrochemical integrated digital micro-fluidic chip
CN107115897B (en) Microfluidic chip and manufacturing method thereof
CN105647799B (en) A kind of circulating tumor cell separator of combined type field flow separation
CN103894248A (en) Micro-fluidic chip and micro-fluidic chip system for single cell analysis and single cell analyzing method
US20190070606A1 (en) Injection molded microfluidic/fluidic cartridge integrated with silicon-based sensor
CN104870093B (en) Manipulation object in microfluidic device carried out using outer electrode
TWI616534B (en) Method and device for purifying and separating blood circulation tumor cells using non-contact and automatic identification
CN109865542A (en) Microparticle multichannel timesharing separator and method based on the oblique finger transducer of arc
CN105136893A (en) Thin film transistor biosensor and preparation method thereof
Kentsch et al. Microdevices for separation, accumulation, and analysis of biological micro-and nanoparticles
CN105797792A (en) Driving method for low-voltage medium liquid drops on digital microfluidic chip
JPWO2002023180A1 (en) Extraction equipment and chemical analysis equipment
CN106694069A (en) Gathering device based on ion concentration polarization technology and preparation method of gathering device
CN110192096B (en) Device and detection apparatus for detecting biological substance, method for measuring ion current, and method for identifying biological substance
TW201736819A (en) Biological micro-particle capture and retrieval system and method especially for capturing a single target biological micro particle and separating from the liquid specimen
CN106190828A (en) A kind of cell Multistage filtering device based on dielectrophoresis effect
CN104923322B (en) A kind of dielectrophoretic particles sorting micro-fluidic chip
CN103412024A (en) Integrated electrochemical sensing chip
CN106085845A (en) Cell electroporation chip apparatus based on U-shaped groove microelectrode array and processing method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination