CN101592627B - Method for manufacturing and integrating multichannel high-sensitive biosensor - Google Patents
Method for manufacturing and integrating multichannel high-sensitive biosensor Download PDFInfo
- Publication number
- CN101592627B CN101592627B CN 200910030342 CN200910030342A CN101592627B CN 101592627 B CN101592627 B CN 101592627B CN 200910030342 CN200910030342 CN 200910030342 CN 200910030342 A CN200910030342 A CN 200910030342A CN 101592627 B CN101592627 B CN 101592627B
- Authority
- CN
- China
- Prior art keywords
- silicon
- silicon chip
- earlier
- lithography
- nanowires
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 64
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims abstract description 130
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 130
- 239000010703 silicon Substances 0.000 claims abstract description 130
- 239000004205 dimethyl polysiloxane Substances 0.000 claims abstract 4
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims abstract 4
- 239000002070 nanowire Substances 0.000 claims description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 43
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- 239000000243 solution Substances 0.000 claims description 32
- 238000002161 passivation Methods 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 238000000276 deep-ultraviolet lithography Methods 0.000 claims description 22
- 239000000377 silicon dioxide Substances 0.000 claims description 22
- 238000001514 detection method Methods 0.000 claims description 20
- 235000012239 silicon dioxide Nutrition 0.000 claims description 19
- 230000004048 modification Effects 0.000 claims description 17
- 238000012986 modification Methods 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 15
- 238000001465 metallisation Methods 0.000 claims description 15
- 229910052581 Si3N4 Inorganic materials 0.000 claims description 12
- HQVNEWCFYHHQES-UHFFFAOYSA-N silicon nitride Chemical compound N12[Si]34N5[Si]62N3[Si]51N64 HQVNEWCFYHHQES-UHFFFAOYSA-N 0.000 claims description 12
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 claims description 12
- 238000013459 approach Methods 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 10
- 238000007254 oxidation reaction Methods 0.000 claims description 10
- 238000000623 plasma-assisted chemical vapour deposition Methods 0.000 claims description 10
- 238000006116 polymerization reaction Methods 0.000 claims description 10
- 239000007853 buffer solution Substances 0.000 claims description 9
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 238000001312 dry etching Methods 0.000 claims description 9
- 230000003628 erosive effect Effects 0.000 claims description 9
- 229920005573 silicon-containing polymer Polymers 0.000 claims description 9
- 230000007797 corrosion Effects 0.000 claims description 8
- 238000005260 corrosion Methods 0.000 claims description 8
- 238000005530 etching Methods 0.000 claims description 7
- 230000012010 growth Effects 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000008363 phosphate buffer Substances 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 150000001299 aldehydes Chemical class 0.000 claims description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 229960002163 hydrogen peroxide Drugs 0.000 claims description 5
- 150000001455 metallic ions Chemical class 0.000 claims description 5
- 238000001259 photo etching Methods 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 235000011149 sulphuric acid Nutrition 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 238000002294 plasma sputter deposition Methods 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000005034 decoration Methods 0.000 claims description 2
- WZJVQUUBEVDURL-UHFFFAOYSA-N pentanedial;phosphoric acid Chemical compound OP(O)(O)=O.O=CCCCC=O WZJVQUUBEVDURL-UHFFFAOYSA-N 0.000 claims description 2
- 239000001117 sulphuric acid Substances 0.000 claims description 2
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 claims description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims 2
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims 2
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims 2
- 201000010099 disease Diseases 0.000 abstract description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 17
- 230000005669 field effect Effects 0.000 abstract description 10
- 230000035945 sensitivity Effects 0.000 abstract description 10
- 241000700605 Viruses Species 0.000 abstract description 3
- -1 polydimethylsiloxane Polymers 0.000 abstract description 3
- 108090000623 proteins and genes Proteins 0.000 abstract description 3
- 102000004169 proteins and genes Human genes 0.000 abstract description 3
- 230000010354 integration Effects 0.000 abstract description 2
- 150000003384 small molecules Chemical class 0.000 abstract 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 12
- 239000012498 ultrapure water Substances 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000004065 semiconductor Substances 0.000 description 8
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 7
- 230000008901 benefit Effects 0.000 description 6
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 5
- 125000003636 chemical group Chemical group 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 150000002500 ions Chemical group 0.000 description 5
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000001459 lithography Methods 0.000 description 4
- 230000002572 peristaltic effect Effects 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 238000004140 cleaning Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000643 oven drying Methods 0.000 description 3
- 238000001020 plasma etching Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 239000004642 Polyimide Substances 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- JWVBTTKFMLEQAJ-UHFFFAOYSA-N azane trichloro(propyl)silane Chemical compound C(CC)[Si](Cl)(Cl)Cl.N JWVBTTKFMLEQAJ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
- 238000013016 damping Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000009616 inductively coupled plasma Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 239000011810 insulating material Substances 0.000 description 2
- 238000010884 ion-beam technique Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229920001721 polyimide Polymers 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- CPRMKOQKXYSDML-UHFFFAOYSA-M rubidium hydroxide Chemical compound [OH-].[Rb+] CPRMKOQKXYSDML-UHFFFAOYSA-M 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- LLNQRNOPJAFMFQ-UHFFFAOYSA-N 11-bromoundecyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CCCCCCCCCCCBr LLNQRNOPJAFMFQ-UHFFFAOYSA-N 0.000 description 1
- CXDHJGCWMIOAQP-UHFFFAOYSA-N 2-pyridin-3-yl-1,4,5,6-tetrahydropyrimidine;hydrochloride Chemical compound Cl.C1CCNC(C=2C=NC=CC=2)=N1 CXDHJGCWMIOAQP-UHFFFAOYSA-N 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical compound C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- 208000017843 C syndrome Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 101710142246 External core antigen Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- HEMINMLPKZELPP-UHFFFAOYSA-N Phosdiphen Chemical compound C=1C=C(Cl)C=C(Cl)C=1OP(=O)(OCC)OC1=CC=C(Cl)C=C1Cl HEMINMLPKZELPP-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108010036226 antigen CYFRA21.1 Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- HAYXDMNJJFVXCI-UHFFFAOYSA-N arsenic(5+) Chemical compound [As+5] HAYXDMNJJFVXCI-UHFFFAOYSA-N 0.000 description 1
- BEWYHVAWEKZDPP-UHFFFAOYSA-N bornane Chemical compound C1CC2(C)CCC1C2(C)C BEWYHVAWEKZDPP-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000005380 borophosphosilicate glass Substances 0.000 description 1
- 208000030303 breathing problems Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 238000005468 ion implantation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000004518 low pressure chemical vapour deposition Methods 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- GHWAWUSLARFVNH-UHFFFAOYSA-N methyl 3-trichlorosilylpropanoate Chemical compound COC(=O)CC[Si](Cl)(Cl)Cl GHWAWUSLARFVNH-UHFFFAOYSA-N 0.000 description 1
- NMJJFJNHVMGPGM-UHFFFAOYSA-N n-butylmethanoate Natural products CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000004528 spin coating Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- NBZBQHNWIXSPLW-UHFFFAOYSA-N tert-butyl n-dec-9-enylcarbamate Chemical compound CC(C)(C)OC(=O)NCCCCCCCCC=C NBZBQHNWIXSPLW-UHFFFAOYSA-N 0.000 description 1
- ZOYFEXPFPVDYIS-UHFFFAOYSA-N trichloro(ethyl)silane Chemical compound CC[Si](Cl)(Cl)Cl ZOYFEXPFPVDYIS-UHFFFAOYSA-N 0.000 description 1
- RCHUVCPBWWSUMC-UHFFFAOYSA-N trichloro(octyl)silane Chemical compound CCCCCCCC[Si](Cl)(Cl)Cl RCHUVCPBWWSUMC-UHFFFAOYSA-N 0.000 description 1
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 1
- 239000005052 trichlorosilane Substances 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 238000001039 wet etching Methods 0.000 description 1
Images
Abstract
The invention provides a method for manufacturing and integrating a multichannel high-sensitive biosensor. The method comprises the following steps: firstly, based on an SOI silicon chip, adopting a top-down method to manufacture an FET field effect transistor of a silicon nanometer wire; secondly, utilizing polydimethylsiloxane (PDMS) to manufacture a plurality of microfluid channels; and finally, modifying the silicon nanometer wires in different microfluid channels to allow the silicon nanometer wire to be modified with different detecting antibodies and small molecules for detecting different target molecules. The sensor manufacture by the method can be used for simultaneously detecting relevant factors (such as DNA, RNA, protein and the like) or virus of different types of diseases and has the characteristics of high sensitivity, stability, easy integration and the like.
Description
Technical field
The present invention relates to a kind of method of making integrated multichannel high-sensitive biosensor, be specifically related to a kind of method based on SOI fabrication techniques silicon nano-wire biological sensor.
Background technology
At present, diabetes, cardiovascular disease, breathing problem, hepatopathy, cancer are the major diseases that threatens human health.Though medical science and related discipline make constant progress, people still make slow progress on the fast diagnosis and treatment of these diseases; If these diseases can not be able to timely find that disease almost is to be difficult to treatment when arriving late period.And the reason that disease can not found early is, one of which, and when early stage, it is not obvious that related diseases is sent out characteristic, and the GAP-associated protein GAP factor quantity of its secretion is less relatively, is not easy to detect with present detection means; Its two, promptly enable to detect relevant disease factor, expense that it is required and time also are many; Therefore, develop and a kind ofly have high sensitivity, detect the sensor of relevant disease fast, cheaply, the diagnosis and treatment of the healthy major disease of harm humans are had far reaching significance.
Be compared to traditional detection device; Field effect FET sensor based on nano wire has following advantage: one, high sensitivity; At first field effect transistor itself just has the effect that signal amplifies, and can amplify a spot of charge signal that effect is got on; Secondly, since the big specific surface area that nano wire itself is had, quantum confined effect etc., and feasible field effect FET sensor based on nano wire has very high sensitivity (Yi Cui, Science Vol 293,1289～1293,2001); Two, quick, can reach the frequency of GHz based on the speed of the semi-conductor chip of silicon, and based on the field effect FET sensor of silicon nanowires even possibly reach higher speed, this compares with traditional detection device, its detection speed is very fast; Three, be easy to integrated and high throughput testing; Compare with checkout equipment with traditional sensors; Have easy of integration and advantage cheaply based on the nanowire field-effect sensor; Because the manufacturing process of device is thought compatibility with semiconductor technology fully, therefore easily with ripe semi-conductor industry and emerging industries such as MEMS compatibility, thereby can obtain the sensor of feature richness, superior performance.Silicon is very abundant at the content of occurring in nature, and simultaneously, the conventional semiconductor industrial technology can reduce device cost.
The most of sensor that has existed at present is based on the sensor of electrochemical principle; Perhaps based on optical principle; Also there are some sensors based on field effect FET; Even some field effect FET sensors based on nanometer technology are arranged, even also these several kinds of modes are combined the sensor of formation.The technological comparative maturity of electrochemical sensor, but compare, solution environmental is required than higher, and volume is also relatively big.And present sensor mainly is to detect to a kind of single target molecule, because a lot of with the molecule of any disease association, and they possibly be separate; Therefore, detect a kind of existence of disease more accurately, must carry out joint-detection multiple disease factor.Patent CN101144809A utilizes argent as surface plasma excimer, and antigen molecule in chemical group in its finishing and connection is through strengthening the intensity of local surface plasma resonance, the sensitivity that improves biomolecule detection.By comparison, be core with the nano thread structure, adopt field effect transistor to realize signals collecting and amplification, can more effective detection signal.Patent CN1585896A utilizes the FET sensor to detect ion concentration and base sequence; Because there are the debye wavelength in charged ion or base sequence in solution; If therefore ion and base sequence are when conducting channel is relatively far away, the sensitivity of its detection also sharply descends.
Summary of the invention
The objective of the invention is to overcome the deficiency that prior art exists, a kind of making integrated approach of multichannel high-sensitive biosensor is provided.
The object of the invention is realized through following technical scheme:
The making integrated approach of multichannel high-sensitive biosensor may further comprise the steps---
(1) adopts the silicon nanowires of method making from top to bottom FET FET based on soi wafer;
(2) utilize dimethyl silicone polymer (PDMS) to produce many microfluid passage;
(3) silicon nanowires in the different microfluid passage is carried out modification, make it to modify different detection antibody or micromolecule, to detect different target molecules.
Further, the making integrated approach of above-mentioned multichannel high-sensitive biosensor, step () comprises following operation:
1) silicon chip cleans, and silicon chip is respectively at 7: 3 the concentrated sulphuric acid and oxydol, and 60 degree heating are 10～15 minutes in 1: 3: 7 ammoniacal liquor and the aqueous hydrogen peroxide solution, 1: 2: 8 hydrochloric acid and aqueous hydrogen peroxide solution, contained organism and the metallic ion of removal silicon chip surface;
2) wafer thinning, earlier with silicon chip in oxidation furnace with wet oxygen or dry-oxygen oxidation, use buffered hydrofluoric acid solution erosion removal silicon dioxide again, make silicon chip reach required thickness, and the surface slightly release souls from purgatory compare less;
3) etching mask growth is with PECVD or plasma sputtering method on silicon chip, the grow silicon dioxide or the silicon nitride film of one deck 20～200 nanometer thickness;
4) back of the body grid are made, and with the method for back of the body grid masterplate through deep-UV lithography, again through the IBE dry etching, on silicon chip, make and obtain carrying on the back gate pattern earlier;
5) silicon nanowires is made; Earlier with the method for silicon nanowires masterplate through deep-UV lithography; Use the IBE dry etching again; Use tetramethyl ammonium hydroxide solution anisotropic etch silicon again, erosion removal silicon dioxide in 5: 1 buffered hydrofluoric acid solutions at last, thereby obtain width at 1～1000nm, height at the good silicon nanowires of the homogeneity of 1～500nm;
6) metallization, with the method for metallization masterplate through deep-UV lithography, the method through peeling off makes silicon chip line and grid, source electrode and drain metallization more earlier;
7) passivation, earlier with the method for passivation masterplate through deep-UV lithography, the same PECVD method of using all covers the last layer passivation layer in the place of silicon chip surface except that silicon nanowires and grid, source, drain electrode.
Further, the making integrated approach of above-mentioned multichannel high-sensitive biosensor, step (two) comprises following operation:
1) stamp fabrication utilizes the method for photoetching on silicon chip, to make earlier and obtains the microchannel mould;
2) build model, the PDMS performed polymer is poured on the microchannel mould, and placed 24 hours, make it complete polymerization;
3) surface modification, the wafer that will pass through step () are under nitrogen protection, and corrosion is 5 seconds in buffered hydrofluoric acid solution; Take out and use ultrapure deionized water rinsing, nitrogen dries up, and oven dry; Silicon chip is immersed in the organic decoration solution (like 2-THP, CAE, APTES etc.) under UV-irradiation handled 2 hours;
4) shift, the PDMS that polymerization is good transfers to through in the step (two) 3) on the wafer after the surface modification treatment, aim at bonding.
Again further, the making integrated approach of above-mentioned multichannel high-sensitive biosensor, step (three) comprises following operation:
1) surperficial aldehyde radicalization, with glutaraldehyde phosphate buffer (PBS) the mixed liquor reaction of silicon slice placed at 1: 15, (30ml PBS, 2ml glutaraldehyde, PBS are phosphate buffer PH=7.2), reaction is one hour on shaking table;
2) combine albumen, in conjunction with the corresponding antibodies of going up material to be detected;
3) clean, reaction finishes, and cleans 3 times with buffer solution, and is every all over 5 minutes, every all over 2 minutes at interval.
Substantive distinguishing features and obvious improvement that technical scheme of the present invention is outstanding are mainly reflected in:
The biology sensor of multichannel high-sensitive of the present invention is made and integrated approach; Adopt PDMS and insulating material to make microchannel; Silicon nanowires in each passage is modified respectively; Make it possible to detect dissimilar biomolecule,, can detect disease more accurately through the information of these biomolecule is carried out Conjoint Analysis.And, through the contrast passage that is provided with, can reduce false drop rate to reducing error, improve the accuracy that detects.Simultaneously, adopt silicon nanowires, have advantages such as the transducer sensitivity of raising and reduction chip size as the core cell that detects.Adopt top-down method to make sensor component, can combine, and solved the arrangement and the lithography alignment problem of nano wire, can improve the precision of element manufacturing, reduce bad ratio defective product, thereby reduce chip cost with conventional semiconductor processing.Adopt passivation layer that device is protected, avoided the infiltration of hydrone, electric current etc. in next step reaction, prolonged the life-span of sensor.The sensor that this method is made can be used for detecting simultaneously the dissimilar disease association factor (like DNA, RNA, albumen etc.) or virus, has high sensitivity, stablizes, is easy to advantages such as integrated.
Description of drawings
Below in conjunction with accompanying drawing technical scheme of the present invention is described further:
Fig. 1 in the element manufacturing of the present invention on soi wafer the sectional view of growthing silica;
Fig. 2 makes sectional view for back of the body grid in the element manufacturing of the present invention;
Fig. 3 obtains the device architecture sectional view of silicon nanowires for after passing through common deep-UV lithography in the element manufacturing of the present invention behind the TMAH wet etching;
Fig. 4 is for metallizing in the element manufacturing of the present invention, obtains device architecture sectional view after grid, source, the drain electrode;
Fig. 5 for surface passivation in the element manufacturing of the present invention after device profile map;
Fig. 6 has made device architecture sectional view behind the microchannel for the present invention;
Fig. 7 is a surface modification of the present invention, in the modification sensor construction sectional view after the detection molecules;
Fig. 8 is doping process sectional view in the element manufacturing of the present invention;
Fig. 9 is a surface modification of the present invention, in the modification sensor construction sectional view after the detection molecules;
Figure 10 is for passing through beamwriter lithography, the device architecture sectional view that obtains behind the IBE dry etching in the element manufacturing of the present invention;
Figure 11 is a surface modification of the present invention, in the modification sensor construction sectional view after the detection molecules.
The implication of each Reference numeral sees the following form among the figure:
| Reference numeral | Implication | Reference numeral | Implication | Reference | Implication | |
| 1 | |
2 | |
3 | |
|
| 4 | The FET |
5 | FET FET source electrode | 6 | The drain electrode of FET |
|
| 7 | Silicon nanowires | 8 | The silicon nitride passivation |
9 | |
|
| 10 | |
11 | The |
12 | The antibody recognition unit |
| Reference numeral | Implication | Reference numeral | Implication | Reference | Implication | |
| 13 | The antibody recognition unit | 14 | The chemical group of modifying on the |
15 | |
|
| 16 | Silicon nanowires | 17 | Silicon nanowires |
Embodiment
The present invention provides a kind of making and integrated approach of highly sensitive multichannel biological and chemical sensor.Through soi wafer, utilize the anisotropic wet caustic solution to obtain silicon nanowires, produce field effect FET transistor from top to bottom with the method for conventional semiconductor processing; Next utilize dimethyl silicone polymer (PDMS) to produce the microfluid hyperchannel; At last, adopt the method for chemistry that the silicon nanowires in the different microchannels is carried out modification, go up different antibody or micromolecule thereby modify.The sensor of making in this way can be used for detecting simultaneously the dissimilar disease association factor (like DNA, RNA, albumen etc.) or virus.This biology sensor has high sensitivity, and is stable, is easy to advantages such as integrated.Simultaneously, this manufacturing approach can be compatible mutually with conventional semiconductor processing, can carry out large-scale production, is convenient to reduce cost.
Sensor construction shown in figure 11, silicon substrate 1, substrate silicon dioxide 2 and top layer silicon 3 threes have constituted the SOI three-decker, FET FET metal source 5, drain electrode 6 and grid 4; And comprised silicon nanowires 7; Chemical group of modifying on the nano wire 14 and antibody 10, antibody recognition unit (11,12,13) have also comprised silicon nitride passivation protective seam 8 at last; Dimethyl silicone polymer (PDMS) 9, and the microfluid passage 15 that forms.Sensor is based on N type or the making of P type (100) soi wafer.Silicon nanowires 7 height are between 1～1000 nanometer, and halfwidth is between 1～500 nanometer, and angle beta=125.26 are spent, and the silicon nanowires homogeneity is good, and is regular.The method for making of silicon nanowires 7 is to make through anisotropic etchs such as KOH, TMAH, EDP, RbOH, LiOH or CsOH solution, and the concentration of solution is 1%～75%.Add isopropyl alcohol (IPA) in the described corrosive liquid, the concentration of IPA is that the method for making of 0%～50% silicon nanowires 7 is to obtain through ion beam etching (IBE), reactive ion beam etching (RIBE) (RIE), dark silicon inductively coupled plasma etching dry etchings such as (dark silicon ICP).The quantity of integrated silicon nanowires 7 is between 1～200 in sensor.The material of silicon nitride passivation protective seam 8 is that silicon nitride film, silica membrane, spin-coating glass (comprise PSG; BPSG), improvement silicon dioxide (fluorinated silica; HSQ), BN Si; Organic type be can also be, polyimide, fluorinated polyimide, Fluoro-polymkeric substance, Si-O-C polyblend etc. comprised.Can use method growths such as CVD, PECVD or LPCVD, SOD, sputter.Passivation layer covers sensor surface silicon nanowires and other outer places of metal electrode.Film protection sensor surface, and form microfluid passage.Microfluid passage 15 is to be formed together by silicon nitride passivation protective seam 8 and dimethyl silicone polymer (PDMS) 9, and the quantity of microfluid passage is between 1～200, and microfluid passage is to carry out chemical modification, and the reaction vessel of target detection.Chemical group 14 that specificity is modified can be allylamine, 11-bromo decyltrichlorosilane (11-bromoundecyltrichlorosilane; BUTCS), 2-methyl esters ethyl trichlorosilane (2-(carbomethoxy) ethyltrichlorosilane; CMECS), octyl group trichlorosilane (n-octyltrichlorosilane; OTCS), 9-alkenyl amino butyl formate (dec-9-enyl-carbamic acid tert-butyl ester; CAE), ammonia propyl trichlorosilane (3-aminopropyl triethoxylsilane, APTES).Antibody 10 is different in different microfluid passage 15, relevant detection biomolecule (like DNA, RNA, albumen etc.), and antibody recognition unit (11,12,13) also are different.The input of sensor is target molecule damping fluid to be detected to be drawn in the microchannel through microflow channels with peristaltic pump, and specific being combined on the corresponding antibody molecule.The change that this has caused sensor electrical to be led.Thereby chemical signal is changed into electric signal and detects through peripheral testing circuit.All contain a reference channel in each sensor, this passage and unmodified chemical group and antibody.The microchannel of each detection all should have a contrast passage mutually, and what flow through in the passage is not contain the corresponding buffer solution that detects target molecule.
Example I
(1) adopt the silicon nanowires of method making from top to bottom FET FET based on soi wafer:
1) silicon chip cleans, and silicon chip is spent with oxydol 60 with 7: 3 concentrated sulphuric acids earlier and boiled 15 minutes, takes out the ultrapure water rinsing then, uses 1: 3: 7 ammoniacal liquor and aqueous hydrogen peroxide solution to boil the rinsing of taking-up ultrapure water 10 minutes again; Next 60 degree heating 10 minutes in 1: 2: 8 hydrochloric acid and aqueous hydrogen peroxide solution are taken out and are used the ultrapure water rinsing, and nitrogen dries up; With buffered hydrofluoric acid solution corrosion in 5: 15 seconds, take out, use the ultrapure water rinsing, nitrogen dries up; 100 degree oven dryings 10 minutes; Through cleaning, remove contained pollution organism and the metallic ion of silicon chip surface;
2) wafer thinning, earlier with silicon chip in oxidation furnace with wet oxygen or dry-oxygen oxidation, and then with buffered hydrofluoric acid solution erosion removal silicon dioxide; Through repeating several steps, make silicon chip reach required thickness, and the surface slightly release souls from purgatory compare less;
3) etching mask growth, as shown in Figure 1, using methods such as PECVD or the plasma sputtering layer thickness of on silicon chip, growing is the silicon dioxide or the silicon nitride mask 16 of 20～100 nanometer thickness;
4) back of the body grid are made, and are as shown in Figure 2, with the method for back of the body grid masterplate through deep-UV lithography, again through reactive ion etching RIE, on silicon chip, make and obtain carrying on the back gate pattern earlier;
5) silicon nanowires is made, and is as shown in Figure 3, earlier with the method for silicon nanowires masterplate through deep-UV lithography; Use the RIE dry etching again, use tetramethyl ammonium hydroxide solution anisotropic etch silicon again, at last erosion removal silica 16 in 5: 1 buffered hydrofluoric acid solutions; Thereby obtain width at 10～100nm; Height is at the good silicon nanowires of the homogeneity of 25～80nm, and wherein the β angle is 125.26 degree, and the quantity of nano wire is 36;
6) metallization is as shown in Figure 4, and with the method for metallization masterplate through deep-UV lithography, the method through peeling off makes silicon chip line and grid again, source electrode and drain metallization earlier;
7) passivation, as shown in Figure 5, earlier with the method for passivation masterplate through deep-UV lithography, same method with PECVD all covers the last layer silicon nitride passivation in the place of silicon chip surface except that silicon nanowires and grid, source, drain electrode;
(2) utilize dimethyl silicone polymer (PDMS) to produce many microfluid passage:
1) stamp fabrication utilizes the method for photoetching on silicon chip, to make earlier and obtains the microchannel mould;
2) build model, as shown in Figure 6, the PDMS performed polymer is poured on the microchannel mould, and placed 24 hours, make it complete polymerization;
3) shift, the PDMS that polymerization is good transfers on the device of making, and aims at bonding;
(3) surface of silicon nanowires is modified and the target molecule detection:
1) surface amination; The wafer that will pass through step (two) is under nitrogen protection, and corrosion is 5 seconds in buffered hydrofluoric acid solution, takes out and uses ultrapure deionized water rinsing; Nitrogen dries up; And oven dry, it is in 0.1～2% 3-aminopropyltriethoxywerene werene (APTES) ethanolic solution that wafer is immersed in concentration, reaction is 2 hours under the room temperature;
2) surperficial aldehyde radicalization, with the glutaraldehyde PBS mixed liquor reaction of silicon slice placed at 1: 10, (15ml PBS, 1.5ml glutaraldehyde, PBS are phosphate buffer PH=7.2), reaction is one hour on shaking table;
3) combine albumen; As shown in Figure 7; Detect the significant albumen of hepatitis B: the buffer solution of HBsAg, HBsAb, HBeAg, HBeAb, HBcAb corresponding monoclonal antibody is placed on peristaltic pump respectively and is drawn into that (each marker protein flows through 2 microchannels respectively, and also having one in addition is the reference channel of not modifying monoclonal antibody, always has 11 microchannels in 11 different fluid channel; Each microchannel has 3 nano wires), reaction is at room temperature spent the night;
4) clean, reaction finishes, and cleans 3 times with buffer solution, and is every all over 5 minutes, every all over 2 minutes at interval.
Example II
(1) adopt the silicon nanowires of method making from top to bottom FET FET based on soi wafer:
1) silicon chip cleans, and silicon chip is spent with 7: 3 concentrated sulphuric acids and oxydol 60 earlier and boiled 15 minutes, takes out the ultrapure water rinsing then; Use 1: 3: 7 ammoniacal liquor and aqueous hydrogen peroxide solution to boil again 10 minutes, take out the ultrapure water rinsing, next 60 degree heated 10 minutes in 1: 2: 8 hydrochloric acid and aqueous hydrogen peroxide solution; Take out and use the ultrapure water rinsing, nitrogen dried up, with buffered hydrofluoric acid solution corrosion in 5: 15 seconds; Take out, use the ultrapure water rinsing, nitrogen dries up; 100 degree oven dryings 10 minutes through cleaning, are removed contained pollution organism and the metallic ion of silicon chip surface;
2) wafer thinning, earlier with silicon chip in oxidation furnace with wet method or dry oxidation, and then, through and repetition several steps with buffered hydrofluoric acid solution erosion removal silicon dioxide, make silicon chip obtain required thickness, and the surface slightly release souls from purgatory compare less;
3) back of the body grid are made, and with the method for back of the body grid masterplate through deep-UV lithography, again through reactive ion etching RIE, on silicon chip, make and obtain carrying on the back gate pattern earlier;
4) the N ion injects, and growth layer of silicon dioxide mask on silicon chip with the method for n type ion injecting mask through deep-UV lithography, injects through phosphorus or arsenic ion more earlier, and silicon is mixed, and removes silicon dioxide mask with buffered hydrofluoric acid solution;
5) the P ion injects, and is as shown in Figure 8, and growth layer of silicon dioxide mask on silicon chip with the method for p type ion implantation mask through deep-UV lithography, injects through the boron ion more earlier, and silicon is mixed, and removes silicon dioxide mask with buffered hydrofluoric acid solution;
6) etching mask growth, using methods such as PECVD or the plasma sputtering layer thickness of on silicon chip, growing is the silicon dioxide or the silicon nitride mask of 20～100 nanometer thickness;
7) silicon nanowires is made; With the method for silicon nanowires masterplate, use the RIE dry etching more earlier, use tetramethyl ammonium hydroxide solution anisotropic etch silicon again through deep-UV lithography; Erosion removal silicon dioxide in 5: 1 buffered hydrofluoric acid solutions at last; Thereby obtain width at 10～100nm, height is at the good silicon nanowires of the homogeneity of 25～80nm, and the quantity of nano wire is 66;
8) metallization, with the method for metallization masterplate through deep-UV lithography, the method through peeling off makes silicon chip line and grid, source electrode and drain metallization more earlier;
9) passivation, earlier with the method for passivation masterplate through deep-UV lithography, same method with PECVD all covers the last layer silicon nitride passivation in the place of silicon chip surface except that silicon nanowires and grid, source, drain electrode;
(2) utilize dimethyl silicone polymer (PDMS) to produce many microfluid passage:
1) Mold Making utilizes the method for photoetching on silicon chip, to make earlier and obtains the microchannel mould;
2) build model, the PDMS performed polymer is poured on the microchannel mould, and placed 24 hours, make it complete polymerization;
3) shift, the PDMS that polymerization is good transfers on the device of making, and aims at bonding;
(3) silicon nanowires to zones of different carries out modification, makes it to modify different detection antibody, to detect different target molecules:
1) surface modification, the wafer that will pass through step (two) are under nitrogen protection, and corrosion is 5 seconds in buffered hydrofluoric acid solution; Take out and use ultrapure deionized water rinsing, nitrogen dries up, and oven dry; It is in 0.1～2% the ammonia propyl trichlorosilane (APTES) that silicon chip is immersed in concentration, and reaction is 2 hours under the room temperature;
2) surperficial aldehyde radicalization, with the glutaraldehyde PBS mixed liquor reaction of silicon slice placed at 1: 15, (30ml PBS, 2ml glutaraldehyde, PBS are phosphate buffer PH=7.2), reaction is one hour on shaking table;
3) combine albumen; As shown in Figure 9; The buffer solution of the serum tumor marker CEA of lung cancer, NSE, CYFRA21-1, TPA, CA15-3, CA242 corresponding monoclonal antibody is drawn in 20 different fluid channel with peristaltic pump respectively that (wherein each label damping fluid all flow into corresponding N type district passage, p type island region passage and contrast passage respectively; Also there is one not modify the N type of monoclonal antibody and the reference channel of P type in addition respectively; Always have 20 microchannels, 3 nano wires arranged in each microchannel), reaction is at room temperature spent the night; Wherein silicon nanowires 7, silicon nanowires 16 and silicon nanowires 17 are respectively N type and P type silicon nanowires, and the antibody recognition unit 13 that is connect respectively on it is the same with antibody recognition unit 12;
4) clean, reaction finishes, and cleans 3 times with buffer solution, and is every all over 5 minutes, every all over 2 minutes at interval.
EXAMPLE III
(1) adopt the silicon nanowires of method making from top to bottom FET FET based on soi wafer:
1) silicon chip cleans, and silicon chip is spent with 7: 3 concentrated sulphuric acids and oxydol 60 earlier and boiled 15 minutes, takes out the ultrapure water rinsing then; Use 1: 3: 7 ammoniacal liquor and aqueous hydrogen peroxide solution to boil again 10 minutes, take out the ultrapure water rinsing, next 60 degree heated 10 minutes in 1: 2: 8 hydrochloric acid and aqueous hydrogen peroxide solution; Take out and use the ultrapure water rinsing, nitrogen dried up, with buffered hydrofluoric acid solution corrosion in 5: 15 seconds; Take out, use the ultrapure water rinsing, nitrogen dries up; 100 degree oven dryings 10 minutes through cleaning, are removed contained pollution organism and the metallic ion of silicon chip surface;
2) wafer thinning, earlier with silicon chip in oxidation furnace with wet method or dry oxidation, and then, through and repetition several steps with buffered hydrofluoric acid solution erosion removal silicon dioxide, make silicon chip obtain required thickness, and the surface slightly release souls from purgatory compare less;
3) back of the body grid are made, and with the method for back of the body grid masterplate through deep-UV lithography, again through reactive ion etching RIE, on silicon chip, make and obtain carrying on the back gate pattern earlier;
4) silicon nanowires is made, and is shown in figure 10, earlier with the method for silicon nanowires masterplate through beamwriter lithography, uses the RIE dry etching again, obtains width at 10～100nm, and height is at the good silicon nanowires of the homogeneity of 25～80nm, and the quantity of nano wire is 12;
5) metallization, with the method for metallization masterplate through deep-UV lithography, the method through peeling off makes silicon chip line and grid, source electrode and drain metallization more earlier;
6) passivation, earlier with the method for passivation masterplate through deep-UV lithography, same method with PECVD all covers the last layer silicon nitride passivation in the place of silicon chip surface except that silicon nanowires and grid, source, drain electrode;
(2) utilize dimethyl silicone polymer (PDMS) to produce many microfluid passage:
1) stamp fabrication utilizes the method for photoetching on silicon chip, to make earlier and obtains the microchannel mould;
2) build model, the PDMS performed polymer is poured on the microchannel mould, and placed 24 hours, make it complete polymerization;
3) surface modification, the wafer that will pass through step () are under nitrogen protection, and corrosion is 5 seconds in buffered hydrofluoric acid solution; Take out and use ultrapure deionized water rinsing, nitrogen dries up, and oven dry; Silicon chip is immersed in the allylamine ethanolic solution, under ultraviolet light (256nm) irradiation, handled 12 hours;
4) shift, the PDMS that polymerization is good transfers to through in the step (two) 3) on the wafer after handling, aim at bonding;
(3) silicon nanowires to zones of different carries out modification, makes it to modify different detection antibody, to detect different target molecules:
1) surperficial aldehyde radicalization, with the glutaraldehyde PBS mixed liquor reaction of silicon slice placed at 1: 15, (30ml PBS, 2ml glutaraldehyde, PBS are phosphate buffer PH=7.2), reaction is one hour on shaking table;
2) combine albumen, shown in figure 11, the buffer solution that detects the significant albumen PSA of prostate cancer corresponding antibodies is used in peristaltic pump and is drawn in 3 different fluid channel, and reaction is at room temperature spent the night;
3) clean, reaction finishes, and cleans 3 times with buffer solution, and is every all over 5 minutes, every all over 2 minutes at interval.
In sum; The biology sensor of multichannel high-sensitive of the present invention is made and integrated approach; Adopt PDMS and insulating material to make microchannel, the silicon nanowires in each passage is modified respectively, make it possible to detect dissimilar biomolecule; Through the information of these biomolecule is carried out Conjoint Analysis, can detect disease more accurately.And, through the contrast passage that is provided with, can reduce false drop rate to reducing error, improve the accuracy that detects.Simultaneously, adopt silicon nanowires, have advantages such as the transducer sensitivity of raising and reduction chip size as the core cell that detects.Adopt top-down method to make sensor component, can combine, and solved the arrangement and the lithography alignment problem of nano wire, can improve the precision of element manufacturing, reduce bad ratio defective product, thereby reduce chip cost with conventional semiconductor processing.Adopt passivation layer that device is protected, avoided the infiltration of hydrone, electric current etc. in next step reaction, prolonged the life-span of sensor.
Above appearance is a concrete exemplary applications of the present invention, and protection scope of the present invention is not constituted any limitation.All employing equivalents or equivalence are replaced and the technical scheme of formation, all drop within the rights protection scope of the present invention.
Claims (1)
1. the making integrated approach of multichannel high-sensitive biosensor is characterized in that: may further comprise the steps---
(1) adopt the silicon nanowires of method making from top to bottom FET FET based on soi wafer, comprise following operation:
1) silicon chip cleans, and at the concentrated sulphuric acid and the oxydol of 7:3,1:3:7 ammoniacal liquor and aqueous hydrogen peroxide solution in 60 degree heating 10 ~ 15 minutes, are removed contained organism and the metallic ion of silicon chip surface in 1:2:8 hydrochloric acid and the aqueous hydrogen peroxide solution to silicon chip respectively;
2) wafer thinning, earlier with silicon chip in oxidation furnace with wet oxygen or dry-oxygen oxidation, use buffered hydrofluoric acid solution erosion removal silicon dioxide again, make silicon chip reach required thickness;
3) etching mask growth is with PECVD or plasma sputtering method on silicon chip, the grow silicon dioxide or the silicon nitride film of one deck 20 ~ 200 nanometer thickness;
4) back of the body grid are made, and with the method for back of the body grid masterplate through deep-UV lithography, again through the IBE dry etching, on silicon chip, make and obtain carrying on the back gate pattern earlier;
5) silicon nanowires is made; Earlier with the method for silicon nanowires masterplate through deep-UV lithography; Use the IBE dry etching again; Use tetramethyl ammonium hydroxide solution anisotropic etch silicon again, erosion removal silicon dioxide in the 5:1 buffered hydrofluoric acid solution at last, thereby obtain width at 1 ~ 1000nm, height at the good silicon nanowires of the homogeneity of 1 ~ 500nm;
6) metallization, with the method for metallization masterplate through deep-UV lithography, the method through peeling off makes silicon chip line and grid, source electrode and drain metallization more earlier;
7) passivation earlier with the method for passivation masterplate through deep-UV lithography, utilizes the PECVD method, all covers the last layer passivation layer in the place of silicon chip surface except that silicon nanowires and grid, source, drain electrode;
(2) utilize dimethyl silicone polymer to produce many microfluid passage, comprise following operation:
1) stamp fabrication utilizes the method for photoetching on silicon chip, to make earlier and obtains the microchannel mould;
2) build model, the PDMS performed polymer is poured on the microchannel mould, and placed 24 hours, make it complete polymerization;
3) surface modification, the wafer that will pass through step () are under nitrogen protection, and corrosion is 5 seconds in buffered hydrofluoric acid solution; Take out and use ultrapure deionized water rinsing, nitrogen dries up, and oven dry; Wafer is immersed in the organic decoration solution, under UV-irradiation, handled 2 hours;
4) shift, the PDMS that polymerization is good transfers to through on the wafer after the surface modification treatment, aims at bonding;
(3) silicon nanowires in the different microfluid passage is carried out modification, makes it to modify different detection antibody or micromolecule,, comprise following operation to detect different target molecules:
1) surperficial aldehyde radicalization, in the glutaraldehyde phosphate buffer mixed liquor of 1:15, reaction is one hour on shaking table with silicon slice placed;
2) combine albumen, in conjunction with the corresponding antibodies of going up material to be detected;
3) clean, reaction finishes, and cleans 3 times with buffer solution, and is every all over 5 minutes, every all over 2 minutes at interval.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910030342 CN101592627B (en) | 2009-03-19 | 2009-03-19 | Method for manufacturing and integrating multichannel high-sensitive biosensor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910030342 CN101592627B (en) | 2009-03-19 | 2009-03-19 | Method for manufacturing and integrating multichannel high-sensitive biosensor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101592627A CN101592627A (en) | 2009-12-02 |
| CN101592627B true CN101592627B (en) | 2012-12-05 |
Family
ID=41407395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200910030342 Expired - Fee Related CN101592627B (en) | 2009-03-19 | 2009-03-19 | Method for manufacturing and integrating multichannel high-sensitive biosensor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101592627B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI611185B (en) * | 2015-12-19 | 2018-01-11 | National Taipei University Of Technology | Detection device |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101893596A (en) * | 2010-07-16 | 2010-11-24 | 复旦大学 | Silicon nano-wire biological sensor for detecting pesticide residues |
| CN102323301A (en) * | 2011-08-15 | 2012-01-18 | 复旦大学 | Silicon nanowire biosensor for detecting organophosphorus pesticide residue and preparation method thereof |
| CN102969222B (en) * | 2011-09-01 | 2015-03-18 | 上海华力微电子有限公司 | Production method for silicon nanowire (SINW) device compatible with complementary metal oxide semiconductor (CMOS) technology |
| CN102435653A (en) * | 2011-09-05 | 2012-05-02 | 湖南大学 | Field effect transistor-based antibiotic medicine screening device and antibiotic medicine screening method |
| CN102435655A (en) * | 2011-09-05 | 2012-05-02 | 湖南大学 | Field effect transistor-based tumor diagnosis apparatus and assay method thereof |
| CN102435654A (en) * | 2011-09-05 | 2012-05-02 | 湖南大学 | Viral disease diagnosis device and method based on field effect transistor |
| CN102299171B (en) * | 2011-09-08 | 2013-12-04 | 上海华力微电子有限公司 | Silicon nanowire apparatus compatible with complementary metal oxide semiconductor (CMOS) process and manufacturing method thereof |
| CN102435747A (en) * | 2011-10-26 | 2012-05-02 | 中国科学院苏州纳米技术与纳米仿生研究所 | Acute myocardial infarction diagnosis-oriented biosensor and preparation method thereof |
| US9459234B2 (en) * | 2011-10-31 | 2016-10-04 | Taiwan Semiconductor Manufacturing Company, Ltd., (“TSMC”) | CMOS compatible BioFET |
| WO2013131411A1 (en) * | 2012-03-08 | 2013-09-12 | Chang He Bio-Medical Science(Yangzhou) Co.,Ltd. | Micro-devices for improved disease detection |
| CN102980920A (en) * | 2012-11-14 | 2013-03-20 | 华东师范大学 | Silicon nanowire chip simultaneously detecting miRNAs and protein markers and detection method and application of silicon nanowire chip |
| CN102951591B (en) * | 2012-11-20 | 2016-01-20 | 华中科技大学 | A kind of for micro-channel structure of catching circulating tumor cell and preparation method thereof |
| CN103558280A (en) * | 2013-11-15 | 2014-02-05 | 中国科学院上海微系统与信息技术研究所 | Biosensor based on tunneling field effect transistor and preparation method of biosensor |
| CN103626120B (en) * | 2013-12-19 | 2015-10-28 | 中国科学院上海微系统与信息技术研究所 | A kind of preparation method of non-sensitive area protection film for sensor |
| CN104880501B (en) * | 2014-02-28 | 2018-05-04 | 中国科学院半导体研究所 | A kind of multichannel sensor of quick detection heavy metal ion and preparation method thereof |
| CN103928342B (en) * | 2014-04-23 | 2017-11-21 | 中国科学院上海微系统与信息技术研究所 | A kind of silicon nanowires tunneling field-effect transistor and preparation method thereof |
| CN105372435B (en) * | 2014-08-26 | 2017-12-05 | 中国科学院苏州纳米技术与纳米仿生研究所 | Biological detection system and its making integrated approach based on graphene |
| CN104730136A (en) * | 2015-03-26 | 2015-06-24 | 中国科学院上海微系统与信息技术研究所 | Biosensor based on germanium nanowire field effect transistor, method and application |
| KR20230078838A (en) | 2015-04-22 | 2023-06-02 | 버클리 라잇츠, 인크. | Microfluidic cell culture |
| CN104807869B (en) * | 2015-05-18 | 2017-05-10 | 哈尔滨理工大学 | Manufacturing and integration method for two-dimensional nanomaterial-based biosensor |
| CN105021680A (en) * | 2015-06-30 | 2015-11-04 | 上海集成电路研发中心有限公司 | Graphene sensor based method for detecting MicroRNA |
| EP3862088A1 (en) * | 2015-10-27 | 2021-08-11 | Berkeley Lights, Inc. | Method of manufcturing microfluidic electrowetting device having a covalently bound hydrophobic surface |
| US10799865B2 (en) | 2015-10-27 | 2020-10-13 | Berkeley Lights, Inc. | Microfluidic apparatus having an optimized electrowetting surface and related systems and methods |
| CN105891296A (en) * | 2016-04-26 | 2016-08-24 | 唐晓武 | Equipment, method and films for detecting contents of to-be-detected substances in samples |
| CN109689213B (en) | 2016-05-26 | 2022-10-14 | 伯克利之光生命科技公司 | Covalently modified surface, kit, preparation method and application |
| KR102138344B1 (en) * | 2016-08-09 | 2020-07-29 | 타이완 세미콘덕터 매뉴팩쳐링 컴퍼니 리미티드 | Cartridge and analyzer for fluid analysis |
| US11119101B2 (en) | 2017-01-13 | 2021-09-14 | Taiwan Semiconductor Manufacturing Co., Ltd. | Cartridge and analyzer for fluid analysis |
| KR101921627B1 (en) * | 2017-06-16 | 2018-11-26 | 한국과학기술연구원 | Field effect transistor, biosensor comprising the same, method for manufacturing Field effect transistor, and method for manufacturing biosensor |
| CN109211852A (en) * | 2017-06-30 | 2019-01-15 | 曦医生技股份有限公司 | biological detection system |
| TWI661568B (en) | 2017-10-05 | 2019-06-01 | 國立清華大學 | Sensing device and biological detection method |
| CN108169485B (en) * | 2017-11-20 | 2019-04-23 | 无锡市人民医院 | A kind of bigrid regulation hypersensitivity biosensor based on metal-oxide-semiconductor |
| CN110028038A (en) * | 2018-01-12 | 2019-07-19 | 天津大学 | A kind of silicon nanowires micro-structure regulation method towards different field application |
| CN109060922B (en) | 2018-08-03 | 2020-06-05 | 京东方科技集团股份有限公司 | Thin film transistor, preparation method thereof and sensor |
| CN111257206A (en) * | 2018-11-30 | 2020-06-09 | 山东大学 | Method for manufacturing cell distribution analysis device |
| TWI765209B (en) * | 2019-01-18 | 2022-05-21 | 國立陽明交通大學 | Field effect transistor-based biosensor for detecting whole-cell bacteria and field effect transistor-based biosensor assembly including the same |
| FR3092103B1 (en) * | 2019-01-29 | 2022-08-05 | Netri | Process for manufacturing 3D microfluidic devices |
| US11534755B2 (en) * | 2019-04-16 | 2022-12-27 | Boe Technology Group Co., Ltd. | Micro-channel device and manufacturing method thereof and micro-fluidic system |
| CN112557456B (en) * | 2019-09-25 | 2021-12-21 | 天津大学 | Silicon nanowire-based gas sensor element, preparation method thereof and application thereof in acetone detection |
| CN111257316A (en) * | 2020-02-11 | 2020-06-09 | 军事科学院系统工程研究院卫勤保障技术研究所 | Portable nanometer detector |
| CN111534430B (en) * | 2020-04-28 | 2023-12-29 | 港岫科技(上海)有限公司 | Ribonucleic acid detection panel and ribonucleic acid detection device |
| CN111781158B (en) * | 2020-05-11 | 2023-08-25 | 韶关学院 | Terahertz biosensor and preparation method and application thereof |
| US20220280935A1 (en) * | 2021-03-05 | 2022-09-08 | Taiwan Semiconductor Manufacturing Company Ltd. | System and method for detecting biomolecules |
| CN113333042B (en) * | 2021-06-21 | 2022-04-22 | 太原理工大学 | Micro-fluidic chip for nucleic acid detection and manufacturing method thereof |
| CN114354722A (en) * | 2021-12-13 | 2022-04-15 | 武汉大学 | Multichannel field effect transistor nano biosensor and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6255678B1 (en) * | 1997-05-29 | 2001-07-03 | Horiba, Ltd. | Apparatus for measuring physical and chemical phenomena |
| CN1585896A (en) * | 2001-11-16 | 2005-02-23 | 株式会社Bio-X | FET type sensor, ion density detecting method comprising this sensor, and base sequence detecting method |
| CN101144809A (en) * | 2007-10-17 | 2008-03-19 | 中国科学院光电技术研究所 | High sensitivity nano biosensor production method |
-
2009
- 2009-03-19 CN CN 200910030342 patent/CN101592627B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6255678B1 (en) * | 1997-05-29 | 2001-07-03 | Horiba, Ltd. | Apparatus for measuring physical and chemical phenomena |
| CN1585896A (en) * | 2001-11-16 | 2005-02-23 | 株式会社Bio-X | FET type sensor, ion density detecting method comprising this sensor, and base sequence detecting method |
| CN101144809A (en) * | 2007-10-17 | 2008-03-19 | 中国科学院光电技术研究所 | High sensitivity nano biosensor production method |
Non-Patent Citations (3)
| Title |
|---|
| JP特开平6-249826A 1994.09.09 |
| JP特表2001-511245A 2001.08.07 |
| 穆丽璇.基于硅纳米线的光响应化学传感器研究.《中国博士学位论文全文数据库》.2008,全文. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI611185B (en) * | 2015-12-19 | 2018-01-11 | National Taipei University Of Technology | Detection device |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101592627A (en) | 2009-12-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101592627B (en) | Method for manufacturing and integrating multichannel high-sensitive biosensor | |
| CN104807869B (en) | Manufacturing and integration method for two-dimensional nanomaterial-based biosensor | |
| CN110632168B (en) | Micro-fluidic magnetic-sensitive immunization device based on magnetic-resistance biosensor and use method thereof | |
| CN101592626B (en) | Quasi-one-dimensional metal oxide nano-material biosensor and method for manufacturing same | |
| US10059982B2 (en) | Nano-sensor array | |
| CN102764677B (en) | Preparation method of localized surface plasmon resonance (LSPR) microfluidic chip | |
| KR20070099151A (en) | Method of detecting bio-molecules using field effect transistor without fixing bio-molecules | |
| CN102435747A (en) | Acute myocardial infarction diagnosis-oriented biosensor and preparation method thereof | |
| KR100969671B1 (en) | High sensitive biosensor, biochip comprising the same and manufacturing method therefor | |
| CN102323301A (en) | Silicon nanowire biosensor for detecting organophosphorus pesticide residue and preparation method thereof | |
| CN103713022A (en) | Preparation method for polydimethylsiloxane micro-thin film capacitive biosensor | |
| CN113960128B (en) | Silicon nanowire field effect transistor biosensor based on modification of potassium ion aptamer | |
| CN103105378B (en) | Biosensor, manufacturing method thereof, and biosensor testing system | |
| CN105372435B (en) | Biological detection system and its making integrated approach based on graphene | |
| CN109507422A (en) | Optics micro-fluidic chip based on polymer and multiple layer metal Nanoparticle Modified | |
| CN109427908A (en) | Three-dimensional silicon nanowire array field effect transistor, biosensor and preparation method | |
| CN115656150B (en) | Device and method for detecting biomolecules | |
| CN201083712Y (en) | Biosensor and detection device adopting same | |
| CN113130648B (en) | Tumor marker sensor based on fin field effect transistor manufacturing process | |
| CN104726559A (en) | Method for detecting bio-molecules | |
| CN204028397U (en) | A kind of micro-dish resonator cavity based on horizontal narrow slit optical waveguide | |
| CN103728273B (en) | The method that the signal that the effect of surfactant, surface plasma resonance detect low molecular weight substance amplifies | |
| Raja et al. | An embedded microretroreflector-based microfluidic immunoassay platform | |
| CN103728279B (en) | The effect of surfactant, surface plasma resonance detect the method that the signal of low molecular weight substance amplifies | |
| CN112881473B (en) | DNA monomolecular device capable of identifying adriamycin through inserting layer and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: SUZHOU INSTITUTE OF NANO-TECH AND NANO-BIONICS(SIN Free format text: FORMER OWNER: SUZHOU NANO TECHNIQUE + NANO BIONIC RESEARCH INST. Effective date: 20100907 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 215125 NO.398, RUOSHUI ROAD, GAOJIAO DISTRICT, DUSHUHU, INDUSTRIAL PARK, SUZHOU CITY, JIANGSU PROVINCE TO: 215123 NO.398, RUOSHUI ROAD, INDUSTRIAL PARK, SUZHOU CITY, JIANGSU PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20100907 Address after: 215123 Suzhou Industrial Park, Jiangsu, if waterway No. 398 Applicant after: Suzhou Institute of Nano-Tech and Bionics (SINANO), Chinese Academy of Sciences Address before: 215125 Jiangsu city of Suzhou province Dushu Lake Industrial Park No. 398 waterway if higher education Applicant before: Suzhou Nano Technique & Nano Bionic Research Inst. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121205 Termination date: 20200319 |