CN101126735B - Field effect transistor biosensor preparation method - Google Patents

Field effect transistor biosensor preparation method Download PDF

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CN101126735B
CN101126735B CN2007101520696A CN200710152069A CN101126735B CN 101126735 B CN101126735 B CN 101126735B CN 2007101520696 A CN2007101520696 A CN 2007101520696A CN 200710152069 A CN200710152069 A CN 200710152069A CN 101126735 B CN101126735 B CN 101126735B
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tube
effect transistor
carbon nano
field effect
basalis
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CN101126735A (en
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董益阳
任冬梅
齐小花
程艳
王军兵
王大宁
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Abstract

The utility model provides a field effect transistor biological sensor, comprising a substrate and a sealing body. The sealing body is provided with a plurality of groove type channels, specimen feeding channels and specimen discharge channels, at least one pair of metal electrodes are horizontally arranged in each groove type channel and are respectively used as a source pole and a leak pole of the field-effect transistor. A carbon nanometer tube is arranged between the metal electrodes, the metal electrodes and the carbon nanometer tube are welded together each other. Pins are arranged below the substrate and are connected with the metal electrodes by conductive glue having insulation layer. The utility model also provides a preparation method based on the field-effect transistor and adopts the inspection device of the sensor. The utility model has the advantages that multi objectives can be used for inspection so as to perform high-flux and high sensitivity, enabling compact structure, less sample usage amount, simple process, low cost, suitability for batch production, simple and convenient operation, rapid analysis speed, thus online control and inspection automation.

Description

A kind of preparation method of field effect transistor biology sensor
Technical field
The present invention relates to biology sensor, particularly a kind of biology sensor and preparation method thereof and the pick-up unit that adopts this sensor.
Background technology
Biology sensor has broad application prospects in fields such as clinical, food, biology, environmental protection tests owing to its excellent selectivity and higher sensitivity.Field effect transistor biology sensor (FET) is a branch very important in the sensor.
The field effect transistor biology sensor is the metal gate electrode that the Biofunctional film replaces isolated gate FET, and the current potential of Biofunctional film and solution or gas interface (or electric charge) changes, and the electric current that is reacted to drain electrode changes, thereby realizes the purpose of detection.Along with the development of micro production technology in recent years, the FET biology sensor is considered to develop the effective means of microbiosensor.
The FET biology sensor of being reported at present utilizes the LB membrane technology mostly, on the FET insulated gate electrode, apply one or more layers Biofunctional materials, or on silicon chip, use the method for making integrated circuit, and several Sensitive Apparatuses are integrated, obtain multi-functional bio-sensing field effect transistor.The preparation of bio-sensitive film is very crucial, the substance fixed technology of multiple biological function of development is such as absorption method at present, cross-linking method, investment, methods such as covalent bond is legal respectively have relative merits, in the substance fixed process of the biological function of reality, usually need as the case may be, the whole bag of tricks is applied in a flexible way, in testing process, conditions such as temperature, pH value of solution value, sample size are also needed in addition strict control.Therefore, the field effect transistor biology sensor is still waiting to improve and development, to improve reliability, stability and the practicality of device.
Since carbon nano-tube in 1991 is found, because its unique 1-dimention nano line structure and electrical properties makes it that immeasurable application prospect be arranged aspect electronic device material.The various countries scientist has carried out the research based on the field effect transistor sensing device of carbon nano-tube in recent years.At present, the biology sensor based on carbon nano-tube also is in the laboratory examination stage.Method for making is carbon nano tube array grows on silicon chip at first, and then structure field effect transistor biology sensor, the sensor object that this method makes up is single, and also there are a lot of problems in the method for preparing carbon nano pipe array at present on chip, because carbon nano tube growth mechanism is complicated, unavoidable impurities (catalyzer, indefinite form carbon etc.) can influence the performance of device greatly in the diameter of carbon pipe, length, the direction of growth and the growth.Simultaneously, this mode can not prepare large-scale high-quality sample in enormous quantities, has seriously restricted its character and applied research.
By above analysis as can be known, at present the problem that exists of field effect transistor biology sensor is also a lot, and helping the biology sensor of marketing and checkout equipment thereof does not have as yet at present and see.
Summary of the invention
The object of the present invention is to provide a kind of high flux and high sensitivity that can detect a plurality of objects and realize detecting, analysis speed is fast, volume is little, sample dosage is few, cost is low, be easy to prepare in enormous quantities and be implemented in line traffic control and detect the field effect transistor biology sensor of robotization, preparation method and adopt the pick-up unit of this sensor.
For achieving the above object, field effect transistor biology sensor provided by the invention, comprise basalis and seal, the composition surface of described seal and described basalis is provided with a plurality of downward opening groove type passages, the two ends of described groove type passage vertically are provided with the sample intake passage and the sample output passage of sample respectively, the common fluid passage that forms sample is plugged with the sample introduction pipe respectively and goes out the sample pipe in described sample feeding passage and sample output passage; Be fixed with at least one pair of metal electrode on the described basalis in each described groove type passage respectively respectively as the source electrode and the drain electrode of field effect transistor, be overlapped with carbon nano-tube between the described metal electrode; Described basalis bottom is provided with stitch, and every pair of described metal electrode is connected by its corresponding a pair of described stitch of the conducting resinl that has insulation course respectively.
Field effect transistor biology sensor of the present invention, wherein said groove type passage is provided with S, P, N, four of B are distributed on the seal.
Field effect transistor biology sensor of the present invention, wherein said basalis is made of silicon chip and deposition silica coating thereon.
Field effect transistor biology sensor of the present invention, wherein said seal adopt the dimethyl silicone polymer oligomer to make.
Field effect transistor biology sensor of the present invention wherein is respectively equipped with a plurality of field effect transistors that are made of metal electrode and carbon nano-tube in each described groove type passage.
Field effect transistor biology sensor of the present invention, the carbon nano-tube f-CNTs of wherein said carbon nano-tube for modifying by covalent bond or non-covalent bond absorption probe molecule.
Field effect transistor biology sensor of the present invention, wherein said metal electrode is to being interlaced fork-join shape.
Field effect transistor biology sensor of the present invention, wherein said groove type passage length is 3-8mm, and width is 0.5-2mm, and the degree of depth is 60-80 μ m, and the diameter of described sample intake passage and sample output passage is respectively 300 μ m-1mm.
For reaching aforementioned purpose, the pick-up unit of employing the sensor provided by the invention, comprise field effect transistor biology sensor, sampling system, receiving system and waste liquid outflow system, wherein said sampling system, field effect transistor biology sensor and waste liquid outflow system link to each other successively, described field effect transistor biology sensor links to each other with described receiving system, described sampling system adopts receives the amount of liter syringe pump, and described receiving system adopts electrochemical analyser.
For reaching aforementioned purpose, the preparation method of field effect transistor biology sensor provided by the invention comprises the steps:
The first step: prepare basalis and seal respectively:
(1) preparation basalis: elder generation's deposition of silica rete on silicon chip, the metal electrode of placing interlaced forked type then is right;
(2) preparation dimethyl silicone polymer oligomer seal: use galvanoplastics to make nickel base mould earlier, water the two ends that have groove type passage, each groove type passage bottom casting out then and have the vertical sample feeding passage and the dimethyl silicone polymer oligomer of sample output passage respectively, wherein said groove type passage length is 3-8mm, width is 0.5-2mm, the degree of depth is 60-80 μ m, and the diameter of described sample intake passage and sample output passage is respectively 300 μ m-1mm;
Second step: the chemical modification of carbon nano-tube: utilize covalent bond or the non-covalent bond mode of carboxyl by amido link or ester bond on the carbon nano-tube, antibody or antigen, DNA, fluorescence molecule biomolecule are fixed on the carbon tube-surface, obtain carbon nano-tube f-CNTs through modifying;
The 3rd step: will be scattered in through the carbon nano-tube f-CNTs of probe molecule covalency or non-covalent bond chemical modification in aqueous solution or the organic solvent, the hanging drop of the carbon nano-tube f-CNTs after will modifying then is added to the silica surface that has electrode pair;
The 4th step: after treating that solvent evaporates fully, utilize the carbon nano-tube f-CNTs after the nano-manipulation instrument moves modification, the carbon nano-tube f-CNTs after modifying is weldingly fixed on metal electrode to last;
The 5th step: adopt deep reaction ion etching technology earlier basalis to be run through punching, the oxide isolated processing is done to the hole in the back that has openning hole, and injects conducting resinl then in the hole, with the stitch of basalis bottom and conducting resinl by being welded together;
The 6th step: the using plasma bonding techniques is glued together above-mentioned dimethyl silicone polymer oligomer seal and basalis.
The preparation method of field effect transistor biology sensor provided by the invention, wherein the organic solvent that adopts in the 3rd step is dimethyl formamide or chlorobenzene.
The advantage of field effect transistor biology sensor of the present invention and preparation method thereof is: adopt one or a branch of right through the carbon nano-tube connection electrode of modifying, owing to removed impurity through chemical treatment, get rid of or reduced the interference of impurity.Utilize the controllable operating of nano-manipulation instrument realization to carbon nano-tube.And this sensor contains at least four sample channels, each passage can be placed arbitrary number, can detect the field effect transistor of different objects, can be used for detecting a plurality of objects, the high flux and the high sensitivity that detect have been realized, have that volume is little, sample dosage is few, the advantage of easy microminiaturization, technology is simple, and is with low cost, is fit to produce in batches.The pick-up unit that field effect transistor biology sensor of the present invention constitutes is simple, convenient, can be widely used in high flux, the detection of aspects such as highly sensitive farming is residual, medicine is residual, gene, accelerated analysis speed, and be easy to be implemented in line traffic control and detect robotization.Be elaborated with reference to accompanying drawing below in conjunction with embodiment, so that purpose of the present invention, feature and advantage are had deep understanding.
Description of drawings
Fig. 1 is the outside synoptic diagram of field effect transistor biology sensor of the present invention;
Fig. 2 adopts the structural representation of the pick-up unit of field effect transistor biology sensor for the present invention;
Fig. 3 is the structure cut-open view of field effect transistor biology sensor of the present invention;
Fig. 4 is Fig. 3 vertical view;
Fig. 5 is the local A amplification view of Fig. 4;
Fig. 6 is the side view of Fig. 3.
Embodiment
With embodiment technical scheme is elaborated below.
With reference to Fig. 3, field effect transistor biology sensor of the present invention comprises basalis and seal.Basalis is by silicon chip 21 and deposition silicon dioxide (SiO thereon 2) rete 22 formations.Seal 20 adopts dimethyl silicone polymer oligomer (PDMS) to make.In other embodiment of field effect transistor biology sensor of the present invention, also can do basalis by the germanium material.Seal 20 also can adopt polymethyl methacrylate oligomer (PMMA) to make.
With reference to Fig. 2 and Fig. 4, in field effect transistor biology sensor of the present invention, seal 20 with the composition surface of basalis on be provided with S, P, N, 1, four groove type passage 1 of four uniform groove type passages of B is respectively applied for treats test sample, the positive control sample, four kinds of sample feedings of negative control sample and blank sample detect.The two ends of groove type passage 1 vertically are provided with the sample intake passage 2 and the sample output passage 3 of sample respectively, form the fluid passage of sample jointly.In the embodiment of field effect transistor biology sensor of the present invention, groove type passage 1 length is elected 7mm as, and width is 0.5mm, and the degree of depth is 70 μ m.Sample feeding passage 2 and sample output passage 3 be diameter 500 μ m.In sample feeding passage 2 and sample output passage 3, be plugged with sample introduction pipe 4 respectively and go out sample pipe 5, sample introduction pipe 4 and go out sample pipe 5 and adopt steel pipes or glass (quartz) pipe, internal diameter is 200 μ m or 300 μ m.
With reference to Fig. 3 and Fig. 6, be fixed with at least one pair of respectively (in different embodiment on the basalis in each groove type passage 1, needing to be provided with many at test to metal electrode) metal electrode 7,8 is as source S and drain D, and the carbon nano-tube 9 that employing is modified by covalent bond or non-covalent bond absorption probe molecule between the metal electrode 7,8 is welded to each other together.With reference to Fig. 5, metal electrode is made interlaced fork-join shape to 7,8, to increase the right contact probability of carbon nano-tube connection electrode.F-CNTs carbon nano-tube 9 is fixed on metal electrode on 7,8 by solder technology, and the lead-in wire of metal electrode 7,8 is drawn via the bottom of silicon chip 21 by conducting resinl 11, prevents that liquid from spilling.Basalis is provided with many to stitch 10, and every pair of metal electrode 7,8 links to each other by conducting resinl 11 its corresponding a pair of stitch 10 respectively.
The present invention is based on the preparation process and the method for the field effect transistor biology sensor of carbon nano-tube below with the embodiment explanation.
At first, preparation basalis: earlier at 1 * 1cm 2The thick silica coating of deposition 200nm on the silicon chip, the Ti/Au metal electrode of placing interlaced forked type then is right.Preparation dimethyl silicone polymer oligomer seal: use galvanoplastics to make nickel base mould earlier, water the dimethyl silicone polymer oligomer (PDMS) that the two ends that have groove type passage, each groove type passage bottom casting out have vertical sample feeding passage and sample output passage respectively then.The groove type passage length is elected 7mm as, and width is 0.5mm, and the degree of depth is 70 μ m.Sample feeding passage and sample output passage be diameter 500 μ m.In sample feeding passage and sample output passage, be plugged with the sample introduction pipe respectively and go out the sample pipe, sample introduction pipe and go out the sample pipe and adopt steel pipe or glass (quartz) pipe, internal diameter is 200 μ m or 300 μ m.
Carry out the chemical modification of carbon nano-tube then: utilize covalent bond or the non-covalent bond mode of carboxyl by amido link or ester bond on the carbon nano-tube, antibody or antigen, DNA, fluorescence molecule biomolecule are fixed on the carbon tube-surface, obtain carbon nano-tube f-CNTs through modifying.
To be scattered in through the carbon nano-tube f-CNTs of probe molecule covalency or non-covalent bond chemical modification in aqueous solution or the organic solvent, then hanging drop is added to the surface of electrode pair, vacuum drying, after treating that solvent evaporates finishes, contact condition at indoor observation carbon nano-tube of focused particle beam (FIB) system vacuum and electrode, utilize the nano-manipulation instrument to move nanotube, it is right to make the nanotube two ends connect metal electrode respectively, after put the position, utilize solder technology that carbon nano-tube is fixed on the electrode pair.
Make the lead-in wire of electrode: adopt deep reaction ion etching (DRIE) technology earlier basalis to be run through punching, after having openning hole the oxide isolated processing is done in the hole, in the hole, inject conducting resinl then, with the stitch of basalis bottom and conducting resinl by being welded together.
At last, the using plasma bonding techniques is glued together above-mentioned dimethyl silicone polymer oligomer seal and basalis.
With reference to Fig. 2, adopt the pick-up unit of the sensor, comprise field effect transistor biology sensor 31, sampling system 30, receiving system 32 and waste liquid outflow system 33.Wherein sampling system 30, field effect transistor biology sensor 31 and waste liquid outflow system 33 link to each other successively, field effect transistor biology sensor 31 links to each other with receiving system 32, sampling system 30 adopts receives the amount of liter syringe pump, and receiving system 32 adopts electrochemical analysers.Pick-up unit is with fluid syringe pump, field effect transistor biology sensor and electrochemical analyser is effective combines, and can reduce sample size, accelerates analysis speed, has realized On-line Control and robotization.
The following describes the use and the course of work that the present invention adopts the pick-up unit of field effect transistor biology sensor:
Four injection ports of micro-injection pump are linked to each other with four injection ports of sensor respectively, inject detected sample solution simultaneously, contain, do not contain antigenic solution, blank solution with the antibody idiosyncrasy with the antigenic solution of antibody idiosyncrasy.Because the idiosyncrasy between antibody and the antigen causes the carbon nanotube field-effect transistor effect change, can observe the electric relatively variation of leading along with the time of concentration of antigen in the solution by the electric signal analyser.Because the difference of target detection antigenic content in the different solutions, therefore exporting different electricity leads time dependent signal curve, thus can the check and analysis unknown sample in target detection antigen.In like manner, also antigen molecule can be fixed on the carbon nano-tube, detect antibody molecule.
Field-effect transistor biology sensor of the present invention can be realized unimolecule, high flux, the high-sensitivity detection of four test sample simultaneously, have that volume is little, sample dosage is few, the advantage of easy microminiaturization, technology is simple, with low cost, be fit to batch production, its checkout gear is simple, and is easy to operate, can be used for high flux, the detection of the aspects such as highly sensitive farming is residual, medicine is residual, gene.

Claims (1)

1. the preparation method of a field effect transistor biology sensor comprises the steps:
The first step: prepare basalis and seal respectively:
(1) preparation basalis: elder generation's deposition of silica rete on silicon chip, the metal electrode of placing interlaced forked type then is right;
(2) preparation dimethyl silicone polymer oligomer seal: use galvanoplastics to make nickel base mould earlier, water the two ends that have groove type passage, each groove type passage bottom casting out then and have the vertical sample feeding passage and the dimethyl silicone polymer oligomer of sample output passage respectively, wherein said groove type passage length is 3-8mm, width is 0.5-2mm, the degree of depth is 60-80 μ m, and the diameter of described sample intake passage and sample output passage is respectively 300 μ m-1mm;
Second step: the chemical modification of carbon nano-tube: utilize covalent bond or the non-covalent bond mode of carboxyl by amido link or ester bond on the carbon nano-tube, antibody or antigen, DNA, fluorescence molecule biomolecule are fixed on the carbon tube-surface, obtain carbon nano-tube f-CNTs through modifying;
The 3rd step: will be scattered in through the carbon nano-tube f-CNTs of probe molecule covalency or non-covalent bond chemical modification in aqueous solution or solvent dimethylformamide or the chlorobenzene solvent, the hanging drop of the carbon nano-tube f-CNTs after will modifying then is added to the silica surface that has electrode pair;
The 4th step: after treating that solvent evaporates fully, utilize the carbon nano-tube f-CNTs after the nano-manipulation instrument moves modification, the carbon nano-tube f-CNTs after modifying is weldingly fixed on metal electrode to last;
The 5th step: adopt deep reaction ion etching technology earlier basalis to be run through punching, the oxide isolated processing is done to the hole in the back that has openning hole, and injects conducting resinl then in the hole, with the stitch of basalis bottom and conducting resinl by being welded together;
The 6th step: the using plasma bonding techniques is glued together above-mentioned dimethyl silicone polymer oligomer seal and basalis.
CN2007101520696A 2007-09-30 2007-09-30 Field effect transistor biosensor preparation method Expired - Fee Related CN101126735B (en)

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