CN102109482B - Light-addressable electropolymerization device and molecular imprinting electrochemical modification method and application thereof - Google Patents
Light-addressable electropolymerization device and molecular imprinting electrochemical modification method and application thereof Download PDFInfo
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- CN102109482B CN102109482B CN 200910243737 CN200910243737A CN102109482B CN 102109482 B CN102109482 B CN 102109482B CN 200910243737 CN200910243737 CN 200910243737 CN 200910243737 A CN200910243737 A CN 200910243737A CN 102109482 B CN102109482 B CN 102109482B
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Abstract
The invention relates to a light-addressable electropolymerization device which consists of a measurement cell, an array chip, an electrochemical workstation, an LED array light source, an LED array light source controller, a phase-locked amplifier, a reference electrode and a contrast electrode, wherein the light-addressable array chip with an MOS (Metal Oxide Semiconductor) array structure is mounted in the light-addressable electropolymerization device; and through infrared LEDs that are subjected to high-frequency modulation, a sensitive unit is selectively excited, so that an MOS capacitor array of the chip is gated. Under the drive of a power supply of the electrochemical workstation in an external circuit, a light-addressable and selective cyclic volt-ampere electrochemical loop is formed by the MOS capacitor array and the reference electrode, so that the light-addressable electropolymerization can be realized. The light-addressable electropolymerization and the molecular imprinting technology are combined to form a light-addressable molecular imprinting electrochemical modification method. The method provided by the invention is effective to solve the electrochemical modification of a sensitive film of the array chip, so that a light-addressable sensor can better exert the advantages that the parameters are multiple and a detection instrument is simple and convenient.
Description
Technical field
The present invention relates to the electrochemical sensor technical field that molecular engram sensitive membrane and light addressing detect, disclose a kind of smooth addressing electropolymerization device particularly.
The invention still further relates to and utilize above-mentioned smooth addressing electropolymerization device to carry out light addressing molecular engram galvanochemistry method of modifying.
The invention still further relates to the application of above-mentioned smooth addressing electropolymerization device.
Background technology
Light addressing detection technique is based on Light Addressable Potentiometric Sensor, and (Light AddressablePotentiometric Sensor, LAPS), this sensor is to be invented at late nineteen eighties by a molecular device company of California, USA.Advantage such as LAPS has applied range, light addressing capability strong, high sensitivity, advantages of higher stability, required sample is few, measurement range is wide, detection time is short becomes the nova of biosensor technique.The basic functional principle of LAPS as shown in Figure 1.Be insulated layer between semiconductor and the electrolyte solution and separate formation EIS structure.Regulating bias voltage makes semiconductor be in different bias states.Light source (as LED or laser) through intensity modulated shines from the back side to this EIS structure, produces electron hole pair in semiconductor.When the surface that semiconductor contacts with insulation course was in spent condition, these electron hole pairs may enter depletion layer by diffusion.Electric field in the depletion layer with the light induced electron hole to separately, thereby in the loop, produce photogenerated current.When semiconductor surface was in the electric charge accumulated state, the electric field of semiconductor surface was zero, and electron hole pair can not separate at this, so photogenerated current is zero substantially.The responsive principle of LAPS is based on field effect makes device to potential change sensitivity in interface between insulation course and electrolyte solution, but, when signals collecting, LAPS adopts the modulated beam of light irradiation, device is modulated by photocurrent the response of this potential change, and adopted phase-locked detection technique that response signal is detected.The typical response curve of LAPS as shown in Figure 2.When the concentration of test solution changed, response curve can be offset to the left or to the right.By detecting the variation that this side-play amount can detect solution concentration.Because the existence of sensitive membrane, sensitive membrane surface absorption one deck ion forms film potential, thereby causes the voltage at insulator and semiconductor two ends to produce certain skew.Therefore photocurrent-bias voltage curve also produces corresponding skew.Treat that the concentration of measured ion is relevant in the side-play amount of curve and the solution.Therefore can detect the concentration for the treatment of measured ion by the side-play amount of measuring curve.Measure empirical curve that the buffer solution of different pH values obtains as shown in Figure 2.Existing many scholars study its function on this basis from single H
+The quick LAPS of ion develops into enzyme LAPS, immune LAPS and biological LAPS.The emphasis of research is to the chemical modification of LAPS chip and the immobilization of sensitive thin film.
The high sensitivity of biology sensor and specific advantage are subjected to extensive concern, but, the recognition component of being made up of biomolecule exists has relatively high expectations to environment for use, is difficult to intrinsic defectives such as long preservation, makes biology sensor run in actual applications much to be difficult for the obstacle that overcomes; Simultaneously, biomolecule derives from biological living, and preparation and purifying are loaded down with trivial details, expensive.Biology sensor face low stable, expensive, can not in pH value higher or on the low side and pyrosol, use, be difficult to do not have corresponding a series of problems such as identification target molecule with micro-processing technology compatibility, some analyte, become a key factor that influences its development.Therefore, obtaining cheap, stable recognition component, is one of key of further developing of biology sensor.By research and the understanding to antigen-antibody, enzyme and substrate reactions principle, scientist has courageously proposed the imagination by the synthetic analog antibody of chemical reaction, has started a brand-new technology molecular imprinting.Molecular imprinting refers to prepare the polymkeric substance that a certain specific target molecules is had specific selectivity, and namely the process of molecularly imprinted polymer often is depicted as the technology of making the artificial lock of identifying the molecule key visually.The molecular engram process was made up of three steps: the first step, and function monomer and template molecule are mixed with out covalent complex, or form the addition compound product of non-covalent combination; Second step was carried out polymerization with above-mentioned monomer-template complex (addition product), was frozen in the high molecular three-dimensional network; The 3rd step removed template molecule from polymkeric substance.The space that former cause mould utmost point molecule occupies will form the cavity that can remember formwork structure, size and other physics, chemical characteristic, can optionally remove the molecule in conjunction with template (or analog) effectively, (molecularly imprinted polymers MIPs) constitutes bionical biology sensor as the bio-sensing functional membrane with molecularly imprinted polymer.
The molecular engram concept has existed for many years, still, to its experimental technique and application thereof, is in recent years along with developing rapidly of hyundai electronics and biotechnology just had considerable progress, becomes the focus of research.The stability of MIPs is higher than the natural biological molecular recognition elements far away, can obtain than high selectivity and specific polymkeric substance, is the ideal material that solves the bio-sensitive film poor stability.Therefore, the research of molecularly imprinted polymer is subject to people's attention.The electropolymerization molecular engram film is very active in galvanochemistry molecular engram sensor research in the recent period.It refers to monomer molecule generation electropolymerization under the situation that template molecule exists, and specific molecule trace selectivity is incorporated in the polymeric membrane.Used polymerization single polymerization monomer mainly contain adjoin cough up, phenols, prophyll beautiful jade (IV) nickel and o-phenylenediamine etc.People such as Spurlock peroxidating poly-adjoin to cough up form recognition site in the film, be used for studying the selective problems to gland battalion and ATP.Panasyuk etc. measure nitrobenzene with electropolymerization prophyll beautiful jade (IV) nickel blotting membrane as recognition component.People such as Cheng have reported that the electropolymerization o-phenylenediamine forms molecular engram film and measures neutral molecule glucose.The major advantage that the electricity consumption polymerization prepares molecular engram film is the electropolymerization film that can obtain different density degree and different-thickness by adjusting sweep velocity and polymerization time, and the electropolymerization film can form on the conductive electrode surface of Any shape and size.
The background technology of relevant light addressing detection technique is all right with reference to following document:
1)Dean?G.Hafeman，J.Wallace?Parce，Harden?M.Mcconnell，Light-addressable?Potentiometric?Sensor?for?Biochemical?Systems，Science，Vol.240，pp.1182-1185，1988；
2)Sergey?A.Piletsky，S.Subrahmanyam，Anthony?P.F.Turner“Applicationof?molecularly?imprinted?polymers?in?sensors?for?the?environment?andbiotechnology”Sensor?Review，Volume?21?Number?4?2001?pp.292-296.；
3)Toshifumi?Takeuchi，Yuji?Minato?et?al.Molecularly?imprintedpolymers?with?halogen?bonding-based?molecular?recognition?sites.TetrahedronLetters?46(2005)9025-9027；
4) " molecular engram-biomimetic sensor progress " analytical chemistry such as He Yonghong, 2004,32 (10): 1407～1412.
5) the two swallows of official " the employing molecular imprinting makes up the electrochemical sensor Study of Interface " Hunan University's doctorate paper.
Summary of the invention
The object of the present invention is to provide a kind of smooth addressing electropolymerization device.
Another purpose of the present invention is to provide utilizes above-mentioned smooth addressing electropolymerization device to carry out light addressing molecular engram galvanochemistry method of modifying.
For achieving the above object, smooth addressing electropolymerization device provided by the invention mainly is made up of organic glass measuring cell, array chip, electrochemical workstation, led array light source, led array light source controller, lock-in amplifier, contrast electrode and comparison electrode; Wherein:
Measuring cell is the circle cup that organic glass is made;
The measuring cell bottom center is being inlayed the infrared LED array light source, and the infrared LED array light source has N light source; A space of placing light addressing molecular engram electropolymerization array chip is established in LED matrix light source top;
Armouring has electrode retaining collar around the measuring cell base inboard, led array light source, and the surface of light source of led array light source and electrode retaining collar are embedded on the same plane; Pick out lead-in wire by electrode retaining collar and link the measuring cell base back surface as working electrode;
Light addressing molecular engram electropolymerization array chip is the planar type array chip: be substrate with the silicon chip, surface at silicon chip is coated with in regular turn: silicon dioxide layer, and silicon nitride film or tantalum pentoxide film, be provided with Cr-Au square formation formation Metal-oxide-semicondutor MOS unit as the sensitive membrane sedimentary province at silicon nitride film or tantalum pentoxide film; The center of this sensitive membrane sedimentary province is corresponding with the center of N light source of infrared LED array light source respectively;
Chip surface beyond the sensitive membrane sedimentary province is insulation course, and this insulation course is in regular turn: thick silicon dioxide layer, and silicon nitride film or tantalum pentoxide film;
Light addressing molecular engram electropolymerization array chip back side N the area of illumination corresponding with the center of N light source of infrared LED array light source is naked silicon, and remainder is the Cr-Au film; Being provided with the Cr-Au metal level around the light addressing molecule electropolymerization array chip back side is contact electrode; Perhaps
Light addressing molecular engram electropolymerization array chip is 3 D stereo type array chip: be substrate with the silicon chip, be equipped with N hole at the surface of silicon chip and the back side and be the sensitive membrane sedimentary province, the corresponding N in the back side hole be for the light source region of acceptance, and Keng center is corresponding with the center of N light source of infrared LED array light source respectively up and down;
The surface in N hole is coated with the silicon dioxide oxide layer in regular turn, and silicon nitride film or tantalum pentoxide film are provided with the Cr-Au square formation at silicon nitride film or tantalum pentoxide film and constitute three-dimensional MOS unit as the sensitive membrane sedimentary province for the sensitive membrane sedimentary province; The remaining surface of chip is coated with the thick silicon dioxide oxide layer in regular turn, and silicon nitride film or tantalum pentoxide film are as the insulation isolated area;
Light addressing molecular engram electropolymerization array chip back side N the area of illumination corresponding with the center of N light source of infrared LED array light source is naked silicon, and remainder is the Cr-Au film; Being provided with the Cr-Au metal level around the light addressing molecule electropolymerization array chip back side is contact electrode.
In the described smooth addressing electropolymerization device, the infrared LED matrix light source side that the measuring cell bottom center is inlayed seals with fluid sealant and circle cup, and the front and back of light source is exposed to the outside.
In the described smooth addressing electropolymerization device, the sensitive membrane sedimentary province of light addressing molecular engram electropolymerization planar type array chip or light addressing molecular engram electropolymerization 3 D stereo type array chip and the chip thickness of light source region of acceptance are less than 200 μ m.
In the described smooth addressing electropolymerization device, the sensing membrane preparation method of light addressing molecular engram array chip is as follows:
1) based on the sensitizing range of the N of light addressing method on an array chip chip, prepares N electropolymerization film that contains the different templates molecule respectively;
2) with polymerization contain N kind template molecule array chip be immersed in the perforating agent template molecule of each sensitizing range of wash-out respectively, the final light addressing molecule electropolymerization array chip that obtains to have the sensitizing range of N recognition capability.
In the described smooth addressing electropolymerization device, silicon nitride film is to adopt the low-pressure chemical vapor deposition preparation; Tantalum pentoxide film is to adopt the magnetron sputtering preparation.
Provided by the inventionly utilize above-mentioned smooth addressing electropolymerization device to carry out light addressing electropolymerization method, its process is, optionally encourage sensing unit by high frequency modulated LED, the MOS array capacitor is strobed, under the electrochemical workstation power drives, constitute light addressing, the galvanochemistry loop of cyclic voltammetric optionally with contrast electrode, thereby can realize the electropolymerization program of light addressing.
Smooth addressing electropolymerization device of the present invention being applied at light addressing molecular engram electrochemical sensor: the difference that forms recognition site according to detected object (being template molecule), adopt constant potential timing ampere method, be background solution with the potassium ferricyanide solution, the detected solution that adds variable concentrations, the electric current changing value of the potassium ferricyanide changes situation in time under the record constant potential, can obtain trace sensitive membrane electrode electro Chemical response corrections curve.
Description of drawings
Fig. 1 is known LAPS system structural framework synoptic diagram;
Fig. 2 is the typical response curve of LAPS system shown in Figure 1;
Fig. 3 is light addressing electropolymerization fundamental diagram;
Fig. 4 is smooth addressing molecular engram electropolymerization schematic representation of apparatus of the present invention;
Fig. 5 is the synoptic diagram of the measuring cell of light addressing molecular engram electropolymerization device among Fig. 4; Wherein Fig. 5 a is the upward view of this measuring cell, and Fig. 5 b is the cross-sectional view of this measuring cell;
Fig. 6 is the cross-sectional view of array chip in the smooth addressing molecular engram electropolymerization device of the present invention among Fig. 5 a, and wherein Fig. 6 a is the cross-sectional view of planar type array chip, and Fig. 6 b is the cross-sectional view of 3 D stereo type array chip.
Main label is among the figure:
1-organic glass measuring cell, 2-array chip, 3-5 * 7LED matrix, 4-contrast electrode and to electrode, 5-working electrode and lead-in wire, 6-electrochemical workstation, 7-lock-in amplifier, 8-LED controller system, the 9-PC machine, the oxygen-free copper ring electrode that 10-contacts with chip, 11-silicon substrate, 12-SiO
2Insulation course, 13-Si
3N
4Or Ta
2O
5Insulation course, 14-sensitive membrane sedimentary province Cr-Au metal level, 15-chip back Cr-Au conductive electrode.
Embodiment
The present invention is directed to N sensitizing range film immobilization problem of molecular engram array chip, propose a kind of electropolymerization method and device thereof based on the light addressing technique, with molecular imprinting with combination, constitute the chemical modification method of light addressing molecular engram.The particular content of this invention is as follows:
1) proposes light addressing electropolymerization concept, make up one based on the electropolymerization device (as shown in Figure 1) of light Addressable Biochemical Sensors detection technique.
The light Addressable Biochemical Sensors is with the light addressing mode information of array chip to be gathered, and has multiparameter, the advantage that detecting instrument is easy.But in the sensitive thin film immobilization program of array chip, because each array does not have contact conductor, can't modify its galvanochemistry of carrying out one by one, can only adopt manual coating method, influence sensitive thin film immobilization quality, and the quantity of restriction array.The electropolymerization concept that the present invention proposes the light addressing as shown in Figure 3, Fig. 3 has provided light addressing electrochemical polymerization schematic diagram.Light addressing array chip is " electrolyte-insulation course-semiconductor " structure (being the EIS structure), or " metal-insulator layer-semiconductor " structure (being the MIS structure).Array chip just as a plurality of EIS structure sensors that have been both a parallel connection.Wherein ψ is the impressed voltage of the electrochemical polymerization that chip applied from external circuit by electrochemical workstation; C
1～C
nIt is the mos capacitance of each EIS structural semiconductor chip equivalence of array chip; A
1～A
nRepresent respectively through optionally light stimulus, make each optionally conducting of branch road electric capacity, the photocurrent of generation.Light addressing electropolymerization device is installed to MOS array structure light addressing array chip in the device as shown in Figure 1.Optionally encourage sensing unit by high frequency modulated LED, make its mos capacitance conducting, exciting light just is equivalent to the mos capacitance gating switch of each branch road, add under the effect of ψ cyclical voltage at electrochemical workstation, with contrast electrode constitute the light addressing, the galvanochemistry loop of cyclic voltammetric optionally, will make each unit of array chip optionally produce the cyclic voltammetric electric current, realize electrochemical polymerization.Realize having light addressing capability electropolymerization thus.
2) basic structure of " based on the electrochemical polymerization device of light addressing technique " partly is made up of organic glass electrochemical cell, led array chip, electrochemical workstation, led array light source and controller, lock-in amplifier, contrast electrode etc.Above-mentioned organic glass electrochemical cell is to inlay one piece of infrared LED array in the central authorities of the bottom of organic glass electrochemical cell, and with fluid sealant will around sealing, guarantee no leakage.Above the led array light source, the space of a rectangular parallelepiped is arranged, just in time place array chip.The position of the chip of placing at the measuring cell base is equipped with the oxygen-free copper electrode, and picks out lead-in wire from base back surface, as the working electrode (seeing Fig. 4 and Fig. 5) of light addressing electrochemical polymerization reaction.
3) basic structure of array chip, array chip is selected N-type＜100 for use 〉, resistivity is that the twin polishing silicon chip of 5～8 Ω-cm is substrate.Each array chip is rectangle, and there is N MOS unit on the surface; The back side of chip does not have insulation course, at the wide Cr-Au metal level that preparing of the 1mm of isolated edge as the contact electrode of working electrode chip.Array chip is the MOS array structure before sensitive membrane is immobilized, and they can be planes, also can be the 3 D stereo type.The former is shown in Fig. 6 a, the latter is shown in Fig. 6 b, the array chip of plane, surface and the back side can be complete in the microelectronics planar technology, and 3 D stereo type array chip is based on the MEMS technology light source region of acceptance and sensitive membrane sedimentary province are processed into three-dimensional structure.
The structure of the array chip of plane (Fig. 6 a):
There is N MOS unit on the surface of array chip: silicon chip surface covers the pure silicon dioxide of one deck CMOS technological level earlier, prepare silicon nitride film or magnetron sputtering tantalum pentoxide film by low-pressure chemical vapor deposition again, prepare Cr-Au metal level square formation at last and constitute the MOS unit, as the sensitive membrane sedimentary province; They the center, corresponding with the center of N light source of infrared LED array light source respectively.
Chip surface beyond the sensitive membrane sedimentary province is insulation course: cover the silicon dioxide of one deck thermal oxide earlier, prepare silicon nitride film or magnetron sputtering tantalum pentoxide film by low-pressure chemical vapor deposition again.
The N at the back side of a chip area of illumination is naked silicon, and remainder is the Cr-Au film of 100nm; Around chip, the Cr-Au metal level of wide 1mm, thick 1 μ m is arranged as the contact electrode of working electrode and chip.
Three-dimensional structure array chip structure (Fig. 6 b):
Each array chip is rectangle twin polishing silicon chip, at silicon chip surface and the back side, all being used each diversity chemical corrosion method processes deserved N hole, the degree of depth of surface imperfection is 10～20 μ m, as the sensitive membrane sedimentary province, the degree of depth in the corresponding N in the back side hole is about 150 μ m, and as the light source region of acceptance, cheating floorage up and down is 1mm * 1mm.Their center, corresponding with the center of N light source of outer led array light source respectively.
The surface coverage in the N of rectangular dies hole oxide layer and is added silicon nitride film or tantalum pentoxide film, prepares Cr-Au metal square formation again, constitutes three-dimensional MOS unit, as the sensitive membrane sedimentary province; The remaining surface of chip is covered with thick oxide layer and adds silicon nitride film and tantalum pentoxide film, as the insulation isolated area.
A back side N area of illumination of three-dimensional structure array chip is naked silicon, and remainder is the Cr-Au film of 100nm; Be that the Cr-Au metal level of 1 μ m is as the contact electrode of working electrode chip at the wide thickness that preparing of the 1mm of isolated edge.
No matter plane still is 3 D stereo type array chip, and the final chip thickness of its light addressing reaction zone (being sensitive membrane sedimentary province and light source region of acceptance) should be less than 200 μ m.
4) light addressing electropolymerization method: MOS array structure light addressing array chip is installed in the device (sees Fig. 1 for details).By the high-frequency signal modulation LED of gating, infrared light optionally encourages sensing unit, makes its mos capacitance conducting.Exciting light just is equivalent to the mos capacitance gating switch of each branch road, under the electrochemical workstation power drives, with contrast electrode constitute the light addressing, the galvanochemistry loop of cyclic voltammetric optionally, thereby finish the electrochemical polymerization of light addressing.
5) sensitive membrane of light addressing molecular engram array chip preparation is that the electropolymerization with the light addressing combines formation light addressing molecular engram galvanochemistry method of modifying with molecular imprinting.Concrete grammar is as follows:
A) based on the sensitizing range of the N of light addressing method on an array chip chip, preparation contains the electropolymerization film of certain template molecule.
B) array chip is immersed in the perforating agent, the various template molecules of difference wash-out, final acquisition has the array chip of the sensitizing range of N recognition capability.
6) the electropolymerization program of light addressing molecular engram is that template molecule is introduced polymerization single polymerization monomer:
C) a series of electropolymerization electrolyte of the polymerization single polymerization monomer of different templates molecule have been mixed with certain proportion configuration.Array chip is positioned over based in the electropolymerization device of light addressing technique (seeing Fig. 1 for details), with silica stationary and sealing.In reaction tank, add the electropolymerization electrolyte that contains certain template molecule.Open when gating circuit makes some luminous points of LED, the back side of the sensitizing range of that corresponding chip is energized the galvanochemistry loop that constitutes electropolymerization.Repeatedly scan with cyclic voltammetry, make sensitive membrane be deposited on electrode surface, the surface, sensitizing range forms polymeric membrane.Change the electropolymerization electrolyte of other template molecule again, select another sensitizing range to carry out electropolymerization.Repeat above program, be formed with the array chip of N electropolymerization film the most at last.
D) monomer of general electropolymerization mainly contains pyrroles, phenols, prophyll beautiful jade (IV) nickel and o-phenylenediamine, o-aminophenol etc., then select to form the various molecules of recognition site for multiple detected object (being template molecule), agricultural chemicals (Insecticides (tech) ﹠ Herbicides (tech)) for example, medicine and biochemical substances etc.Prepare molecule engram film technology comparative maturity as for electropolymerization, about electropolymerization solution and perforating agent have a lot of reports.
7) smooth addressing molecular engram galvanochemistry method of modifying of the present invention being applied at light addressing molecular engram electrochemical sensor: can form the difference of recognition site according to detected object (being template molecule), adopt constant potential timing ampere method.Be background solution with the potassium ferricyanide solution, after background current is stable, the detected solution that adds variable concentrations in the background solution, the peak current changing value of the potassium ferricyanide changes situation in time under the record constant potential. on this basis, the potassium ferricyanide peak current changing value of response along with the variation drafting pattern of tested molecular conecentration, can be obtained trace sensitive membrane electrode electro Chemical response corrections curve.
The invention will be further described below in conjunction with accompanying drawing.
The principle of work of light addressing electropolymerization as shown in Figure 3.Light addressing array chip is " electrolyte-insulation course-semiconductor " structure (being the EIS structure), or " metal-insulator layer-semiconductor " structure (being the MIS structure).Array chip is equivalent to N mos capacitance arranged side by side.Be added in dc offset voltage between electrolytic solution and the silicon chip substrate by adjusting, be in different states near can making semiconductor and interfacial dielectric layer, shine certain unit of array chip then with the exciting light source (as LED, laser) of modulation, just externally produce the photocurrent of being modulated in the loop.Adopt two DG508 eight of MAXIM company to select a multiplexer in the system, respectively the row, column of LED matrix is carried out gating addressing and driving, and by the sine output signal that the voltage controlled oscillator of lock-in amplifier provides LED is carried out the light signal irradiation chip that ac modulation produces.Optionally encourage sensing unit by high frequency modulated LED, make its mos capacitance conducting, under electrochemical workstation power supply ψ drives, with contrast electrode constitute the light addressing, the galvanochemistry loop of cyclic voltammetric optionally, thereby finish the electropolymerization of light addressing.
Based on the electropolymerization apparatus structure of light addressing technique as shown in Figure 4, whole device is by organic glass measuring cell 1, array chip 2, led array light source 3, contrast electrode and comparison electrode 4, working electrode and go between 5, electrochemical workstation 6, lock-in amplifier 7, light source controller 8, PC 9, the oxygen-free copper ring electrode 10 that contacts with chip etc. partly form in concrete enforcement.Wherein,
The measuring cell 1 of light addressing molecular engram electropolymerization device is of a size of in the present embodiment shown in Fig. 5 a and Fig. 5 b:
Circle cup profile Ф 50mm * 50mm;
One piece of 5 * 7 infrared LED array light source 3 (commodity) inlayed by central authorities in circle cup bottom, and its physical dimension is 14.70mm * 19.80mm, and spot diameter is Ф 1.9mm, and spot distance 2.54mm with fluid sealant sealing all around, guarantees no leakage;
Above led array light source 3, the space of a rectangular parallelepiped 19.85mm * 14.75mm * 1mm is arranged, just in time place light addressing molecule electropolymerization array chip;
In measuring cell base inboard, around the led array light source 3 armouring the gold-plated oxygen-free copper electrode retaining collar 10 of a rectangle, its physical dimension is 19.8mm * 14.7mm, endoporus is 14.75mm * 19.85mm, surface of light source and the electrode retaining collar of guaranteeing led array are embedded on the same plane, in addition, pick out the back side that lead-in wire is linked base from electrode retaining collar 10, working electrode 5 as light addressing measurement, light source controller 8 is by Single-chip Controlling, adopt two DG508 eight of MAXIM company to select a multiplexer in the system, respectively to the row of LED matrix, row carry out gating addressing and driving.
Led array chip 2 is selected thickness 180～300 μ m, N-type＜100 for use 〉, resistivity is that the twin polishing silicon chip of 5～8 Ω-cm is substrate.Each array chip is the rectangle of 19.8mm * 14.7mm, and there is N MOS unit on the surface; The back side of chip does not have insulation course, is that the Au layer of 1 μ m is as the contact electrode 15 of working electrode chip at the wide thickness that preparing of the 1mm of isolated edge.Array chip is the MOS array structure before sensitive membrane is immobilized, and they can be planes, also can be the 3 D stereo type.Former structure is shown in Fig. 6 a, and the latter is shown in Fig. 6 b.The array chip surface of plane and the back side can be complete in the microelectronics planar technology, and 3 D stereo type array chip is based on the MEMS technology light source region of acceptance and sensitive membrane sedimentary province are processed into three-dimensional structure.No matter plane still is 3 D stereo type array chip, and the final chip thickness of its light addressing reaction zone (being sensitive membrane sedimentary province and light source region of acceptance) should be less than 200 μ m.
The concrete technology of the array chip of plane is as follows:
The thickness of array chip 2 is less than 200 μ m, there is N MOS unit on the surface: silicon chip 11 surfaces cover the pure silicon dioxide 100nm 12 of one deck CMOS technological level earlier, prepare silicon nitride film 100nm or magnetron sputtering tantalum pentoxide film 100nm 13 by low-pressure chemical vapor deposition again, prepare the above Cr-Au square formation 14 of 1 μ m at last, constitute the MOS unit, as the sensitive membrane sedimentary province; They the center, corresponding with the center of N light source of 5 * 7 infrared LED array light sources 3 respectively.
Chip surface beyond the sensitive membrane sedimentary province is insulation course: cover the silica 1 μ m 12 of one deck thermal oxide earlier, prepare silicon nitride film 100nm or magnetron sputtering tantalum pentoxide film 100nm 13 by low-pressure chemical vapor deposition again.
The N at the back side of a chip area of illumination is naked silicon, and remainder is the Cr-Au film 15 of 100nm; Around chip, the Cr-Au metal level 15 of wide 1mm, thick 1 μ m is arranged as the contact electrode of working electrode and chip.
The three-dimensional structure array chip structure:
Each array chip 2 is 19.8mm * 14.7mm, thickness is the rectangle silicon chip of 300 μ m, at silicon chip surface and the back side, all being used each diversity chemical corrosion method processes deserved N hole, the degree of depth of surface imperfection is 10～20 μ m, and as the sensitive membrane sedimentary province, the degree of depth in the corresponding N in the back side hole is about 100 μ m, as the light source region of acceptance, cheating floorage up and down is 1mm * 1mm.Their center is respectively with the center corresponding (seeing accompanying drawing 4 for details) of N light source of 5 * 7 infrared LED array light sources 3.
The oxide layer 12 that the surface coverage in the N of rectangular dies hole 100nm adds silicon nitride film or the 100nm tantalum pentoxide film 13 of 100nm, prepares the above Cr-Au metal level 14 of 1 μ m again, constitutes three-dimensional MOS unit, as the sensitive membrane sedimentary province; The oxide layer 12 that the chip remaining surface is covered with 1 μ m adds silicon nitride film and the 100nm tantalum pentoxide film 13 of 100nm, as the insulation isolated area.
The N at the back side of a chip area of illumination is naked silicon, and remainder is the Cr-Au film 15 of 100nm; Around chip, the Cr-Au metal level 15 of wide 1mm, thick 1 μ m is arranged as the contact electrode of working electrode and chip.
In addition, contrast electrode and comparison electrode 4 are accessory commonly used in the electrochemical workstation, and contrast electrode can be mercurous chloride electrode or AgCl/Ag contrast electrode, and electrode is adopted the Pt electrode; Working electrode and to go between 5 be to draw from electrochemical workstation; Electrochemical workstation 6, lock-in amplifier 7 and PC 9 are general electrochemical known equipment.
Light addressing molecular engram galvanochemistry method of modifying comprises two steps: 1) monomer molecule generation electropolymerization under the situation of template molecule existence, 2) again template molecule is removed from polymkeric substance.The space that former cause template molecule occupies will form the cavity that can remember formwork structure, size and other physics, chemical characteristic, can optionally remove the molecule in conjunction with template (or analog) effectively.Like this, specific molecule trace selectivity is incorporated in the electropolymerization film.The general polymerization monomer mainly contain adjoin cough up, phenols, prophyll beautiful jade (IV) nickel and o-phenylenediamine, o-aminophenol etc., detected object (being template molecule) then is the various molecules that can form recognition site, agricultural chemicals (Insecticides (tech) ﹠ Herbicides (tech)) for example, medicine and biochemical substances etc.
Be example with detection urea, creatinine below, narrate embodiment:
Selecting o-aminophenol for use is function monomer, o-aminophenol and template molecule (urea, creatinine) are prepared with 10: 1 volumetric molar concentration respectively, wherein o-aminophenol dissolves with the perchloric acid solution of 0.1mol/L, and the pH value of regulator solution is led to high pure nitrogen and the oxygen in the solution is discharged back standby in the faintly acid scope.Array chip is positioned over based in the electropolymerization device of light addressing technique (seeing Fig. 4 for details), with silica stationary and sealing.In reaction tank, add the o-aminophenol polymer fluid that contains a kind of template molecule (urea).By high frequency (30KHz) the signal modulation LED of gating, infrared light optionally encourages sensing unit, makes its mos capacitance conducting.Exciting light just is equivalent to the mos capacitance gating switch of each branch road.Under the electrochemical workstation power drives, led light source of light addressing, the sensitizing range of a corresponding chip, with contrast electrode constitute the light addressing, the galvanochemistry loop of cyclic voltammetric optionally.Carrying out the polymerization number of turns with cyclic voltammetry in-0.2V～1.2V scope is 30～50 circle polymerizations, forms the o-aminophenol polymeric membrane that contains template molecule (urea); Change the polymer fluid of template molecule (creatinine) again, select another sensitizing range to carry out electropolymerization, obtain to contain the o-aminophenol polymeric membrane of template molecule (creatinine).Be formed with the array chip of 2 electropolymerization films the most at last.Chip after the polymerization is carried out 24 hours demoulding processing with the sulfuric acid solution of 0.5mol/L, be formed with the array chip of 2 sensitizing ranges the most at last.
The method of testing of light addressing molecular engram electrochemical sensor then is the difference that can form recognition site according to detected object (being template molecule), and light addressing molecular engram electrochemical sensor can be divided into two kinds of electric current and potentiometric sensors.The former adopts saturated calomel electrode as contrast electrode, and platinum black electrode adopts constant potential timing ampere method as auxiliary electrode.Be background solution with the 0.01mol/L potassium ferricyanide solution, after background current is stable, the detected solution (urea, creatinine) that adds variable concentrations in the background solution, the peak point current changing value of the potassium ferricyanide changes situation in time under the record constant potential. on this basis, the potassium ferricyanide peak current changing value of response along with the variation drafting pattern of tested molecular conecentration, can be obtained trace sensitive membrane electrode electro Chemical response corrections curve.
Claims (8)
1. light addressing electropolymerization device is mainly formed by organic glass measuring cell, light addressing molecular engram electropolymerization array chip, electrochemical workstation, infrared LED array light source, led array light source controller, lock-in amplifier, contrast electrode with to electrode; Wherein:
Measuring cell is the circle cup that organic glass is made;
The measuring cell bottom center is being inlayed the infrared LED array light source, and the infrared LED array light source has N light source; A space of placing light addressing molecular engram electropolymerization array chip is established in infrared LED array light source top;
In measuring cell base inboard, armouring has gold-plated oxygen-free copper electrode retaining collar around the infrared LED array light source, and the surface of light source of infrared LED array light source and gold-plated oxygen-free copper electrode retaining collar are embedded on the same plane; Pick out lead-in wire by gold-plated oxygen-free copper electrode retaining collar and link the measuring cell base back surface, this lead-in wire is received electrochemical workstation, as the working electrode of light addressing molecular engram electric polymerization reaction;
Light addressing molecular engram electropolymerization array chip is the planar type array chip: be substrate with the silicon chip, a surface at silicon chip is coated with in regular turn: silicon dioxide layer, and silicon nitride film or tantalum pentoxide film, be provided with N Metal-oxide-semicondutor unit of N Cr-Au square formation formation as the sensitive membrane sedimentary province at silicon nitride film or tantalum pentoxide film; The center of this sensitive membrane sedimentary province is corresponding with the center of N light source of infrared LED array light source respectively;
Surface beyond the sensitive membrane sedimentary province is insulation course, and this insulation course is in regular turn: than the thick silicon dioxide layer of sensitive membrane sedimentary province silicon dioxide bed thickness, and silicon nitride film or tantalum pentoxide film;
The reverse side of above-mentioned silicon chip surface is the light addressing molecular engram electropolymerization array chip back side, and N the light source region of acceptance corresponding with the center of N the light source infrared LED array light source that be provided with at this back side is naked silicon, and remainder covers the Cr-Au film; Around the light addressing molecular engram electropolymerization array chip back side, be provided with the Cr-Au metal level as the contact electrode of working electrode and chip; Perhaps
Light addressing molecular engram electropolymerization array chip is 3 D stereo type array chip: be substrate with the silicon chip, be provided with N hole on a surface of silicon chip and be the sensitive membrane sedimentary province, the another side corresponding with this surface is provided with N hole for the light source region of acceptance, and Keng center is corresponding with the center of N light source of infrared LED array light source respectively up and down;
The surface in the hole of N sensitive membrane sedimentary province is coated with the silicon dioxide oxide layer in regular turn, and silicon nitride film or tantalum pentoxide film, on silicon nitride film or tantalum pentoxide film, prepare the Cr-Au square formation again and constitute three-dimensional Metal-oxide-semicondutor unit as the sensitive membrane sedimentary province; Zone on the one side of the chip that is provided with the sensitive membrane sedimentary province beyond the sensitive membrane sedimentary province is coated with the thick silicon dioxide oxide layer than sensitive membrane sedimentary province silicon dioxide oxidation bed thickness in regular turn, and silicon nitride film or tantalum pentoxide film are as the insulation course district;
The back side on the above-mentioned surface of light addressing molecular engram electropolymerization array chip N the light source region of acceptance corresponding with the center of N light source of infrared LED array light source is naked silicon, and remainder is the Cr-Au film; Around the light addressing molecular engram electropolymerization array chip back side, be provided with the Cr-Au metal level as the contact electrode of working electrode and chip.
2. light addressing electropolymerization device according to claim 1, wherein, four sides of the infrared LED array light source that the measuring cell bottom center is inlayed are with fluid sealant and the sealing of circle cup, and the front and back of light source is exposed to the outside.
3. light addressing electropolymerization device according to claim 1, wherein, the chip thickness of the sensitive membrane sedimentary province of light addressing molecular engram electropolymerization planar type array chip or light addressing molecular engram electropolymerization 3 D stereo type array chip and light source region of acceptance is less than 200 μ m.
4. according to the described smooth addressing electropolymerization device of claim 1, wherein, the sensing membrane preparation method of light addressing molecular engram electropolymerization array chip is as follows:
1) based on the sensitive membrane sedimentary province of N the chip of light addressing method on light addressing molecular engram electropolymerization array chip, prepares N electropolymerization film that contains the different templates molecule respectively;
2) the light addressing molecular engram electropolymerization array chip that will contain N different templates molecule is immersed in the perforating agent, the wash-out template molecule of sensitive membrane sedimentary province separately respectively, the final light addressing molecular engram electropolymerization array chip with N recognition capability of obtaining.
5. light addressing electropolymerization device according to claim 1, wherein, silicon nitride film is to adopt the low-pressure chemical vapor deposition preparation; Tantalum pentoxide film is to adopt the magnetron sputtering preparation.
6. method of utilizing the described smooth addressing electropolymerization device of claim 1 to carry out light addressing electropolymerization, its process is, by the high frequency modulated infrared LED array light source light source region of acceptance at the exciting light addressing molecular engram electropolymerization array chip back side optionally, the Metal-oxide-semicondutor unit of light source region of acceptance is strobed, under the electrochemical workstation power drives, constitute light addressing, the galvanochemistry loop of cyclic voltammetric optionally with contrast electrode, thereby can realize the electropolymerization program of light addressing.
7. the described smooth addressing electropolymerization device of claim 1 is in the application of light addressing molecular engram electrochemical sensor: the difference that forms recognition site according to detected object, adopt constant potential timing ampere method, be background solution with the potassium ferricyanide solution, the detected solution that adds variable concentrations, the electric current changing value of the potassium ferricyanide changes situation in time under the record constant potential, can obtain trace sensitive membrane electrode electro Chemical response corrections curve.
8. application as claimed in claim 7, wherein, detected object is template molecule.
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| CN111220667B (en) * | 2020-02-27 | 2022-07-22 | 江苏大学 | Light-addressable electrochemical sensor and preparation method and detection method thereof |
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