CN1645141A - Polydimethylsiloxane based microorgan reagent analyzing and testing chip - Google Patents
Polydimethylsiloxane based microorgan reagent analyzing and testing chip Download PDFInfo
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- CN1645141A CN1645141A CN 200510023457 CN200510023457A CN1645141A CN 1645141 A CN1645141 A CN 1645141A CN 200510023457 CN200510023457 CN 200510023457 CN 200510023457 A CN200510023457 A CN 200510023457A CN 1645141 A CN1645141 A CN 1645141A
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Abstract
A detecting chip is featured as sealing glass layer and PDMS layer together by interlinking, having reagent sample input and output on PDMS layer and channel start point and end point on glass layer as they being corresponded to each other, setting ceramic piezoelectric value sample feed controller at outer side of PDMS, setting chip on base, sticking ultrasonic biological reagent mixing system on PDMS layer, placing integrated temperature control system at outer side of glass layer.
Description
Technical field
What the present invention relates to is a kind of biological reagent analyzing and testing chip, particularly a kind of miniature organism reagent analysis efficient detection chip based on dimethyl silicone polymer.Belong to microelectronics technology.
Background technology
In biological chemistry and medical science check and analysis system, it is vital composition link that biological reagent and chemical agent concentration and component detect, and the development of micro-electromechanical technology (MEMS) can be finished this detection on chip.The numerous detection methods that detect principle based on difference all are used in biological reagent and chemical agent concentration and the component detection research, detection means generally detects principle by it classifies, and roughly can be divided into fluorescence detector, electrochemical detector, mass detector etc.Up to the present, fluorescence detector is a kind of technology that is most widely used, and as important of this big class of fluorescence detector, fluorescence detector is for the high material of some fluorescence efficiency, by adopting the photon numeration, some improved technology such as two-photon excitation even can reach Single Molecule Detection, in addition, optical detecting method also has the good selectivity and the range of linearity of broad, and it is many as amino acid, important biochemical substances sample such as DNA all can carry out mark and detection with fluorescent reagent, therefore in biological reagent and chemical agent concentration and component detection, optical detection be a kind of application the earliest, and still using more optical detecting method so far, also is only adopted detection approach in the commercialization chemical analysis system at present.
Through the literature search of prior art is found: people such as Grewe delivered on " Applied Physics B " (" applied physics B volume ") in 2000 " Theoretical and experimental investigationsof the optical waveguiding properties of on-chip microfabricatedcapillaries " theory and the experimental study of microscopic capillary photoconductive property on (" sheet "), mentioned the optical detection system in this article, utilize photoetching, technologies such as bonding are made capillary chip, experiment and theoretical analysis have been carried out for the characteristic of extensively leading capillaceous, be connected the only 3dB that decays in the detection of 514nm wavelength period light path, yet this systemic-function is still more single, the fluorescence induction that can only carry out biological reagent detects, and can't detect for reagent concentration, this device also can't carry out mixing in early stage and temperature control reaction to test agent, also resting on single device makes, be not one integrated, the biological and chemical reagent analysis disposal system of complete function, and, the manufacturing of these devices all is subjected to the limitation of LCVD (low pressure chemical vapor phase deposition) technology, application surface is wideless, and it is very expensive to make cost, and peripheral light path coupling step is very complicated.In addition, the optical detection pattern all is to lead operation by monochromatic light to finish, and causes the undulatory property of determination data, causes lacking good repeatability, is unfavorable for carrying out system and data quantitative test all sidedly for the test agent component.Because test agent mixes in earlier stage, reaction and dosage control etc. need the auxiliary device branch to come to carry out, restricted the speed that photoconduction detects to a certain extent, make instant sense cycle longer, be unfavorable in the high efficiency requirement for the biological reagent detection.
Summary of the invention
It is single to the objective of the invention is to overcome existing miniature analyzing and testing chip functions, the unfavorable shortcoming of integrated level and measurement stability, a kind of microorgan reagent analyzing and testing chip based on dimethyl silicone polymer is proposed, by integrated a plurality of function elements on a chip, make the conveying of test agent, mix, temperature control reaction and optical detection are finished on the chip on one, shortened the sense cycle of test agent, improved whole work efficiency, simultaneously, utilize two-way photoconduction detection method to improve accuracy of detection and stability, make the detection of test agent have better repeatability and systematized feature, solved the problem that exists in the background technology.
The present invention is achieved through the following technical solutions, the present invention includes: dimethyl silicone polymer layer, glassy layer, piezoelectric ceramics valve injection controller, chip tighten up chucking appliance system, ultrasound biological reagent mix system, integrated temperature control reactive system.Its connected mode is: glassy layer and dimethyl silicone polymer layer are sealed by plasma oxidation technology bonding, on the PMDS layer, be provided with the reagent sample input port, the reagent sample delivery outlet, the reagent sample input port, the reagent sample delivery outlet respectively with glassy layer on each passage starting point, tunnel end points is corresponding, piezoelectric ceramics valve injection controller is in the outside of chip dimethyl silicone polymer layer, by computer control, thereby the electricity of piezoelectric ceramics sheet causes the switch closure of crooked extruding dimethyl silicone polymer layer distortion causing reagent flow-guiding channel on the glassy layer, chip tightens up dimethyl silicone polymer substrate one side that chucking appliance system fits tightly piezoelectric ceramics valve injection controller chip behind bonding, chip tightens up chucking appliance system and chip can be fixed on the base simultaneously, be convenient to carry out external pipe and the stable of utility appliance is connected, the ultrasound biological reagent mixer is the piezoelectric ceramics sheet that an embedding sticks on the dimethyl silicone polymer layer, its vibration causes the concussion of reagent in the glassy layer mixing microcavity to mix, the glassy layer outside corresponding with mixing microcavity is integrated temperature control reactive system, and it is responsible for the mix reagent temperature of reaction of microcavity.
Chip of the present invention is made in package shape of glass and two kinds of materials of dimethyl silicone polymer, comprise reagent sample input port, four parallel reagent sample delivery outlets on the dimethyl silicone polymer layer, reserves with 2mm diameter aluminum post when injection molding.
Glassy layer comprises: two-way photoconduction check point, the reagent flow-guiding channel that forms by multiple layer metal mask etching technology, 30 degree taper withdrawing pattern cell bodies, mix microcavity, main sense channel, its connected mode is: totally four of 30 degree taper withdrawing pattern cell bodies, it between per two a parallel reagent flow-guiding channel that passes through, the reagent flow-guiding channel is connected with the mixing microcavity, mixing microcavity and main sense channel joins, integrated two-way photoconduction detection system is arranged at the glassy layer inboard, is connected to two-way photoconduction check point mutually with main sense channel quadrature.The closed unlatching of reagent flow-guiding channel is controlled by piezoelectric ceramics valve injection controller, optionally importing reagent enters into and mixes microcavity and carry out ultrasonic mixing and temperature control reaction, main sense channel utilizes vacuum or electrophoresis method to drive test agent, integrated two-way photoconduction detection system and main sense channel quadrature join, and utilize the optical induction fluorescence detection method that the test agent of flowing through in the main sense channel is carried out concentration and component detection.The tip designs of mixing microcavity on the glassy layer is a taper, upholds and becomes owner of sense channel, and the reagent flow-guiding channel in both sides cooperates, and is convenient to make the reagent after the hybrid reaction to be injected into main sense channel in the mode of extraining sampling.
Chip of the present invention is by the closed and unlatching of piezoelectric ceramics valve injection controller control reagent flow-guiding channel, carry out the selectivity allotment for entering the reagent that mixes microcavity on the glassy layer, the execution unit of piezoelectric ceramics valve injection controller is the piezoelectric patches of an etching machine-shaping, and the two groups of parallel piezoelectricity execution units that distribute on every reagent flow-guiding channel are to improve the closure effect of piezo electric valve sample feeding controller for flow-guiding channel.
Chip tightens up the chucking appliance system stainless steel and makes, form by last compressing tablet, lower sheeting and elastic rubber fitting, last compressing tablet is one to be bent into the thin slice of T-shape, lower sheeting is a horizontal sheet, utilization 30 degree taper withdrawing pattern cell bodies and chips on glassy layer tighten up the elastic rubber fitting of chucking appliance system, chip tightens up dimethyl silicone polymer substrate one side that chucking appliance system fits tightly piezoelectric ceramics valve injection controller chip behind bonding, chip can be fixed on the base simultaneously, be convenient to carry out external pipe and the stable of utility appliance is connected.
The ultrasound biological reagent mixer is the piezoelectric ceramics sheet that an embedding sticks on the dimethyl silicone polymer layer, the concussion that its vibration causes mixing reagent in the microcavity on the glassy layer mixes, integrated temperature control reactive system is responsible for implementing regulation and control for the temperature of mixing microcavity in the glassy layer outside of mixing the microcavity correspondence.Integrated temperature control reactive system is made up of little Pt (platinum) film sensors and little platinum film well heater, and Lift-Off behind the employing sputter platinum (is the method that sacrifice layer is made the metal function layer with the photoresist) technology is made.
Integrated two-way photoconduction detection system is made up of dimethyl silicone polymer wrapper layer and SU8 (a kind of negative photoresist of doing high aspect ratio structure) fuse, the light wave of these two kinds of materials about for 400-600nm has good transmissivity, becomes the photoconduction transmission apparatus and the refractive index difference of two kinds of materials can be made it.This photoconduction path and main sense channel quadrature, when test agent is flowed through in main sense channel, specific wavelength laser by the one side incident of two-way photoconduction detection system passes through mix reagent to be measured, amplify by the modulation of PMT (integrated electro multiplication modules) device at two-way photoconduction detection system opposite side, be converted to corresponding electric signal, the concentration of mix reagent to be measured and change of component can cause that the light intensity attenuation in the photoconduction transmission channel changes in the main sense channel, this variation makes the electric signal respective change of collection, by signals collecting and analysis, draw the instant concentration and the component of test agent in the microchannel to two-way photoconduction path.
Detection chip among the present invention is when carrying out the detection of biological reagent and chemical agent concentration, utilizing vacuum action to drive test agent flows in microchannel, on the microchannel sidewall, be integrated with two-way photoconduction detection system, the variation of reagent concentration can cause that the light intensity attenuation in the photoconduction transmission channel changes, and this variation is passed to PMT modulation amplify, form the fluctuation of electric signal, by the Computer signal picking up system to this electric signal analytical calculation, draw the instant concentration of test agent in the microchannel, and draw time-domain curve.The present invention is when carrying out the detection of biological reagent and chemical reagent component, test agent and fluorescence associated reagent need mix in the integrated ultrasonic mixing system on chip in advance, drive the passage of the integrated two-way photoconduction detection system of flowing through then by electrophoresis, the laser induced fluorescence reagent of the respective wavelength of transmitting in the photoconduction transmission channel is luminous, the attenuation change scioptics system of light intensity and PMT are mapped as change in electric after amplifying, the computer data picking up system detects this variation, draws the shared proportioning of reagent different component by contrast and computing.The present invention is integrated multichannel piezo electric valve, microreactor and microanalysis passage on many passages turnover sheets that allotment control walks abreast, realization check and analysis.Miniature analyzing and testing chip is the focus of current biochemical analysis research, result of study show miniature analyzing and testing chip with the characteristics of himself structure overcome that traditional optical induced fluorescence checkout equipment volume is big, complex structure and the higher shortcoming of cost, simultaneously, the efficient in the molecular chemistry analysis is improved greatly.
The present invention has substantial characteristics and progress, it is single that the present invention has changed existing biological reagent analyzing and testing chip functions, the shortcoming that cost of manufacture is high and compatible not strong, pass through Micrometer-Nanometer Processing Technology, not only reduced device volume greatly, reduced cost, also made its mass be processed into possibility.Be used different type of drive, fluorescent reagent and excitation wavelength, the concentration that chip of the present invention not only can be used for chemical reagent detects, and also can carry out the quantitative test of biomolecule and cell granulations.In addition, chip of the present invention is because adopted optical detecting method at a high speed, have very high response speed, can be widely used in the The real time measure of biological reagent, chemical agent concentration and component, all have very strong practical value for preventive medicine, environmental water systems monitoring.
Description of drawings
Fig. 1 Facad structure synoptic diagram of the present invention
Fig. 2 local enlarged diagram shown in Figure 1
Fig. 3 rear view of the present invention
Fig. 4 local enlarged diagram shown in Figure 3
Each ingredient structural drawing of Fig. 5 the present invention
Wherein, integrated two-way photoconduction detection system 1, dimethyl silicone polymer layer 2, glassy layer 3, ultrasound biological reagent mix system 4, chip tightens up chucking appliance system 5, integrated temperature control reactive system 6, piezoelectric ceramics valve injection controller 7, reagent sample input port 8, reagent sample delivery outlet 9, passage starting point 10, tunnel end points 11, two-way photoconduction check point 12, reagent flow-guiding channel 13,30 degree taper withdrawing pattern cell bodies 14, mix microcavity 15, main sense channel 16, execution unit 17, last compressing tablet 18, lower sheeting 19, elastic rubber fitting 20, little platinum film sensor 21, little platinum film well heater 22, dimethyl silicone polymer foreskin 23, SU8 fuse 24, gold electrode 25.
Embodiment
Shown in Fig. 1-5, the present invention includes: integrated two-way photoconduction detection system 1, dimethyl silicone polymer layer 2, glassy layer 3, ultrasound biological reagent mix system 4, chip tighten up chucking appliance system 5, integrated temperature control reactive system 6, piezoelectric ceramics valve injection controller 7.Its connected mode is: glassy layer 3 is sealed by plasma oxidation technology bonding with dimethyl silicone polymer layer 2, on PMDS layer 2, be provided with reagent sample input port 8, reagent sample delivery outlet 9, glassy layer 3 is provided with each passage starting point 10, tunnel end points 11, reagent sample input port 8, reagent sample delivery outlet 9 respectively with each passage starting point 10, tunnel end points 11 is corresponding, piezoelectric ceramics valve injection controller 7 the outsides at dimethyl silicone polymer layer 2, chip tightens up chucking appliance system 5 piezoelectric ceramics valve injection controller 7 is fitted tightly dimethyl silicone polymer layer 2 one side behind bonding, chip tightens up chucking appliance system 5 and simultaneously chip is fixed on the base, is convenient to carry out external pipe and the stable of utility appliance is connected.Ultrasound biological reagent mix system 4 embeds and sticks on the dimethyl silicone polymer layer, and its below is a glassy layer 3, and glassy layer 3 outsides are integrated temperature control reactive system 6.
Reagent sample input port 8 on the dimethyl silicone polymer layer 2, reagent sample delivery outlet 9 are reserved with 2mm diameter aluminum post when injection molding, and reagent sample delivery outlet 9 has four, and parallel.
Glassy layer 3 comprises: two-way photoconduction check point 12, reagent flow-guiding channel 13,30 degree taper withdrawing pattern cell bodies 14, mixing microcavity 15, main sense channel 16, its connected mode is: 30 degree taper withdrawing pattern cell bodies 14 totally four, it between per two a parallel reagent flow-guiding channel 13 that passes through, reagent flow-guiding channel 13 is connected with mixing microcavity 15, mixing microcavity 15 joins with main sense channel 16, integrated two-way photoconduction detection system 1 is arranged at glassy layer 3 inboards, is connected to two-way photoconduction check point 12 mutually with main sense channel 16 quadratures.The end that mixes microcavity 15 is a taper, stretches to enter main sense channel 16, cooperates with the reagent flow-guiding channel 13 of both sides.
The photoconduction path that the core of integrated two-way photoconduction detection system 1 is made up of dimethyl silicone polymer foreskin 23 and SU8 fuse 24, this photoconduction path and main sense channel 16 quadratures.Be positioned at two-way photoconduction detection system 1 outer field dimethyl silicone polymer foreskin 23 and be closely linked, be responsible for the light signal conduction with the SU8 fuse 24 that is positioned at two-way photoconduction detection system 1 inner core.
Ultrasound biological reagent mix system 4 is the piezoelectric ceramics sheet that an embedding sticks on the dimethyl silicone polymer layer, and the correspondence position under it on glassy layer 3 has the microcavity 15 of mixing, and glassy layer 3 outsides are integrated temperature control reactive system 6 under mixing microcavity 15.
Be provided with execution unit 17 in the piezoelectric ceramics valve injection controller 7, execution unit 17 is the piezoelectric patches of an etching machine-shaping, two groups of parallel piezoelectricity execution units distribute on every reagent flow-guiding channel 13, cause flexural deformation by the computer control electricity, thereby extruding dimethyl silicone polymer layer 2 causes the switch closure of reagent flow-guiding channel 13 on the glassy layer 3.
Chip tightens up chucking appliance system 5 and adopts stainless steel to make, form by last compressing tablet 18, lower sheeting 19 and elastic rubber fitting 20, last compressing tablet 18 closely contacts with lower sheeting 19 and links together, elastic rubber fitting 20 is between last compressing tablet 18 and lower sheeting 19, the three closely connects, chip is fixed on the base, is convenient to carry out external pipe and the stable of utility appliance is connected.
Integrated temperature control reactive system 6 is made up of little platinum film sensor 21 and little platinum film well heater 22, platinum film sensor 21 is parallel winding in glassy layer 3 outsides with platinum film well heater 22, on little platinum film sensor 21 and little platinum film well heater 22 is gold electrode 25, make by the secondary sputter, be connected with power-supply controller of electric with the external signal picking up system.
Claims (8)
1, a kind of microorgan reagent analyzing and testing chip based on dimethyl silicone polymer, comprise: dimethyl silicone polymer layer (2), glassy layer (3), it is characterized in that, also comprise: integrated two-way photoconduction detection system (1), ultrasound biological reagent mix system (4), chip tightens up chucking appliance system (5), integrated temperature control reactive system (6), piezoelectric ceramics valve injection controller (7), glassy layer (3) and dimethyl silicone polymer layer (2) bonded seal are together, on dimethyl silicone polymer layer (2), be provided with reagent sample input port (8), reagent sample delivery outlet (9), glassy layer (3) is provided with each passage starting point (10), tunnel end points (11), reagent sample input port (8), reagent sample delivery outlet (9) respectively with each passage starting point (10), tunnel end points (11) is corresponding, piezoelectric ceramics valve injection controller (7) is in the outside of dimethyl silicone polymer layer (2), chip tightens up chucking appliance system (5) piezoelectric ceramics valve injection controller (7) is fitted tightly dimethyl silicone polymer layer (2) one side behind bonding, chip tightens up chucking appliance system (5) and simultaneously chip is fixed on the base, ultrasound biological reagent mix system (4) embeds and sticks on the dimethyl silicone polymer layer (2), its below is glassy layer (3), and glassy layer (3) outside is an integrated temperature control reactive system (6).
2, miniature organism reagent analysis efficient detection chip based on dimethyl silicone polymer according to claim 1, it is characterized in that, glassy layer (3) comprising: two-way photoconduction check point (12), reagent flow-guiding channel (13), 30 degree taper withdrawing pattern cell bodies (14), mix microcavity (15), main sense channel (16), its connected mode is: 30 degree taper withdrawing pattern cell body (14) totally four, it between per two a parallel reagent flow-guiding channel (13) that passes through, reagent flow-guiding channel (13) is connected with mixing microcavity (15), mixing microcavity (15) joins with main sense channel (16), integrated two-way photoconduction detection system (1) is arranged at glassy layer (3) inboard, be connected to two-way photoconduction check point (12) mutually with main sense channel (16) quadrature, the end that mixes microcavity (15) is a taper, stretching, extension enters main sense channel (16), cooperates with the reagent flow-guiding channel (13) of both sides.
3, the miniature organism reagent analysis efficient detection chip based on dimethyl silicone polymer according to claim 2, it is characterized in that, the photoconduction path that the core of integrated two-way photoconduction detection system (1) is made up of dimethyl silicone polymer foreskin (23) and SU8 fuse (24), the SU8 fuse (24) that is positioned at the outer field dimethyl silicone polymer foreskin of two-way photoconduction detection system (1) (23) and is positioned at two-way photoconduction detection system (1) inner core is closely linked, and is responsible for the light signal conduction.
4, according to claim 1 or 2 described miniature organism reagent analysis efficient detection chips based on dimethyl silicone polymer, it is characterized in that, ultrasound biological reagent mix system (4) is that an embedding sticks on the piezoelectric ceramics sheet on the dimethyl silicone polymer layer (2), correspondence position on the glassy layer under it (3) has mixing microcavity (15), and glassy layer (3) outside is an integrated temperature control reactive system (6) under mixing microcavity (15).
5, the miniature organism reagent analysis efficient detection chip based on dimethyl silicone polymer according to claim 1, it is characterized in that, reagent sample input port (8) on the dimethyl silicone polymer layer (2), reagent sample delivery outlet (9) are reserved with 2mm diameter aluminum post when injection molding, reagent sample delivery outlet (9) has four, and parallel.
6, the miniature organism reagent analysis efficient detection chip based on dimethyl silicone polymer according to claim 1, it is characterized in that, be provided with execution unit (17) in the piezoelectric ceramics valve injection controller (7), execution unit (17) is the piezoelectric patches of an etching machine-shaping, every reagent flow-guiding channel (13) is gone up the two groups of parallel piezoelectricity execution units that distribute, cause flexural deformation by the computer control electricity, extruding dimethyl silicone polymer layer (2) thus cause that glassy layer (3) goes up the switch closure of reagent flow-guiding channel (13).
7, the miniature organism reagent analysis efficient detection chip based on dimethyl silicone polymer according to claim 1, it is characterized in that, chip tightens up chucking appliance system (5) and adopts stainless steel to make, form by last compressing tablet (18), lower sheeting (19) and elastic rubber fitting (20), last compressing tablet (18) closely contacts with lower sheeting (19) and links together, elastic rubber fitting (20) is between last compressing tablet (18) and lower sheeting (19), the three closely connects, chip is fixed on the base, is convenient to carry out external pipe and the stable of utility appliance is connected.
8, the miniature organism reagent analysis efficient detection chip based on dimethyl silicone polymer according to claim 1, it is characterized in that, integrated temperature control reactive system (6) is made up of little platinum film sensor (21) and little platinum film well heater (22), platinum film sensor (21) is parallel with platinum film well heater (22) winding in glassy layer (3) outside, on little platinum film sensor (21) and little platinum film well heater (22), be Au electrode (25), make by the secondary sputter, be connected with power-supply controller of electric with the external signal picking up system.
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