CN101109748B - Detecting biologic sensor combining evanescent field and flexible flat plate wave - Google Patents
Detecting biologic sensor combining evanescent field and flexible flat plate wave Download PDFInfo
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- CN101109748B CN101109748B CN 200710055948 CN200710055948A CN101109748B CN 101109748 B CN101109748 B CN 101109748B CN 200710055948 CN200710055948 CN 200710055948 CN 200710055948 A CN200710055948 A CN 200710055948A CN 101109748 B CN101109748 B CN 101109748B
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Abstract
The invention relates to a biologic detecting sensor combining evanescent field with flexible plate wave that is applicable for detecting the biologic affinity reaction feature in such fields as clinic inspection, medicine screening, environment and food inspection, etc., which comprises an optic sensing component and a sound wave sensor, between which a sample pond for bearing the object to be detected is arranged. By the biologic sensor, a plurality of parameters of the object can be measured in the same test condition, and the accuracy of the physical characterization of the biologic reacting object can be greatly improved.
Description
Technical field
The present invention relates to be applicable to the biology sensor of the biological compatible reaction Characteristics Detection in fields such as clinical examination, drug screening, environment, Food Inspection, but the biology sensor that physical quantitys such as particularly a kind of synchronizing detection biological respinse bond quality and substrate refractive index, specific inductive capacity change.
Background technology
Biological affine detection is not only the chemical process that is confined to biological respinse, but according to the various information of biological respinse, wait process and the result who surveys biological respinse as light, heat, field effect and mass change, compare, can shorten detection time greatly with chemical method.In the affine detection of biology, energy-changing methods such as optics, galvanochemistry and sound wave have highly sensitive, but advantages such as real-time continuous detection have become the main flow of current biosensor technique.But it is perfect also not having a kind of biology sensor up to now, common a kind of biology sensor is based on a kind of transduction principle, can only survey the variation of a certain physical quantity, its output signal can not characterize the physicochemical property of reactant fully exactly, thereby the preparation homogeneity and the specificity of molecular recognition elements proposed very high requirement, bring inconvenience to use; Problems such as omission or false positive appear in its test result poor specificity sometimes.
Sonic sensors such as flexible flat plate wave (Lamb ripple) or love ripple mainly are to survey because the variation of caused resonance frequency of mass change or phase place, and the size of unit mass is directly related with the thickness and the density of responding layer, the Sauerbrey equation is deposited as the basis with unimolecular film and derives out, because sonic sensor can't directly record reacted molecular layers thick, can't guarantee also in the experiment that the antibody coating must be a unimolecular layer, thereby test value is difficult to consistent with theoretical value.The biology sensor of micro-cantilever array has high sensitivity, and has the advantage that to make in batches, need not mark, but with sonic sensor similarly be: temperature influence is serious, although adopt the binary channels compensation, also be difficult to have good consistance and reappearance, the detection of fluid sample is needed dry process etc.Surface plasma resonance (SPR) sensor forms evanescent field and evanescent field when propagating at two interfaces by light forms plasma resonance after satisfying certain condition and absorbs the characteristic of a large amount of incident lights in the metal surface, study the dynamic process of molecule combination.Main limitation of this detection method can't be distinguished non-specific adsorption exactly, the variation of SPR incident light resonant angle is the function of absorber thickness and refractive index, can't know whether contain too much moisture or other non-specific materials in the absorption layer, often cause the deviation of test result bigger.Based on the disappearance wave sensor of attenuated total internal reflection (ATR), the existence by the disappearance ripple extends to transmitting beam in the covering medium, and the absorption of clad region reduces the inner full-reflection wave amplitude.Remove the original covering of optical fiber and replace with measured medium with absorbing medium, sensitive element (search coverage) as sensor-based system, the amplitude fading of transmitting beam directly reacts the characteristic (as refractive index, concentration etc.) of measured medium, can by measuring light by the time power attenuation learn concentration of measured medium etc.
Summary of the invention
The objective of the invention is to propose the evanescent field and the flexible flat plate wave combined detection biologic sensor of a kind of energy synchronizing detection biological respinse bond quality and physical quantitys variations such as substrate refractive index, specific inductive capacity.Adopt this biology sensor can be under same test condition, realize the synchronous acousto-optic complementary detection of bioaffinity.
Evanescent field of the present invention and flexible flat plate wave combined detection biologic sensor are to be combined by optical sensor unit and sound wave sensing element, and described optical sensor unit is that two ends are arranged on the optical fibers on the structure of fiber_optic; Described sound wave sensing element is by silicon thin film, is laid on the aluminium stratum on the silicon thin film bottom surface, and the aluminum nitride piezoelectric film that is laid on the bottom surface, aluminium stratum constitutes with the interdigitated electrodes that is laid on the aluminum nitride piezoelectric film outside surface; Structure of fiber_optic is installed with on silicon thin film, can carry the microfluid groove of detected material by surrounding one between structure of fiber_optic and the silicon thin film middle part notch face, and the naked fine transducing part of optical fibers is in this microfluid groove.
Using method and principle of work: when adopting this working sensor, for Lamb ripple sensing element, signal processing module sends the alternating voltage signal and drives interdigital transducer, itself and voltage difference between the conductive formation are periodically exchange variation, working lining is a piezoelectric thin film layer, exchanging the voltage that changes makes piezoelectric thin film layer produce periodic vibration, thereby on piezoelectric thin film layer, formed the Lamb ripple, fluctuation is propagated on silicon thin film, when fluctuation propagates on the interdigital transducer respectively, be detected and pass back signal processing module and carry out signal Processing, because the fluctuation in the flexible flat plate wave comprises the relevant information of characteristic many and in the film, resonance frequency comprising film, amplitude and phase place are so we can obtain the resonance frequency of film by separate information from signal processing module, amplitude and phase place.Finishing, sessile antibody are carried out in its sensing unit surface, when measured object with after molecular recognition elements combines specifically, the mass change that is produced will make resonance frequency, amplitude and the phase place etc. of film change, so we can obtain the mass change amount of film by the information of measuring and handle in the flexible flat plate wave, thereby obtain the concentration of determinand.For the fiber evanescent field sensing element, the light beam that certain intensity is I is coupled to the optical fiber from optical fiber one end to be propagated, the optical fiber sensitizing range that is arranged in microfluidic channel is removed covering and is made fibre core expose out, the test substance bag is seen through the interface and can be transmitted in the test substance by the optical fiber ripple that then disappears, light wave and test substance effect absorb, cause the loss Δ I of evanescent field energy, the light intensity decreasing that comes out through Optical Fiber Transmission becomes I=I-Δ I.When measured object with after molecular recognition elements combines specifically, antigen in the reactant solution reduces, concentration reduces, specific inductive capacity changes, the change of specific inductive capacity causes the change of disappearance ripple penetration depth, and after the concentration change, how much the measured object particle also can change in the test substance, increase accordingly or reduce according to the chance of bright baer's law photon and measured matter collision, and then Δ I is changed.By the variation of monitoring fiber output intensity I, calculate what of Δ I, and then obtain the size of measured matter concentration.
Because biology sensor of the present invention has optical sensing and sound wave sensing element simultaneously, and formation one can be carried the microfluidic channel of detected material between two sensing elements, thereby the consistance and the synchronism of the tested biological respinse experiment condition of two perception informations that sensing element obtains have been guaranteed.Adopt biology sensor of the present invention can realize measuring multiple parameters, greatly improve the accuracy that biological respinse physics characterizes measured object.
Description of drawings
Fig. 1 is that the master of biosensor structure of the present invention looks synoptic diagram;
Fig. 2 is the schematic top plan view of biosensor structure of the present invention;
Fig. 3 is that A shown in Figure 1 is to view.
Embodiment
Below the embodiment that provides with regard to accompanying drawing biosensor structure of the present invention is described in further detail.
With reference to Fig. 1, a kind of evanescent field and flexible flat plate wave combined detection biologic sensor are to be combined by optical sensor unit and sound wave sensing element, and described optical sensor unit is that two ends are arranged on the optical fibers 1 on the structure of fiber_optic 5; Described sound wave sensing element, be by a silicon thin film 4 and on the bottom surface of silicon thin film 4 by magnetron sputtering technique sputter layer of aluminum stratum 6, sputter one deck aluminium nitride forms on aluminium stratum 6 again aluminum nitride piezoelectric film 7, the interdigitated electrodes 8 of on aluminum nitride piezoelectric film 7 outside surfaces, laying and constituting; Structure of fiber_optic 5 is installed with on silicon thin film 4, can carry the microfluid groove 3 of detected material by surrounding one between structure of fiber_optic 5 and the silicon thin film 4 middle part notch faces, and the Fibre Optical Sensor part 2 of optical fibers 1 is in this microfluid groove 3.
The concrete manufacture craft of the present invention can be divided into following three steps substantially:
1. the making of optical sensor unit:
1) selection of optical fiber.In order to guarantee the having of sensor, therefore require the fibre core of selected optical fiber that higher intensity and toughness are arranged than higher serviceable life.The size of fiber core refractive index directly has influence on the measurement range of sensor, according to the size of measurand refractive index, carries out the selection of fiber core refractive index.
2) optical fiber is fixing.Behind the selected good optical fiber, at first peel off the protective seam of appropriate length.The length (transducing part length) that optical fiber is exposed and the sensitivity of sensor have direct relation, adopt the theoretical method that combines with experiment to determine its optimization length, thereby the support bracket fastened size of optical fiber is also just decided thereupon, at last optical fiber is fixed on the structure of fiber_optic.
3) the further processing of optical fiber.The transducing part of optical fiber corrodes on the structure of fiber_optic to being fixed in hydrofluorite.To required diameter, fibre core is carried out cleaning treatment in corrosion.
2. the making of sound wave sensing element:
1) preparation of silicon thin film.Get a silicon chip, utilize silicon dioxide, prepare silicon thin film with wet etching or ICP technology as mask.
2) preparation on stratum.Adopt magnetron sputtering technique on silicon chip the sputter layer of aluminum as the stratum.
3) preparation of piezoelectric membrane.Sputter one deck aluminum nitride piezoelectric film on the aluminium stratum.
4) on piezoelectric membrane, prepare interdigital electrode.
3. the assembling of fiber evanescent field transducing part and Lamb ripple transducing part: because the Fibre Optical Sensor after the corrosion partly is easy to disconnect, the film of the transducing part of Lamb ripple also very easily is damaged, so this step also is a crucial step.Assemble method mainly contains two kinds, and the first adopts the technology of Si-Si bonding, and it two is to utilize PDMS as adhesive both to be bonded together.
Claims (1)
1. evanescent field and flexible flat plate wave combined detection biologic sensor is characterized in that being combined by optical sensor unit and sound wave sensing element, and described optical sensor unit is that two ends are arranged on the optical fibers (1) on the structure of fiber_optic (5); Described sound wave sensing element is to lay layer of aluminum stratum (6) by a silicon thin film (4) with on the bottom surface of silicon thin film (4), on aluminium stratum (6), re-lay one deck aluminum nitride piezoelectric film (7), on aluminum nitride piezoelectric film (7) outside surface, lay interdigitated electrodes (8) and constitute; Structure of fiber_optic (5) is installed with on silicon thin film (4), can carry the microfluid groove (3) of detected material by surrounding one between structure of fiber_optic (5) and silicon thin film (4) the middle part notch face, and the Fibre Optical Sensor part (2) of optical fibers (1) is in this microfluid groove (3).
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200710055948 CN101109748B (en) | 2007-08-09 | 2007-08-09 | Detecting biologic sensor combining evanescent field and flexible flat plate wave |
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| CN 200710055948 CN101109748B (en) | 2007-08-09 | 2007-08-09 | Detecting biologic sensor combining evanescent field and flexible flat plate wave |
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| CN101109748A CN101109748A (en) | 2008-01-23 |
| CN101109748B true CN101109748B (en) | 2011-04-20 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102520160B (en) * | 2011-12-02 | 2014-10-15 | 苏州生物医学工程技术研究所 | Lamb wave immunosensor and manufacturing method thereof |
| CN104345015B (en) * | 2013-07-30 | 2017-01-11 | 黄辉 | Image sensor based on micro-nanofibers and micro-fluidic chip and preparation method of image sensor |
| US11009487B2 (en) * | 2016-09-19 | 2021-05-18 | The Regents Of The University Of Michigan | Multi-modal biosensor having an acoustic detector with integrated optical interferometry |
| CN107979352B (en) * | 2016-10-24 | 2021-07-06 | 天津大学 | Film bulk acoustic microfluidic mixing device |
| CN109870504A (en) * | 2019-01-16 | 2019-06-11 | 东南大学 | A kind of microchannel sonic sensor for liquid detecting |
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