CN101968464B - Inverted liquid-phase acoustic surface wave detection device and array thereof - Google Patents

Inverted liquid-phase acoustic surface wave detection device and array thereof Download PDF

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Publication number
CN101968464B
CN101968464B CN2010102922602A CN201010292260A CN101968464B CN 101968464 B CN101968464 B CN 101968464B CN 2010102922602 A CN2010102922602 A CN 2010102922602A CN 201010292260 A CN201010292260 A CN 201010292260A CN 101968464 B CN101968464 B CN 101968464B
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China
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reaction tank
substrate
liquid
interdigital transducer
acoustic wave
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CN2010102922602A
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CN101968464A (en
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陈鸣
贾双荣
徐清华
唱凯
张可珺
李发科
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Third Military Medical University TMMU
Third Affiliated Hospital of TMMU
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Third Affiliated Hospital of TMMU
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Abstract

The invention discloses an inverted liquid-phase acoustic surface wave detection device, which comprises a substrate and a reaction tank, wherein the substrate is provided with at least one pair of interdigital transducers, and the input interdigital transducer, the output interdigital transducer and lead areas thereof are provided with waterproof isolation layers; and the substrate is vertically inserted into the reaction tank so that the detection area is soaked into the reaction tank. The reaction tank with constant size for bearing reaction liquid is adopted in the device so as to ensure consistency of the injected liquid amount in repeated experiments and solve the problem that the consistency of the liquid dropping amount in the repeated experiments is difficult to ensure in liquid dropping detection of the traditional acoustic surface wave sensor in the detection area; the substrate is vertically inserted into the reaction tank to form a closed reaction area, so the liquid sample cannot be volatilized and the defect that the liquid sample is easy to volatilize in the liquid dropping detection of the acoustic surface wave sensor is overcome; compared with the conventional acoustic surface wave detection device for detection through microfluidic inlet liquid, the standing closed reaction structure avoids liquid flowing interference; and the inverted liquid-phase acoustic surface wave detection device is arranged in an array form to realize simultaneous detection of multiple detected liquid samples.

Description

Inverted plug type liquid phase surface acoustic wave pick-up unit and array thereof
Technical field
The present invention relates to liquid phase surface acoustic wave sensor field, be specifically related to a kind of inverted plug type liquid phase surface acoustic wave pick-up unit and array thereof.
Background technology
Surface acoustic wave sensor (SAW sensor) is included in input interdigital transducer (IDT) and the output interdigital transducer that is provided with on the substrate; Input electrical signal is transfused to interdigital transducer and converts a polarized shear wave with the sensor surface horizontal infection to; Polarized shear wave transfers to output interdigital transducer along substrate; The specific biological reaction that polarized shear wave takes place sensor surface in transmission course is very responsive, and sound wave passes the sensitizing range, and corresponding change can take place for its velocity of propagation, amplitude, phase place.Acoustic signals after the variation converts electric signal into through output interdigital transducer again.The change of input and output electric signal frequency or phase place is associated with the variation of sensor surface liquid property (quality, viscosity, density etc.).Therefore, can realize detecting the reaction of the associated biomolecule molecule (as: antigen-antibody, enzyme, nucleic acid etc.) of the surveyed area that is fixed between the input and output interdigital transducer through surface acoustic wave sensor.
During the biomolecular reaction of prior art detects; The surveyed area of surface acoustic wave sensor adopts 1) micro-fluidic feed liquor, 2) directly carry out the biomolecular reaction detection in the mode of surveyed area dropping detection liquid sample, the advantage of first kind of mode is to make things convenient for sample introduction and wash appearance; And detect continuously; But since the liquid flow disturbance sensitive sensor signal, require flow rate of liquid very low, but this be difficult to control and can not accomplish to stablize.And liquid flow can influence the dynamic characteristic of association reaction between the biomolecule, possibly destroy the authenticity of testing result.Though second kind of input mode liquid appearance is stable, the amount that liquid drips needs each the same, and the area on covering sensor surface also wants the same, just can guarantee the repeatability that detects, thereby increase the application of sample operating difficulties, and it is inconvenient to wash appearance; Do not handle because liquid appearance is done sealing, the sample of dropping is under certain temperature control system, and when temperature was higher, volatile dry can not carry out detection easily.
Summary of the invention
In view of this; In order to address the above problem; The invention discloses inverted plug type liquid phase surface acoustic wave pick-up unit, the reactant liquor application of sample is gone into reaction tank, the surface acoustic wave sensor substrate that will carry out the circuit water-proof processing vertically inserts reaction tank and carries out the reactant liquor detection; Reduce traditional surface acoustic wave sensor because of reactant liquor adds the experiment detection signal error that inequality, reactant liquor solution evaporation and reactant liquor flow and cause, improved the accuracy of detection of experiment repetitive operation.And each substrate employing binary channels detection architecture, wherein the reference interdigital transducer guarantees the accuracy that detects to being used to eliminate the non-special interference of liquid environment.
The objective of the invention is to realize like this: inverted plug type liquid phase surface acoustic wave pick-up unit comprises substrate and reaction tank; Said substrate is provided with at least one pair of interdigital transducer of being made up of input interdigital transducer and output interdigital transducer, is provided with watertight insulation at input interdigital transducer and output interdigital transducer and the zone that goes between thereof; Said substrate inserts reaction tank, and surveyed area is immersed in the reaction tank.
Further, said substrate vertically inserts reaction tank;
Further, said substrate upper end is equipped with suspender, makes the substrate suspension type immerse reaction tank;
Further, paste said suspender and substrate upper end, and after substrate inserted reaction tank, the suspender lower surface contacted with reaction tank edge upper surface;
Further, the lead-in wire upper end of input interdigital transducer is used for being connected with the signal source output terminal of external signal generation collector;
Further, the lead-in wire of output interdigital transducer upper end is used for being connected with the signals collecting end of external signal generation collector;
Further, said reaction tank is polypropylene material qualitative response pond.
Also disclose the array that adopts inverted plug type liquid phase surface acoustic wave pick-up unit, said array is made up of two above inverted plug type liquid phase surface acoustic wave pick-up units.
The invention has the beneficial effects as follows: the present invention adopts the reaction tank of fixed size to carry reactant liquor; In repeated experiments, guarantee to inject the consistance of liquid appearance amount easily; Overcome traditional flush system surface acoustic wave sensor and detected, be difficult to guarantee the conforming problem of dropping liquid amount in the repeated experiments at the surveyed area dropping liquid; Substrate of the present invention vertically inserts reaction tank and constitutes the capping zone, and liquid appearance can't be volatilized, and has overcome in the detection of tiling surface acoustic wave sensor dropping liquid, and liquid appearance is the shortcoming of volatilization easily.
Detect through micro-fluidic feed liquor with existing surface acoustic wave sensor and to compare, the present invention adopts and leaves standstill the capping structure, has overcome the acoustic signals that liquid flow brought and has disturbed.
Inverted plug type liquid phase surface acoustic wave pick-up unit is array arranges, detect when can realize multiple detection liquid sample.
Description of drawings
In order to make the object of the invention, technical scheme and advantage clearer, will combine accompanying drawing that the present invention is made further detailed description below:
Fig. 1 shows the substrate of inverted plug type liquid phase surface acoustic wave pick-up unit;
Fig. 2 shows the substrate that has suspender and be bonded with the PCB circuit board;
Fig. 3 shows reaction tank;
Fig. 4 shows inverted plug type liquid phase surface acoustic wave pick-up unit;
Fig. 5 shows inverted plug type liquid phase surface acoustic wave pick-up unit array.
Embodiment
Below will describe in detail the preferred embodiments of the present invention.
The invention discloses a kind of inverted plug type liquid phase surface acoustic wave pick-up unit, comprise substrate 6 and reaction tank 8; As shown in Figure 1, substrate 6 is provided with two pairs of interdigital transducers, a pair of be the reference interdigital transducer to 2, another is to for detecting interdigital transducer to 3; Two pairs of interdigital transducer middle parts are surveyed area 1; Detect interdigital transducer and in the middle of 3, be coated with golden film, be used for fixing biomolecule.
The surveyed area 1 except that between input interdigital transducer and output interdigital transducer, input interdigital transducer and output interdigital transducer and lead-in wire zone 4 thereof are coated with SiO 2Watertight insulation is used for preventing interdigital transducer in the liquid short circuit, and the detection interdigital transducer does not cover SiO to 3 golden film 2Watertight insulation fully contacts with liquid, detection of biological reaction stably;
As shown in Figure 2, the lead-in wire upper end 5 of input interdigital transducer comprises the reference interdigital transducer pair input end lead-in wire upper end right with detecting interdigital transducer; The lead-in wire upper end 10 of output interdigital transducer comprises the reference interdigital transducer pair output terminal lead-in wire upper end right with detecting interdigital transducer; The reference interdigital transducer pair input end lead-in wire upper end right with detecting interdigital transducer is connected through the signal source output terminal of the same sub-miniature A connector 9 on the PCB circuit board with signal generation collector, and the reference interdigital transducer pair output terminal lead-in wire upper end right with detecting interdigital transducer is connected with the unlike signal collection terminal of signal picker through each self-corresponding two other sub-miniature A connector 9 on the PCB circuit board respectively; Pick-up transducers reference interdigital transducer changes with the signal that detects the interdigital transducer passage in this way; The directly variation of response sensor chip surface mass loading of variation through frequency/phase; Data after the processing are preserved into data file and are carried out record, on display, show real-time testing result simultaneously.Signal generation collector of the present invention adopts NI PXI system.
Substrate 6 upper ends are equipped with suspender 7, and suspender 7 is pasted with substrate 6 upper ends, and after substrate 6 inserted reaction tank 8, suspender 7 lower surfaces contacted with reaction tank 8 upper surfaces, made the substrate suspension type immerse reaction tank 8, and substrate surveyed area 1 immerses in the reaction tank.
Fig. 3 shows reaction tank 8 structures, and reaction tank 8 is processed for the polypropylene for medical article material, i.e. the material of PCR pipe or the use of EP pipe.Characteristics are good heat conductivity, and the acid-fast alkali-proof anticorrosion is not with biomolecule generation non-specific binding.Whole detection cell volume is the hundreds of micro updating, and the volume that is used to detect only needs the immersion sensor surveyed area to get final product, about tens micro updatings.Reaction tank 8 is a disposable product.
In the reaction tank 8 temperature control device can be installed, select temperature range 22-70 ℃ for use, precision reaches ± 0.3 ℃ temperature control device.Temperature control device can cover general biologically temperature, for example antigen-antibody reaction, the optimal reaction active temperature of various enzymes, nucleic acid hybridization reaction temperature etc.Because variation of temperature is arranged, be more suitable for the biologically condition, shorten the reaction time.Increase biologically type and range of application.Reaction tank is carried out temperature control, avoided directly sensor chip being heated, can not damage substrate.
As shown in Figure 4, with injection experiments liquid appearance in the groove of reaction tank 8, substrate 6 is poured in reaction tank 8 grooves, form inverted plug type liquid phase surface acoustic wave pick-up unit.
The present invention adopts the reaction tank 8 of fixed size to carry reactant liquor; In repeated experiments, guaranteed to inject the consistance of liquid appearance amount easily; Overcome traditional flush system surface acoustic wave sensor and detected, be difficult to guarantee the conforming problem of dropping liquid amount in the repeated experiments at the surveyed area dropping liquid; Substrate of the present invention vertically inserts reaction tank 8 and constitutes the capping zone, and liquid appearance can't be volatilized, and has overcome in the detection of tiling surface acoustic wave sensor dropping liquid, and liquid appearance is the shortcoming of volatilization easily.
Detect through micro-fluidic feed liquor with existing surface acoustic wave sensor and to compare, the present invention adopts and leaves standstill the capping structure, has overcome the acoustic signals that liquid flow brought and has disturbed.
As shown in Figure 5; Inverted plug type liquid phase surface acoustic wave pick-up unit of the present invention also can be formed array format; Comprise 6 inverted plug type liquid phase surface acoustic wave pick-up units like array, inverted plug type liquid phase surface acoustic wave pick-up unit is along reaction tank 8 side surfaces and other inverted plug type liquid phase surface acoustic wave pick-up unit matrix form are arranged separately.
In antigen-antibody reaction; The active observation of the optimal reaction of various enzymes; Multi-usage experimental study such as nucleic acid hybridization reaction with detect; According to the number of detected object, the inverted plug type liquid phase surface acoustic wave pick-up unit of choosing in the inverted plug type liquid phase surface acoustic wave pick-up unit array one or more arranged side by side detects simultaneously.
The above is merely the present invention that preferably is not limited to of the present invention, and obviously, those skilled in the art can carry out various changes and modification and not break away from the spirit and scope of the present invention the present invention.Like this, belong within the scope of claim of the present invention and equivalent technologies thereof if of the present invention these are revised with modification, then the present invention also is intended to comprise these changes and modification interior.

Claims (6)

1. inverted plug type liquid phase surface acoustic wave pick-up unit is characterized in that: comprise substrate (6) and reaction tank (8); Said substrate (6) is provided with at least one pair of interdigital transducer of being made up of input interdigital transducer and output interdigital transducer, is provided with watertight insulation at input interdigital transducer and output interdigital transducer and the zone (4) that goes between thereof; Said substrate (6) inserts reaction tank (8), and surveyed area (1) is immersed in the reaction tank;
Said substrate (6) vertically inserts reaction tank (8);
Said substrate (6) upper end is equipped with suspender (7), makes substrate (6) suspension type immerse reaction tank (8).
2. inverted plug type liquid phase surface acoustic wave pick-up unit as claimed in claim 1 is characterized in that: said suspender (7) is pasted with substrate (6) upper end, and after substrate (6) inserted reaction tank (8), suspender (7) lower surface contacted with reaction tank (8) edge upper surface.
3. inverted plug type liquid phase surface acoustic wave pick-up unit as claimed in claim 2 is characterized in that: the lead-in wire upper end (5) of input interdigital transducer is used for being connected with the signal source output terminal of external signal generation collector.
4. inverted plug type liquid phase surface acoustic wave pick-up unit as claimed in claim 3 is characterized in that: the lead-in wire upper end (10) of output interdigital transducer is used for being connected with the signals collecting end of external signal generation collector.
5. inverted plug type liquid phase surface acoustic wave pick-up unit as claimed in claim 1 is characterized in that: said reaction tank (6) is polypropylene material qualitative response pond.
6. adopt the array like each described inverted plug type liquid phase surface acoustic wave pick-up unit of claim 1 to 5, it is characterized in that: said array is made up of two above inverted plug type liquid phase surface acoustic wave pick-up units.
CN2010102922602A 2010-09-26 2010-09-26 Inverted liquid-phase acoustic surface wave detection device and array thereof Expired - Fee Related CN101968464B (en)

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CN103454346B (en) * 2013-08-27 2015-10-28 中国科学院苏州生物医学工程技术研究所 A kind of microfluidic chip analysis platform based on sonic sensor
CN108254437B (en) * 2018-03-01 2023-12-19 中国人民解放军陆军军医大学第三附属医院(野战外科研究所) Acoustic surface wave biosensor fixture and test system

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CN1239902C (en) * 2004-01-14 2006-02-01 浙江大学 Liquid phase components analyzer for acoustic surface wave array transducer
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JP4830070B2 (en) * 2006-05-11 2011-12-07 セイコーエプソン株式会社 Surface acoustic wave device, liquid level detection device
JP2008064646A (en) * 2006-09-08 2008-03-21 Epson Toyocom Corp Liquid level detector
KR20080052296A (en) * 2006-12-05 2008-06-11 한국전자통신연구원 Micro fluidic transportation device and method for manufacturing the same

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