CN102288675B - Liquid-phase detection device of series surface acoustic wave type piezoelectric sensor and manufacturing method thereof - Google Patents
Liquid-phase detection device of series surface acoustic wave type piezoelectric sensor and manufacturing method thereof Download PDFInfo
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Abstract
The invention discloses a liquid-phase detection device of a series surface acoustic wave type piezoelectric sensor and a manufacturing method thereof. The liquid-phase detection device of the series surface acoustic wave type piezoelectric sensor comprises two differential circuits, one differential circuit adopts a feedback circuit formed by a first surface acoustic wave resonator, a first oscillation circuit and a series interdigital gold electrode, the first surface acoustic wave resonator, the first oscillation circuit and the series interdigital gold electrode are coupled sequentially, and the series interdigital gold electrode is then coupled with the first surface acoustic wave resonator and is used for testing endotoxin solution to be tested; the other differential circuit comprises a second surface acoustic wave resonator and a second oscillation circuit, and the second surface acoustic wave resonator is coupled with the second oscillation circuit for compensation for environmental noise; and the first oscillation circuit, the series interdigital gold electrode, the second oscillation circuit and the second surface acoustic wave resonator are coupled with a frequency mixer, and oscillation signals output by the two circuits are differenced by the frequency mixer and are then input into a frequency detection circuit. When the liquid-phase detection device is used, no liquid working environment or fixed sensitive layer is needed. Moreover, the liquid-phase detection device has high detection accuracy and good stability.
Description
Technical field
The invention belongs to the liquid-phase detection device technical field, particularly a kind of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor and manufacture method thereof.
Background technology
Endotoxin is the most direct pathogenic toxicants of microorganism such as bacterium, endotoxic principal ingredient is the compound of liopopolysaccharides, mainly from the cell membrane of gram-negative bacteria, not only can discharge behind the dead bacterolysis, bacterium also can discharge endotoxin in growth course.Clinical common some diseases such as infectious shock, septicemia, multiple organ dysfunction sexual exhaustion etc. are all closely related with endotoxin.The rising of endotoxin content can cause many bad reactions such as pyrogenicity reaction, leukocytoreaction, lethal infection shock, disseminated intravascular coagulation MOF of general, makes many patients sb.'s illness took a turn for the worse even dead.
At present, the detection method of being included in the bacterial endotoxin of state-promulgated pharmacopoeia by countries in the world all is based on the gel method of tachypleus amebocyte lysate, and this method is also authenticated by U.S. food Drug Administration.No matter be the gel method of limiting the quantity of qualitatively, semiquantitative chromogenic substrate method, or quantitative nephelometry are to utilize tachypleus amebocyte lysate and the mechanism of bacterial endotoxin generation agglutinating reaction to carry out bar none.The amebocyte lysate that the method is based on king crab is extremely responsive to liopopolysaccharides, the amebocyte lysate of minute quantity can act on it the generation gel reaction, and endotoxic concentration is measured in the absorbance that occurs during according to gel formation time or gel-forming and the variation of state.The sensitivity of its detection sensitivity and tachypleus amebocyte lysate standard items is relevant with the precision of checkout equipment.The range of sensitivity that the tachypleus amebocyte lysate standard items of commonly using at present can provide is 0.03~0.5EU/mL.But because the king crab resource is very limited, expensive, and this gel-forming need to just can finish in the lower reaction of 37 ℃ of constant temperature in 60 ± 2 minutes, even the fast dynamic turbidity detection method that the present published U.S. newly develops, time shorten is 30 minutes, but still needs to test in water-bath.Therefore, it exists testing cost height, length consuming time, complicated operation, is affected by human factors the defectives such as large, that automaticity is low, lowest detectable limit is higher, is difficult to realize on-line quick detection.
Surface acoustic wave techniques is an emerge science technology that grows up the latter stage sixties in last century, and it is the cross discipline that acoustics, electronics, optics, piezoelectric and semiconductor planar technique combine.Since surface acoustic wave piezoelectric sensor is applied to the liquid phase sensing, the broad spectrum activity of phase acoustic surface wave piezoelectric sensor response is that the application of various modes is provided convenience, but the frequency stability of phase acoustic surface wave piezoelectric sensor is also because of the too late gas phase surface acoustic wave piezoelectric sensor of the loss of solution.If measure merely the variation of electrical conductivity of solution with surface acoustic wave piezoelectric sensor, in the two-sided immersion electrolyte solution of surface acoustic wave piezoelectric sensor, this method has 2 deficiencies: the one, and the two-sided tactile liquid of crystal, the dielectric loss of surface acoustic wave is very large, has damaged the stability of quartz crystal oscillation frequency; The 2nd, the bypass of solution (measuring principle institute must) can cause crystal failure of oscillations in high concentration electrolysis matter solution slightly.
Utilize the association reaction of piezoeletric quartz sensor research liopopolysaccharides and reach a conclusion from Chang in 1999 etc.: can have in conjunction with the material of liopopolysaccharides following several: lipopolysaccharide binding protein, CD14 antigen, polymyxins, the king crab lipotropism polysaccharide factor, bactericidal properties/power/permeability increasing protein etc., wherein, the polymyxins specificity is best, and is the strongest with endotoxic binding ability.Domestic and international many researchers launch test at this point, have confirmed the feasibility that polymyxins is combined with liopopolysaccharides, and the biology sensor based on polymyxins of releasing thus detects endotoxic method and launches rapidly.
Summary of the invention
The present invention aims to provide a kind of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor and manufacture method thereof, comprises the design of SAW (Surface Acoustic Wave) resonator and processing, the pre-service of interdigital gold electrode, the polymyxins immobilization of interdigital gold electrode, two-way differential detection circuit.The liquid-phase detection device of series surface acoustic wave type piezoelectric sensor that the inventive method is made has the advantages such as accuracy of detection height, good stability.
The present invention takes following technical scheme: liquid-phase detection device of series surface acoustic wave type piezoelectric sensor, comprise the two-way difference channel, one route SAW (Surface Acoustic Wave) resonator one, oscillatory circuit one, the interdigital gold electrode of series connection form backfeed loop, SAW (Surface Acoustic Wave) resonator one, oscillatory circuit one, the interdigital gold electrode of series connection link successively, the interdigital gold electrode of connecting links with SAW (Surface Acoustic Wave) resonator one again, for detection of endotoxin solution to be measured; Another route SAW (Surface Acoustic Wave) resonator two, oscillatory circuit two form, and SAW (Surface Acoustic Wave) resonator two links with oscillatory circuit two, is used for the compensation of neighbourhood noise; Oscillatory circuit one, the interdigital gold electrode of connecting, oscillatory circuit two, SAW (Surface Acoustic Wave) resonator two all link with frequency mixer, and aforementioned two circuit outputting oscillation signals carry out difference through frequency mixer, last incoming frequency testing circuit.
Preferably, oscillatory circuit comprises SAW2 Header3, resistance R 1, R3, capacitor C 1, C2, C5, C7, inductance L 1, L3, triode Q1, Q3, the 3 pin ground connection of SAW2 Header3, series resistor R1 between 1 pin and 2 pin, 1 pin connects the base stage of triode Q1, collector, capacitor C 7 that the emitter of triode Q1 divides two-way to meet triode Q3,2 pin of another termination SAW2 Header3 of capacitor C 7; Series resistor R3 between the base stage of triode Q3 and VCC, the grounded emitter of triode Q3; The collector of triode Q1 divides two-way to connect capacitor C 5, inductance L 3,2 pin of another termination SAW2 Header3 of inductance L 3, and 2 pin of SAW2 Header3 also connect inductance L 1, another termination VCC of inductance L 1, shunt capacitance C1, C2 between VCC and ground connection.
The invention also discloses a kind of manufacture method of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor, its as follows: A) set the SAW (Surface Acoustic Wave) resonator parameter, make SAW (Surface Acoustic Wave) resonator;
B) choose interdigital gold electrode and carry out pre-service;
C) pretreated interdigital gold electrode surfaces is carried out the immobilization of polymyxins;
D) design two-way difference channel, one route steps A) SAW (Surface Acoustic Wave) resonator one that makes, oscillatory circuit one, step C) the interdigital gold electrode of the series connection that makes forms backfeed loop, SAW (Surface Acoustic Wave) resonator one, oscillatory circuit one, the interdigital gold electrode of series connection link successively, the interdigital gold electrode of connecting links with SAW (Surface Acoustic Wave) resonator one again, for detection of endotoxin solution to be measured; Another route steps A) SAW (Surface Acoustic Wave) resonator two that makes, oscillatory circuit two compositions, SAW (Surface Acoustic Wave) resonator two links with oscillatory circuit two, is used for the compensation of neighbourhood noise; Oscillatory circuit one, the interdigital gold electrode of connecting, oscillatory circuit two, SAW (Surface Acoustic Wave) resonator two all link with frequency mixer, and aforementioned two circuit outputting oscillation signals carry out difference through frequency mixer, and last incoming frequency testing circuit is measured testing concentration according to frequency shift amount.
Preferably, steps A): set the slotting finger widths of SAW (Surface Acoustic Wave) resonator, slotting IDS, sound aperture, insert the parameter that refers to logarithm, reflecting grating width, gap, left and right sides number, transmission range, make mask blank with aforementioned parameters; Adopt electron beam transpiration deposited gold film at the bottom of the lithium niobate base, rear employing precision photolithography processes interdigital electrode and reflecting grating figure, and lead-in wire is drawn.
Preferably, step B) in: selected interdigital gold electrode, be soaked in the piranha solution, again through sonic oscillation, adopt afterwards nitrogen to dry up after cleaning with absolute ethyl alcohol.
Compared with prior art, the advantage of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor of the present invention: 1) surface acoustic wave piezoelectric sensor is connected with interdigital gold electrode, make surface acoustic wave piezoelectric sensor break away from the liquid working environment, and need not fixedly sensitive layer; 2) the double path system structural design of reference channel and sensing passage and the processing of difference channel can overcome the impact of the factors such as ground unrest, temperature, environment, have improved accuracy of detection and the stability of system.
Description of drawings
Fig. 1 is the structural representation of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor.
Among Fig. 1: the 1st, SAW (Surface Acoustic Wave) resonator, the 2nd, oscillatory circuit, the 3rd, interdigital gold electrode, the 4th, endotoxin solution to be measured, the 5th, frequency mixer, the 6th, frequency detection circuit.
Fig. 2 is the plan structure figure of interdigital gold electrode.
Among Fig. 2: 2a is interdigital logarithm, and 2b is interdigital length, and 2c is interdigital width, and 2d is interdigital spacing.
Fig. 3 is that series surface acoustic wave type piezoelectric sensor is tested endotoxic concentration-frequency curve chart.
Fig. 4 is the oscillatory circuit schematic diagram.
Among Fig. 4: SAW2 Header3 is the 433MHz quartz crystal oscillator.
Fig. 5 is the mixting circuit schematic diagram.
Among Fig. 5: Res2 is the adjustable resistance of 0~50K, and M1 MC1496 is the mixing integrated chip.
Fig. 6 is the frequency detection circuit schematic diagram.
Among Fig. 6: Res1 is the adjustable resistance of 0~50K, and U1 MAX998 is comparer, and U2 74LS393 is frequency divider.
Embodiment
Below in conjunction with accompanying drawing embodiments of the invention are elaborated.
Liquid-phase detection device of series surface acoustic wave type piezoelectric sensor of the present invention, comprise the two-way difference channel, shown in Fig. 1-6, the sensor of a passage forms backfeed loop by SAW (Surface Acoustic Wave) resonator 1, oscillatory circuit 1, the interdigital gold electrode 1 of series connection, SAW (Surface Acoustic Wave) resonator 1, oscillatory circuit 1, the interdigital gold electrode 1 of series connection link successively, the interdigital gold electrode 1 of connecting links with SAW (Surface Acoustic Wave) resonator 1 again, for detection of endotoxin solution 4 to be measured; Another passage is comprised of a SAW (Surface Acoustic Wave) resonator 21, oscillatory circuit 22, and SAW (Surface Acoustic Wave) resonator 21 links with oscillatory circuit 22, is used for the compensation of neighbourhood noise.Oscillatory circuit one, the interdigital gold electrode of connecting, oscillatory circuit two, SAW (Surface Acoustic Wave) resonator two all link with frequency mixer 5, the two-way outputting oscillation signal carries out difference through frequency mixer 5, remove the impact of neighbourhood noise, be input at last in the frequency detection circuit 6, measure testing concentration according to frequency shift amount.
Oscillatory circuit sees Fig. 4 for details, it comprises SAW2 Header3, resistance R 1, R3, capacitor C 1, C2, C5, C7, inductance L 1, L3, triode Q1, Q3, the 3 pin ground connection of SAW2 Header3, series resistor R1 between 1 pin and 2 pin, 1 pin connects the base stage of triode Q1, collector, capacitor C 7 that the emitter of triode Q1 divides two-way to meet triode Q3,2 pin of another termination SAW2 Header3 of capacitor C 7.Series resistor R3 between the base stage of triode Q3 and VCC, the grounded emitter of triode Q3.The collector of triode Q1 divides two-way to connect capacitor C 5, inductance L 3,2 pin of another termination SAW2 Header3 of inductance L 3, and 2 pin of SAW2 Header3 also connect inductance L 1, another termination VCC of inductance L 1, shunt capacitance C1, C2 between VCC and ground connection.
Mixting circuit sees Fig. 5 for details, and it comprises M1, and 5 pin of M1 are by resistance R 18 ground connection, and 4 pin are by resistance R 17 ground connection, and 4 pin also access 3 pin of Res2,14 pin of the 2 pin access M1 of Res2, and 1 pin of Res2 is by 1 pin of resistance R 15 access M1.Shunt capacitance C20, C21, C22 between 14 pin of M1 and ground connection.10 pin of M1 meet capacitor C 18,10 pin and the indirect electric capacity R9 of 8 pin, and 8 pin divide two-way to pass through capacitor C 11, resistance R 5 ground connection, and 8 pin are series resistor R6, capacitor C 12 rear ground connection also.2 pin of M1 and 3 pin indirect resistance R7, the indirect inductance L5 of 12 pin and 8 pin, 6 pin connect inductance L 6, shunt capacitance C13, C14, C15 between the other end of L6 and ground connection; 6 pin connect capacitor C 19, and the other end of C19 divides two-way to connect capacitor C 23, inductance L 7, the other end ground connection of C23, and the other end of L7 is by capacitor C 24 ground connection.
Frequency detection circuit sees Fig. 6 for details, and it comprises U1, U2, the 2 pin ground connection of U1, and 2 pin of 4 pin access Res1,3 pin of Res1 meet VCC, 1 pin ground connection, 5 pin, 6 pin of U1 meet VCC, shunt capacitance C9, C10 between VCC and ground connection, 1 pin of U1 connects 1 pin of U2.2 pin and 7 pin of U2 link and ground connection, and 3,4,5,6 pin of U2 connect respectively 8,7,6,5 pin of S1,8,9,10,11,12, the 13 pin ground connection of U2, and 14 pin meet VCC, shunt capacitance C16, C17 between VCC and ground connection.
The manufacture method of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor of the present invention, carry out as follows:
A) take lithium niobate as the piezoelectric crystal base material, make SAW (Surface Acoustic Wave) resonator: setting the slotting finger widths of SAW (Surface Acoustic Wave) resonator is 2.3 μ m, insert IDS 2.3 μ m, sound aperture is 780 μ m, inserts to refer to that logarithm is 80 pairs, and the reflecting grating width is 2.3 μ m, the gap is 2.3 μ m, left and right sides number respectively is 160, and transmission range is 784.5 μ m, makes mask blank with this parameter; Adopting electron beam transpiration deposit thickness on the lithium niobate base bottom material is 150nm gold film, adopts precision photolithography to process interdigital electrode and reflecting grating figure, and lead-in wire is drawn, and it is 1mm * 1mm that humidity sensing film becomes diaphragm area;
B) selected interdigital logarithm 2a is that 20 pairs of interdigital gold electrodes are as sensor electrode, interdigital length 2b is 1.5mm, interdigital width 2c and interdigital spacing 2d are all 40 μ m, in piranha solution (concentrated sulphuric acid and hydrogen peroxide volume ratio are configuration in 7: 3), soaked 10 minutes, again through sonic oscillation 10 minutes, dry up afterwards for subsequent use with nitrogen after cleaning with absolute ethyl alcohol;
C) with interdigital gold electrode after the pre-service as working electrode, Ag/Agcl and platinum filament be respectively as contrast electrode with to electrode, the Fe of 5mM (CN)
6 3-/4-As redox couple, in the perchloric acid of 2-(N-morpholine) ethyl sulfonic acid (EMS) of 50mM and 1M, carry out respectively CV scanning, obtain carrying out drying and processing behind the stable scanning curve; Secondly, working electrode is put in 4,4 '-two sulfo-s, two butyric acid (DTBA) of 100mM and carried out self assembly; Then, with introduced-electrode of COOH is immersed in the 50mM 2-of 0.6mL (N-morpholine) ethyl sulfonic acid (EMS)/23.2mM1-(3-dimethylamino-propyl)-3-ethyl carbodiimide (EDC)/9.3mM N-hydroxy-succinamide (NHS) mixed solution and carries out bonding reaction; At last, electrode is put into polymyxins/2-(N-morpholine) ethyl sulfonic acid (EMS) solution and carried out the immobilization of polymyxins;
D) design two-way difference channel, as shown in Figure 1, the sensor of a passage forms backfeed loop by SAW (Surface Acoustic Wave) resonator 1 (steps A makes), oscillatory circuit 1, the interdigital gold electrode 1 of series connection (step C makes), SAW (Surface Acoustic Wave) resonator 1, oscillatory circuit 1, the interdigital gold electrode 1 of series connection link successively, the interdigital gold electrode 1 of connecting links with SAW (Surface Acoustic Wave) resonator 1 again, for detection of endotoxin solution 4 to be measured; Another passage is comprised of a SAW (Surface Acoustic Wave) resonator 21 (steps A makes), oscillatory circuit 22, and SAW (Surface Acoustic Wave) resonator 21 links with oscillatory circuit 22, is used for the compensation of neighbourhood noise.Oscillatory circuit one, the interdigital gold electrode of connecting, oscillatory circuit two, SAW (Surface Acoustic Wave) resonator two all link with frequency mixer 5, the two-way outputting oscillation signal carries out difference through frequency mixer 5, remove the impact of neighbourhood noise, be input at last in the frequency detection circuit 6, measure testing concentration according to frequency shift amount.
Oscillatory circuit is referring to Fig. 4, and mixting circuit is referring to Fig. 5, and frequency detection circuit is referring to Fig. 6.
Liquid-phase detection device of series surface acoustic wave type piezoelectric sensor of the present invention, its resonance frequency will change with the endotoxin concns of solution to be measured, and concentration-frequency curve that test obtains is as shown in Figure 3.
Certainly; those of ordinary skill in the art should be familiar with, and is above-mentioned just to the explaining of the preferred embodiment of the present invention, and is not limitation of the invention; every in essential scope of the present invention, all will fall within protection scope of the present invention variation, the modification of above embodiment.
Claims (5)
1. liquid-phase detection device of series surface acoustic wave type piezoelectric sensor, it is characterized in that comprising the two-way difference channel, one route SAW (Surface Acoustic Wave) resonator one, oscillatory circuit one, the interdigital gold electrode of series connection form backfeed loop, SAW (Surface Acoustic Wave) resonator one, oscillatory circuit one, the interdigital gold electrode of series connection link successively, the interdigital gold electrode of connecting links with SAW (Surface Acoustic Wave) resonator one again, for detection of endotoxin solution to be measured; Another route SAW (Surface Acoustic Wave) resonator two, oscillatory circuit two form, and SAW (Surface Acoustic Wave) resonator two links with oscillatory circuit two, is used for the compensation of neighbourhood noise; Oscillatory circuit one, the interdigital gold electrode of connecting, oscillatory circuit two, SAW (Surface Acoustic Wave) resonator two all link with frequency mixer, and aforementioned two circuit outputting oscillation signals carry out difference through frequency mixer, last incoming frequency testing circuit.
2. liquid-phase detection device of series surface acoustic wave type piezoelectric sensor as claimed in claim 1, it is characterized in that: described oscillatory circuit one or oscillatory circuit two comprise SAW2 Header3, resistance R 1, R3, capacitor C 1, C2, C5, C7, inductance L 1, L3, triode Q1, Q3, the 3 pin ground connection of SAW2 Header3, series resistor R1 between 1 pin and 2 pin, 1 pin connects the base stage of triode Q1, collector, capacitor C 7 that the emitter of triode Q1 divides two-way to meet triode Q3,2 pin of another termination SAW2 Header3 of capacitor C 7; Series resistor R3 between the base stage of triode Q3 and VCC, the grounded emitter of triode Q3; The collector of triode Q1 divides two-way to connect capacitor C 5, inductance L 3,2 pin of another termination SAW2 Header3 of inductance L 3, and 2 pin of SAW2 Header3 also connect inductance L 1, another termination VCC of inductance L 1, shunt capacitance C1, C2 between VCC and ground connection.
3. the manufacture method of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor is characterized in that as follows: A) set the SAW (Surface Acoustic Wave) resonator parameter, make SAW (Surface Acoustic Wave) resonator one, SAW (Surface Acoustic Wave) resonator two;
B) choose interdigital gold electrode and carry out pre-service;
C) pretreated interdigital gold electrode surfaces is carried out the immobilization of polymyxins;
D) design two-way difference channel, one route flapping circuit one, steps A) SAW (Surface Acoustic Wave) resonator one, the step C that make) the interdigital gold electrode that makes forms backfeed loop, SAW (Surface Acoustic Wave) resonator one, oscillatory circuit one, interdigital gold electrode link successively, interdigital gold electrode links with SAW (Surface Acoustic Wave) resonator one again, for detection of endotoxin solution to be measured; Another route flapping circuit two, steps A) SAW (Surface Acoustic Wave) resonator two compositions that make, SAW (Surface Acoustic Wave) resonator two links with oscillatory circuit two, is used for the compensation of neighbourhood noise; Oscillatory circuit one, interdigital gold electrode, oscillatory circuit two, SAW (Surface Acoustic Wave) resonator two all link with frequency mixer, and aforementioned two circuit outputting oscillation signals carry out difference through frequency mixer, and last incoming frequency testing circuit is measured testing concentration according to frequency shift amount.
4. the manufacture method of liquid-phase detection device of series surface acoustic wave type piezoelectric sensor as claimed in claim 3 is characterized in that: steps A): the SAW (Surface Acoustic Wave) resonator parameter comprises slotting finger widths, inserts IDS, sound aperture, insert and refer to logarithm, reflecting grating width, gap, left and right sides number, transmission range.
5. such as the manufacture method of claim 3 or 4 described liquid-phase detection device of series surface acoustic wave type piezoelectric sensors, it is characterized in that: step B): selected interdigital gold electrode, be soaked in the piranha solution, again through sonic oscillation, adopt afterwards nitrogen to dry up after cleaning with absolute ethyl alcohol.
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CN103134606B (en) * | 2013-02-06 | 2014-10-22 | 常州智梭传感科技有限公司 | Differential type acoustic surface wave temperature sensor |
CN103149135B (en) * | 2013-03-07 | 2015-04-15 | 浙江工商大学 | Cell suspension concentration sensor |
CN104034798A (en) * | 2013-03-07 | 2014-09-10 | 浙江工商大学 | Cell suspension concentration detection system and its detection method |
CN103424468A (en) * | 2013-08-22 | 2013-12-04 | 浙江工商大学 | System and method for detecting adulterated milk by aid of SAWR (surface acoustic wave resonator) |
CN104089996A (en) * | 2014-01-17 | 2014-10-08 | 浙江工商大学 | Taste cell sensor using surface acoustic wave resonator and preparation method thereof |
CN111189911B (en) * | 2020-01-10 | 2022-07-15 | 西安科技大学 | Mine safety monitoring system design method based on surface acoustic wave sensor |
CN114046916B (en) * | 2022-01-12 | 2023-03-24 | 南通大学 | Self-powered pressure measurement system based on surface acoustic wave sensor and working method thereof |
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CN202110164U (en) * | 2011-05-06 | 2012-01-11 | 浙江省医疗器械研究所 | Liquid phase detection device for series surface acoustic wave piezoelectric sensor |
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