CN106788317B - Piezoelectric thin film vibrator, its production method and the method for carrying out clotting time detection - Google Patents
Piezoelectric thin film vibrator, its production method and the method for carrying out clotting time detection Download PDFInfo
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- CN106788317B CN106788317B CN201611026774.7A CN201611026774A CN106788317B CN 106788317 B CN106788317 B CN 106788317B CN 201611026774 A CN201611026774 A CN 201611026774A CN 106788317 B CN106788317 B CN 106788317B
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- 238000001514 detection method Methods 0.000 title claims abstract description 31
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Classifications
-
- H—ELECTRICITY
- H03—ELECTRONIC CIRCUITRY
- H03H—IMPEDANCE NETWORKS, e.g. RESONANT CIRCUITS; RESONATORS
- H03H9/00—Networks comprising electromechanical or electro-acoustic devices; Electromechanical resonators
- H03H9/15—Constructional features of resonators consisting of piezoelectric or electrostrictive material
- H03H9/17—Constructional features of resonators consisting of piezoelectric or electrostrictive material having a single resonator
- H03H9/171—Constructional features of resonators consisting of piezoelectric or electrostrictive material having a single resonator implemented with thin-film techniques, i.e. of the film bulk acoustic resonator [FBAR] type
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
-
- H—ELECTRICITY
- H03—ELECTRONIC CIRCUITRY
- H03H—IMPEDANCE NETWORKS, e.g. RESONANT CIRCUITS; RESONATORS
- H03H3/00—Apparatus or processes specially adapted for the manufacture of impedance networks, resonating circuits, resonators
- H03H3/007—Apparatus or processes specially adapted for the manufacture of impedance networks, resonating circuits, resonators for the manufacture of electromechanical resonators or networks
- H03H3/02—Apparatus or processes specially adapted for the manufacture of impedance networks, resonating circuits, resonators for the manufacture of electromechanical resonators or networks for the manufacture of piezoelectric or electrostrictive resonators or networks
-
- H—ELECTRICITY
- H03—ELECTRONIC CIRCUITRY
- H03H—IMPEDANCE NETWORKS, e.g. RESONANT CIRCUITS; RESONATORS
- H03H3/00—Apparatus or processes specially adapted for the manufacture of impedance networks, resonating circuits, resonators
- H03H3/007—Apparatus or processes specially adapted for the manufacture of impedance networks, resonating circuits, resonators for the manufacture of electromechanical resonators or networks
- H03H3/02—Apparatus or processes specially adapted for the manufacture of impedance networks, resonating circuits, resonators for the manufacture of electromechanical resonators or networks for the manufacture of piezoelectric or electrostrictive resonators or networks
- H03H2003/023—Apparatus or processes specially adapted for the manufacture of impedance networks, resonating circuits, resonators for the manufacture of electromechanical resonators or networks for the manufacture of piezoelectric or electrostrictive resonators or networks the resonators or networks being of the membrane type
Abstract
The invention discloses a kind of piezoelectric thin film vibrators for hemostasis examination, including piezoelectric film and annular groove.The invention also discloses a kind of production methods of piezoelectric thin film vibrator for hemostasis examination, have hydrophilic polymer material including the inner surface coating in annular groove；Oxygen plasma treatment or ultraviolet light are carried out to the inner surface of annular groove；Piezoelectric thin film vibrator is placed in sodium carbonate liquor, calcium chloride solution is then added in the solution；Piezoelectric thin film vibrator is baked to drying.The invention also discloses a kind of methods for carrying out clotting time detection using piezoelectric thin film vibrator, the mixing liquid including instilling blood sample and blood coagulation test agent in annular groove center；Measure piezoelectric thin film vibrator resonance frequency；The second dervative that resonant frequency on time variation is calculated according to the resonance frequency after the stabilization of record, takes the maximum value of second dervative as the clotting time.Hemostasis examination is carried out using the piezoelectric thin film vibrator to use suitable for family.
Description
Technical field
The invention belongs to field of clinical medical detection more particularly to a kind of piezoelectric thin film vibrator, its production method and into
The method of row clotting time detection.
Background technique
Blood clotting time detection is preoperative important one of the routine inspection of surgical operation, while its clinical effectiveness prompts
A variety of thrombus diseases or hemorrhage risk.In addition, the patient for using anticoagulation, the testing result in clotting time is adjustment
The important reference of anticoagulation dosage.Especially for certain oral anticoagulations that need to be taken for a long time, such as warfarin,
Anticoagulant effect is larger to individual difference, and the interaction with other drugs is complicated, and natural food also has its anticoagulation
It influences.Therefore, to guarantee anticoagulant effect and avoiding bleeding risk, patient needs often to check every clotting time to hospital, and
Adjustment drug dose in due course, brings certain inconvenience to life.
There are many instruments of clotting time detection at present, but most of apparatus structures are complex, need professional operation, institute
Need sample size more, testing cost is higher, is not suitable for the routine testing of Long-term Oral anticoagulation patient in the family.Therefore,
Miniaturization, the clotting time detection technique automated are widely paid close attention to.
According to testing principle, blood clotting time inspection method can be divided into two class of freezing method and substrate development process at present.Freezing method
Blood clotting is determined by physical quantity variations such as a series of optics, electricity, mechanics of the detection blood sample under coagulation activation agent effect
Gu the time.Immunoturbidimetry makes determinand and is marked with its specificity using the characteristics of specifically binding between antigen and antibody
The particle of antibody combines, and the turbidity of reaction system is caused to change, the quantitative determinand of the variation by detecting its luminous intensity
Method.
The clotting time detection technique of some miniaturizations existing at present, automation.
The Chinese patent of Publication No. CN 103487377A discloses a kind of detector for coagulation function of whole blood and detection side
Method, including for placing whole blood detection vessel, with detection vessel connect rotating device, light wave generator, Lightwave receiver,
Timer and shell.For driving detection vessel to rotate around central axis, light wave generator and light wave receive rotating device
Device is arranged oppositely in the two sides of detection vessel.When the whole blood in detection vessel does not condense, in detection vessel rotary course,
Lightwave receiver persistently receives the light of stronger light wave generator transmitting always or can not or can only receive light wave generator
The faint optical signal of transmitting.Timer is added clotting reagent and cannot receive or not to Lightwave receiver first time for recording
The time for receiving the light of light wave generator transmitting can be stablized, or receive the time of stronger optical signal for the first time.
The Chinese patent of Publication No. CN 105588945A discloses a kind of micro-fluidic hemostasis detestion device and its detection side
Method, including disc ontology are equipped with 1 or more hemostasis examination unit on the disc ontology.Hemostasis examination unit includes complete
Blood injects slot, and whole blood injection slot is connected installation with blood plasma waste liquid tank, and be also connected with 1 or more quick mixed cell peace
Dress.Quick mixed cell is connected installation with blood plasma waste liquid tank.The micro-fluidic hemostasis detestion device and its detection method are efficiently, surely
It is fixed, easy, it can be not required to additional Sample pretreatment with whole blood sample direct injected, whole blood separation, quantitative blood can be rapidly achieved
Slurry transmission, it is supper-fast mixing and etc..
Periodical " Analytical Chemistry " entitled " Investigation of of page 658 of volume 82 in 2010
Prothrombin Time in Human Whole-Blood Samples with a Quartz Crystal
The paper of Biosensor " report it is a kind of using quartz microbalance sensor (quartz crystal microbalance,
QCM the method for clotting time detection) is carried out.This method is using the resonance frequency of quartz microbalance sensor to external liquid viscosity
Sensitive feature.Blood sample is placed in crystal microbalance surface, when coagulation process occurs, blood viscosity changes, from
And lead to resonance frequency decline and resonance oscillation attenuation.By measuring the resonance frequency and damping characteristic coefficient of crystal microbalance, determine
The clotting time of blood sample.
The shortcomings that above-mentioned technical proposal, is that (1) apparatus structure is complicated, and manufacture difficulty is larger；(2) blood sample used
Measure it is more, need specially take a blood sample and processing, be not suitable for family use；(3) outside noise introduced in test process is larger, determines
The clotting time method of point is less reliable, and test result needs further progress to calibrate.
It can be seen that the existing technology needs further improvement and improves.
Summary of the invention
The present invention is to provide a kind of piezoelectric thin film vibrator, its system in place of avoiding above-mentioned the shortcomings of the prior art
The method made method and carry out clotting time detection.
The technical scheme adopted by the invention is as follows:
A kind of piezoelectric thin film vibrator for hemostasis examination, including piezoelectric film and the upper table being arranged in piezoelectric film
Face electrode offers annular groove in piezoelectric film, and the inner surface of annular groove, which is coated with, has hydrophilic polymer material,
The coating of annular groove inner surface carries out peroxide plasma treatment or ultraviolet light, and ring after having hydrophilic polymer material
Connected in star inner surface is deposited with one layer of calcium carbonate.
The width of the annular groove is not less than the maximum width of piezoelectric thin film vibrator upper surface electrode, annular groove
Depth is not less than the one third of piezoelectric thin film vibrator piezoelectric film thickness, on annular groove inner ring and piezoelectric thin film vibrator
The distance between surface electrode range is 1 times to 1.5 times of the maximum width of upper surface electrode.
It is described to have hydrophilic polymer material for polyacrylic acid, hydroxyethyl methacrylate, polyethylene glycol, polyethylene
Pyrrolidones, polytetrahydrofuran ether, polytetramethylene glycol it is one or more.
It is described with hydrophilic polymer material with a thickness of 100 nanometers to 200 nanometers.
The invention also discloses a kind of production method of above-mentioned piezoelectric thin film vibrator for hemostasis examination, this method packets
Include following steps:
Step 1, the annular groove is etched in piezoelectric film；
Step 2, there is hydrophilic polymer material in the inner surface coating of the annular groove；
Step 3, oxygen plasma treatment or ultraviolet light are carried out to the inner surface of the annular groove；
Step 4, piezoelectric thin film vibrator is placed in sodium carbonate liquor, calcium chloride solution is then added in the solution；
Step 5, piezoelectric thin film vibrator is taken out, baking is until dry.
In the step 5, the temperature of baking should not exceed 100 DEG C.
The invention also discloses a kind of piezoelectric thin film vibrators produced using above-mentioned production method to carry out the clotting time
The method of detection, this method comprises the following steps:
Step A instills the mixing liquid of blood sample and blood coagulation test agent in the annular groove center；
Step B, the resonance frequency of test constantly piezoelectric thin film vibrator；
Step C calculates resonant frequency on time and becomes according to the piezoelectric thin film vibrator resonance frequency after the stabilization recorded
The second dervative of change takes the maximum value of the second dervative as the clotting time.
In the step A, calcium ion is not contained in blood coagulation test agent.
In the step A, the upper surface electrode of piezoelectric thin film vibrator should be completely covered in the minimum volume of mixing liquid, most
Large volume is no more than the volume of annular groove.
In the step A, if blood sample is that acquisition, Ying Jinhang anticoagulation are simultaneously stored in low temperature environment in advance, with
The spontaneous coagulation of anti-Hemostatic Oral Liquid before test, need to restore blood sample to room temperature；If blood sample is now to adopt, can directly make
With；Whether the blood sample acquired in advance or the blood sample now adopted when test, all need for blood sample to be diluted,
Blood coagulation test agent and evenly dispersed is added after the completion of dilution in blood sample.
By adopting the above-described technical solution, obtained by the present invention have the beneficial effect that
1, the piezoelectric thin film vibrator structure of the present invention for hemostasis examination is simple, and easily fabricated, size is smaller,
Only millimeter magnitude can be integrated in wearable electronic or other miniaturized electronics for hemostasis examination.
2, clotting time detection is carried out using method of the present invention, the blood sample amount consumed in test is less, only
For a microlitre magnitude, it is suitable for home use.
3, clotting time detection is carried out using method of the present invention, frequency response output noise is small, and the clotting time is sentenced
It is disconnected accurate.
Detailed description of the invention
Fig. 1 is piezoelectric thin film vibrator structural side view used by the embodiment of the present invention.
Fig. 2 is piezoelectric thin film vibrator structure top view used by the embodiment of the present invention.
Fig. 3 is after instilling mixed fluid sample in the embodiment of the present invention, and piezoelectric thin film vibrator resonance frequency is at any time
Change curve.
Fig. 4 is the Second derivative curves that piezoelectric thin film vibrator resonance frequency changes over time in the embodiment of the present invention.
Fig. 5 is that the present invention uses the method for the present invention and conventional Blood coagulation instrument that multiple plasma samples are measured with pair after comparing
According to figure.
Specific embodiment
The present invention is described in further detail with specific embodiment with reference to the accompanying drawing, but the present invention is not limited to
These embodiments.
Piezoelectric thin film vibrator used in the present invention is generally made of silicon chip, support film layer, piezoelectric layer and electrode,
Its structure can be tabula model, air-gap type and solid assembly type etc..To guarantee the membrane resonant in blood adhesive environment
Device can effective resonance, the measurement in clotting time is carried out preferably with the piezoelectric thin film vibrator that works with shear wave modes.
Piezoelectric thin film vibrator electrode, which can be, is arranged in parallel within piezoelectric layer upper surface, can also be placed in the two sides of piezoelectric layer.Piezoelectricity is thin
The shape of film resonator electrode can be round, rectangular or other irregular shapes.
The piezoelectricity that hemostasis examination is used in the present invention is now illustrated by taking piezoelectric thin film vibrator as depicted in figs. 1 and 2 as an example
Film Resonator.
In the present embodiment, piezoelectric thin film vibrator is tabula model structure, carries out the detection of prothrombin time.The device
Circular electrode 104, the ring of piezoelectric layer upper surface are arranged in parallel within by silicon chip 101, support film layer 102, piezoelectric layer 103 and two
Shape electrode 105 forms.Transverse electric field is generated by parallel two electrodes 104,105, excites resonator works in shear wave modes.
The piezoelectric thin film vibrator can be manufactured by the semiconducter process combination bulk silicon technological of standard.In the present embodiment,
The support film layer 102 of piezoelectric thin film vibrator can use silicon oxide film or silicon nitride film, support film layer 102 with a thickness of
0.8 micron.Within the scope of the underlying device effective coverage of support film layer 102, silicon chip 101 is etched, and forms hanging diaphragm
Membrane structure.Piezoelectric layer 103 is aluminium nitride film or zinc-oxide film, with a thickness of 1 micron.Electrode material is golden material or other gold
Belong to material, with a thickness of 100 nanometers.The diameter of inner circular electrode 104 is 100 microns, and the width of exterior annular electrode 105 is 50
Micron, the distance between two electrodes are 20 microns.
Utilize the specific steps of production method of the present invention production piezoelectric thin film vibrator are as follows:
Step 1, annular groove 106 is etched in the piezoelectric film of piezoelectric thin film vibrator.
To guarantee that shearing wave vibrational energy can be concentrated on effectively within the scope of blood sample, the width of annular groove 106, depth
Degree and piezoelectric thin film vibrator electrode should be in appropriate ranges at a distance from annular groove 106.According to the knot of optimization design
Fruit, the width of annular groove 106 are not less than the maximum width of piezoelectric thin film vibrator upper surface electrode, the depth of annular groove 106
Degree is not less than the one third of piezoelectric thin film vibrator piezoelectric film thickness, the inner ring and piezoelectric membrane resonance of annular groove 106
The distance between device upper surface electrode range is 1 times to 1.5 times of the maximum width of upper surface electrode.In the present embodiment, annular
The width of groove 106 is 120 microns, and the depth of annular groove 106 is 0.5 micron, 106 inner ring of annular groove and upper surface electrode
The distance between range be 120 microns.
Wet etching or dry etching method can be used in the method for etching annular groove 106.In the present embodiment, for nitridation
The reactive ion etching process of chlorine-based gas or fluorine base gas can be used in aluminium film, and for zinc-oxide film, chloro gas can be used
Precursor reactant ion etch process or the etching liquid of hydrochloric acid-base perform etching.
Step 2, there is hydrophilic polymer material in the coating of annular groove inner surface.
The effect of the step is the contact area enhanced between annular groove inner surface and following drop of blood, is obtained preferable
Measurement effect.Used polymer material is polyacrylic acid, hydroxyethyl methacrylate, polyethylene glycol, polyvinyl pyrrole
Alkanone, polytetrahydrofuran ether, polytetramethylene glycol it is one or more, used polymer material is preferably with a thickness of 100 nanometers
To 200 nanometers.Spin-coating method or vapour deposition method can be used in the method for coating.It is thick using spin-coating method polyacrylic acid coating in the present embodiment
Degree is 150 nanometers.
Step 3, oxygen plasma treatment or ultraviolet light are carried out to the inner surface of annular groove.
The effect of the step is to further strengthen annular groove inner surface to insoluble fibrinous suction-operated.This
In embodiment, using power density is 10 milliwatts ultraviolet light every square centimeter to the polymer material of annular groove inner surface
Surface is irradiated, and the time is 10 minutes.
Step 4, piezoelectric thin film vibrator is placed in sodium carbonate liquor, calcium chloride solution is then added in the solution.
The effect of the step is to deposit one layer of calcium carbonate on piezoelectric thin film vibrator surface, when blood sample contacts the surface
When can be activated and start coagulation process.Piezoelectric thin film vibrator annular recess inner surface should be placed in top, so that carbonic acid
Calcium precipitate to contact blood surface.The concentration and reaction time of sodium carbonate liquor and calcium chloride solution should ensure that appropriate
Precipitation of calcium carbonate neither gives the biggish load of resonator in the inner surface of piezoelectric thin film vibrator surface, especially annular groove
Cause its performance to decline, and can guarantee to activate the coagulation process of blood.In the present embodiment, sodium carbonate liquor and calcium chloride solution
Concentration be 1 mole every liter, the reaction time be 5 minutes.
Step 5, piezoelectric thin film vibrator is taken out, baking is until dry.
For the stabilization for guaranteeing hydrophilic polymer material on piezoelectric thin film vibrator surface, baking temperature should not exceed 100
Degree Celsius, the time is unsuitable too long.Before baking, high pressure gas blow pressure conductive film resonator surface cannot be used, to guarantee to be deposited in
The calcium carbonate on piezoelectric thin film vibrator surface is not destroyed.In the present embodiment, piezoelectric membrane resonance will be directly taken out from solution
Device is toasted 15 minutes using 80 degrees Celsius.
It is able to carry out clotting time detection using the piezoelectric thin film vibrator that above-mentioned production method is produced, can be measured more
Kind clotting time, including but not limited to prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time
(TT), fibrinogen (FIB).Used blood coagulation test agent is depended on using the clotting time that the present invention measures.This hair
It is bright to test whole blood or plasma sample.
The method for carrying out clotting time detection using the piezoelectric thin film vibrator that above-mentioned production method is produced, specifically includes
Following steps:
Step A instills the mixed liquor of blood sample and blood coagulation test agent in 106 center of piezo-electric resonator annular groove
Body.
In general, if whole blood sample or plasma sample are that acquisition, Ying Jinhang anticoagulation are simultaneously stored in low temperature ring in advance
In border, to prevent the spontaneous coagulation of Hemostatic Oral Liquid.Before test, blood sample should be made to restore to room temperature.If blood sample is to adopt at that time
Collection, can directly use.When test, blood sample is diluted first, blood coagulation test examination is then added in blood sample
Agent is simultaneously evenly dispersed.The coagulation process of blood is activated by the calcium carbonate that piezo-electric resonator surface is precipitated, therefore blood coagulation is surveyed
Having a try should not contain calcium ion in agent.To guarantee that test is accurate, piezoelectricity should be completely covered in the minimum volume of the mixing liquid of instillation
The upper surface electrode of film Resonator, maximum volume are no more than the annular groove 106 of electrode periphery.
In the present embodiment, the measurement of prothrombin time is carried out to plasma sample.The plasma sample uses 3.8% in advance
Liquor sodii citratis carries out anticoagulation according to the ratio of 1:9 (liquor sodii citratis: blood plasma).Before measurement, ammonia is further used
Butantriol buffer is diluted anticoagulation slurry, and the ratio of blood plasma and tromethamine buffer is 1:3.Instill the specific of sample
Operating process are as follows: take 5 microlitres of diluting plasma samples and 5 microlitres of prothrombin time test agents to be sufficiently mixed and shaken up,
Then 1 microlitre of mixing liquid is taken to instill 106 center of piezo-electric resonator annular groove.
Step B, the resonance frequency of test constantly piezoelectric thin film vibrator.
In specific implementation, the resonance frequency of piezoelectric thin film vibrator can be measured using a variety of methods, such as by device
It is connect with Network Analyzer or impedance analyzer and carries out frequency measurement；Or the resonance circuit and frequency-discriminating circuit of design and device matching
Carry out frequency measurement；Or beat method measurement is carried out using two or more piezoelectric thin film vibrators.In the present embodiment, using two
The identical piezoelectric thin film vibrator for having done the above processing accesses test circuit respectively as senser element and parametric device
In.In test, only senser element loads blood sample, and parametric device is unloaded.Two resonators are driven by identical resonance circuit
Dynamic, two resonance frequencies are filtered after mixed, amplify, waveform conversion and frequency dividing, output transducer part and parametric device
Frequency difference reduces external environmental interference to the full extent.
Step C calculates resonant frequency on time and becomes according to the piezoelectric thin film vibrator resonance frequency after the stabilization recorded
The second dervative of change takes the peak of the second dervative as the clotting time.
In the present embodiment, the piezoelectric thin film vibrator resonance frequency after instillation mixed fluid sample as shown in Figure 3 is at any time
Between change curve.After instillation, due to the percussion of mixing liquid, larger fluctuation occurs for resonance frequency.Therefore, it takes 4 seconds
Data later are analyzed as valid data.Piezoelectric thin film vibrator resonance frequency, which changes with time, is presented apparent three
A stage.First stage, resonance frequency kept stable, the reaction process corresponding to prothombin fibrin ferment；Second
Stage resonance frequency rapid decrease is changed into fibrin monomer, and final crosslinking mutually corresponding to fibrinogen in blood
Form the process of grumeleuse；Phase III, resonance frequency is constant for a long time, illustrates that coagulation process terminates, blood solidifies completely.
It is crucial it needs to be determined that the time point that blood sample coagulation process is completed in the test in clotting time.By repeatedly
Experimental demonstration discovery, with the peak of the second dervative of resonant frequency on time variation closest to the actual clotting time, because
This present invention proposes the peak of the second dervative changed using resonant frequency on time as the clotting time.In the present embodiment, such as
Fig. 4 show the second dervative of resonant frequency on time variation, and available prothrombin time is 41.5 seconds.
It is right respectively using the method for the present invention and conventional Blood coagulation instrument for the application method and validity that the present invention is further explained
Multiple plasma samples measure control, as a result as shown in Figure 5.Three groups of difference clotting times corresponding plasma sample is dilute in figure
Releasing ratio (blood plasma: tromethamine buffer) is respectively 1:1,1:3 and 1:5.It can be seen that the slope of regression equation is close to 1,
Intercept is only about 0.5 second, and the value of the coefficient of determination (R2) is 0.9837, illustrates the method for the present invention and the result that conventional Blood coagulation instrument obtains
With preferable correlation and consistency.
The part that do not address in the present invention uses or uses for reference prior art and can be realized.
Specific embodiment described herein is only to spiritual example explanation of the invention.Belonging to the present invention
Those skilled in the art can make various modifications or additions to the described embodiments or using similar
Mode substitutes, and however, it does not deviate from the spirit of the invention or beyond the scope of the appended claims.
Claims (9)
1. a kind of piezoelectric thin film vibrator for hemostasis examination, including piezoelectric film and the upper surface being arranged in piezoelectric film
Electrode, which is characterized in that annular groove is offered in piezoelectric film, the inner surface of annular groove, which is coated with, has hydrophilic gather
Object material is closed, the coating of annular groove inner surface carries out peroxide plasma treatment or ultraviolet light after having hydrophilic polymer material
Irradiation, and annular groove inner surface is deposited with one layer of calcium carbonate；The width of the annular groove is not less than piezoelectric thin film vibrator
The maximum width of upper surface electrode, the depth of annular groove not less than piezoelectric thin film vibrator piezoelectric film thickness three/
One, the distance between annular groove inner ring and piezoelectric thin film vibrator upper surface electrode range are the maximum width of upper surface electrode
1 times to 1.5 times.
2. a kind of piezoelectric thin film vibrator for hemostasis examination according to claim 1, which is characterized in that described to have
Hydrophilic polymer material is polyacrylic acid, hydroxyethyl methacrylate, polyethylene glycol, polyvinylpyrrolidone, poly- tetrahydro
Furans ether, polytetramethylene glycol it is one or more.
3. a kind of piezoelectric thin film vibrator for hemostasis examination according to claim 2, which is characterized in that described to have
Hydrophilic polymer material with a thickness of 100 nanometers to 200 nanometers.
4. a kind of production method for the piezoelectric thin film vibrator of hemostasis examination as claimed any one in claims 1 to 3,
It is characterized in that, this method comprises the following steps:
Step 1, the annular groove is etched in piezoelectric film；
Step 2, there is hydrophilic polymer material in the inner surface coating of the annular groove；
Step 3, oxygen plasma treatment or ultraviolet light are carried out to the inner surface of the annular groove；
Step 4, piezoelectric thin film vibrator is placed in sodium carbonate liquor, calcium chloride solution is then added in the solution；
Step 5, piezoelectric thin film vibrator is taken out, baking is until dry.
5. the production method of the piezoelectric thin film vibrator according to claim 4 for hemostasis examination, which is characterized in that institute
It states in step 5, the temperature of baking should not exceed 100 DEG C.
6. a kind of piezoelectric thin film vibrator that the production method using as described in any one of claim 4 to 5 is produced carries out
The method of clotting time detection, which is characterized in that this method comprises the following steps:
Step A instills the mixing liquid of blood sample and blood coagulation test agent in the annular groove center；
Step B, the resonance frequency of test constantly piezoelectric thin film vibrator；
Step C calculates resonant frequency on time variation according to the piezoelectric thin film vibrator resonance frequency after the stabilization recorded
Second dervative takes the maximum value of the second dervative as the clotting time.
7. a kind of production method using as described in any one of claim 4 to 5 according to claim 6 is produced
The method of piezoelectric thin film vibrator progress clotting time detection, which is characterized in that in the step A, in blood coagulation test agent not
Contain calcium ion.
8. a kind of production method using as described in any one of claim 4 to 5 according to claim 6 is produced
The method of piezoelectric thin film vibrator progress clotting time detection, which is characterized in that in the step A, the most corpusculum of mixing liquid
The upper surface electrode of piezoelectric thin film vibrator should be completely covered in product, and maximum volume is no more than the volume of annular groove.
9. a kind of production method using as described in any one of claim 4 to 5 according to claim 6 is produced
The method of piezoelectric thin film vibrator progress clotting time detection, which is characterized in that in the step A, if blood sample is prior
Acquisition, Ying Jinhang anticoagulation is simultaneously stored in low temperature environment,, need to be by blood sample before test to prevent the spontaneous coagulation of Hemostatic Oral Liquid
Product restore to room temperature；If blood sample is now to adopt, can be used directly；Whether it the blood sample that acquires in advance or now adopts
Blood sample when test, all needs for blood sample to be diluted, and blood coagulation test agent is added after the completion of dilution in blood sample
And it is evenly dispersed.
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| CN107271498B (en) * | 2017-06-16 | 2019-04-23 | 哈尔滨工业大学 | Glucose quantitation test sensor and preparation method based on microwave patch resonator |
| CN107991385B (en) * | 2017-11-28 | 2020-05-22 | 中国科学院苏州生物医学工程技术研究所 | Method and device for determining blood coagulation time |
| CN108414571A (en) * | 2018-02-11 | 2018-08-17 | 中国科学院苏州生物医学工程技术研究所 | Clotting time detection method and device |
| TWI662282B (en) * | 2018-10-19 | 2019-06-11 | 國立臺北科技大學 | Vibrating system for measuring blood coagulation reaction time |
| CN111010100A (en) * | 2019-03-02 | 2020-04-14 | 天津大学 | Bulk acoustic wave resonator with piezoelectric layer having recessed structure, filter, and electronic device |
| CN111351848B (en) * | 2020-03-19 | 2020-10-16 | 山东科技大学 | Preparation method of sensor, sensor and detection method of sensor |
| CN112834583A (en) * | 2021-01-06 | 2021-05-25 | 厦门大学 | Electrochemical spectroscopy in-situ pool with thin film optical window and application thereof |
| CN113676152A (en) * | 2021-08-26 | 2021-11-19 | 中国科学院上海微系统与信息技术研究所 | Elastic wave resonator and preparation method thereof |
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