CN106596642A - Hydrophobic modification based blood coagulation sensor, preparation method and application thereof - Google Patents
Hydrophobic modification based blood coagulation sensor, preparation method and application thereof Download PDFInfo
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- CN106596642A CN106596642A CN201611112697.7A CN201611112697A CN106596642A CN 106596642 A CN106596642 A CN 106596642A CN 201611112697 A CN201611112697 A CN 201611112697A CN 106596642 A CN106596642 A CN 106596642A
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Abstract
The invention relates to a hydrophobic modification based blood coagulation detection sensor, preparation method and application thereof. The blood coagulation detection sensor includes a piezoelectric film sensor; the surface of the piezoelectric film sensor is modified with a hydrophobic layer, the hydrophobic layer is made from polyphenylene oxide. The preparation method plates the parylene to the surface of the piezoelectric film sensor through vacuum evaporation to improve the hydrophobicity of the surface in order to achieve the adsorption result of a fibrin hydrophobic domain, the influence on piezoelectric sensor is reduced, the combining capacity of the sensor surface and the fibrin, namely blood coagulation end-product is enhanced, thereby the effect of improving the output signal frequency stability is achieved. In addition, the preparation method has the advantage of mass modifications and is beneficial for eliminating the differences of chip modification inter-assay.
Description
Technical field
The present invention relates to a kind of Hemostasis examination sensor, more particularly to a kind of Hemostasis examination sensing based on hydrophobic modification
Device, its preparation method and application.
Background technology
At present, optical detecting method is widely used to Hemostasis examination, and in inspection, the most frequently used Testing index has thrombin
Former time (PT), activated partial thromboplastin time (aPTT), Fibrinogen (FIB), thrombin time (TT), endogenous blood coagulation
The factor, external source thrombin, high molecular weight heparin, low molecular weight heparin, PROTEIN C, Protein S etc., detection project are enriched but optics
Sample this requirement harshness is treated in detection, and detection time is long, has some limitations.Optical principle is mainly scattered light urbidmetry：
Detection terminal is determined according to the change of sample to be tested scattered light in process of setting.The monochromatic light of sense channel in the method
Source is in 90 ° of right angles with photo-detector, after adding coagulation activation agent in sample, with the formation of fibrin clot in sample
Journey, the scattered light intensity of sample are stepped up.After sample solidifies completely, the intensity of scattered light no longer changes, typically handle
The starting point of solidification as 0%, Coagulated hemothorax as 100%, using 50% as setting time.Photo-detector receives this optics
Change, be translated into the signal of telecommunication, be sent on monitor again and processed through amplifying, describe freezing curve, therefore,
When to light transmissions such as whole bloods, poor complex samples are detected, optical detecting method cannot obtain correct testing result, and be based on
Optical principle is set up light path and is difficult to realize microminiaturization, portability equipment again.
Piezoelectric film sensor (QCM) is a kind of highly sensitive mass sensor, its Cleaning Principle be blood to be measured by
Fibrinogen is combined with thin film sensor surface after being changed into fibrin, is produced viscoelasticity change and is caused changing for resonant frequency
Become, the features such as there is high sensitivity, fast response time to the response of surface nanogram level mass change.It is light tight in detection high viscosity
Complex samples detection performance be better than existing optical detection means, piezoelectric film sensor detected compared with optics blood coagulation instrument
Project is few, but can realize multiple determination by multichannel, and detection time is short.Piezoelectric membrane class sensor has small volume in addition
The characteristics of, it is easy to accomplish the exploitation and production application of compact apparatus.
Piezoelectric film sensor is directly used in when the complex samples such as serum or whole blood are detected and equally faces group in sample system
Divide numerous and diverse problem, substantial amounts of non-targeted albumen and soluble component cause very big ambient interferences.Conventional solution exists
The affinity albumen such as sensor surface deposition protein A, Streptavidin and biotin, improve specific antibody or biological point with this
The joint efficiency of son.But the method that antigen-antibody is combined needs the long response time, it is impossible to meet blood coagulation quick detection again
The requirement of (in 3mins), aPTT normal values (change according to different reagents) in 28s～33s, and PT normal values are in 12s～16s.
Therefore this case is necessary a kind of brand-new Hemostasis examination sensor of exploitation can both improve absorption specificity, and can shorten detection
Time.
The content of the invention
For technical problem present in prior art, this case provides a kind of Hemostasis examination based on hydrophobic modification and senses
Device, its preparation method and application, by polyxylene (Parylene) this materials application is detected in clotting time, so as to increase
The surface modification method of conductive film sensor performance (signal to noise ratio, specificity, repeatability) is suppressed, to solve piezoelectricity in prior art
Thin film sensor is subject to non-specific adsorption interference to cause in detection coagulation process, and chip detection frequency is unstable, detection time
Long the problems such as.
For achieving the above object, this case is achieved through the following technical solutions：
A kind of Hemostasis examination sensor, which includes piezoelectric film sensor, in the piezoelectric film sensor surface modification
There is hydrophobic layer, the hydrophobic layer is polyxylene.
Preferably, described Hemostasis examination sensor, wherein, the thickness of the hydrophobic layer is 100-1500nm.
A kind of preparation method of Hemostasis examination sensor, which adopts vacuum evaporation that hydrophobic layer is plated on piezoelectric film sensor
Surface, the hydrophobic layer are polyxylene.
Preferably, the preparation method of described Hemostasis examination sensor, wherein, the thickness of the hydrophobic layer is 100-
1500nm。
A kind of Hemostasis examination sensor as above is carrying out the application in Hemostasis examination to blood serum sample.
A kind of Hemostasis examination sensor as above is carrying out the application in Hemostasis examination to whole blood sample.
The invention has the beneficial effects as follows：
(1) in order to solve the problems, such as blood coagulation generation fibrin to be adsorbed onto piezoelectric film sensor surface, first will
Parylene vacuum evaporations realize the raising of surface hydrophobic to piezoelectric film sensor surface, have reached adsorbing fiber albumen
The effect of hydrophobic domains.
(2) with good hydrophobic nano level thickness material Parylene, the impact to piezoelectric transducer is reduced, strengthens and pass
Sensor surfaces and blood coagulation end-product fibrin binding ability, realize improving the effect of sensor output signal frequency stability.
(3) inherently a kind of strong acid-base resistance materials of Parylene, with excellent protection chip ability.
(4) Parylene materials have can mass the characteristics of modify, contribute to eliminating chip modification lot-to-lot variability.
Description of the drawings
Fig. 1 is the sensor chip detection activated partial thromboplastin time aPTT detection knots after this case Parylene modifications
Fruit and the sensor chip testing result comparison diagram of unmodified Parylene.
Fig. 2 is the result pair that the same Parylene modifications sensor chip inspection of this case detects same patient blood sample for three times
Than figure.
Fig. 3 is the sensor chip detection activated partial thromboplastin time aPTT detection knots after this case Parylene modifications
Fruit and Lambda950 UV spectrophotometer measuring comparative result figures.
Fig. 4 is the sensor chip detection activated partial thromboplastin time aPTT detection knots after this case Parylene modifications
Fruit and Sysmex 2000i testing result comparison diagrams.
Specific embodiment
The present invention is described in further detail below in conjunction with the accompanying drawings, to make those skilled in the art with reference to description text
Word can be implemented according to this.
This case will have the material of hydrophobic property using vacuum evaporation technology, and polyxylene (parylene) is covered in piezoelectricity
Thin film sensor surface, forms one layer of fine and close hydrophobic membrane structure, detects clotting time, including prothrombin time PT, activation
Partial thromboplastin time aPTT etc..
Concrete preparation process is as follows：Parylene (a class material) pressed powder is steamed under 150 DEG C, 1Torr environmental conditions
Send out, crack under 690 DEG C, 0.5Torr environmental conditions, form Parylene gaseous moleculars, piezoelectricity is reached by dredging pipeline thin
The vacuum reaction chamber that film sensors chip is located, with the temperature drop of within the chamber, Parylene gaseous moleculars are in piezoelectric membrane
The hydrophobic membrane structures of sensor surface one layer of fine and close Parylene of formation.Film piezo-electric chip after Parylene modifications prepares to use
Detect in clotting time.Additionally, the modification technique is carried out in vacuum tank, can batched operation, it is easy to accomplish miniaturization sensing
Technical products are developed and are manufactured.
After chip is placed in detecting system, with totally 100 microlitres of liquid-transfering gun Deca blood sample and aPTT mixed liquors, then plus
Enter (50 microlitres) startup Coagulation tests of calcium ion, blood coagulation end-product fibrin is a kind of hydrophobic structure albumen, when blood coagulation terminates
Afterwards, fibrin can be cross-linked into network structure, expose its hydrophobic domains to greatest extent, according to hydrophobic interaction, the albumen
Hydrophobic domains the mutually affine absorption of the hydrophobic surface to be formed can be modified with Parylene, finally cause as viscoelasticity changes
Piezoelectric film sensor surface produces mass change, and so as to be reacted to frequency change, transducing signal is transferred to display screen output knot
Really.
As shown in figure 1, the negative experimental result (curve 1) for not adding blood plasma or whole blood will not be produced under obvious frequency
Drop, this is to be adsorbed onto sensor surface due to no fibrin.The tests of aPTT twice of not modified piezoelectric membrane chip
As a result (curve 2) shows obvious frequency jitter, and this is, as fibrin is combined with the surface insecure, to float in liquid phase
Cause.Parylene modifications chip clotting time test result (curve 3) forms sharp contrast with curve 2, and stability is obtained
Significantly improve, after this benefits from hydrophobic modification, sensor sheet is improved in the face of fibrin-specific.Further, since not modified
The frequency jitter (see 2 afterbody of curve) of chip detection result (curve 2), experiment are difficult have repeatability say.
As shown in Fig. 2 three curves of the same sample clotting time of chip detection after modification embody good weight
Renaturation, is on the one hand, as the hydrophobic surface that Parylene is formed is improved to fibrin-specific, to be on the other hand because
Parylene materials have good biocompatibility, it is only necessary to which clear water is rinsed and can be detected again, and differences between batches are little.
As shown in figure 3, optical standard checks aPTT curves 1 and the chip detection aPTT curve 2 after Parylene modifications, it is right
The clotting time point (position 3) answered coincide good, it was demonstrated that the program and standard detecting method (YY/T0659-2008) result one
Cause.
As shown in figure 4, this is the chip detection aPTT result and Clinical detection instrument Sysmex after Parylene modifications
2000i aPTT testing result linear relationship comparison diagrams, it shows QCM chips and existing clinical instrumentation after Parylene modifications
Test result be identical, can as medical instruments and equipment for clinical medical aPTT detect.
Although embodiment of the present invention is disclosed as above, which is not restricted to listed by description and embodiment
With, it can be applied to various suitable the field of the invention completely, for those skilled in the art, can be easily
Other modification is realized, therefore under the general concept limited without departing substantially from claim and equivalency range, the present invention is not limited
In specific details and shown here as the legend with description.
Claims (6)
1. a kind of Hemostasis examination sensor, it is characterised in that include piezoelectric film sensor, in the piezoelectric film sensor table
Face is modified with hydrophobic layer, and the hydrophobic layer is polyxylene.
2. Hemostasis examination sensor as claimed in claim 1, it is characterised in that the thickness of the hydrophobic layer is 100-
1500nm。
3. a kind of preparation method of Hemostasis examination sensor, it is characterised in that hydrophobic layer is plated on by piezoelectricity using vacuum evaporation thin
Film sensors surface, the hydrophobic layer are polyxylene.
4. the preparation method of Hemostasis examination sensor as claimed in claim 3, it is characterised in that the thickness of the hydrophobic layer is
100-1500nm。
5. a kind of Hemostasis examination sensor as claimed in claim 1 or 2 is carrying out the application in Hemostasis examination to blood serum sample.
6. a kind of Hemostasis examination sensor as claimed in claim 1 or 2 is carrying out the application in Hemostasis examination to whole blood sample.
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| CN201611112697.7A CN106596642A (en) | 2016-12-06 | 2016-12-06 | Hydrophobic modification based blood coagulation sensor, preparation method and application thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107024509A (en) * | 2017-05-15 | 2017-08-08 | 中国科学院苏州生物医学工程技术研究所 | A kind of preparation method of blood coagulation test paper and its piezoelectric transducer chip |
| CN107991385A (en) * | 2017-11-28 | 2018-05-04 | 中国科学院苏州生物医学工程技术研究所 | A kind of method and device in definite clotting 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 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107024509A (en) * | 2017-05-15 | 2017-08-08 | 中国科学院苏州生物医学工程技术研究所 | A kind of preparation method of blood coagulation test paper and its piezoelectric transducer chip |
| WO2018209923A1 (en) * | 2017-05-15 | 2018-11-22 | 中国科学院苏州生物医学工程技术研究所 | Clotting test paper and method for preparing piezoelectric sensor chip thereof |
| CN107991385A (en) * | 2017-11-28 | 2018-05-04 | 中国科学院苏州生物医学工程技术研究所 | A kind of method and device in definite clotting time |
| WO2019104754A1 (en) * | 2017-11-28 | 2019-06-06 | 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 |
| 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 |
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