CN106248919A - Method based on blood sample vibration detection coagulation - Google Patents

Method based on blood sample vibration detection coagulation Download PDF

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Publication number
CN106248919A
CN106248919A CN201610560461.3A CN201610560461A CN106248919A CN 106248919 A CN106248919 A CN 106248919A CN 201610560461 A CN201610560461 A CN 201610560461A CN 106248919 A CN106248919 A CN 106248919A
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blood sample
vibration
capillary tube
meniscus
sample
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CN106248919B (en
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罗小刚
侯长军
唐靖
王刚林
严俊
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Chongqing Ding Ding Medical Equipment Co Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/49Blood
    • G01N33/4905Determining clotting time of blood

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Abstract

The invention discloses a kind of method based on blood sample vibration detection coagulation, blood sample to be detected is added in the capillary tube of pendency, to produce the blood sample drop of the band meniscus connected by surface tension at the mouth of pipe of capillary tube lower end;On the capillary arrange vibration generation cavity connect with capillary tube, by the capillary tube other end close, then vibration generation cavity on apply thrust alternately with suction so that blood sample drop meniscus generation of reciprocating vibration;The change in location of blood sample drop meniscus bottom in detection vibration processes, and calculate the elastic modelling quantity of blood sample, thus realize coagulation detection.Hemostasis examination result of the present invention is more accurate, more simplifies according to the structure of the detecting device of method design, it is possible to achieve on-line real-time measuremen.

Description

Method based on blood sample vibration detection coagulation
Technical field
The present invention relates to Hemostasis examination, be specifically related to a kind of method based on blood sample vibration detection coagulation, belong to blood Liquid detection technique field.
Background technology
Human body has complicated and complete hemostasis, blood coagulation and anticoagulant mechanism, and the formation of thrombosis is relevant with whole clotting mechanism, And the research of thrombosis relates to generation and the development of the multiple diseases such as atherosclerosis, coronary heart disease, myocardial infarction;Coagulation analysis The project checked be widely used in hemorrhage, thrombotic disease and the diagnosis of Pre-thrombosis State, observation of curative effect, anticoagulant dosage and Prognostic analysis, the various primary or diagnosis of Secondary cases fibrinolytic and observation of curative effect.Automatically coagulation analysis refers to be divided by automatic blood coagulation Analyzer or other analysers are analyzed to hemostasis and Related Component in thrombosis system and are applied to hemorrhage, thrombotic disease and examine Break, treat and Index for diagnosis;The application of Automatic coagulometer so that hemostasis and thrombosis item inspection become easy, accurate, can do Go out multinomial quantitative result accurately.
Full automatic blood-coagulation detects at present mainly following several method: 1, optical method;2, paramagnetic particle method;3, immunoturbidimetry;
The Cleaning Principle of optical method is to determine setting time by the change of detection blood sample turbidity to be measured.Treat test sample This is during solidification, and the component content of blood all there occurs change, according to lambert's beer's law, when a branch of parallel list When coloured light is perpendicular through the extinction material of uniform non-scatter, its absorbance just becomes with concentration and the absorber thickness of extinction material Ratio.When blood constituent changes, the intensity of transmission light and scattered light also can change, and can be used to according to this characteristic optical method Carry out Hemostasis examination.The shortcoming of optical method is susceptible to interference, the bubble in the fineness of test cup, blood sample, sample to be tested Turbidity higher (such as situations such as jaundice, hyperlipidemia) all can become the interference factor of measurement.
Paramagnetic particle method refers to add magnetic bead in the sample during detection, utilizes the motion of instrument monitoring magnetic bead thus reacts blood coagulation shape The detection method of condition.In Blood Coagulation Process, the change of blood viscosity can produce impact to magnetic bead motion, can pass through instrument Detect this change, thus measure the coagulation of blood sample.The shortcoming of paramagnetic particle method is that Cleaning Principle is complicated, to detection knot Fruit produces the factor of impact and includes: the degree of sample, and magnetic bead drives coagulated mass motion, and wall of cup and the technique etc. of magnetic bead.
Immunoturbidimetry refers to, when the monochromatic light that coagulo meter light source part produces passes through blood plasma to be checked, add people's examination in specimen After agent, antigen and antibody response will form composite particles so that the turbidity of specimen to be checked increases, then the light intensity meeting passed through Weaken.The degree that light intensity changes becomes certain quantitative relation with the amount of antigen, utilize antigen body specific binding instead Should come detected blood sample to carry out qualitative and quantitative determination, to determine every Solidification Parameters.The shortcoming of immunoturbidimetry is mesh The blood clotting project that front immunization can detect is less, makes the function of instrument be restricted.Reagent price is high simultaneously, improves measurement Cost.
Summary of the invention
For deficiencies of the prior art, it is an object of the invention to provide a kind of solidifying based on blood sample vibration detection The method of blood state, Hemostasis examination result of the present invention is more accurate, more simplifies according to the structure of the detecting device of method design, Ke Yishi Existing on-line real-time measuremen.
The technical scheme is that and be achieved in that:
Method based on blood sample vibration detection coagulation, adds in the capillary tube of pendency by blood sample to be detected, with The blood sample drop of the band meniscus connected by surface tension is produced at the mouth of pipe of capillary tube lower end;Vibration is set on the capillary The capillary tube other end, to connect with capillary tube, is closed by generation cavity, then applies thrust alternately and suction on vibration generation cavity Power is so that blood sample drop meniscus produces of reciprocating vibration;In detection vibration processes, the position of blood sample drop meniscus bottom becomes Change, and calculate the elastic modelling quantity of blood sample, thus realize coagulation detection.
This method uses following detection device to detect, and detection device includes vibrational system and the big portion of detecting system two Point;Described capillary tube and vibration generation cavity are vibrational system component parts, and outside defeathering tubule and vibration generation cavity, vibrational system is also Including sample introduction tank, sample presentation pipe, sacculus and vibration power, sample introduction tank is connected with capillary tube by sample presentation pipe, to be added by sample introduction tank Add blood sample and at the mouth of pipe of capillary tube lower end, produce the blood sample drop of the band meniscus connected by surface tension;At sample presentation pipe It is provided with check valve so that blood sample can only be flowed toward capillary tube direction by sample introduction tank and can not flow backwards;Vibration generation cavity is located at list Connecting on valve with intercapillary sample presentation pipe and with capillary tube, described sacculus is arranged on vibration generation cavity, vibrates power It is connected with sacculus by drive mechanism so that sacculus produces reciprocating motion, and then makes blood sample drop meniscus up-down vibration;Capillary The size of pipe is so that Surface Tension of Liquid Drops is applied to the thrust sum of drop more than drop gravity and vibration power, so that drop Reciprocating motion will not be dripped;
Described detecting system includes daylighting module and the signal processing module that light emitting module is relative with light emitting module, luminous Module is positioned at capillary tube lower end vertical with capillary tube with daylighting module line, and the light beam that light emitting module sends is curved from blood sample drop Lunar surface side is irradiated in the daylighting module of meniscus opposite side, and the light detected in daylighting module impinges upon meniscus and air Intersection have a boundary signal, demarcated in daylighting module the change of signal position by detection meniscus, and Output, to signal processing module, thus detects the change of capillary meniscus, corresponding calculating blood elastic modelling quantity, thus traces Coagulation process.
Described daylighting module is made up of silicon cell and optical fiber flexible pipe, and optical fiber flexible pipe one end is connected on silicon cell, separately One end is towards light emitting module.
Described vibration power is air pump, and the piston of air pump is connected with sacculus, and air pump is connected with electromagnetic valve with by electromagnetic valve control Air pump operating frequency processed.
Compared with prior art, there is advantages that
1, compared with optical method, the impact of the bubble in present invention fineness the most test tube, blood, can improve detection essence Degree.
2, the electromagnetic field change caused by magnetic bead motion needs to reach certain motion amplitude (> 5mm) just can cause examining The electromagnetic field parameters change surveyed, therefore the reciprocating frequency of vibration of magnetic bead can not be the highest, causes Blood Coagulation Process Sample frequency also suffers restraints, and typically up to can only achieve 1-2Hz sample frequency.The present invention is compared with paramagnetic particle method, due to optics Detection has high sensitivity and high-speed response characteristic, therefore can apply higher frequency of vibration to blood sample, and therefore the present invention is for solidifying The temporal resolution that blood state is traced is higher than paramagnetic particle method, and sample frequency, up to more than 30Hz, substantially increases accuracy of detection.
3, present invention detection is the blood elastic modelling quantity the most relevant to coagulation, compared with immunoturbidimetry, no Need to add antibody, reduce cost, by compositions etc. such as Blood Cholesterol, blood glucose, blood fat, light transmittance is not affected simultaneously, Accuracy of detection can be improved further.
4, the present invention can reduce the design difficulty of vibrational system, simplifies structure, improves blood coagulation analyzer internal structure Stability, it is achieved be easier to.
Accompanying drawing explanation
The structure of the detecting device schematic diagram that Fig. 1-detection method is corresponding.
Fig. 2-Cleaning Principle figure of the present invention.
The Cleaning Principle figure of Fig. 3-stereoscopic-state of the present invention.
Detailed description of the invention
With detailed description of the invention, the present invention is described in further detail below in conjunction with the accompanying drawings.
Present invention method based on blood sample vibration detection coagulation, adds the capillary tube of pendency to by blood sample to be detected In, to produce the blood sample drop of the band meniscus connected by surface tension at the mouth of pipe of capillary tube lower end;On the capillary Arrange vibration generation cavity connect with capillary tube, by the capillary tube other end close, then vibration generation cavity on apply replace Thrust with suction so that blood sample drop meniscus produce of reciprocating vibration;Blood sample drop meniscus bottom in detection vibration processes Change in location, and calculate the elastic modelling quantity of blood sample, thus realize coagulation detection.
This method uses following detection device to detect, and detection device includes vibrational system and the big portion of detecting system two Point;The hovering drop that vibrational system is formed through capillary tube for making detection blood sample produces of reciprocating vibration, and detecting system then detects liquid Drip the situation of change of meniscus in vibration processes, the elastic modelling quantity of blood sample can be calculated according to the situation of change of meniscus, thus Detection coagulation.Seeing Fig. 1, Fig. 2 and Fig. 3, described capillary tube 3 and vibration generation cavity 7 is vibrational system component parts, defeathering Outside tubule 3 and vibration generation cavity 7, vibrational system also includes sample introduction tank 1, sample presentation pipe 2, sacculus 4 and vibration power 5, at capillary tube 3 In overhang, sample introduction tank 1 is connected with capillary tube 3 by sample presentation pipe 2, to add blood sample and in capillary tube 3 times by sample introduction tank 1 The blood sample drop 6 of the band meniscus connected by surface tension is produced at the end mouth of pipe;Sample presentation pipe 2 is provided with check valve so that Blood sample can only be flowed toward capillary tube direction by sample introduction tank and can not flow backwards;Vibration generation cavity 7 be located at check valve and capillary tube it Between sample presentation pipe 2 on and connect with capillary tube 3, described sacculus 4 is arranged on vibration generation cavity 7, and vibration power 5 passes through driver Structure is connected with sacculus 4 so that sacculus 4 produces reciprocating motion, and then makes blood sample drop 6 meniscus up-down vibration;Capillary tube 3 big It is little so that Surface Tension of Liquid Drops is applied to the thrust sum of drop more than drop gravity and vibration power, so that drop is back and forth Motion will not be dripped.
Described detecting system includes daylighting module 9 and the signal processing module that light emitting module 8 is relative with light emitting module, sends out Optical module 8 and daylighting module 9 line are positioned at capillary tube 3 lower end vertical with capillary tube 3, and light emitting module 8 can use maturation LED light source.Daylighting module 9 is for gathering the illumination after light emitting module passes through capillary tube lower end meniscus (by illumination variation feelings Condition can reflect the change of meniscus) and be converted to the signal of telecommunication, daylighting module 9 output connects signal processing module, by signal The signal of telecommunication that daylighting module is exported by reason module carries out calculating process, obtains the elastic modelling quantity of blood sample.
Described daylighting module 9 is made up of silicon cell 10 and optical fiber flexible pipe 11, and optical fiber flexible pipe 11 one end is connected to silicon photoelectricity On pond 10, the other end is towards light emitting module 8.The light sent by light emitting module by optical fiber flexible pipe 11 imports silicon cell 10, this The layout of sample more convenient daylighting module.Silicon cell is a kind of semiconductor device directly converting optical energy into electric energy, and technology becomes Ripe, the situation of change of drop meniscus can be reflected easily by it.
Vibration power 5 can have multiple way of realization, as long as sacculus can be made to produce the reciprocating motion that frequency is controlled. Implementing form as one, vibration power 5 can be air pump 12, and the piston of air pump 12 is connected with sacculus 4, air pump 12 and electricity Magnet valve 13 connects to be controlled air pump work and work range and frequency by electromagnetic valve.
The computing formula of blood elastic modulus E is:
E=K Δ L
Wherein K is resonance amplitude difference and the elastic modelling quantity conversion coefficient of blood coagulation, by clotting assay process record " amplitude difference-elastic modelling quantity " experiment value is obtained by linear regression analysis;Δ L is the difference of resonance amplitude before and after blood sample blood coagulation Value, reflects the change of blood sample natural frequency before and after blood coagulation.
In Hemostasis examination, indirectly can reflect solidifying by blood sample liquid level motion amplitude in process of setting during detection vibration Blood process.Traditional blood coagulation sample method for oscillating is that the machinery such as vibration table of blood coagulation sample Yu vibration is carried out Hard link, Blood coagulation sample is driven to produce vibration by vibration table.The present invention changes by controlling vibration generation cavity intravascular coagulation sample liquid level pressure Make blood coagulation sample produce vibration, as it is shown in figure 1, blood is loaded from sample introduction tank 1, arrive vibration generation cavity 7 through sample presentation pipe 2.Ball Capsule 4 is flexible material, and balloon membrane can control sacculus by the micro air pump of connection and electromagnetic valve and move back and forth, and this athletic meeting makes to shake Dynamic generation cavity 7 produces pressure or suction, so that blood sample produces motion and enters in capillary tube 3.Owing to blood sample is to capillary tube Not immersional wetting (capillarity), blood sample enters can hover after capillary tube and is that, below capillary tube 3, the surface tension of blood sample makes The meniscus of evagination is formed bottom capillary tube.Control sacculus 4 by air pump 12, electromagnetic valve 13 the most again to move with certain frequency Making vibration generation cavity 7 produce pressure change, this pressure can make the blood sample in capillary tube also with a certain frequency vibration, and finally pass It is delivered on the drop 6 of hovering, thus controls the up-down vibration of blood sample coagulation liquid level.Compared with the mode of vibration of vibration table, this Bright need not designs the vibration damping of complexity, stabilization measure for vibrating device, improves stablizing of coagulation analysis instrument internal structure Property and the precision of optical detection.
The present invention is by pressure in change capillary liquid linker so that the blood sample in capillary tube produces reciprocal fortune Dynamic, thus cause the blood meniscus of capillary exit evagination to produce vibration.The amplitude of blood sample vibration is relevant with coagulation, blood Solidification rate is the highest, and elastic modelling quantity is the biggest, it was observed that the motion amplitude of capillary meniscus the least.As shown in Figure 2 and Figure 3, LED The light beam that light source sends is irradiated to the optical fiber flexible pipe on the left of meniscus on the right side of meniscus, owing to blood is opaque thickness Liquid, the light detected on silicon cell impinges upon the intersection of meniscus and air and has a boundary signal, by detection Meniscus is demarcated the change of signal position on silicon cell, detects the change of capillary meniscus, corresponding calculates blood Liquid elastic modelling quantity, thus trace coagulation process.Compared with turbidimetry, testing result is affected relatively by the bubble in blood sample of the present invention Little;Compared with substrate development process (absorbance method), present invention detection is the blood springform the most relevant to coagulation Amount, is affected less by blood constituent;Compared with suspension method and microsphere method, higher frequency of vibration can be applied to blood sample, therefore originally Invent the temporal resolution that coagulation is traced high.
Last it should be noted that the examples detailed above of the present invention is only for example of the present invention is described, and not It it is the restriction to embodiments of the present invention.Although the present invention has been described in detail by applicant with reference to preferred embodiment, right For those of ordinary skill in the field, can also make on the basis of the above description other multi-forms change and Variation.Here cannot all of embodiment be given exhaustive.Every belong to that technical scheme amplified out aobvious and The change that is clear to or variation are still in the row of protection scope of the present invention.

Claims (4)

1. method based on blood sample vibration detection coagulation, it is characterised in that: blood sample to be detected is added to the capillary of pendency In pipe, to produce the blood sample drop of the band meniscus connected by surface tension at the mouth of pipe of capillary tube lower end;At capillary tube On arrange vibration generation cavity connect with capillary tube, by the capillary tube other end close, then vibration generation cavity on apply replace Thrust with suction so that blood sample drop meniscus produce of reciprocating vibration;Blood sample drop meniscus bottom in detection vibration processes Change in location, and calculate the elastic modelling quantity of blood sample, thus realize coagulation detection.
Method based on blood sample vibration detection coagulation the most according to claim 1, it is characterised in that: this method uses Following detection device detects, and detection device includes vibrational system and detecting system two large divisions;Described capillary tube and shaking Dynamic generation cavity is vibrational system component parts, and outside defeathering tubule and vibration generation cavity, vibrational system also includes sample introduction tank, sample presentation Pipe, sacculus and vibration power, sample introduction tank is connected with capillary tube by sample presentation pipe, to add blood sample and at capillary tube by sample introduction tank The blood sample drop of the band meniscus connected by surface tension is produced at the mouth of pipe of lower end;Sample presentation pipe is provided with check valve so that Blood sample can only be flowed toward capillary tube direction by sample introduction tank and can not flow backwards;Vibration generation cavity is located between check valve and capillary tube Sample presentation pipe on and connect with capillary tube, described sacculus is arranged on vibration generation cavity, and vibration power is by drive mechanism and ball Capsule connects so that sacculus produces reciprocating motion, and then makes blood sample drop meniscus up-down vibration;The size of capillary tube is so that drop Surface tension is applied to the thrust sum of drop more than drop gravity and vibration power, so that drop will not in reciprocating motion Drippage;
Described detecting system includes daylighting module and signal processing module, the light emitting module that light emitting module is relative with light emitting module Be positioned at capillary tube lower end vertical with capillary tube with daylighting module line, the light beam that light emitting module sends is from blood sample drop meniscus Side is irradiated in the daylighting module of meniscus opposite side, and the light detected in daylighting module impinges upon the friendship of meniscus and air A boundary signal is had at boundary, the change of the signal position that demarcated in daylighting module by detection meniscus, and export To signal processing module, thus detect the change of capillary meniscus, corresponding calculating blood elastic modelling quantity, thus trace blood coagulation Process.
Method based on blood sample vibration detection coagulation the most according to claim 2, it is characterised in that: described daylighting mould Block is made up of silicon cell and optical fiber flexible pipe, and optical fiber flexible pipe one end is connected on silicon cell, and the other end is towards light emitting module.
Method based on blood sample vibration detection coagulation the most according to claim 2, it is characterised in that: described vibration is moved Power is air pump, and the piston of air pump is connected with sacculus, and air pump is connected with electromagnetic valve to be controlled air pump operating frequency by electromagnetic valve.
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CN108663502A (en) * 2017-03-28 2018-10-16 王英吉 Full-automatic thrombelastogram instrument
CN111420858A (en) * 2020-04-24 2020-07-17 北京森美希克玛生物科技有限公司 Vibration exciting device
CN111855732A (en) * 2019-04-28 2020-10-30 北京碧澄生物科技有限公司 Device and method for detecting liquid phase change
CN113552025A (en) * 2021-06-23 2021-10-26 安图实验仪器(郑州)有限公司 Method for detecting blood sample resonance frequency and blood sample resonance detector
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