CN102818822B - To utilize in analyzing samples reactance change to measure diagnostic device and the method for prothrombin time and hematocrit ratio (HCT%) - Google Patents
To utilize in analyzing samples reactance change to measure diagnostic device and the method for prothrombin time and hematocrit ratio (HCT%) Download PDFInfo
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Abstract
Open a kind of utilization of the present invention analyzes reactance change to measure diagnostic device and the method for prothrombin time and hematocrit ratio (HCT%).The diagnostic device of described measurement hematocrit ratio and/or prothrombin time, comprising: comparative electrode type sensor device; And test card assembly, comprise one or multipair working electrode; Wherein provide interchange (AC) signal by this sensor device, by reactance analysis with the prothrombin time in measurement and calculation blood testing and hematocrit ratio.
Description
Related application is quoted alternately
Subject application is by being proposed on June 9th, 2010, title is the 61/353rd of " utilize and analyze reactance change to measure diagnostic device and the method for prothrombin time and hematocrit ratio (HCT%) " the, the non-provisional case of No. 137 U.S. Provisional Patent Application cases, the complete content of above-mentioned application case is incorporated herein by reference.
Technical field
The present invention relates to a kind of biochemical detection device, be particularly to a kind of utilization and analyze reactance change to measure diagnostic device and the method for prothrombin time and hematocrit ratio (HCT%).
Background technology
Human body blood coagulation reaction can be divided into external path (extrinsic pathway) and inherent path (intrinsicpathway).As personal injury, first external path can be started with the Coagulation test in control volume, this Coagulation test is except needs blood, needing tissue factor (tissue factor) in addition, is factor Xa (factor Xa) not having factor X (factor X) catalysis of activity.Moreover, factor Xa through the effect of factor Ⅴ a (factor Va), acidic phospholipid and calcium ion factor (prothrombin, factor II) become fibrin ferment (thrombin, factor IIa), and fibrin ferment becomes fibrinogen (fibrinogen) into fibrin again, strengthen the blood platelet being gathered in endothelial cell injury, and fibrin ferment also can promote the effect of factor XIII, the stable fibers albumen other Fibrin molecules Colaesce each.Therefore, the inspection of blood coagulation Enzyme former time (prothrombin time), except being whether extrinsic factor activation coagulation system function normally detects except pointer, can also being used for observing oral anticoagulant therapy, liver function, shortage vitamin K, lacking coagulation factors, the assessment of diffusivity IC disease (DIC) and monitoring.
The method in known detection clotting time is when solidifying with analyzing blood, in this serum, soluble protein changes the coacervation that insolubility protein produces into, and utilize as the optical meanss such as color change, reflection, refraction, cold light and fluorescence detect, but this analytical approach needs a large amount of blood samples and highly purified reagent and expends the longer time, as United States Patent (USP) the 5th, shown in 418, No. 141.But, the detection time required for these detection modes compared with long, consumptive material is many, real be inconvenient.
Separately there is known electric chemical detection method, United States Patent (USP) the 3rd, 699, No. 437, it is for observing impedance from initial to the rate of descent of the comparison of minimum point, using its result of calculation as the foundation judging blood coagulation, for using impedance (impedance) or resistance (resistance) signal as blood coagulation measurement mechanism.And after which, also have United States Patent (USP) the 6th, 060, No. 323, the 6th, 338, No. 821, the 6th, 066, No. 504, the 6th, 673, No. 622, and the 6th, 046, No. 051 etc., openly be designed to unitary electrode or plurality of electrodes according to measurement demand, utilize the difference of viscosity before and after blood clotting, the method for the impedance variation caused is to measure the technology of blood sample blood coagulation.But this technology can cause the error of testing because the electrolyte concentration of hematocrit when between individuality in blood is different.Moreover, United States Patent (USP) the 7th, 005, No. 857 patents separately disclose a kind of Hemostasis examination device comprising automatic blood sampling, and this testing mechanism is that the change of measurement two interelectrode capacitance (capacitance) or impedance (impedance) decides the clotting time.Therefore, these technology improve the simplicity of detection greatly, but cannot reach the precision that optical means detects.
In view of this, the measurement prothrombin time (PT) that reality is necessary to provide can detect fast, easy to use and accuracy is high and the biology sensor of hematocrit ratio (HCT%).
Summary of the invention
In view of this, one of the present invention object is to provide one to utilize reactance (reactance, X) to carry out measuring method to blood.Wherein this reactance is analyzed and can be provided blood properties analysis more accurately, and effectively reduces test error and improve the accuracy measured.
Another object of the present invention is to provide a kind of detection system measuring prothrombin time and HCT% with reactance analytic approach, this system comprises sensor and uses test pieces, mean this test piece comprise a pair or plural number to noble metal electrode, be arranged at respectively on same plane or on non-same plane, system utilizes sensor to provide an alternating current (Alternating current, AC), measure and computing prothrombin time and HCT% with reactance analytic approach.
Be to provide a kind of test card assembly increasing the contact area of blood and reaction reagent in the another object of the present invention.According to some embodiments of the invention, described test card assembly adopts the material of multiple hole, and such as glass-fiber-plate (FR-4) as this test card substrate at least partially.Due to this test card substrate at least partially, be preferably on whole surfaces and there is poriness, such as can have multiple hole, hole and hole in it on the surface, therefore material can better and break up blood equably, increase the contact area of blood and reagent thus, and effectively improve the shortcoming of traditional non-hole material.According to the present invention, can effectively reduce or eliminate because using non-hole material substrate to cause blood cohesion to improve, cause the problem that the surface of contact of blood and reagent is not good.
According to the present invention on the one hand, provide a kind of diagnostic device measuring hematocrit ratio (HCT%) and/or prothrombin time, it comprises comparative electrode type sensor device; And test card assembly, comprise one or multipair working electrode; Wherein provide interchange (AC) signal by this sensor device, by reactance analysis with the prothrombin time in measurement and calculation blood testing and hematocrit ratio.
In an embodiment, this sensor device comprises test card accommodating unit to hold this test card assembly; Temperature maintains unit to control and to maintain this test card accommodating unit to steady temperature; AC signal generation unit provides the alternating current of frequency and voltage to this test card assembly; Signal reception unit, intercepts the response signal from this test card component responds; One processor calculates this response signal and obtains the result of this hematocrit ratio and this prothrombin time; And display unit, show the testing result of this hematocrit ratio and this prothrombin time calculated from this microprocessor.
According to a further aspect of the invention, provide a kind of method measuring hematocrit ratio (HCT%) and prothrombin time, it comprises provides test card assembly to test card accommodating unit; Control and the temperature maintaining this test card accommodating unit to steady temperature; There is provided sample to be detected to this test card assembly; There is provided the alternating current of characteristic frequency and voltage to this test card assembly by AC signal generation unit; Receive response signal by this test card assembly, and calculate this response signal by microprocessor and obtain this hematocrit ratio and this prothrombin time; And provide testing result to show to display unit.
Accompanying drawing explanation
1st figure shows the block schematic diagram of the diagnostic device of measurement hematocrit ratio (HCT) according to some embodiments of the invention and/or prothrombin time.
2nd figure shows the exploded perspective view of the blood testing card assembly according to one of the present invention embodiment, and wherein dotted line represents the relative position between each component.
3A and 3B figure side by side display utilizes electron microscope observation test card assembly without the microstructure photo of hole and tool hole substrate.
4th figure system shows the process flow diagram according to the measurement hematocrit ratio (HCT%) of the embodiment of the present invention and the diagnostic method of prothrombin time.
5th figure shows the experimental data figure of impedance variation to clotting time (second), and it represents with the slope variation of general impedance measurement measurement when whole blood sample is solidified.
6th figure shows the experimental data figure of reactance change to clotting time (second), and it represents with the slope variation of reactance measurement method measurement when whole blood sample is solidified.
7th and 8 figure show experimental data figure, its represent respectively PT to the calibration curve (the 7th figure) of impedance rate of change and represent PT to the calibration curve (the 8th figure) of reactance change rate.
9th and 10 figure show an example, by LCR ammeter every 0.5 second measurement impedance value and reactance value in 60 seconds.
11st and 12 figure show experimental paradigm, its represent respectively PT to the calibration curve of impedance rate of change (impedancechange rate) and represent PT to the calibration curve of reactance change rate (reactance change rate).
13rd and 14 figure show experimental data figure, its represent respectively the PT of correction to real number PT by impedance measurement and represent correct PT to real number PT by reactance measurement.
15A and 15B figure shows experimental data figure, and it is illustrated respectively on the poriness substrate of test card and imporosity substrate and carries out coagulation analysis.
16A ~ 16C figure shows experimental data figure, and it represents respectively and carries out coagulation analysis according to the embodiment of the present invention at different frequencies by reactance measurement method.
Primary clustering symbol description
100 diagnostic devices
110 test card assemblies
120 sensor devices
122 test card accommodating unit
124 AC signal generation unit
126 phasing degree computing units
128 signal reception unit
130 microprocessors
132 temperature sensors
134 temperature maintain unit
136 display units
210 insulated substrates
220 electrode systems
222 sample areas
224 conversion zones
225 test electrodes
226 working electrodes
228 reference electrodes
230 separate layers
232 spacers
236 passages
240 top covers
242 introducing ports
244 vent ports
S410-S480 measures the step of hematocrit ratio and prothrombin time
For making the present invention become apparent, special embodiment below, and coordinate institute's accompanying drawings, be described in detail below:
Embodiment
To describe in detail with multiple embodiment below and along with the example of graphic explanation, as the reference frame of the present invention.In graphic or instructions describe, similar or identical part all uses identical figure number.And in the drawings, the shape of embodiment or thickness can expand, and indicate with clear or convenient.Moreover, in graphic each assembly part to describe explanation respectively, the assembly not illustrating or describe will be it should be noted that in figure, for having the form usually known known to the knowledgeable in art.Moreover, when description one deck be positioned at another layer or a substrate it " on ", can represent and be located immediately at another layer or substrate, or can indicate that middle layer is present in therebetween.
Enforcement examples more of the present invention not illustrate in more detail along with the application is graphic.It should be noted, feature shown in graphic is not with specific scale.Known component, material and process technique can be selected to omit to avoid optionally fuzzy embodiments of the invention.Component, material and process technique described in those embodiments are only the describing mode disclosing the present invention's use, and it is also not used to limit the present invention.
In view of above-mentioned known technology problem, following examples provide one to utilize reactance analysis to measure the system of prothrombin time and hematocrit ratio (hematocrit, HCT%), are also commonly referred to as reactance measurement module.More particularly, detection system can be used to improve corpse or other object for laboratory examination and chemical testing placing characteristic and measurement precision.Utilize reactance to compare the analysis of detection for blood clotting measurement characteristics or hematocrit, be more preferably applied to the quantitative test in clotting time.Below, hematocrit is than the number percent of general reference Packed Red Blood Cells in the volume of whole blood.
One of the present invention embodiment provides a kind of comparative electrode type sensor device, and it has test card and comprises one or more pairs of working electrodes.The substrate of described test card can be made up of porous material or non-porous base material.Described working electrode can be made up of precious metal, and it is including but not limited to gold (Au), silver (Ag), palladium (Pd), platinum (Pt), the alloy of above-mentioned metal and the combination in any of above-mentioned metal.In the one side of the present invention, with alternating current module or to exchange and direct current interactive module, a test signal is provided to make it have hunting of frequency to this blood testing card, this frequency range is about 0.1KHz to about 50KHz, and voltage supplied is to carry out reactance measurement, this voltage range can between about 0.05V to about 5V.As relevant with measured value in this embodiment system, described " about " to mean in this area that tool knows that the knowledgeable implements to measure and careful operation measuring equipment usually, use this measuring equipment reach measurement object and measuring accuracy and measurement magnitude variations that expectability reaches.
In a preferred aspect, when the reaction between enzyme and blood causes blood clotting phenomenon, by sensor device receive and the reaction signal processed, in Main Basis coagulation process, time length causes the difference of slope to carry out reactance analysis.In an embodiment, described electrode can be gold electrode.In this specific embodiment, an alternating current module is adopted to carry out reactance measurement according to the vibration concussion test signal responded from blood testing card, wherein when the reaction of enzyme and blood causes blood clotting phenomenon, by sensor device receive and the reaction signal processed, in Main Basis coagulation process, time length causes the difference of slope to carry out reactance analysis.
The principle of carrying out reactance measurement is according to some embodiments of the invention as follows.In alternating circuit (ACcurcuit), impedance is that resistance (R) adds that the summation in phasing degree (θ) is taken advantage of in reactance (X), shown in following formula:
Wherein reactance (X) is the imaginary part of complex impedance (Z), for representing that inductance (L) and electric capacity (C) are to the inhibition of electric current, and the real part that resistance (R) is complex impedance.Known to those skilled in the art, reactance along with alternating circuit frequency change, along with capacitance variations and/or along with inductance change and change.When the reactance change in alternating circuit, the current waveforms of alternating circuit and the phase place of voltage waveforms also change thereupon.Described impedance is defined as:
Z=R+jX, and | Z|=(R
2+ Z
2)
1/2(1)
Wherein Z is impedance (impedance), R be resistance (resistance), j is phasing degree, and X is reactance (reactance); And
X=X
c+ X
l, X
l=2 π fL, and X
c=1/2 π fC (2)
Wherein X
cfor capacitive reactance (capacitor reactance), be X
linduction reactance (inductor reactance) is circular constant, and f is frequency, and L is inductance, and C is electric capacity.
In an embodiment aspect, when operating, the AC signal generation unit of described detection system provides interchange (AC) to test signal.When blood sample is between electrode, induced charge in the electric field can be stressed and mobile form electric capacity.When blood sample solidifies, between working electrode, constitute medium, thus hinder electric charge and move and make charge accumulation on conductor.The electric charge of this accumulation can cause capacitive reactance to produce.In a preferred aspect, the frequency (f) that the AC signal generation unit of detection system provides is definite value, therefore inductance (L) and induction reactance (XL) are also definite value, the variable quantity of therefore capacitive reactance (XC) equals the variable quantity of reactance, as shown by the following formula.
X
C2-X
C1＝X
2-X
1(3)
Wherein X
c2-X
c1for capacitive reactance (X
c) variable quantity, and X
2-X
1for the variable quantity of reactance.
By the variable quantity of reactance under measuring unit's time, when can learn blood clotting its relatively capacitive reactance under the unit interval variable quantity and under the unit interval variable quantity of electric capacity.By the assistance of reactance measurement module of the present invention, calculate the length that can analyze blood coagulation Enzyme former time (blood coagulation time) via slope.
1st figure shows the block schematic diagram of the diagnostic device of measurement hematocrit ratio (HCT) according to some embodiments of the invention and/or prothrombin time.As shown in Figure 1, a kind of diagnostic device 100 measuring hematocrit ratio (HCT) and/or prothrombin time comprises comparative electrode type sensor device 120 and has the test card assembly 110 of one or multipair working electrode, wherein provide interchange (AC) signal by this sensor device, by reactance analysis with the prothrombin time in measurement and calculation blood testing and hematocrit ratio.This sensor device 120 comprises test card accommodating unit 122 to hold this test card assembly 110, temperature maintains unit 134 to control and to maintain this test card accommodating unit to steady temperature, AC signal generation unit 124 provides the alternating current of frequency and voltage to this test card assembly 110, signal reception unit 128 intercepts the response signal from this test card component responds, microprocessor 130 calculates this response signal and obtains the result of this hematocrit ratio and this prothrombin time, and display unit 136 shows the testing result of this hematocrit ratio and/or this prothrombin time calculated from this microprocessor 130.
The display of 2nd figure system is according to the exploded perspective view of the blood testing card assembly of the embodiment of the present invention, and wherein dotted line represents the relative position between each component.Described blood testing card assembly comprises insulated substrate 210, electrode system 220, separation and responding layer 230 and top cover 240.Insulated substrate 210 is for being electrically insulated, and its material can including but not limited to the substrate be made up of porous material.In an embodiment, the substrate of test card assembly comprises multiple hole, and its diameter range is on the whole between about 0.1 μm to about 10 μm, about 0.01 μm to about 100 μm, about 0.1 μm to about 50 μm, about 0.1 μm to about 20 μm, about 0.1 μm to about 5 μm, or about 5 μm to about 10 μm.Electrode system 220 can be made up of any conductive material, and it is including but not limited to the combination in any of carbon, Jin-Yin, copper, carbon silver, palladium, platinum, nickel, other similar material or above-mentioned material.Described electrode system 220 can comprise one or more pairs of noble metal electrodes, establishes respectively as in identical or different plane.Such as, one group of test electrode 225 comprises pair of electrodes 226,228.According to principle of the present invention, above-mentioned structure does not limit and test electrode 225 is arranged with specific configuration, or limits the number of electrode.Also extra electrode can be provided according to different application demands.This electrode system is further electrically connected to the electrode system (not illustrating) of measurement mechanism.
Illustrated separate layer 230 comprises spacer 232, if as on electrode system 220.Described separate layer 230 can also comprise conversion zone 224, the reaction reagent (not illustrating) of exposed portion and sample areas 222.Channel 236 can be communicated with sample areas 222 and conversion zone 224.Described conversion zone 224 is preferably dimensioned to be the electrode 226 and 228 that can be enough to exposed portion.In this embodiment, conversion zone 224 is the regions measuring prothrombin time, and sample areas 222 measures the region of hematocrit ratio.
Cap layer 240 establishes the top as separate layer 230.In an embodiment, this cap layer 240 can comprise introducing port 242 and vent port 244, and it is connected to sample areas 222 and conversion zone 224 respectively.The size system of sample space determined by the thickness of separate layer 230.
3A and 3B figure respectively display utilizes electron microscope observation test card assembly without the microstructure photo of hole and tool hole substrate.In 3B figure, show hole hole dia magnitude range can between about 0.1 μm to about 10 μm, and mean diameter is about 3.39m; And the situation that is evenly distributed of hole is about 5.04 × 106/cm2 hole.
4th figure system shows the process flow diagram according to the measurement hematocrit ratio (HCT) of the embodiment of the present invention and the diagnostic method of prothrombin time.The method of described measurement hematocrit ratio (HCT) and prothrombin time, comprises and provides test card assembly to test card accommodating unit (step S410); Control and the temperature maintaining this test card accommodating unit to steady temperature (step S420); There is provided sample to be detected to this test card assembly (step S430); There is provided the alternating current of characteristic frequency and voltage to this test card assembly (step S440) by AC signal generation unit; Response signal is drawn from this this AC signal of test card component responds, relatively this response signal and this AC signal, calculate the phase angle variations (phase angle) of this AC signal, and calculate electric capacity and this hematocrit ratio (step S450) by microprocessor; Change this electric capacity with algorithm and be modified to this prothrombin time (step S460) with reference to this hematocrit ratio; This prothrombin time is revised by an AC signal generation unit (step S470) with the regular ratio in the world (internationalnormalized ratio, INR); And provide testing result to display unit display (step S480).
According to some embodiments of the invention, described response signal is digitized and changes (discrete fourier transformation, DFT) with discrete Fourier.Therefore, the computing method of real part and imaginary part are expressed as follows respectively.
Wherein X (k) the Fourier value that is digital signal, the original value that x (n) is digital signal, n is the current point of digital signal, and N is the sum of digital signal.Moreover phasing degree can draw according to following formulae discovery real part and imaginary part:
Phasing degree=tan-1 (Im/Re) (3)
Wherein Im is imaginary value (such as reactance) and Re is real number value (such as resistance).As shown in above formula (3), in sample, the change along with reactance offsets by phasing degree.
In some embodiment, in above step S450 describes, compare the step obtaining response signal and original AC signal from pattern detection and comprise: by the amount measuring response signal and applying voltage calculating reactance; The phase angle variations calculating impressed voltage wave mode and measure between wave mode; By described phase angle variations calculating reactance.It is to be understood that because alternating current has fixing frequency, the change as previous described phasing degree is attributable to the change of electric capacity in sample.Because the change of electric capacity causes reactance change in the sample, HCT and prothrombin time (PT) can be calculated by reactance change, be further discussed below.
From the measured reactance obtained, HCT can be calculated by interpolation method (interpolation).The concrete example calculating hematocrit ratio is below described.Tradition uses the method for impedance computation hematocrit ratio to be also described as comparative example.
5th and 6 figure show experimental data figure, and it represents that impedance and reactance are along with higher hematocrit is than change respectively.As shown in the data plot of the 6th figure, in this particular example, the reactance locating different HCT (29.3 and 47%) at the 11st second is respectively 620.29,625.17 and 676.59 nurses difficult to understand (ohm).Then, the relation (the 7th figure) of HCT and impedance or the relation (the 8th figure) of HCT and reactance is calculated.As shown in Figure 5, in this particular example, the optimum impedance sample time of HCT was about more than 20 seconds, and impedance is to the calibration curve coincidence formula y=90.253x+2347.7 of HCT.Moreover as shown in Figure 6, the optimum impedance sample time of HCT was about more than 11 seconds, and reactance is to the calibration curve coincidence formula y=3.1304x+529.68 of HCT.It should be understood that x represents HCT and y represents impedance or reactance.
9th and 10 figure show an example, by LCR ammeter every 0.5 second measurement impedance value and reactance value in 60 seconds.In an example, the blood whole from experimental subjects collection and various sample system are by adding the anticoagulant (heparin (heparin)) of different amount in the whole blood gathered.Such as, the heparin concentration for the modulation clotting time (PT) is about between every milliliter of 1U to 30U.Then, described in LCR ammeter (HiokiModel No.3532-50) analysis, there is the blood sample of different PT to record impedance or reactance.
11st and 12 figure show experimental paradigm, its represent respectively PT to the calibration curve of impedance rate of change (impedancechange rate) and represent PT to the calibration curve of reactance change rate (reactance change rate).In this particular example, impedance or reactance change rate can calculate in U.S. by LCR ammeter for 10 seconds.Such as, rate of change between 30 to 40 seconds can be tried to achieve by following formula: Impedance changerate 30 to 40=(Z40-Z30)/(Time40-Time30), wherein Z is impedance, and Reactancechange rate 30 to 40=(X40-X30)/(Time40-Time30), wherein X is reactance.Calculation procedure is repeatedly calculate the impedance and reactance change rate with different PT blood sample, and determine thus PT to the calibration curve (the 7th figure) of impedance rate of change and represent PT to the calibration curve (the 8th figure) of reactance change rate.Described PT is to the calibration curve coincidence formula y=-0.1849x+4.562 of impedance rate of change, and PT is to the calibration curve coincidence formula y=-0.0256x+0.3604 of reactance change rate.It should be understood that x represents real number PT and y represents impedance or reactance change rate.
As shown in the 11st and 12 figure, the diagnostic result (the 12nd figure) of reactance measurement method manifests more excellent standard deviation (SD value) compared to the diagnostic result (the 11st figure) of Conventional impedance mensuration.More particularly, according to the present invention adopt the advantage of reactance measurement method to be significantly to reduce the standard deviation of reactance measurement method, and be about 0.9986 in this example.In view of this, adopt the impedance measurement that reactance measurement method is more traditional more accurate, even and if extend the process of blood clotting, the skew of slope also be acceptable, therefore can easier logarithm value correction.
On the other hand, in this particular example, the linear regression value (R2) of PT to the calibration curve of impedance rate of change is about 0.939, as shown in Figure 11.In view of this, impedance measurement more may cause coarse measurement result.
In above-mentioned example, impedance and the reactance of a blood sample can be measured by LCR ammeter, and difference computing impedance rate of change and reactance change rate.More particularly, HCT system obtains according to following formulae discovery by use HCT calibration curve: HCT=(impedance-2347.7)/90.253 or HCT=(reactance-529.68)/3.1304.Then, real number PT is calculated by PT calibration curve.Different HCT may correspond to different PT calibration curves.In this particular example, PT system obtains according to following formulae discovery by use PT calibration curve: PT=(impedance change rate-4.562)/-0.1849 or PT=(reactance change reate-0.3604)/-0.0256.
13rd and 14 figure show experimental data figure, its represent respectively the PT of correction to real number PT by impedance measurement and represent correct PT to real number PT by reactance measurement.By the PT value calculated by calibration curve with measured compared with the real number PT value that obtains by automatic blood Solidification Analysis instrument (Sysmex CA-500series).
The increase of described HCT or minimizing can affect the value of prothrombin time (PT) and impedance or reactance change rate.More particularly, higher HCT can cause the increase of impedance or reactance change rate value.Therefore, the process of measurement in PT described in some embodiment can comprise HCT correction step.Therefore, device according to some embodiments of the invention comprises internal storage, in order to store the interpolate value between described HCT and impedance variation.
Know on the one hand in the present invention, the PT value calculated by above example can be revised by the regular ratio in the world (international normalized ratio, INR), as shown by the following formula:
Wherein INR is international regular ratio, and PT is prothrombin time, the international sensitivity indices (international sensitivity index) of JiISIWei.
15A and 15B figure shows experimental data figure, and it is illustrated respectively on the poriness substrate of test card and imporosity substrate and carries out coagulation analysis.As shown in FIG., adopt poriness substrate to carry out analysis and can obtain more excellent result.
16A ~ 16C figure shows experimental data figure, and it represents respectively and carries out coagulation analysis according to the embodiment of the present invention at different frequencies by reactance measurement method.Measuring between 15 seconds to 50 seconds clotting time is respectively blood sample, and provides the survey frequency of 0.1kHz, 10kHz and 50kHz, and it is 0.9636,0.9923 and 0.9828 respectively that the detection of gained reads value with the R2 value of the calculating of regretional analysis.In this example, shown compared to frequency 0.1kHz by regretional analysis, use the survey frequency of 10kHz and 50kHz can obtain higher accuracy rate.
Though the present invention is with various embodiment openly as above, so itself and be not used to limit scope of the present invention, have in any art and usually know the knowledgeable, without departing from the spirit and scope of the invention, when doing a little change and retouching.The protection domain of the present invention when depending on after the attached claim person of defining be as the criterion.
Claims (13)
1. measure a diagnostic device for hematocrit ratio and/or prothrombin time, comprising:
Comparative electrode type sensor device; With
Test card assembly, comprises one or multipair working electrode;
Wherein provide interchange (AC) signal by this sensor device, by reactance analysis with the prothrombin time in measurement and calculation blood testing and/or hematocrit ratio (hematocrit),
Wherein this reactance is analyzed and is comprised:
Draw response signal from this this AC signal of test card component responds, compare this response signal and this AC signal, calculate the phase angle variations of this AC signal, and calculate electric capacity and this hematocrit ratio,
Wherein this reactance is analyzed and is also comprised:
Calculate electric capacity; And
Change this electric capacity with algorithm and be modified to this prothrombin time with reference to this hematocrit ratio.
2. diagnostic device as claimed in claim 1, wherein this reactance is analyzed also to comprise and is revised this prothrombin time with the regular ratio in the world (international normalized ratio, INR).
3. diagnostic device as claimed in claim 1, wherein this test card assembly comprises one or multipair noble metal electrode, is located at respectively in same level or Different Plane.
4. diagnostic device as claimed in claim 1, wherein this test card assembly comprises the substrate be made up of porosint.
5. diagnostic device as claimed in claim 4, wherein the pertusate diameter range of this substrate tool of this test card assembly is between 0.1 micron to 10 microns.
6. diagnostic device as claimed in claim 1, wherein this sensor device comprises:
Test card accommodating unit is to hold this test card assembly;
Temperature maintains unit to control and to maintain this test card accommodating unit to steady temperature;
AC signal generation unit provides the alternating current of frequency and voltage to this test card assembly;
Signal reception unit, intercepts the response signal from this test card component responds;
Microprocessor calculates this response signal and obtains the result of this hematocrit ratio and this prothrombin time; And
Display unit, shows the testing result of this hematocrit ratio and this prothrombin time calculated from this microprocessor.
7. diagnostic device as claimed in claim 6, wherein this response signal compares with this AC signal by this microprocessor, calculates the phase angle variations of this AC signal, and calculates electric capacity and this hematocrit ratio.
8. diagnostic device as claimed in claim 7, wherein this microprocessor changes this electric capacity with algorithm further, is modified to this prothrombin time with reference to this hematocrit ratio, and with regular this prothrombin time of ratio correction in the world.
9. measure a method for hematocrit ratio and/or prothrombin time, comprising:
There is provided test card assembly to test card accommodating unit;
Control and the temperature maintaining this test card accommodating unit to steady temperature;
There is provided sample to be detected to this test card assembly;
There is provided the alternating current of characteristic frequency and voltage to this test card assembly by AC signal generation unit;
Receive response signal by this test card assembly, and calculate this response signal by microprocessor and obtain this hematocrit ratio and/or this prothrombin time; And
Testing result is provided to show to display unit,
Wherein said by this test card assembly reception response signal, and calculate by microprocessor the step that this response signal obtains this hematocrit ratio and/or this prothrombin time, comprising:
Draw response signal from this this AC signal of test card component responds, compare this response signal and this AC signal, calculate the phase angle variations of this AC signal, and calculate electric capacity and this hematocrit ratio,
Wherein said by this test card assembly reception response signal, and calculate by microprocessor the step that this response signal obtains this hematocrit ratio and/or this prothrombin time, also comprise:
Calculate electric capacity; And
Change this electric capacity with algorithm and be modified to this prothrombin time with reference to this hematocrit ratio.
10. the method for measurement hematocrit ratio as claimed in claim 9 and/or prothrombin time, wherein saidly receives response signal by this test card assembly, and calculates by microprocessor the step that this response signal obtains this prothrombin time, also comprises:
This prothrombin time is revised with the regular ratio in the world (international normalized ratio, INR).
The method of 11. measurement hematocrit ratios as claimed in claim 9 and/or prothrombin time, wherein this test card assembly comprises one or multipair noble metal electrode, is located at respectively in same level or Different Plane.
The method of 12. measurement hematocrit ratios as claimed in claim 9 and/or prothrombin time, wherein this test card assembly comprises the substrate be made up of porosint.
The method of 13. measurement hematocrit ratios as claimed in claim 9 and/or prothrombin time, wherein the pertusate diameter range of substrate tool of this test card assembly is between 0.1 micron to 10 microns.
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| US13/156,693 | 2011-06-09 | ||
| US13/156,693 US8828322B2 (en) | 2010-06-09 | 2011-06-09 | Device and method for measuring prothrombin time and hematocrit by analyzing change in reactance in a sample |
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| TWI504889B (en) * | 2013-11-19 | 2015-10-21 | Apex Biotechnology Corp | Hematocrit measurement system and measurement method using the same |
| CA2947000C (en) * | 2014-05-23 | 2018-12-11 | Nova Biomedical Corporation | Hemolysis detection method and system |
| JP6589613B2 (en) | 2015-12-10 | 2019-10-16 | いすゞ自動車株式会社 | Reactance measuring device |
| CN107144697A (en) * | 2017-05-15 | 2017-09-08 | 银翮蔚蓝健康产业研究院（南京）有限公司 | Clotting time monitoring device and method |
| CN107036738A (en) * | 2017-06-01 | 2017-08-11 | 黄昱 | A kind of blood platelet Micro-force sensor of the elastic film variable capacitance based on nanometer technique |
| CN108318560B (en) * | 2018-01-19 | 2021-06-04 | 国力天（深圳）科技有限公司 | Portable microelectrode method blood detector and detection method thereof |
| CN110954687B (en) * | 2019-11-18 | 2022-06-07 | 深圳微点生物技术股份有限公司 | Method and device for detecting blood coagulation |
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| CN112034009A (en) * | 2020-08-21 | 2020-12-04 | 深圳市康立生物医疗有限公司 | Sodium ion corrected erythrocyte volume test system and test method |
| CN113063833B (en) * | 2021-03-12 | 2023-09-08 | 三诺生物传感股份有限公司 | Measurement method of hematocrit |
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