CN115876863B - Blood detection system and method - Google Patents
Blood detection system and methodInfo
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Abstract
本发明公开了一种血液检测系统和方法。其中，该系统包括：检测仪器和检测条；所述检测仪器包括温度传感器、微处理器、检测条连接口以及显示窗；所述检测条包括第三层板、电极层、试剂层、第二层板以及第一层板，所述试剂层的制作原料含有水溶性的金属盐。本发明基于电化学检测技术，利用盐类溶解度与检测条获得的电信号之间的相关性，可以检测较宽的温度范围下血液样本的粘度，检测准确性高。
The present invention discloses a blood testing system and method. The system comprises: a testing instrument and a testing strip; the testing instrument comprises a temperature sensor, a microprocessor, a testing strip connection port and a display window; the testing strip comprises a third layer, an electrode layer, a reagent layer, a second layer and a first layer, and the raw material for making the reagent layer contains a water-soluble metal salt. The present invention is based on electrochemical detection technology and utilizes the correlation between the solubility of salts and the electrical signal obtained by the testing strip to detect the viscosity of blood samples in a wide temperature range with high detection accuracy.
Description
Technical Field
The embodiment of the invention relates to the technical field of blood physicochemical property detection, in particular to the technical field of blood electrochemical detection.
Background
Blood consists of plasma and blood cells suspended therein. Its physicochemical properties include colour and specific gravity, viscosity, osmotic pressure and acid-base level. Viscosity, which is one of the physicochemical properties of blood, is an important index reflecting the smoothness of blood flow in blood vessels. When blood runs in a blood vessel, resistance is generated due to friction between molecules or particles of various substances in the blood, so that the blood has certain viscosity. Blood viscosity is mainly dependent on the number of erythrocytes and the content of plasma proteins, and in addition, the shape of blood cells and their distribution characteristics in the blood stream, surface structure and internal state, deformability, interactions between them, etc. The fluidity of a fluid is generally reflected and measured by viscosity, and therefore the most important sign of the fluidity and viscosity of blood is the viscosity of blood. Human whole blood viscosity is primarily affected by the percentage of red blood cells in whole blood volume, and is also dependent on factors such as temperature, state of Red Blood Cells (RBC) (e.g., erythrocyte deformability and erythrocyte aggregation), the content of hemoglobin and other proteins, and plasma viscosity. And because whole blood is a non-newtonian fluid, its viscosity is affected by the shear rate of the blood. At room temperature, the apparent viscosity of human whole blood at a high shear rate (200/s) is generally between 4 and 6 mPa.s. Long-term dynamic monitoring of blood viscosity is of great importance for the monitoring and prevention of cardiovascular diseases, since the onset of cardiovascular diseases and the long-term accumulation of pathological features are associated, in the course of which a change in the state of blood viscosity is often accompanied. The factors such as increased number of red blood cells and decreased deformability of red blood cells, increased blood viscosity caused by increased plasma protein and blood fat, etc. may induce the increase of blood flow resistance, slow down blood flow, decrease of blood supply to viscera, and cause coronary heart disease, myocardial infarction, cerebral thrombosis, etc. Anemia and some hemorrhagic diseases (such as digestive tract bleeding, advanced tumors, functional uterine bleeding, etc.) are accompanied by a decrease in blood viscosity.
Currently, methods for measuring the viscosity of a liquid mainly include a capillary viscosimetry method, a rotational viscosimetry method, a micro-flow-pressure sensing measurement method, and the like, wherein the capillary viscosimetry method can only be used for measuring the viscosity of blood, and a current apparatus for measuring the viscosity of blood in a hospital is mainly a blood rheometer based on the rotational viscosimetry method or the micro-flow-pressure sensing measurement method. The instrument has various and accurate test results, but the instrument is expensive, the test period is long, hundreds of microliters of blood is required for each test, and real-time and rapid viscosity test is difficult to realize. The principle of the noninvasive blood viscosity detection system proposed by the patent CN 110897617a is based on the linear relation between the finger tip volume pulse wave waveform coefficient and the blood viscosity, and the accuracy and reliability of the test result are not as good as those of the invasive method. Electrochemical biosensors are now widely used to determine the concentration of various analytes in blood samples.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention provides a blood detection system and a blood detection method, which can rapidly and accurately measure the viscosity of blood with a small blood volume in a wider use temperature range based on an electrochemical method.
In a first aspect, the present invention also provides a blood test system comprising a test instrument and a test strip;
the detecting instrument comprises a temperature sensor, a microprocessor, a detecting strip connector and a display window, wherein the detecting strip comprises a third layer plate, an electrode layer, a reagent layer, a second layer plate and a first layer plate.
Optionally, the raw materials for preparing the reagent layer contain water-soluble metal salts.
Optionally, the preparation raw materials of the reagent layer further comprise a surfactant, a water-soluble polymer and deionized water.
Optionally, the water-soluble metal salt includes at least one of sodium chloride, potassium chloride, sodium sulfate, potassium carbonate, sodium nitrate, potassium nitrate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, and potassium dihydrogen phosphate.
Optionally, the preparation raw materials of the reagent layer comprise 10-30% by mass of water-soluble metal salt, 0.1-4% by mass of surfactant and 2-15% by mass of water-soluble polymer.
Optionally, the electrode layer is located above the third layer board, the reagent layer is located above the electrode layer, the second layer board material has an adhesive force for adhering the third layer board to the first layer board, and a suction groove is formed in the second layer board for accommodating a blood sample.
In a second aspect, the present invention further provides a blood testing method, implemented by the blood testing system according to any one of the above embodiments, comprising:
S110, inserting a detection strip into a detection instrument, starting the detection instrument, and applying a first direct-current voltage to a first electrode and a second electrode of the detection strip;
S120, introducing a blood sample into a suction groove of the detection strip, connecting the first electrode with the second electrode, identifying a first current signal through a detection instrument, and recording the environment temperature at the moment through a temperature sensor of the detection instrument;
s130, applying a second alternating voltage to the first electrode after the detection instrument recognizes the first current signal, and detecting a second electric signal of the blood sample after a certain time by the detection instrument;
s140, processing the second electric signal through a microprocessor of the detecting instrument to obtain a processed second electric signal;
And S150, bringing the processed second electric signal and the environment temperature into a preset calculation formula of the viscosity of the blood sample in the microprocessor, and calculating to obtain the viscosity value of the blood sample.
Optionally, the calculation formula of the viscosity of the blood sample is:
η=(K1*T+B1)x+(K2*T+B2);
Wherein η represents a blood viscosity value, T represents an ambient temperature, x represents a processed second electrical signal, and K 1、B1、K2、B2 are constant coefficients.
Optionally, the value range of K 1 is 0.5-3.0, the value range of B 1 is 2.0-6.0, the value range of K 2 is-1.0-0, and the value range of B 2 is 0-2.0.
Optionally, the value range of the first direct current voltage is 0.1-0.8 v.
Optionally, the second ac voltage is a low-frequency ac voltage or a high-frequency ac voltage, a peak value range of the second ac voltage is 0.05-1 v, a frequency range of the second ac voltage is 10-1000 hz, and a time range of applying the second ac voltage is 1-10 seconds.
The invention calculates the viscosity of the blood sample based on the electrochemical detection technology by utilizing the correlation between the salt solubility and the electric signal obtained by the detection strip, can detect the viscosity of the blood sample in a wider temperature range, and has high detection accuracy. The invention has the advantages of less blood sample amount, simple and quick operation process, short detection time of only a few seconds to tens of seconds, very quick detection, capability of overcoming the problems of poor real-time performance, overlarge blood sampling amount and the like of the traditional blood viscosity detection and remarkably improving the detection efficiency, and simple and reasonable and small structural design, portability, economic manufacturing cost and contribution to mass production and manufacturing.
Drawings
FIG. 1 is a schematic diagram showing the structure of a test strip according to embodiment 1 of the present invention;
FIG. 2 is a schematic circuit diagram of a detecting instrument according to an embodiment 1 of the present invention;
FIG. 3 is a flow chart of the blood test method in example 1 of the present invention;
FIG. 4 is a graph showing the change of the electrical signal value (test AD value) obtained by testing a solution sample by the blood test system according to example 2 of the present invention with time;
FIG. 5 is a graph showing the relationship between the processed value of the electrical signal value obtained by testing the solution sample by the blood test system in example 2 and the mass fraction of sodium chloride;
FIG. 6 is a graph showing the relationship between the processed value of the electrical signal value obtained by testing the solution sample by the blood test system in example 2 and polyethylene glycol-6000 mass fraction;
FIG. 7 is a graph showing the relationship between the processed value of the electrical signal value obtained by testing the solution sample by the blood test system in example 2 of the present invention and the solution viscosity;
FIG. 8 is a graph showing the comparison of the results of a blood test with a blood testing system and a blood rheometer for 50 blood samples of different sources (including human fingertip blood sample and a modulated human blood sample) according to an embodiment of the present invention;
The device comprises a reference numeral 1, a third layer plate, a 2, an electrode layer, a 201, a first electrode, a 202, a 3, a reagent layer, a 4 second layer plate, a 401, a suction groove, a5, a first layer plate, a 501, an air outlet, a 6, a microprocessor, a 7, a test strip connector, a 8, a temperature sensor and a 9, a display window.
Detailed Description
The invention is described in further detail below with reference to the drawings and examples. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting thereof. It should be further noted that, for convenience of description, only some, but not all of the structures related to the present invention are shown in the drawings.
The technical scheme of the embodiment of the invention is based on an electrochemical detection technology, when the detection strip detects a blood sample, alternating current working voltage is provided for the electrode system, so that an electric signal related to the dynamic performance of the blood sample is obtained, and the electric signal is converted into an Analog-to-Digital Converter (AD) value, namely an AD value. The AD value change in the process of contacting the blood with the electrode is related to the hydration process of the electrode surface, and after a large amount of data analysis, the detection strip surface salt dissolution dynamics in a specific period is found to be related, namely the AD value is directly proportional to the concentration of dissolved sodium chloride on the electrode surface.
Example 1
As shown in fig. 1-2, fig. 1 and fig. 2 are a test strip and a test instrument in a blood test system according to embodiment 1 of the present invention, respectively.
The detection instrument comprises a microprocessor 6, a detection strip connecting port 7, a temperature sensor 8 and a display window 9, wherein the detection strip comprises a third layer plate 1, an electrode layer 2, a reagent layer 3, a second layer plate 4 and a first layer plate 5.
The raw materials for preparing the reagent layer 3 comprise water-soluble metal salts, wherein the water-soluble metal salts are one or a mixture of more of sodium chloride, potassium chloride, sodium sulfate, potassium carbonate, sodium nitrate, potassium nitrate, sodium dihydrogen phosphate, potassium dihydrogen phosphate and potassium dihydrogen phosphate.
Further, the preparation raw materials of the reagent layer further comprise a surfactant, a water-soluble polymer and deionized water, wherein the surfactant can be one or more of Triton X-100, sodium dodecyl sulfate, perfluorooctane sulfonate, sodium stearate, sodium dodecyl alcohol polyoxyethylene ether sulfate, ammonium dodecyl sulfate, dodecylbenzenesulfonic acid, triethanolamine lauryl sulfate and fatty alcohol sodium isethionate, and the water-soluble polymer can be one or more of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), polyethylene acrylate (PEA), polyethylene oxide (PEO), polyacrylamide (PAM), hydrolyzed Polyacrylamide (HPAM), polyvinylpyrrolidone-vinyl acetate (PVP-VA), polyvinylamine, cellulose acetate and polyamide.
Optionally, the raw materials for preparing the reagent layer contain 10-30% of water-soluble metal salt, 0.1-4% of surfactant and 2-15% of water-soluble polymer.
Further, the electrode layer 2 is located above the third layer board 1, and at least comprises a first electrode 201 and a second electrode 202, the reagent layer 3 is located above the electrode layer 2, the material of the second layer board 4 has an adhesive force and is used for adhering the third layer board 1 and the first layer board 5, a suction groove 401 is formed in the second layer board 4 and is used for accommodating a blood sample, preferably, the material of the first layer board 5 and the third layer board 1 can be ceramic, glass and organic polymer materials, preferably, the first layer board 5 and the third layer board 1 can be respectively made of one of polyethylene terephthalate, polyvinyl chloride and polycarbonate, and preferably, the volume of the suction groove 6 is 0.5 microliter to 20 microliter. The transparent confirmation window corresponding to the suction groove 401 is arranged on the first layer plate 5, so that the loading state of the blood sample in the suction groove can be observed conveniently, the air outlet hole 501 is arranged at the tail end of the confirmation window, the suction groove 401 and the air outlet hole 501 are matched, the blood sample can be continuously led into the suction groove, and the blood sample can be enabled to fully contact and react with the reagent layer.
With further reference to fig. 3, fig. 3 is a blood detection method provided in embodiment 1, and the method specifically includes:
S110, inserting the detection strip into a detection instrument, starting the detection instrument, and applying a first direct-current voltage to a first electrode and a second electrode of the detection strip.
S120, introducing a blood sample into a suction groove of the detection strip, connecting the first electrode with the second electrode, identifying a first current signal through a detection instrument, and recording the environment temperature at the moment through a temperature sensor of the detection instrument.
The peak value of the second alternating voltage is preferably 0.1-0.8 v, more preferably 0.2-0.5 v, the frequency of the second alternating voltage is preferably 50-500 hz, and the application time of the second alternating voltage is preferably 2-5 seconds.
S130, applying a second alternating voltage to the first electrode after the detecting instrument recognizes the first current signal, and detecting a second electric signal of the blood sample after a certain time by the detecting instrument.
The second alternating voltage may be a low-frequency or high-frequency alternating voltage, the peak value is 0.05-1V, the frequency is 10-1000 Hz, the application time is 1-10 seconds, and the second electric signal of the blood sample, namely the AD value, is detected.
And S140, processing the second electric signal by a microprocessor of the detecting instrument to obtain a processed second electric signal.
The method for processing the AD value by the microprocessor can adopt the steps of selecting the AD value at a certain moment, selecting the maximum value of a plurality of AD values, selecting the minimum value of a plurality of AD values, selecting the AD value at a plurality of moments and calculating the average value of the AD values or selecting the AD value within a certain period of time and calculating the average value of the AD values, and then performing basic algebraic operation, preferably selecting the AD value within a certain period of time and calculating the average value of the AD value, and then performing linear mapping to a specific interval and then taking the reciprocal to obtain the AD signal processing value x.
And S150, bringing the processed second electric signal and the environment temperature into a preset calculation formula of the viscosity of the blood sample in the microprocessor, and calculating to obtain the viscosity value of the blood sample.
Specifically, the calculation formula of the viscosity of the blood sample is:
η=(K1*T+B1)x+(K2*T+B2);
Wherein η represents a blood viscosity value, T represents an ambient temperature recognized by a temperature sensor, x represents a calculated value of an electric signal recognized by a microprocessor, and K 1、B1、K2、B2 is a constant coefficient.
Optionally, the value range of K 1 is 0.5-3.0, the value range of B 1 is 2.0-6.0, the value range of K 2 is-1.0-0, and the value range of B 2 is 0-2.0.
The viscosity of the blood sample is calculated based on the electrochemical detection technology by utilizing the correlation between the salt solubility and the electric signals obtained by the detection strip, the viscosity of the blood sample in a wider temperature range can be detected, the required blood sample amount is small, the operation process is simple and quick, the detection time is short, the detection accuracy is high, the problems of poor real-time performance, overlarge blood sampling amount and the like in the traditional blood viscosity detection are overcome, the detection efficiency can be obviously improved, in addition, the system has simple structural design, convenient carrying and economic manufacturing cost, and is beneficial to mass production and manufacturing.
Example 2
The blood test system provided in this embodiment includes a test instrument and a test strip. The detection instrument comprises a microprocessor, a detection strip connector, a temperature sensor and a display window, wherein the detection strip comprises a third layer plate, an electrode layer, a reagent layer, a second layer plate and a first layer plate.
In the embodiment, the third layer is made of polyethylene terephthalate serving as a bottom plate of a detection strip, the electrode layer is formed on the third layer and at least comprises a first electrode and a second electrode, the first electrode and the second electrode are made of conductive carbon paste through screen printing, the reagent layer is formed on the first electrode, manufacturing raw materials of the reagent layer comprise water-soluble metal salt sodium chloride, a surfactant Triton X-100, water-soluble polymer polyvinyl alcohol (PVA) and deionized water, wherein the mass fraction of the sodium chloride is 20%, the mass fraction of the Triton X-100 is 1%, the mass fraction of the polyvinyl alcohol (PVA) is 10%, the surfactant Triton X-100 is favorable for uniformly spreading the reagent layer above the electrode layer in the manufacturing process to form uniform thickness, the water-soluble polymer polyvinyl alcohol (PVA) plays a role of a bracket, the second layer is made of double-sided adhesive with the first layer, a suction groove is formed on the second layer, the volume of the suction groove is 0.5 microliter, the material of the first 5 is the polyethylene terephthalate, the suction groove is arranged on the first layer, the suction groove is corresponding to the suction groove and can be matched with the suction groove, the suction groove is formed in the first layer, the position can be matched with the suction groove, and the suction groove can be fully matched with the suction groove, and the vent hole is formed in the sample, the suction groove can be matched with the suction groove, and the condition can be fully confirmed, and the condition can be matched with the suction hole is arranged in the position of the suction groove and the suction groove can be matched with the suction hole.
Sodium chloride dissolution, controlled by diffusion processes and surface reactions or by mixing reactions, can generally be described by the Stumm equation. It is reported that alkali metal dissolution kinetics satisfies a first-order Stumm equation, which is a diffusion control process, and dissolution rate and current concentration are proportional to the difference between saturated concentration, namely, concentration Ct of dissolved salt at time t satisfies a first-order Stumm equation, wherein dct/dt=k (Cs-Ct), and parameters are involved in the equation, wherein Cs is the saturated concentration of salt in the solvent, K is a kinetic coefficient, and the parameters are related to the diffusion coefficient, kinetic viscosity and the like of a solvent sample. The first-order Stumm equation is integrated to obtain Ct=Cs-exp (-K t+B), and B is an integration constant.
Since the AD value is related to Ct, in a certain viscosity range, the AD signal processing value obtained by subjecting the AD value at a specific time or the AD value in a specific period of time to basic arithmetic processing at a specific temperature and the liquid viscosity may be regarded as having a linear relationship. By using the relation, a blood viscosity test equation containing temperature can be obtained, and the accurate blood viscosity can be obtained by substituting the environmental temperature T and AD signal processing value into the test equation.
The blood test system of this example was used to perform a simulated solution viscosity test, using solutions of sodium chloride and polyethylene glycol-6000 (PEG-6K) at gradient concentrations as simulated solutions, evaluating the conductivity of the sample and the effect of salt concentration on the test strip, and determining the measurable viscosity range. Sodium chloride in the gradient concentration sodium chloride solution is 0.10%, 0.15%, 0.20%, 0.25%, 0.30% and 0.35% by mass, and contains glycerin with a volume fraction of 1.2%, and PEG-6k in the gradient concentration PEG-6k solution is 0, 4.2%, 10%, 15%, 20% and 25% by mass, and contains sodium chloride with a mass fraction of 0.3%.
The tests in this example were all completed at room temperature (23.+ -. 2 ℃). The conductivity of the two solutions was measured in mS/cm using a conductivity meter, and the viscosity of the gradient concentration PEG-6k solution was measured in mPa.s using a rotational viscometer. During detection, an alternating current working voltage with a peak value of 200mV and a frequency of 200Hz is applied to the electrode system, and an electric signal within 0-3 s, namely an AD value, is obtained. Each test condition was tested 5 times.
Next, a time frame in which the effective AD value can be measured is preferable. For ease of processing, the AD value is first divided by 200 to obtain a test AD value. Selecting a test AD value and corresponding time, and performing multi-parameter fitting on the data according to different time ranges, such as four sections of 0-3.0 s, 0.5-3.0 s, 1.5-3.0 s and 2.0-3.0 s according to a function y=y 0+A1*exp(-(x-x0)/t1) by using a nonlinear fitting method. Preferably R2>0.99 and the longest time span. As shown in fig. 4, a schematic diagram of the change of the AD value with time is tested on a 25% PEG-6k mass fraction solution sample, and the fitting R 2 is greater than 0.995 as a result of the multi-parameter fitting with the optimal time length. Thereby selecting a period conforming to the first-order Stumm equation from the periods. The preferred effective AD value time range in this example is 0.5-3 s, the average of the test AD values within 0.5-3.0 s is calculated, the average is inverted, and the inverted value of the average is recorded as the AD signal processing value x for convenience in expressing the average.
As shown in FIG. 5, the test strip tests a gradient concentration sodium chloride solution, the AD signal processing value measured by the instrument slightly decreases with the increase of the mass fraction of sodium chloride in the solution, and the conductivity of the solution increases with the increase of the sodium chloride concentration.
As shown in FIG. 6, the test strip tests the gradient concentration PEG-6k solution, the instrument measured AD signal treatment value increased with increasing mass fraction of PEG-6k in the solution, while the conductivity of the solution decreased with increasing concentration of PEG-6 k.
As shown in fig. 7, the AD signal processing value obtained by testing the gradient concentration PEG-6k solution with the test strip is taken as an ordinate, the viscosity of the corresponding solution measured by the rotational viscometer is taken as an abscissa, and the average value of the test AD values is linearly fitted by using the least square method, and the result shows that for the PEG-6k venous blood simulation solution, the AD signal processing value and the viscosity value have a better linear relationship when the viscosity is within 1-12 mpa·s, and R 2 =0.995.
Example 3
The blood viscosity detection system provided in this embodiment includes a detection instrument and a detection strip. The detection instrument comprises a microprocessor, a detection strip connector, a temperature sensor and a display window, wherein the detection strip comprises a third layer plate, an electrode layer, a reagent layer, a second layer plate and a first layer plate.
The third layer is made of polyethylene glycol terephthalate and serves as a bottom plate of a detection strip, an electrode layer is formed on the third layer and at least comprises a first electrode and a second electrode, the first electrode and the second electrode are made of conductive carbon paste through screen printing, a reagent layer is formed on the first electrode, manufacturing raw materials of the reagent layer comprise water-soluble metal salt sodium chloride, a surfactant Triton X-100, water-soluble polymer hydroxyethyl cellulose (HEC) and deionized water, the mass fraction of the sodium chloride is 15%, the mass fraction of the Triton X-100 is 2%, the mass fraction of the hydroxyethyl cellulose (HEC) is 8%, a surfactant Triton X-100 is favorable for uniformly spreading the reagent layer above the electrode layer in the manufacturing process to form uniform thickness, the water-soluble polymer hydroxyethyl cellulose (HEC) plays a role of a bracket, the second layer is made of double-sided adhesive tape, the third layer is adhered with the first layer, a suction groove is formed on the second layer, the volume of a blood sample to be detected is 3 microliters, the first layer is made of polyethylene glycol chloride, the mass fraction of the sodium chloride is 2%, the mass fraction of the Triton X-100 is favorable for being filled with the sample to be detected, and the suction groove is formed in the transparent layer, the suction groove is corresponding to the suction groove is formed in the first layer, the suction groove is arranged, the position can be matched with the suction groove is corresponding to the suction groove, and the suction groove is arranged, the suction groove is can be matched with the suction hole of the sample, and the sample can be fully, and the suction hole can be matched with the test sample.
5 Venous whole blood samples with 15%, 30%, 42%, 55%, 70% of the whole blood volume were prepared, and then tested and recorded using a rotational viscometer at ambient temperatures of 4 ℃,10 ℃, 17 ℃, 23 ℃ and 30 ℃ respectively, as apparent viscosity values in mpa·s at 200/s shear rate for the plasma and the 5 venous whole blood samples.
The blood test system of this example was used to test plasma and the 5 venous whole blood samples described above in sequence, 5 times under each test condition. The method comprises the steps of firstly inserting a detection strip into a detection instrument, starting the detection instrument, introducing a sample to be detected into a suction groove of the detection strip, enabling the blood sample to contact a reagent layer, enabling the first electrode to be communicated with the second electrode, enabling the detection instrument to recognize a first current signal, enabling a temperature sensor to record the environment temperature T at the moment, and then enabling a second alternating voltage to be 200mV, wherein the frequency is 200Hz, and the duration is 3 seconds, so that a second electric signal within 0-3 s, namely an AD value, is obtained. The microprocessor 6 performs AD value processing, and divides the AD value by 200 to obtain a test AD value. Selecting a test AD value and corresponding time, selecting different time ranges, such as four sections of 0-3.0 s, 0.5-3.0 s, 1.0-3.0 s and 2.0-3.0 s, and performing multi-parameter fitting on the data according to a function y=y 0+A1*exp(-(x-x0)/t1) by using a nonlinear fitting method. Preferably R 2 >0.99 and the longest time span. In this embodiment, an average value of the AD values within 1-3 s is selected, the average value is inverted to obtain an AD signal processing value x, the AD signal processing value x is recorded, and the average value is calculated as shown in tables 1-5, wherein CV represents a variation coefficient and is the ratio of standard deviation to the average value.
Table 1 AD signal processing value data at 4 °c
Table 2 AD signal processing value data at 10 °c
Table 3 AD signal processing value data at 17 °c
Table 4 AD signal processing value data at 23 °c
Table 5 AD signal processing value data at 30 °c
From the CV values in tables 1 to 5, it is understood that the AD signal processing values measured by the blood test system provided in this example have good reproducibility.
The experimental data in tables 1-5 were processed:
(1) At 4 ℃, 10 ℃, 17 ℃, 23 ℃ and 30 ℃ respectively, the average value of the AD signal processing values is taken as an abscissa, the high-cut apparent viscosity of the corresponding blood sample is taken as an ordinate, and the linear fitting is carried out according to a least square method, so that 5 groups of viscosity test equations are obtained, and are shown in table 6.
TABLE 6 viscosity test equation coefficients and R at different ambient temperatures 2
| Ambient temperature (° C) | Coefficient of primary term | Constant term | R2 |
| 4 | 12.27 | 0.6457 | 0.9978 |
| 10 | 21.03 | -0.1567 | 0.9934 |
| 17 | 34.40 | -0.9851 | 0.9961 |
| 23 | 54.83 | -2.0295 | 0.9990 |
| 30 | 59.07 | -1.8540 | 0.9892 |
(2) Linear fitting is carried out by taking 4 ℃, 10 ℃, 17 ℃, 23 ℃ and 30 ℃ as the abscissa and taking the coefficient of the primary term of the viscosity test equation at each temperature as the ordinate to obtainWhere K represents a first order coefficient, T represents temperature, and K 1 and B 1 are fitting coefficients.
(3) Taking 4 ℃, 10 ℃, 17 ℃, 23 ℃ and 30 ℃ as the abscissa and taking the constant term of the viscosity test equation at each temperature as the ordinate, carrying out linear fitting to obtain b=k 2*T+B2, wherein B represents the constant term, T represents the temperature, and K 2 and B 2 are fitting coefficients.
(4) The viscosity test equation containing temperature parameters is eta= (K 1*T+B1)x+(K2*T+B2), eta represents a blood viscosity value, T represents an ambient temperature, x represents an AD signal processing value, K 1 and B 1 and K 2 and B 2 are fitting coefficients;
Substituting the AD signal processing value x of the blood sample and the ambient temperature T into eta= (K 1*T+B1)*x+(K2*T+B2) to obtain the apparent viscosity of the blood sample. From the linear fit R 2 of table 6, it can be seen that there is a better linearity between the measured high shear viscosity of the blood sample at different ambient temperatures and the test AD value data.
And (3) performing linear fitting by using the linear fitting results of the viscosity test equations under different environmental temperatures in table 6, wherein each temperature is taken as an abscissa, and the coefficient of a first term corresponding to each viscosity test equation is taken as an ordinate, so as to obtain an empirical equation (1):
k=1.955*T+3.4841 (1)
Where k represents the first order coefficient in the viscosity test equation, T represents temperature, R 2 = 0.9640.
And then taking each temperature as an abscissa and a constant term coefficient corresponding to each viscosity test equation as an ordinate, and performing linear fitting to obtain an empirical equation (2):
b=-0.1051*T+0.8904 (2)
Where b represents a constant term coefficient in the viscosity test equation, T represents temperature, R 2 = 0.9107.
Combining the above empirical equations (1) and (2) yields a temperature-containing blood viscosity test equation, equation (3):
η=(1.955*T+3.4841)*x+(-0.1051*T+0.8904) (3)
where η represents a blood viscosity value, T represents a temperature, and x represents an AD signal processing value.
After the microprocessor obtains the AD signal processing value x, the calculating module obtains the viscosity values of the blood plasma and the 5 venous whole blood samples according to the environmental temperature T, AD signal processing value x and a calculating formula eta= (1.955 x T+3.4841) x+ (-0.1051 x T+0.8904).
And (3) counting down for 5 seconds by the detection instrument from the time when the sample to be detected is introduced into the suction groove, and displaying the detection result by the display window. The measurement results were recorded, and absolute deviation and relative deviation between the average of 5 test results and the rotational viscometer test result using the blood measurement system of this example were calculated, wherein absolute deviation=average of blood viscosity measured by the test strip-blood viscosity measured by the rotational viscometer, and relative deviation=average of absolute deviation/average of blood viscosity measured by the test strip, and specific data are shown in tables 7 to 11:
TABLE 7 viscosity test results (units: mPa. Multidot.s) for plasma and 5 venous whole blood samples at 4C
Table 8 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 10C
Table 9 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 17C
Table 10 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 23 ℃
Table 11 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 30C
Example 4
The blood test system provided in this embodiment differs from the blood test system provided in embodiment 3 only in the following ways:
The third layer plate of the detection strip is made of polyvinyl chloride, the first electrode and the second electrode are made of conductive silver paste through screen printing, the preparation raw materials of the reagent layer comprise water-soluble metal salt sodium sulfate, surface active agent dodecyl benzene sulfonic acid, water-soluble polymer polyvinylpyrrolidone-vinyl acetate (PVP-VA) and deionized water, wherein the mass fraction of the sodium sulfate is 30%, the mass fraction of the dodecyl benzene sulfonic acid is 4%, the mass fraction of the polyvinylpyrrolidone-vinyl acetate (PVP-VA) is 15%, and the volume of the suction tank is 10 microliters.
The same test ambient temperature, plasma and 5 venous whole blood samples as in example 3 were used. The blood test system of this example was used to sequentially test plasma and 5 venous whole blood samples, 5 times under each test condition, with only the following differences from the test procedure of example 3:
the method comprises the steps of applying a first direct current voltage to a first electrode and a second electrode to be 1000mV, applying a second alternating current voltage to be 1000mV, applying a frequency to be 1000Hz, obtaining a second electric signal within 0-1 s, namely an AD value, for 1 second, performing AD value processing by a microprocessor, selecting the AD value within 0.5-1 s, and performing operation to obtain an AD signal processing value x. The procedure is similar to that of example 3 and will not be repeated here. The calculation formula in the calculation module of the finally obtained microprocessor is eta= (0.498 x T+6.1761) x+ (-0.0651 x T+2.1317).
And (3) counting down for 3 seconds from the time when the sample to be detected is introduced into the suction groove, and displaying a detection result by a display window. The measurement results were recorded, and absolute deviation and relative deviation between the average of 5 test results and the rotational viscometer test result using the blood measurement system of this example were calculated, wherein absolute deviation=average of blood viscosity measured by the test strip-blood viscosity measured by the rotational viscometer, and relative deviation=average of absolute deviation/average of blood viscosity measured by the test strip, and specific data are shown in tables 12 to 16:
table 12 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 4C
TABLE 13 viscosity test results (units: mPa. Multidot.s) for plasma and 5 venous whole blood samples at 10C
Table 14 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 17C
Table 15 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 23 ℃
Table 16 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 30C
Example 5
The blood test system provided in this embodiment differs from the blood test system provided in embodiment 3 only in the following ways:
The third layer plate and the third layer plate of the detection strip are made of polycarbonate, the preparation raw materials of the reagent layer comprise water-soluble metal salt potassium dihydrogen phosphate, surfactant sodium dodecyl sulfate, water-soluble polymer polyvinylpyrrolidone (PVP) and deionized water, wherein the mass fraction of the potassium dihydrogen phosphate is 10%, the mass fraction of the ammonium dodecyl sulfate is 0.1%, the mass fraction of the polyvinylpyrrolidone (PVP) is 2%, and the volume of the suction tank is 20 microliters.
The same test ambient temperature, plasma and 5 venous whole blood samples as in example 3 were used. The blood test system of this example was used to sequentially test plasma and 5 venous whole blood samples, 5 times under each test condition, with only the following differences from the test procedure of example 3:
The method comprises the steps of applying a first direct current voltage to a first electrode and a second electrode to be 50mV, applying a second alternating current voltage to be 50mV, applying a frequency to be 10Hz and applying a duration to be 10 seconds to obtain a second electric signal within 0-10 s, namely an AD value, performing AD value processing by a microprocessor, selecting the AD value within 1-10 s, calculating an average value of the AD value, linearly mapping the AD value to a specific interval, and taking the reciprocal to obtain an AD signal processing value x. The procedure is similar to that of example 3 and will not be repeated here. The calculation formula in the calculation module of the finally obtained microprocessor is η= (3.179×t+1.9416) ×x+ (-0.9678×t+0.1801).
And (3) counting down for 12 seconds from the time when the sample to be detected is introduced into the suction groove, and displaying a detection result by a display window. The detection results were recorded, and absolute deviation and relative deviation between the average of 5 test results and the rotational viscometer test result using the blood detection system of this example were calculated, wherein absolute deviation=average of blood viscosity measured by the test strip-blood viscosity measured by the rotational viscometer, relative deviation=average of absolute deviation/average of blood viscosity measured by the test strip, and specific data are shown in tables 17 to 21:
table 17 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 4C
TABLE 18 viscosity test results (units: mPa. Multidot.s) for plasma and 5 venous whole blood samples at 10C
Table 19 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 17C
Table 20 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 23 ℃
Table 21 results of viscosity tests (units: mPa. Multidot.s) of plasma and 5 venous whole blood samples at 30 ℃
As can be seen from the data in tables 7 to 21, the relative errors between the viscosity values measured by the blood test systems of examples 3, 4 and 5 and the viscosity value measured by the rotational viscometer are all within ±5% for the same blood sample in the range of 4 ℃ to 30 ℃, so that the blood test system provided by the embodiment of the invention can obtain the viscosity of the accurately measured blood in a wider temperature range, the measurement time is only several seconds to tens of seconds, and compared with the rotational viscometer, the required measurement time is greatly shortened, and the detection efficiency is obviously improved.
In addition, 50 blood samples (including a human fingertip blood sample and a modulated human blood sample) from different sources are tested at room temperature by adopting the blood detection system in the embodiment 3, and the read value of the blood detection system in the embodiment 3 is respectively recorded and compared with the high shear viscosity test value of the blood rheometer, and as shown in fig. 8, the result shows that the deviation between the blood detection system provided in the embodiment 3 and the blood rheometer is within 20% in the actual use process (clinic), and the accuracy is higher.
Note that the above is only a preferred embodiment of the present invention and the technical principle applied. It will be understood by those skilled in the art that the present invention is not limited to the particular embodiments described herein, but is capable of various obvious changes, rearrangements and substitutions as will now become apparent to those skilled in the art without departing from the scope of the invention. Therefore, while the invention has been described in connection with the above embodiments, the invention is not limited to the embodiments, but may be embodied in many other equivalent forms without departing from the spirit or scope of the invention, which is set forth in the following claims.
Claims (11)
1. A blood testing system comprising a testing instrument and a test strip;
the detection instrument comprises a temperature sensor, a microprocessor, a detection strip connector and a display window, wherein the detection strip comprises a third layer plate, an electrode layer, a reagent layer, a second layer plate and a first layer plate;
the blood testing system is configured to perform a blood testing method comprising:
S110, inserting a detection strip into a detection instrument, starting the detection instrument, and applying a first direct-current voltage to a first electrode and a second electrode of the detection strip;
S120, introducing a blood sample into a suction groove of the detection strip, connecting the first electrode with the second electrode, identifying a first current signal through a detection instrument, and recording the environment temperature at the moment through a temperature sensor of the detection instrument;
s130, applying a second alternating voltage to the first electrode after the detection instrument recognizes the first current signal, and detecting a second electric signal of the blood sample after a certain time by the detection instrument;
s140, processing the second electric signal through a microprocessor of the detecting instrument to obtain a processed second electric signal;
s150, bringing the processed second electric signal and the environment temperature into a preset calculation formula of the viscosity of the blood sample in the microprocessor, and calculating to obtain a viscosity value of the blood sample;
The calculation formula of the viscosity of the blood sample is as follows:
η=(K1*T+B1)x+(K2*T+B2);
Wherein η represents a blood viscosity value, T represents an ambient temperature, x represents a processed second electrical signal, and K 1、B1、K2、B2 are constant coefficients.
2. The system of claim 1, wherein the reagent layer is made from a material comprising a water-soluble metal salt.
3. The system of claim 2, wherein the reagent layer is made from a material further comprising a surfactant, a water-soluble polymer, and deionized water.
4. The system of claim 3, wherein the water-soluble metal salt comprises at least one of sodium chloride, potassium chloride, sodium sulfate, potassium carbonate, sodium nitrate, potassium nitrate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate.
5. The system of claim 4, wherein the reagent layer is made from a raw material comprising 10-30% by mass of water-soluble metal salt, 0.1-4% by mass of surfactant and 2-10% by mass of water-soluble polymer.
6. The system of claim 1, wherein the electrode layer is positioned over a third laminate and the reagent layer is positioned over the electrode layer, wherein the second laminate material has an adhesive force for adhering the third laminate to the first laminate, and wherein the second laminate has a suction slot for receiving a blood sample.
7. A blood testing method implemented using the blood testing system of any one of claims 1-6, comprising:
S110, inserting a detection strip into a detection instrument, starting the detection instrument, and applying a first direct-current voltage to a first electrode and a second electrode of the detection strip;
S120, introducing a blood sample into a suction groove of the detection strip, connecting the first electrode with the second electrode, identifying a first current signal through a detection instrument, and recording the environment temperature at the moment through a temperature sensor of the detection instrument;
s130, applying a second alternating voltage to the first electrode after the detection instrument recognizes the first current signal, and detecting a second electric signal of the blood sample after a certain time by the detection instrument;
s140, processing the second electric signal through a microprocessor of the detecting instrument to obtain a processed second electric signal;
And S150, bringing the processed second electric signal and the environment temperature into a preset calculation formula of the viscosity of the blood sample in the microprocessor, and calculating to obtain the viscosity value of the blood sample.
8. The method of claim 7, wherein the viscosity of the blood sample is calculated as:
η=(K1*T+B1)x+(K2*T+B2);
Wherein η represents a blood viscosity value, T represents an ambient temperature, x represents a processed second electrical signal, and K 1、B1、K2、B2 are constant coefficients.
9. The method of claim 8, wherein the range of K 1 is 0.5-3.0, the range of B 1 is 2.0-6.0, the range of K 2 is-1.0-0, and the range of B 2 is 0-2.0.
10. The method of claim 7, wherein the first dc voltage has a value ranging from 0.1 v to 0.8v.
11. The method of claim 7, wherein the second ac voltage is a low frequency ac voltage or a high frequency ac voltage, the peak value of the second ac voltage ranges from 0.05 to 1v, the frequency of the second ac voltage ranges from 10 to 1000hz, and the time period for which the second ac voltage is applied ranges from 1 to 10 seconds.
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