This application claims priority to Taiwan Application Serial Number 106104836, filed Feb. 15, 2017, which is herein incorporated by reference.
The present disclosure relates to a method for calculating hematocrit in blood, a method for calibrating biochemical index value in blood, and a system thereof.
During the inspection of whole blood, the hematocrit (HCT) in the whole blood often affects inspection values. Take blood glucose as an example, when the hematocrit is large, the glucose concentration of the whole blood will be underestimated. On the contrary, when the hematocrit is small, the glucose concentration of the whole blood will be overestimated. Presently, most of the electrochemical sensors use AC signal to reduce the interference that the hematocrit causes to the blood glucose. However, most of the electrode designs for performing the foregoing approach need four or more than four electrodes. In addition to the electrode designs, the circuit designs of blood glucose meters are also complex because AC and DC signals are used for inspection at the same time.
In addition, if the DC signal is used for the HCT inspection, conventional sensors mostly apply only one voltage signal and the methods of calculating the hematocrit mostly use current value. However, the inspection results of the hematocrit calculated by the methods are extremely inaccurate owing to interferences of reagent layers or other substances in the blood. Furthermore, ifs difficult to control the production processes of the test strips so as to impair the reproducibility of the inspection values.
Accordingly, how to provide a calibration method and a calibration system to solve the above-mentioned problems becomes an important issue to be solved by those in the industry.
An aspect of the disclosure is to precisely calculate the hematocrit in a blood sample and calibrate an inspected biochemical index value in the blood sample by using the hematocrit.
According to an embodiment of the disclosure, a method for calculating hematocrit in blood includes: applying a blood sample to a reagent layer on an electrochemical test strip; sequentially applying a first high positive voltage and a second high positive voltage to the blood sample, in which the second high positive voltage is greater than the first high positive voltage, and the first high positive voltage is greater than or equal to 1.0 V; calculating a quantity of electricity corresponding to the period of applying the second high positive voltage; and calculating a hematocrit of the blood sample according to the quantity of electricity.
In an embodiment of the disclosure, the calculating the hematocrit according to the quantity of electricity includes: mapping the quantity of electricity based on a standard quantity of electricity-hematocrit curve to obtain the hematocrit.
In an embodiment of the disclosure, the first high positive voltage is 1.0-2.0 V, and the second high positive voltage is 2.4-4.0 V.
In an embodiment of the disclosure, the applying of the first high positive voltage is continuously performed for a first time period, the applying of the second high positive voltage is continuously performed for a second time period, and the second time period is greater than or equal to the first time period.
In an embodiment of the disclosure, the first time period is 0.1-1.0 second, and the second time period is 1.0-10 seconds.
In an embodiment of the disclosure, an interval period between the first time period and the second time period is 0-10 seconds.
According to another embodiment of the disclosure, a method for calibrating biochemical index value in blood sequentially includes: applying a blood sample to a reagent layer on an electrochemical test strip; applying a low voltage to the blood sample to obtain an original biochemical index value of the blood sample, in which an absolute value of the low voltage is smaller than 1.0 V; applying a first high positive voltage to the blood sample, in which the first high positive voltage is greater than or equal to 1.0 V; applying a second high positive voltage to the blood sample, in which the second high positive voltage is greater than the first high positive voltage; calculating a quantity of electricity corresponding to the period of applying the second high positive voltage; calculating a hematocrit of the blood sample according to the quantity of electricity; and calibrating the original biochemical index value according to the hematocrit.
In an embodiment of the disclosure, the calculating the hematocrit according to the quantity of electricity includes: mapping the quantity of electricity based on a standard quantity of electricity-hematocrit relationship to obtain the hematocrit.
In an embodiment of the disclosure, the calibrating the original biochemical index value according to the hematocrit includes: calculating the hematocrit based on a standard calibration value-hematocrit relationship to obtain a calibration value; and multiplying the original biochemical index value by the calibration value.
In an embodiment of the disclosure, the absolute value of the low voltage is 0.1-0.7 V.
In an embodiment of the disclosure, a time period for which the low voltage is continuously applied is 1.0-10 seconds.
According to another embodiment of the disclosure, a system for calibrating biochemical index value in blood includes an electrochemical test strip and a processor. The electrochemical test strip includes a substrate, a first electrode, a second electrode, and a reagent layer. The first electrode is connected to the positive terminal of the processor, and the second electrode is connected to the negative terminal of the processor. The first electrode is disposed on a surface of the substrate. The second electrode is also disposed on the surface of the substrate. The reagent layer is disposed on the surface of the substrate and partially covers the first electrode and the second electrode. The processor is configured to sequentially applying a low voltage to obtain an original biochemical index value of a blood sample, a first high positive voltage, and a second high positive voltage between the first electrode and the second electrode. An absolute value of the low voltage is smaller than 1.0 V. The first high positive voltage is greater than or equal to 1.0 V, and the second high positive voltage is greater than the first high positive voltage. The processor is further configured to calculate a quantity of electricity corresponding to the period of applying the second high positive voltage, configured to calculate a hematocrit of the blood sample according to the quantity of electricity, and configured to calibrate the original biochemical index value according to the hematocrit.
In an embodiment of the disclosure, the material of the first electrode includes at least one of carbon, palladium, platinum, and gold.
In an embodiment of the disclosure, the material of the second electrode includes at least one of carbon, palladium, platinum, and gold.
In an embodiment of the disclosure, a sum of external resistance of the first electrode and the second electrode is 300-1500 ohm.
In an embodiment of the disclosure, the reagent layer includes an enzyme and an electron mediator.
In an embodiment of the disclosure, a contact area between the second electrode and the reagent layer is 0.8-1.2 mm2.
In an embodiment of the disclosure, the first electrode contacts the reagent layer with a first contact area, the second electrode contacts the reagent layer with a second contact area, and a ratio of the second contact area to the first contact area is 1.0-2.0.
In an embodiment of the disclosure, the thicknesses of the first electrode and the second electrode are 6-20 μm.
Accordingly, the method for calculating hematocrit in blood of the disclosure can be used to precisely calculate the hematocrit in the blood sample by sequentially applying two high positive voltages and using the quantity of electricity corresponding to the period of applying the second high positive voltage. The hematocrit obtained by mapping the quantity of electricity based on the standard quantity of electricity-hematocrit curve is precise owing to the standard quantity of electricity-hematocrit curve is very linear. The method and system for calibrating biochemical index value in blood of the disclosure can be used to calibrate the inspected biochemical index value in the blood sample by using the precisely calculated hematocrit. In addition, in the system for calibrating biochemical index value in blood of the disclosure, the electrode design is simple (only two electrodes are required), the approach of applying voltages is simple (only DC voltages are applied), and the inspection time is short. The biochemical index value mentioned in the disclosure can be the blood glucose concentration or the uric acid concentration, or other biochemical index values that will be influenced by the hematocrit.
It is to be understood that both the foregoing general description and the following detailed description are by examples, and are intended to provide further explanation of the disclosure as claimed.
The disclosure can be more fully understood by reading the following detailed description of the embodiment, with reference made to the accompanying drawings as follows:
Reference will now be made in detail to the present embodiments of the disclosure, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used in the drawings and the description to refer to the same or like parts.
Reference is made to
In some embodiments, the material of the first electrode 112 includes at least one of carbon, palladium, platinum, and gold, but the disclosure is not limited in this regard.
In some embodiments, the material of the second electrode 113 includes at least one of carbon, palladium, platinum, and gold, but the disclosure is not limited in this regard.
Reference is made to
Firstly, in step S101, a blood sample is applied to a reagent layer 114 on an electrochemical test strip 110.
Afterwards, in step S102, the blood sample is sequentially applied with a first high positive voltage and a second high positive voltage, in which the second high positive voltage is greater than the first high positive voltage, and the first high positive voltage is greater than or equal to 1.0 V. Reference is further made to
It should be pointed out that the purpose of forming the potential difference between the first electrode 112 and the second electrode 113 is to catalyze the blood sample on the reagent layer 114 to undergo a chemical reaction, so as to generate an electronic transmission signal (i.e., the so-called current value).
In an example of inspecting blood glucose by using the electrochemical test strip 110, the main ingredients contained in the reagent layer 114 can convert the blood glucose in the blood sample into gluconolactone, and then the electron mediator can be transformed from the oxidation state to the reduction state. By forming the potential difference between the first electrode 112 and the second electrode 113, the reduced state substance can be catalyzed into an oxidation state substance. The substances in the reagent layer 114 include an enzyme that can accelerate the reaction, a buffer solution, an electron mediator, an enzyme stabilizer, a molding agent, a surfactant, or a thickener. The enzyme can be Glucose dehydrogenase (GDH) enzyme or Glucose oxidase (GOD) enzyme.
In an embodiment, the first high positive voltage H1 is 1.0-2.0 V, and preferably 1.2-1.8 V.
In an embodiment, the second high positive voltage H2 is 2.4-4.0 V, and preferably 2.8-3.6 V.
In an embodiment, the applying of the first high positive voltage H1 is continuously performed for a first time period, the applying of the second high positive voltage H2 is continuously performed for a second time period, and the second time period is greater than or equal to the first time period. For example, the first time period is 0.1-1.0 second, and the second time period is 1.0-10 seconds.
As shown in
In addition, in the embodiment, an interval period between the first time period and the second time period is preferably 0 second (i.e., the second high positive voltage H2 is uninterruptedly applied after the first high positive voltage H1). In an embodiment, the interval period between the first time period and the second time period is 0-10 seconds.
Afterwards, in step S103, a quantity of electricity corresponding to the period of applying the second high positive voltage H2 is calculated. Reference is made to
Reference is made to
In other embodiments, the foregoing standard quantity of electricity-hematocrit curve can be transformed to a standard quantity of electricity-hematocrit relationship. Therefore, by substituting a quantity of electricity corresponding to the applying of the specific second high positive voltage H2 into the relationship, the hematocrit HCT corresponding to the quantity of electricity can be obtained.
It should be pointed out that some prior arts only apply a high positive voltage and estimate different hematocrits by using the current values at the end of the applying of the high positive voltage. However, the current-hematocrit curves produced by the prior arts are nonlinear (i.e., a current value may correspond to two hematocrits), so different hematocrits cannot be effectively identified. On the contrary, it can be clearly seen from
Finally, in step S104, a hematocrit HCT of the blood sample according to the quantity of electricity is calculated. As discussed above, the relationship between the quantities of electric charge and hematocrits is very linear, so as long as the quantity of electricity corresponding to the applying of the specific second high positive voltage H2 is known, a more accurate hematocrit HCT can be obtained by mapping the quantity of electricity based on the quantity of electricity-hematocrit curve diagram shown in
In an embodiment, steps S102-S104 can be performed by the processor 120, but the disclosure is not limited in this regard.
Reference is made to
Reference is made to
Reference is made to
In an embodiment, the contact area (i.e., the second contact area A2) of the second electrode 113 contacting the reagent layer 114 is 0.8-1.2 mm2.
Reference is made to
Firstly, in step S201, a blood sample is applied to a reagent layer 114 on an electrochemical test strip 110.
In step S202, a low voltage is applied to the blood sample to obtain an original biochemical index value of the blood sample, in which an absolute value of the low voltage is smaller than 1.0 V.
In an embodiment, the absolute value of the low voltage is 0.1-0.7 V, and preferably 0.3-0.5 V.
In an embodiment, a time period for which the low voltage is continuously applied is 1.0-10 seconds.
In step S203, a first high positive voltage is applied to the blood sample, in which the first high positive voltage is greater than or equal to 1.0 V.
In step S204, a second high positive voltage is applied to the blood sample, in which the second high positive voltage is greater than the first high positive voltage.
Reference is made to
In step S205, a quantity of electricity corresponding to the period of applying the second high positive voltage H2 is calculated.
In step S206, a hematocrit HCT of the blood sample according to the quantity of electricity is calculated.
It should be pointed out that steps S203-S206 regarding calculating the hematocrit HCT in the method for calibrating biochemical index value in blood of the embodiment are substantially the same as steps S102-S104 regarding calculating the hematocrit HCT in the method for calculating hematocrit in blood shown in
Finally, in step S207, the original biochemical index value is calibrated according to the hematocrit HCT.
Specifically, reference is made to
In an example of inspecting blood glucose by using the electrochemical test strip 110 (i.e., the biochemical index inspected by applying the low voltage L is the blood glucose), the electrode design of the electrochemical test strip 110 includes following conditions: a sum of a first external resistance R1 of the first electrode 112 and a second external resistance R2 of the second electrode 113 being 800 ohm; a ratio the second contact area A2 of the second electrode 113 to the first contact area A1 of the first electrode 112 being 1.0-2.0; the second contact area A2 being 0.9 mm2; the first thickness T1 of the first electrode 112 being about 15 um; and the second thickness T2 of the second electrode 113 being about 14 um.
Under the foregoing conditions of the electrode design, a hematocrit HCT can be obtained by comparing the area under the current-time curve (i.e., the quantity of electricity) corresponding to the applying of the specific second high positive voltage H2 with the standard quantity of electricity-hematocrit curve shown in
In an embodiment, steps S202-S207 can be performed by the processor 120, but the disclosure is not limited in this regard.
According to the foregoing recitations of the embodiments of the disclosure, it can be seen that the method for calculating hematocrit in blood of the disclosure can be used to precisely calculate the hematocrit in the blood sample by sequentially applying two high positive voltages and using the quantity of electricity corresponding to the period of applying the second high positive voltage. The hematocrit obtained by mapping the quantity of electricity based on the standard quantity of electricity-hematocrit curve is precise owing to the standard quantity of electricity-hematocrit curve is very linear. The method and system for calibrating biochemical index value in blood of the disclosure can be used to calibrate the inspected biochemical index value in the blood sample by using the precisely calculated hematocrit. In addition, in the system for calibrating biochemical index value in blood of the disclosure, the electrode design is simple (only two electrodes are required), the approach of applying voltages is simple (only DC voltages are applied), and the inspection time is short. The biochemical index value mentioned in the disclosure can be the blood glucose concentration or the uric acid concentration, or other biochemical index values that will be influenced by the hematocrit.
Although the present disclosure has been described in considerable detail with reference to certain embodiments thereof, other embodiments are possible. Therefore, the spirit and scope of the appended claims should not be limited to the description of the embodiments contained herein.
It will be apparent to those skilled in the art that various modifications and variations can be made to the structure of the present disclosure without departing from the scope or spirit of the disclosure. In view of the foregoing, it is intended that the present disclosure cover modifications and variations of this disclosure provided they fall within the scope of the following claims.
Number | Date | Country | Kind |
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106104836 | Feb 2017 | TW | national |