TWI481869B - Methods for measuring a hematocrit value and a glucose concentration, and electrochemical measuring device - Google Patents

Methods for measuring a hematocrit value and a glucose concentration, and electrochemical measuring device Download PDF

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TWI481869B
TWI481869B TW100101359A TW100101359A TWI481869B TW I481869 B TWI481869 B TW I481869B TW 100101359 A TW100101359 A TW 100101359A TW 100101359 A TW100101359 A TW 100101359A TW I481869 B TWI481869 B TW I481869B
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blood
glucose concentration
predetermined voltage
blood glucose
cell volume
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TW201229512A (en
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Wei Jen Ho
Jung Chun Li
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Eps Bio Technology Corp
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血球容積比測量方法、血糖濃度測量方法及使用前述方法的電化學量測裝置Blood cell volume ratio measuring method, blood sugar concentration measuring method, and electrochemical measuring device using the same method

本發明係關於一種測量血球容積比及血糖濃度的方法;以及使用前述測量方法的電化學量測裝置,尤其關於一種利用電化學方式來測量血球容積比及血糖濃度的方法;以及使用前述測量方法的電化學量測裝置。The present invention relates to a method for measuring a hematocrit ratio and a blood glucose concentration; and an electrochemical measuring device using the foregoing measuring method, and more particularly to a method for measuring a hematocrit ratio and a blood glucose concentration by electrochemical means; and using the aforementioned measuring method Electrochemical measuring device.

電化學式感測試片(Electrochemical Sensor Strip)已成熟地被應用於檢測流體中的各種物質,而其基本原理為利用一化學試劑(Reagent),使其與一待測流體中之一待分析物產生一電化學作用,以產生一電輸出信號,此電輸出信號與待測流體之待分析物有關。當待測流體為人的血液,而待分析物為血醣時,即可利用一葡萄糖氧化酵素及其他複合物來作為化學試劑。Electrochemical Sensor Strips have been used to detect various substances in fluids. The basic principle is to use a chemical reagent (Reagent) to generate one analyte to be analyzed. An electrochemical action to generate an electrical output signal associated with the analyte to be measured. When the fluid to be tested is human blood and the analyte is blood sugar, a glucose oxidase and other complexes can be used as a chemical reagent.

血球容積比(hematocrit,HCT)是指在一定量的血液中含有多少比例的紅血球。一般男性之血液的血球容積比大約為36~50%,而女性之血液的血球容積比大約為34~47%。根據血液中的血球容積比能夠讓人們了解血液的品質。此外,要測量血液之血糖濃度時,血糖濃度的測量值亦會隨著血球容積比而有所變化。Hematocrit (HCT) refers to the proportion of red blood cells contained in a given amount of blood. In general, the blood volume ratio of male blood is about 36 to 50%, and the blood volume ratio of female blood is about 34 to 47%. According to the blood cell volume ratio in the blood, people can understand the quality of blood. In addition, when measuring the blood glucose concentration, the blood glucose concentration measurement will also vary with the blood cell volume ratio.

圖1顯示在不同血球容積比下,習知血糖機所測得之血糖濃度的測量值以及血糖濃度的實際值,兩者間的關係圖。圖1之縱軸為血糖機所測得之血糖濃度的測量值,圖1之橫軸為血糖濃度的實際值。如圖1所示,以血球容積比為41%為基準,當血球容積比(例如60%)大於41%時,血糖濃度的測量值(300 mg/dL)會低於血糖濃度的實際值(400 mg/dL)。反之,當血球容積比(例如20%)小於41%時,血糖濃度的測量值(500 mg/dL)會高於血糖濃度的實際值(400 mg/dL)。因此,為了求得較正確的血糖濃度的實際值時,需要預先測量血球容積比,並依據血球容積比對血糖濃度的測量值進行補償。Figure 1 is a graph showing the relationship between the measured value of blood glucose concentration measured by a conventional blood glucose meter and the actual value of blood glucose concentration at different hematocrit ratios. The vertical axis of Fig. 1 is a measurement of the blood glucose concentration measured by the blood glucose meter, and the horizontal axis of Fig. 1 is the actual value of the blood glucose concentration. As shown in Fig. 1, when the hematocrit ratio (for example, 60%) is greater than 41% based on the hematocrit ratio of 41%, the measured value of blood glucose concentration (300 mg/dL) is lower than the actual value of the blood glucose concentration ( 400 mg/dL). Conversely, when the hematocrit ratio (eg 20%) is less than 41%, the measured blood glucose concentration (500 mg/dL) is higher than the actual value of the blood glucose concentration (400 mg/dL). Therefore, in order to obtain a realistic value of a relatively accurate blood glucose concentration, it is necessary to measure the blood cell volume ratio in advance, and compensate the blood glucose concentration measurement value according to the blood cell volume ratio.

測量血球容積比的方法有很多種,例如可以利用測量血液阻抗的方式;利用光學方式;利用氧化還原反應;以及利用電化學方式,來求得血球容積比。於公開號第EP1707953A1號之歐盟專利申請案,揭示一種利用氧化還原反應方式來求得血球容積比的方法。依據其測量方法,是於電化學式感測試片中,必須在計數電極(counter electrode)上設有一氧化還原反應物質(redox substance),來產生明顯的氧化還原電流,以測量相關之血球容積比。There are many methods for measuring the volume ratio of blood cells, for example, a method of measuring blood impedance; an optical method; a redox reaction; and an electrochemical method to obtain a blood cell volume ratio. The European Patent Application Publication No. EP 1 707 953 A1 discloses a method for determining the hematocrit ratio by means of a redox reaction. According to the measurement method, in the electrochemical sensing test piece, a redox substance must be provided on the counter electrode to generate a significant redox current to measure the relevant hematocrit ratio.

然而,依據習知技術之血球容積比測量方法尚存在有更一步改善的空間。However, there is still room for improvement in the blood cell volume ratio measurement method according to the prior art.

本發明一實施例之目的在於提供一種測量血球容積比及血糖濃度的方法;以及使用前述測量方法的電化學量測裝置。本發明一實施例之目的在於提供一種利用電化學方式來測量血球容積比及血糖濃度的方法;以及使用前述測量方法的電化學量測裝置。It is an object of an embodiment of the present invention to provide a method of measuring a hematocrit ratio and a blood glucose concentration; and an electrochemical measuring device using the aforementioned measuring method. An object of an embodiment of the present invention is to provide a method for measuring a hematocrit ratio and a blood glucose concentration by an electrochemical method; and an electrochemical measuring device using the above measuring method.

依據本發明一實施例,提供一種血球容積比測量方法,其利用包含多個電極的一感測試片及耦接該感測試片的一電化學量測裝置,其中該些電極間無需氧化還原反應物質即可來測量位於該些電極間之一血液中的一血球容積比。血球容積比測量方法包含:透過該些電極供給一第一預定電壓至該血液,並於一第一測量期間測得一第一電流值;及依據第一電流值及一關係式計算出該血球容積比,其中該關係式是利用具有相異且已知的血球容積比的多個樣本血液所求得。According to an embodiment of the present invention, a blood cell volume ratio measuring method is provided, which utilizes a sensing test piece including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece, wherein no redox reaction is required between the electrodes. The substance can be used to measure a hematocrit ratio in the blood of one of the electrodes. The blood cell volume ratio measuring method includes: supplying a first predetermined voltage to the blood through the electrodes, and measuring a first current value during a first measurement period; and calculating the blood cell according to the first current value and a relationship Volume ratio, wherein the relationship is obtained using a plurality of sample blood having different and known hematocrit ratios.

依據本發明一實施例,提供一種血糖濃度測量方法,其利用包含多個電極的一感測試片及耦接感測試片的一電化學量測裝置,來測量位於該些電極間之一血液中的一血糖濃度。血糖濃度測量方法包含:透過該些電極供給一第一預定電壓至該血液,並於一第一測量期間測得一第一電流值;及依據該第一電流值及一關係式計算出一血球容積比,其中該關係式是利用具有相異且已知的血球容積比的多個樣本血液所求得;透過該些電極供給一第二預定電壓至該血液,並於一第二測量期間測得一第二電流值,依據該第二電流值求得該血糖濃度的一測量值;依據該血球容積比來補償該血糖濃度的測量值,以求得該血糖濃度的一實際值。According to an embodiment of the present invention, a blood glucose concentration measuring method is provided, which uses an electrochemical measuring device including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece to measure the blood located in one of the electrodes. One blood sugar concentration. The blood glucose concentration measuring method includes: supplying a first predetermined voltage to the blood through the electrodes, and measuring a first current value during a first measurement period; and calculating a blood cell according to the first current value and a relationship a volume ratio, wherein the relationship is obtained by using a plurality of sample blood having different and known hematocrit ratios; supplying a second predetermined voltage to the blood through the electrodes, and measuring during a second measurement period A second current value is obtained, and a measured value of the blood glucose concentration is obtained according to the second current value; the measured value of the blood glucose concentration is compensated according to the blood cell volume ratio to obtain an actual value of the blood glucose concentration.

於一實施例中,該關係式為利用分別供給一第三預定電壓至該些樣本血液,並於一第三測量期間測得多個樣本電流值,依據該些樣本電流值及該些已知的血球容積比來加以求得。較佳的情況是,該關係式為y=ax+b,且y代表該第一電流值,x代表該血球容積比,且a及b分別代表一常數,且常數a及b是依據該些樣本電流值及該些已知的血球容積比來加以求得。In an embodiment, the relationship is that a third predetermined voltage is respectively supplied to the sample blood, and a plurality of sample current values are measured during a third measurement period, according to the sample current values and the known The blood volume ratio is obtained. Preferably, the relationship is y=ax+b, and y represents the first current value, x represents the hematocrit ratio, and a and b respectively represent a constant, and the constants a and b are based on the The sample current value and the known hematocrit ratios are obtained.

於一實施例中,第一預定電壓的絕對值大於0.5V即可實際應用於血球容積比檢測,較佳的情況是第一預定電壓的絕對值大於0.7v和小於等於3V。In an embodiment, the absolute value of the first predetermined voltage is greater than 0.5 V, which can be practically applied to the hematocrit ratio detection. Preferably, the absolute value of the first predetermined voltage is greater than 0.7 v and less than or equal to 3 V.

依據本發明一實施例,提供一種電化學量測裝置,其適於耦接於包含多個電極的一感測試片。電化學量測裝置包含兩個連接部及一處理器。兩個連接部分別耦接感測試片的該些電極。處理器耦接於該些連接部,並且處理器透過該些連接部及該些電極,供給一第一預定電壓至位於該些電極的一血液,並於一第一測量期間測得一第一電流值;及依據該第一電流值及一關係式計算出一血球容積比,其中該關係式是利用具有相異且已知的血球容積比的多個樣本血液所求得。According to an embodiment of the invention, an electrochemical measuring device is provided that is adapted to be coupled to a sensing test piece comprising a plurality of electrodes. The electrochemical measuring device comprises two connections and a processor. The two connecting portions are respectively coupled to the electrodes of the sensing test piece. The processor is coupled to the connecting portions, and the processor supplies a first predetermined voltage to a blood located at the electrodes through the connecting portions and the electrodes, and measures a first period during a first measurement period a current value; and calculating a blood cell volume ratio based on the first current value and a relationship, wherein the relationship is obtained by using a plurality of sample blood having different and known hematocrit ratios.

於一實施例中,處理器更透過該些電極供給一第二預定電壓至該血液,並於一第二測量期間測得一第二電流值,依據該第二電流值求得該血糖濃度的一測量值;並且依據該血球容積比來補償該血糖濃度的測量值,以求得該血糖濃度的一實際值。In one embodiment, the processor further supplies a second predetermined voltage to the blood through the electrodes, and detects a second current value during a second measurement period, and determines the blood glucose concentration according to the second current value. a measured value; and the measured value of the blood glucose concentration is compensated according to the hematocrit ratio to obtain an actual value of the blood glucose concentration.

於一實施例中,電化學量測裝置更包含一記憶裝置,記憶裝置儲存有該關係式,且該關係式為一線性關係式,該線性關係式是利用分別供給一第三預定電壓至該些樣本血液,並於一第三測量期間測得多個樣本電流值,依據該些樣本電流值及該些已知的血球容積比來加以求得,該關係式為y=ax+b,且y代表該第一電流值,x代表該血球容積比,且a及b分別代表一常數。In one embodiment, the electrochemical measuring device further includes a memory device, wherein the memory device stores the relationship, and the relationship is a linear relationship, wherein the linear relationship is utilized to respectively supply a third predetermined voltage to the The sample blood is measured, and a plurality of sample current values are measured during a third measurement period, and the relationship is obtained according to the sample current values and the known blood cell volume ratios, wherein the relationship is y=ax+b, and y represents the first current value, x represents the hematocrit ratio, and a and b represent a constant, respectively.

於一實施例中,記憶裝置更儲存有另一線性關係式,且處理器更利用該另一線性關係式來補償該血糖濃度的測量值,該另一線性關係式為Gluacu =m*Glumea +n,且Gluacu 代表該血糖濃度的實際值,Glumea 代表該血糖濃度的測量值,m及n分別代表一常數。In one embodiment, the memory device further stores another linear relationship, and the processor further compensates the measured value of the blood glucose concentration by using the other linear relationship, the other linear relationship is Glu acu =m*Glu Mea + n, and Glu acu represents the actual value of the blood glucose concentration, Glu mea represents the measured value of the blood glucose concentration, and m and n represent a constant, respectively.

依據本發明一實施例,可以於無需將氧化還原反應物質點佈於該些電極下,單純使用電化學量測裝置來求得血球容積比,相較於習知技術,使用上更具有方便性且能夠求得血球容積比,及補償後之血糖濃度。According to an embodiment of the present invention, the blood volume ratio can be obtained by simply using an electrochemical measuring device without arranging the redox reaction substance under the electrodes, which is more convenient to use than the prior art. And can determine the hematocrit ratio, and the compensated blood glucose concentration.

本發明的其他目的和優點可以從本發明所揭露的技術特徵中得到進一步的了解。為讓本發明之上述和其他目的、特徵和優點能更明顯易懂,下文特舉實施例並配合所附圖式,作詳細說明如下。Other objects and advantages of the present invention will become apparent from the technical features disclosed herein. The above and other objects, features, and advantages of the invention will be apparent from

圖2顯示依本發明一實施例電化學量測裝置之功能方塊圖。如圖2所示,感測試片200包含一兩個工作電極211及212。電化學量測裝置100包含一兩個連接部(connector)111及112、一參考電壓源120、一電流電壓轉換電路130、一類比數位轉換電路140、一處理器150及一顯示器160。於一實施例中,還可以更包含一記憶體170。連接部111及112適於分別電連接工作電極211及212。參考電壓源120可以為接地端。工作電極211透過連接部111電連接參考電壓源120,工作電極212透過連接部112電連接類比數位轉換電路140、電流電壓轉換電路130及處理器150。顯示器160電連接處理器150。記憶體170中可以儲存有多個線性關係式或資料,用以供處理器150使用該些線性關係式資料,以計算出血球容積比及較準確的血糖濃度(將於後述)。2 is a functional block diagram of an electrochemical measuring device in accordance with an embodiment of the present invention. As shown in FIG. 2, the sensing test strip 200 includes one or two working electrodes 211 and 212. The electrochemical measuring device 100 includes one or two connectors 111 and 112, a reference voltage source 120, a current-voltage conversion circuit 130, an analog-to-digital conversion circuit 140, a processor 150, and a display 160. In an embodiment, a memory 170 may further be included. The connecting portions 111 and 112 are adapted to electrically connect the working electrodes 211 and 212, respectively. The reference voltage source 120 can be a ground terminal. The working electrode 211 is electrically connected to the reference voltage source 120 through the connection portion 111, and the working electrode 212 is electrically connected to the analog digital conversion circuit 140, the current-voltage conversion circuit 130, and the processor 150 through the connection portion 112. Display 160 is electrically coupled to processor 150. A plurality of linear relationships or data may be stored in the memory 170 for the processor 150 to use the linear relationship data to calculate a hemorrhage volume ratio and a more accurate blood glucose concentration (described later).

於操作時,感測試片200插入於電化學量測裝置100中,使血液流至工作電極211及212間,依據處理器150的指示,從電流電壓轉換電路130及參考電壓源120提供一固定的電壓於工作電極211及212間,藉以於工作電極211及212間產生一電流,前述電流對應血液中的血球容積比。隨後,電流電壓轉換電路130將前述電流轉換成一電壓,類比數位轉換電路140將前述電壓的類比值轉換成數位值後,將前述電壓的數位值輸出至處理器150。處理器150依據前述電壓的數位值計算出一血球容積比,最後透過顯示器150顯示該血球容積比。During operation, the sensing test strip 200 is inserted into the electrochemical measuring device 100 to allow blood to flow between the working electrodes 211 and 212, and a fixed voltage is supplied from the current-voltage converting circuit 130 and the reference voltage source 120 according to the instruction of the processor 150. The voltage is between the working electrodes 211 and 212, so that a current is generated between the working electrodes 211 and 212, and the current corresponds to the hematocrit ratio in the blood. Subsequently, the current-voltage conversion circuit 130 converts the aforementioned current into a voltage, and the analog-to-digital conversion circuit 140 converts the analog value of the aforementioned voltage into a digital value, and outputs the digital value of the aforementioned voltage to the processor 150. The processor 150 calculates a blood cell volume ratio based on the digit value of the voltage, and finally displays the blood cell volume ratio through the display 150.

此外,雖然於圖2中,顯示感測試片200具有兩個工作電極211的實施例,然而工作電極的數量並非本發明所限定者,於一實施例中亦可以採用兩個以上的工作電極。例如感測試片200可以更包含有第一工作電極、第二工作電極及第三工作電極(未圖示)。第一工作電極及第二工作電極耦接於連接部112,而第三工作電極耦接於連接部111。如此,即可藉由第二工作電極及第三工作電極測量血球容積比,並藉由第一工作電極及第三工作電極測量血糖。此外,於一較佳的實施例中該些工作電極是以血液流經第二工作電極、第三工作電極及第一工作電極的方式來配置。於本實施例中,第二工作電極及第三工作電極上皆設有酵素,但於另一實施例中於量測HCT的電極(第二工作電極)亦可以不設有酵素。當然應了解的是本發明不限定第一工作電極、第二工作電極及第三工作電極的配置位置,依據不同的目的,該些工作電極是以血液流經第三工作電極、第二工作電極及第一工作電極的方式來配置。In addition, although in FIG. 2, the display sensing strip 200 has two embodiments of the working electrode 211, the number of working electrodes is not limited by the present invention, and in one embodiment, more than two working electrodes may be employed. For example, the sensing test strip 200 may further include a first working electrode, a second working electrode, and a third working electrode (not shown). The first working electrode and the second working electrode are coupled to the connecting portion 112 , and the third working electrode is coupled to the connecting portion 111 . Thus, the blood cell volume ratio can be measured by the second working electrode and the third working electrode, and the blood glucose can be measured by the first working electrode and the third working electrode. Moreover, in a preferred embodiment, the working electrodes are configured such that blood flows through the second working electrode, the third working electrode, and the first working electrode. In this embodiment, the enzyme is provided on the second working electrode and the third working electrode, but in another embodiment, the electrode (second working electrode) for measuring the HCT may not be provided with an enzyme. It should be understood that the present invention does not limit the arrangement positions of the first working electrode, the second working electrode, and the third working electrode. According to different purposes, the working electrodes are blood flowing through the third working electrode and the second working electrode. And the first working electrode is configured in a manner.

圖3顯示依本發明一實施例之血液中血球容積比、電壓及電流間的關係圖。為了解血液中血球容積比、電壓及電流間的關係,發明人準備具有相異且已知的血球容積比的多組樣本血液進行實驗,例如分別為60%、40%及20%的血球容積比。在+3V至-3V的電壓區間,以0.1V/s的掃描速度改變電壓,並隨時間改變供給該些樣本血液不同的電壓,以量測不同電壓下的電流,實驗結果顯示於圖3。如圖3所示,當電壓大於+0.5V且小於-0.5V(電壓的絕對值大於0.5V)時,具有60%、40%及20%之血球容積比的血液,所產生的電流值即有明顯隨電壓改變的現象。因此若要測量血液中的血球容積比,所提供的電壓的絕對值應可以採用大於0.5V的電壓。請留意,圖3中,當電壓的絕對值大於0.7V和小於等於3V,隨電壓改變之電流值的變化量更為明顯。因此若要測量血液中的血球容積比,較佳的情況是所提供的電壓的絕對值可以採用其絕對值大於0.7V和小於等於3V。Fig. 3 is a graph showing the relationship between blood cell volume ratio, voltage and current in blood according to an embodiment of the present invention. In order to understand the relationship between blood volume ratio, voltage and current in blood, the inventors prepared multiple sets of sample blood having different and known hematocrit ratios, for example, blood cell volumes of 60%, 40%, and 20%, respectively. ratio. In the voltage range of +3V to -3V, the voltage is changed at a scanning speed of 0.1 V/s, and different voltages supplied to the blood of the samples are changed with time to measure currents at different voltages, and the experimental results are shown in FIG. As shown in FIG. 3, when the voltage is greater than +0.5 V and less than -0.5 V (the absolute value of the voltage is greater than 0.5 V), the blood generated by the blood cell volume ratio of 60%, 40%, and 20% is the current value generated. There is a phenomenon that changes significantly with voltage. Therefore, to measure the hematocrit ratio in blood, the absolute value of the voltage supplied should be greater than 0.5V. Please note that in Figure 3, when the absolute value of the voltage is greater than 0.7V and less than or equal to 3V, the amount of change in the current value as a function of voltage is more pronounced. Therefore, in order to measure the hematocrit ratio in blood, it is preferable that the absolute value of the supplied voltage can be greater than 0.7 V and less than or equal to 3 V.

圖4顯示依本發明一實施例,在固定電壓下,血液中血球容積比、時間及電流間的關係圖。如圖4所示,當電壓設為絕對值大於0.7V和小於等於3V時,具有60%、40%及20%之血球容積比的血液,在10秒內的任一時間下所產生的電流皆相異,因此可選擇一適當的固定測量時間用來量測血球容積比。Figure 4 is a graph showing the relationship between blood volume ratio, time and current in blood at a fixed voltage according to an embodiment of the present invention. As shown in FIG. 4, when the voltage is set to be greater than 0.7 V and less than or equal to 3 V, blood having a blood cell volume ratio of 60%, 40%, and 20%, current generated at any time within 10 seconds. They are all different, so you can choose an appropriate fixed measurement time to measure the hematocrit ratio.

圖5顯示依本發明一實施例,在固定電壓及固定測量時間下,血液中血球容積比及電流間的關係圖。如圖5所示,當電壓設為絕對值大於0.7V和小於等於3V且固定測量時間時,血液中的血球容積比與電流,具有一線性關係。發明人進行過多次的實驗,皆發現於特定之固定電壓及測量時間下,血液中的血球容積比與電流間能夠具有一相關性線性關係。因此,要求得血糖濃度的實際值時,可預先求得血球容積比與電流間的一相關性線性關係式,再對電化學量測裝置100所測得之血糖濃度的測量值,利用內插或外插的方式進行補償,即可求得血糖濃度的實際值。Figure 5 is a graph showing the relationship between blood volume ratio and current in blood at a fixed voltage and a fixed measurement time according to an embodiment of the present invention. As shown in FIG. 5, when the voltage is set to be greater than 0.7 V and less than or equal to 3 V and a fixed measurement time, the hematocrit ratio in the blood has a linear relationship with the current. The inventors have conducted many experiments, and found that the blood volume ratio in the blood can have a linear relationship with the current at a specific fixed voltage and measurement time. Therefore, when the actual value of the blood glucose concentration is required, a linear relationship between the blood volume ratio and the current can be obtained in advance, and the measured value of the blood glucose concentration measured by the electrochemical measuring device 100 can be interpolated. Or the extrapolation method to compensate, you can get the actual value of blood glucose concentration.

於本發明一實施例中,求得前述線性關係式包含以下步驟。步驟S02:準備多個樣本血液,且該些樣本血液具有相異且已知的血球容積比。步驟S04:分別供給一預定電壓至該些樣本血液,並於一測量期間測得多個樣本電流值。步驟S06:依據該些樣本電流值及該些已知的血球容積比,利用線性迴歸(linear regression)來求得前述線性關係式。於本實施例中前述預定電壓可以設為絕對值大於0.7V和小於等於3V且固定測量時間可以設為小於10秒。於一實施例中,是利用最小平方誤差線性迴歸(Least Squares Linear Regression Analysis)法,依據該些樣本電流值及該些已知的血球容積比求得常數a及b。In an embodiment of the invention, determining the linear relationship includes the following steps. Step S02: preparing a plurality of sample blood, and the sample blood has a different and known hematocrit ratio. Step S04: respectively supplying a predetermined voltage to the sample blood, and measuring a plurality of sample current values during a measurement. Step S06: determining linear relations by linear regression according to the sample current values and the known blood cell volume ratios. In the present embodiment, the aforementioned predetermined voltage may be set to be greater than 0.7 V and less than or equal to 3 V and the fixed measurement time may be set to be less than 10 seconds. In one embodiment, the constants a and b are obtained based on the sample current values and the known blood cell volume ratios using a Least Squares Linear Regression Analysis method.

圖6顯示依本發明一實施例,量測血糖濃度時之電化學量測裝置中電壓及時間的關係圖。於本發明一實施例中,量測血液中的血球容積比的方法包含以下步驟。步驟S12:透過工作電極211及212供給一第一預定電壓V1至血液,並於一第一測量期間測得一第一電流值。於本實施例中,第一預定電壓V1的絕對值大於0.7V和小於等於3V,而第一測量期間可以為小於10秒。步驟S14:依據該第一電流值及前述線性關係式,計算出一血球容積比。Figure 6 is a graph showing the relationship between voltage and time in an electrochemical measuring device for measuring blood glucose concentration according to an embodiment of the present invention. In an embodiment of the invention, the method of measuring the hematocrit ratio in blood comprises the following steps. Step S12: supplying a first predetermined voltage V1 to the blood through the working electrodes 211 and 212, and measuring a first current value during a first measurement. In the present embodiment, the absolute value of the first predetermined voltage V1 is greater than 0.7V and less than or equal to 3V, and the first measurement period may be less than 10 seconds. Step S14: Calculate a blood cell volume ratio according to the first current value and the linear relationship.

於本發明一實施例中,量測血液中的血糖濃度的方法可以更包含以下步驟。步驟S16:於一預定期間內停止供給電壓至血液。於本實施例中,預定期間可以為1秒。步驟S17:供給一第二預定電壓V2至血液,並於一第二測量期間測得一第二電流值,並依據該第二電流值求得血糖濃度的測量值。於本實施例中,第二預定電壓V2可以為小於第一預定電壓V1,而第二測量期間可以為小於10秒。步驟S08:依據該血球容積比對該血糖濃度的測量值進行補償,計算出該血糖濃度的實際值。In an embodiment of the invention, the method of measuring blood glucose concentration in blood may further comprise the following steps. Step S16: The supply of the voltage to the blood is stopped for a predetermined period of time. In this embodiment, the predetermined period may be 1 second. Step S17: Supply a second predetermined voltage V2 to the blood, and measure a second current value during a second measurement period, and obtain a measured value of the blood glucose concentration according to the second current value. In this embodiment, the second predetermined voltage V2 may be less than the first predetermined voltage V1, and the second measurement period may be less than 10 seconds. Step S08: Compensating for the measured value of the blood glucose concentration according to the hematocrit ratio, and calculating the actual value of the blood glucose concentration.

於本發明中,不限定前述步驟S08中的補償方法,於本發明領域具有通常知識者,可以利用目前已知及未來發展之補償關係,來求得血糖濃度。In the present invention, the compensation method in the foregoing step S08 is not limited, and those having ordinary knowledge in the field of the present invention can obtain the blood sugar concentration by utilizing the compensation relationship currently known and developed in the future.

於一實施例中,可以採用各種血球容積比的血液進行實驗,以求得血糖濃度的測量值以及血糖濃度的實際值的關係,並建立各種血球容積比之血糖濃度測量值及血糖濃度實際值間關係的表格,並儲存於電化學量測裝置100的記憶體170中。在求得該血球容積比後,取出該血球容積比之血糖濃度測量值及血糖濃度實際值間關係的表格,依據該表格及血糖濃度測量值來求得血糖濃度實際值。In one embodiment, experiments can be performed using blood of various hematocrit ratios to determine the relationship between the measured value of the blood glucose concentration and the actual value of the blood glucose concentration, and establish the blood glucose concentration measurement value and the actual blood glucose concentration value of various blood cell volume ratios. A table of relationships is stored in the memory 170 of the electrochemical measuring device 100. After obtaining the hematocrit ratio, the table of the relationship between the blood cell volume measurement value and the actual blood glucose concentration value is taken out, and the actual blood glucose concentration value is obtained based on the table and the blood glucose concentration measurement value.

於一實施例中,亦可以預先在第二預定電壓V2及第二測量期間的情況下,對多組已知血糖濃度的樣本血液進行測量求得多組血糖濃度的測量值,再利用線性迴歸方式找出血糖濃度的測量值與血糖濃度的實際值間的一線性關係,例如Gluacu =m*Glumea +n,並依據該血糖濃度的測量值及該線性關係來求得血糖濃度的實際值。In an embodiment, the measurement blood of the plurality of sets of blood glucose concentrations of the known blood glucose concentration may be measured in advance in the case of the second predetermined voltage V2 and the second measurement period, and then the linear regression is performed. The way to find a linear relationship between the measured value of blood glucose concentration and the actual value of blood glucose concentration, such as Glu acu = m * Glu mea + n, and based on the measured value of the blood glucose concentration and the linear relationship to obtain the actual blood glucose concentration value.

依據本發明一實施例,可以單純使用電化學量測裝置來求得血球容積比,相對於習知使用測量血液阻抗的方式及利用光學方式等的技術,而不需要額外之阻抗量測設備及光學設備,更適合於使用於一般家庭。且相對於需利用氧化還原物質方可檢測血球容積比的技術,可以不需要設計額外的電化學式感測試片,能夠減少製造成本。According to an embodiment of the present invention, an electrochemical measuring device can be used to obtain a blood cell volume ratio, and a method for measuring blood impedance and a method using optical methods can be used, without requiring an additional impedance measuring device and Optical equipment is more suitable for general household use. And compared with the technique of using a redox substance to detect the blood cell volume ratio, it is not necessary to design an additional electrochemical sensing test piece, which can reduce the manufacturing cost.

雖然本發明已以較佳實施例揭露如上,然其並非用以限定本發明,任何熟習此技藝者,在不脫離本發明之精神和範圍內,當可作些許之更動與潤飾,因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。另外,本發明的任一實施例或申請專利範圍不須達成本發明所揭露之全部目的或優點或特點。此外,摘要部分和標題僅是用來輔助專利文件搜尋之用,並非用來限制本發明之權利範圍。While the present invention has been described in its preferred embodiments, the present invention is not intended to limit the invention, and the present invention may be modified and modified without departing from the spirit and scope of the invention. The scope of protection is subject to the definition of the scope of the patent application. In addition, any of the objects or advantages or features of the present invention are not required to be achieved by any embodiment or application of the invention. In addition, the abstract sections and headings are only used to assist in the search of patent documents and are not intended to limit the scope of the invention.

100...電化學量測裝置100. . . Electrochemical measuring device

111...連接部111. . . Connection

112...連接部112. . . Connection

120...參考電壓源120. . . Reference voltage source

130...電流電壓轉換電路130. . . Current-voltage conversion circuit

140...類比數位轉換電路140. . . Analog digital conversion circuit

150...處理器150. . . processor

160...顯示器160. . . monitor

170...記憶體170. . . Memory

200...感測試片200. . . Sense test piece

211...工作電極211. . . Working electrode

212...工作電極212. . . Working electrode

圖1顯示在不同血球容積比下,習知血糖機所測得之血糖濃度的測量值以及血糖濃度的實際值,兩者間的關係圖。Figure 1 is a graph showing the relationship between the measured value of blood glucose concentration measured by a conventional blood glucose meter and the actual value of blood glucose concentration at different hematocrit ratios.

圖2顯示依本發明一實施例電化學量測裝置之功能方塊圖。2 is a functional block diagram of an electrochemical measuring device in accordance with an embodiment of the present invention.

圖3顯示依本發明一實施例之血液中血球容積比、電壓及電流間的關係圖。Fig. 3 is a graph showing the relationship between blood cell volume ratio, voltage and current in blood according to an embodiment of the present invention.

圖4顯示依本發明一實施例,在固定電壓下,血液中血球容積比、時間及電流間的關係圖。Figure 4 is a graph showing the relationship between blood volume ratio, time and current in blood at a fixed voltage according to an embodiment of the present invention.

圖5顯示依本發明一實施例,在固定電壓及固定測量時間下,血液中血球容積比及電流間的關係圖。Figure 5 is a graph showing the relationship between blood volume ratio and current in blood at a fixed voltage and a fixed measurement time according to an embodiment of the present invention.

圖6顯示依本發明一實施例,量測血糖濃度時之電化學量測裝置中電壓及時間的關係圖。Figure 6 is a graph showing the relationship between voltage and time in an electrochemical measuring device for measuring blood glucose concentration according to an embodiment of the present invention.

100...電化學量測裝置100. . . Electrochemical measuring device

111...連接部111. . . Connection

112...連接部112. . . Connection

120...參考電壓源120. . . Reference voltage source

130...電流電壓轉換電路130. . . Current-voltage conversion circuit

140...類比數位轉換電路140. . . Analog digital conversion circuit

150...處理器150. . . processor

160...顯示器160. . . monitor

170...記憶體170. . . Memory

200...感測試片200. . . Sense test piece

211...工作電極211. . . Working electrode

212...工作電極212. . . Working electrode

Claims (17)

一種血球容積比測量方法,其利用包含多個電極的一感測試片及耦接該感測試片的一電化學量測裝置,來測量位於該些電極間之一血液中的一血球容積比,該測量方法包含:透過該些電極供給一第一預定電壓至該血液,並於一第一測量期間測得一第一電流值;及依據該第一電流值及一關係式計算出該血球容積比,其中該關係式是利用具有相異且已知的血球容積比的多個樣本血液所求得,其中該關係式為一線性關係式,且該線性關係式是利用分別供給一第二預定電壓至該些樣本血液,並於一第二測量期間測得多個樣本電流值,依據該些樣本電流值及該些已知的血球容積比來加以求得,該第一預定電壓及該第二預定電壓的絕對值大於0.5V和小於等於3V,而且該第一測量期間及該第二測量期間小於10秒。 A blood cell volume ratio measuring method for measuring a blood cell volume ratio in a blood between one of the electrodes by using a sensing test piece including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece, The measuring method includes: supplying a first predetermined voltage to the blood through the electrodes, and measuring a first current value during a first measurement period; and calculating the blood cell volume according to the first current value and a relationship Ratio, wherein the relationship is obtained by using a plurality of sample blood having different and known hematocrit ratios, wherein the relationship is a linear relationship, and the linear relationship is utilized to separately supply a second predetermined And measuring a plurality of sample current values during a second measurement period, and determining the sample current value and the known blood cell volume ratio, the first predetermined voltage and the first The absolute value of the two predetermined voltages is greater than 0.5V and less than or equal to 3V, and the first measurement period and the second measurement period are less than 10 seconds. 如申請專利範圍第1項所述之血球容積比測量方法,其中該些相異且已知的血球容積比包含60%、40%及20%的血球容積比。 The blood cell volume ratio measuring method according to claim 1, wherein the different and known hematocrit ratios comprise blood cell volume ratios of 60%, 40%, and 20%. 如申請專利範圍第1項所述之血球容積比測量方法,其中該第一預定電壓等於該第二預定電壓,且該第一測量期間等於該第二測量期間。 The method for measuring a hematocrit ratio according to claim 1, wherein the first predetermined voltage is equal to the second predetermined voltage, and the first measurement period is equal to the second measurement period. 如申請專利範圍第2項所述之血球容積比測量方法,其中,該線性關係式為y=ax+b,且y代表該第一電流值,x代表該血球容積比,且a及b分別代表一常數,且該些常數a及b是利用線性迴歸,依據該些樣本電流值及該些已知的血球容積比來加以求得。 The blood cell volume ratio measuring method according to claim 2, wherein the linear relationship is y=ax+b, and y represents the first current value, x represents the blood cell volume ratio, and a and b respectively Represents a constant, and the constants a and b are determined by linear regression based on the sample current values and the known hematocrit ratios. 如申請專利範圍第1項所述之血球容積比測量方法,其中該第一預定電壓的絕對值大於0.7V。 The blood cell volume ratio measuring method according to claim 1, wherein the absolute value of the first predetermined voltage is greater than 0.7V. 如申請專利範圍第5項所述之血球容積比測量方法,其中,該線性關係式為y=ax+b,且y代表該第一電流值,x代表該血球容積比,且a及b分別代表一常數,且該些常數a及b是利用線性迴歸,依據該些樣本電流值及該些已知的血球容積比來加以求得。 The blood cell volume ratio measuring method according to claim 5, wherein the linear relationship is y=ax+b, and y represents the first current value, x represents the blood cell volume ratio, and a and b respectively Represents a constant, and the constants a and b are determined by linear regression based on the sample current values and the known hematocrit ratios. 一種血糖濃度測量方法,其利用包含多個電極的一感測試片及耦接該感測試片的一電化學量測裝置,來測量位於該些電極間之一血液中的一血糖濃度,該測量方法包含: 透過該些電極供給一第一預定電壓至該血液,並於一第一測量期間測得一第一電流值;及依據該第一電流值及一關係式計算出一血球容積比,其中該關係式是利用具有相異且已知的血球容積比的多個樣本血液所求得,而且該關係式為一線性關係式,該線性關係式是利用分別供給一第三預定電壓至該些樣本血液,並於一第三測量期間測得多個樣本電流值,依據該些樣本電流值及該些已知的血球容積比來加以求得,該第一預定電壓及該第三預定電壓的絕對值大於0.5v和小於等於3V,而且該第一測量期間及該第三測量期間小於10秒;透過該些電極供給一第二預定電壓至該血液,並於一第二測量期間測得一第二電流值,依據該第二電流值求得該血糖濃度的一測量值;依據該血球容積比來補償該血糖濃度的該測量值,以求得該血糖濃度的一實際值。 A blood glucose concentration measuring method for measuring a blood glucose concentration in blood between one of the electrodes by using a sensing test piece including a plurality of electrodes and an electrochemical measuring device coupled to the sensing test piece The method includes: Supplying a first predetermined voltage to the blood through the electrodes, and measuring a first current value during a first measurement period; and calculating a blood cell volume ratio according to the first current value and a relationship, wherein the relationship is The formula is obtained by using a plurality of sample blood having different and known hematocrit ratios, and the relationship is a linear relationship by supplying a third predetermined voltage to the sample blood respectively. And measuring a plurality of sample current values during a third measurement period, and determining the absolute values of the first predetermined voltage and the third predetermined voltage according to the sample current values and the known blood cell volume ratios More than 0.5v and less than or equal to 3V, and the first measurement period and the third measurement period are less than 10 seconds; a second predetermined voltage is supplied to the blood through the electrodes, and a second is measured during a second measurement period The current value is obtained according to the second current value to obtain a measured value of the blood glucose concentration; the measured value of the blood glucose concentration is compensated according to the blood cell volume ratio to obtain an actual value of the blood glucose concentration. 如申請專利範圍第7項所述之血糖濃度測量方法,其中,該些相異且已知的血球容積比包含60%、40%及20%的血球容積比。 The blood glucose concentration measuring method according to claim 7, wherein the different and known blood cell volume ratios comprise blood cell volume ratios of 60%, 40%, and 20%. 如申請專利範圍第8項所述之血糖濃度測量方法,其中該線性關係式為y=ax+b,且y代表該第一電流值,x代 表該血球容積比,且a及b分別代表一常數,且該些常數a及b是利用線性迴歸,依據該些樣本電流值及該些已知的血球容積比來加以求得。 The blood glucose concentration measuring method according to Item 8 of the patent application, wherein the linear relationship is y=ax+b, and y represents the first current value, x generation The hematocrit ratio is represented, and a and b represent a constant, respectively, and the constants a and b are obtained by linear regression based on the sample current values and the known hematocrit ratios. 如申請專利範圍第7項所述之血糖濃度測量方法,其中該依據該血球容積比來補償該血糖濃度的該測量值的步驟,包含利用另一線性關係式來補償該血糖濃度的該測量值,該另一線性關係式為Gluacu =m * Glumea +n,且Gluacu 代表該血糖濃度的該實際值,Glumea 代表該血糖濃度的該測量值,m及n分別代表一常數。The method for measuring blood glucose concentration according to claim 7, wherein the step of compensating the measured value of the blood glucose concentration according to the hematocrit ratio comprises compensating the measured value of the blood glucose concentration by using another linear relationship. The other linear relationship is Glu acu = m * Glu mea + n, and Glu acu represents the actual value of the blood glucose concentration, Glu mea represents the measured value of the blood glucose concentration, and m and n represent a constant, respectively. 如申請專利範圍第7項所述之血糖濃度測量方法,其中該依據該第一預定電壓大於該第二預定電壓,且該第一測量期間小於該第二測量期間。 The method for measuring blood glucose concentration according to claim 7, wherein the first predetermined voltage is greater than the second predetermined voltage, and the first measurement period is less than the second measurement period. 如申請專利範圍第7項所述之血糖濃度測量方法,其中該第一預定電壓及該第三預定電壓的絕對值大於0.7V。 The blood glucose concentration measuring method according to claim 7, wherein the absolute value of the first predetermined voltage and the third predetermined voltage is greater than 0.7V. 一種電化學量測裝置,適於耦接於一感測試片,該感測試片包含多個電極,該電化學量測裝置包含:兩個連接部,分別耦接該感測試片的該些電極;一處理器,耦接於該些連接部,並且透過該些連接部及該些電極,供給一第一預定電壓至位於該些電極的一血液,並於一第一測量期間測得一第一電流值;及 依據該第一電流值及一關係式計算出一血球容積比,其中該關係式是利用具有相異且已知的血球容積比的多個樣本血液所求得,而且該關係式為一線性關係式,該線性關係式是利用分別供給一第三預定電壓至該些樣本血液,並於一第三測量期間測得多個樣本電流值,依據該些樣本電流值及該些已知的血球容積比來加以求得,該第一預定電壓及該第三預定電壓的絕對值大於0.5v和小於等於3V,而且該第一測量期間及該第三測量期間小於10秒;該些電極供給一第二預定電壓至該血液,並於一第二測量期間測得一第二電流值,依據該第二電流值求得該血糖濃度的一測量值;並且依據該血球容積比來補償該血糖濃度的該測量值,以求得該血糖濃度的一實際值。 An electrochemical measuring device is adapted to be coupled to a sensing test piece, the sensing test piece comprising a plurality of electrodes, the electrochemical measuring device comprising: two connecting portions respectively coupled to the electrodes of the sensing test piece a processor coupled to the connecting portions, and through the connecting portions and the electrodes, supplies a first predetermined voltage to a blood located at the electrodes, and measures a first period during a first measurement period a current value; and Calculating a blood cell volume ratio according to the first current value and a relation, wherein the relationship is obtained by using a plurality of sample blood having different and known hematocrit ratios, and the relationship is a linear relationship The linear relationship is obtained by separately supplying a third predetermined voltage to the sample blood, and measuring a plurality of sample current values during a third measurement period, according to the sample current values and the known blood cell volumes. Obtaining, the absolute values of the first predetermined voltage and the third predetermined voltage are greater than 0.5v and less than or equal to 3V, and the first measurement period and the third measurement period are less than 10 seconds; Dividing a predetermined voltage to the blood, and measuring a second current value during a second measurement period, determining a measured value of the blood glucose concentration according to the second current value; and compensating the blood glucose concentration according to the blood cell volume ratio The measured value is used to determine an actual value of the blood glucose concentration. 如申請專利範圍第13項所述之電化學量測裝置,其中,該線性關係式為y=ax+b,且y代表該第一電流值,x代表該血球容積比,且a及b分別代表一常數。 The electrochemical measuring device according to claim 13, wherein the linear relationship is y=ax+b, and y represents the first current value, x represents the blood cell volume ratio, and a and b respectively Represents a constant. 如申請專利範圍第14項所述之電化學量測裝置,更包含一記憶裝置,儲存有該關係式。 The electrochemical measuring device of claim 14, further comprising a memory device storing the relationship. 如申請專利範圍第15項所述之電化學量測裝置,其中, 該記憶裝置更儲存有另一線性關係式,且該處理器更利用該另一線性關係式來補償該血糖濃度的該測量值,該另一線性關係式為Gluacu =m * Glumea +n,且Gluacu 代表該血糖濃度的該實際值,Glumea 代表該血糖濃度的該測量值,m及n分別代表一常數。The electrochemical measuring device of claim 15, wherein the memory device further stores another linear relationship, and the processor further utilizes the other linear relationship to compensate for the measurement of the blood glucose concentration. Value, the other linear relationship is Glu acu = m * Glu mea + n, and Glu acu represents the actual value of the blood glucose concentration, Glu mea represents the measured value of the blood glucose concentration, and m and n represent a constant, respectively. 如申請專利範圍第14項所述之電化學量測裝置,其中該依據該第一預定電壓大於該第二預定電壓,且該第一測量期間小於該第二測量期間。 The electrochemical measuring device of claim 14, wherein the first predetermined voltage is greater than the second predetermined voltage, and the first measurement period is less than the second measurement period.
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