TW201310027A - Biosensor, sensing unit and method - Google Patents

Abstract

A biosensor is adapted to a sensing unit. The sensing unit comprises a first electrode, a second electrode, and a reaction chamber for receiving a sample. The biosensor couples to a DC voltage source and comprises a control unit, and a switch device. The switch device is coupled to the DC voltage source, the first electrode and the second electrode. The control unit controls the switch device and thus a DC voltage is applied to the sample via the first electrode and the second electrode.

Description

Biosensor, sensing unit and method

The invention relates to a biosensor, a sensing unit and a method, in particular to a biosensor, a sensing unit and a method which are corrected according to a blood cell volume ratio.

The detection principle of the general electrochemical sensing test piece is mainly to use the test object in the blood sample to react with the reagent on the test piece, and to measure the current value of the test piece through a fixed voltage, and then use a conversion formula to Find the concentration of the analyte. However, such a single-voltage current detecting device is easily interfered by blood cells in the blood, thereby affecting the accuracy of the measurement. The effect of blood volume ratio (HCT) on the whole blood test is twofold: (1) changing the viscosity of the blood, causing the efficiency of electron transfer to be different, affecting the measured current value; (2) causing detection The volume ratio of serum is inconsistent, which in turn leads to differences in measurement standards.

Taking blood glucose testing as an example, since the concentration of serum and blood cells in different users is different, the reagents on the blood glucose test strip can only react with the serum. For the same volume of whole blood samples, the higher the blood cell content is, the actual The volume of serum that can react with the reagent is also less. Even if the blood glucose concentration (glucose concentration in the blood) is the same, different detection results are caused by different blood cell volume ratios.

In order to reduce or eliminate measurement errors caused by different blood cell volume ratios, the prior art utilizes a blood cell separation membrane to exclude blood cells in the specimen. However, such a method would require more samples and the reaction time would be longer. Another method is to use the AC impedance measurement method to estimate the blood volume ratio of the sample, and to compensate for the detection result. However, such an approach requires an additional set of measuring electrodes, or an alternating voltage, which increases the complexity of the test strip fabrication.

SUMMARY OF THE INVENTION An object of the present invention is to provide a whole blood detecting apparatus which employs an alternating DC voltage and which can reduce an error caused by a blood volume ratio or use this characteristic to correct a blood cell volume ratio.

An embodiment of the present invention provides a biosensor for use with a sensing unit. The sensing unit includes a first electrode, a second electrode, and a reaction cavity that houses a sample to be tested. The biosensor is coupled to the DC voltage source and includes a control unit and a converter. The converter is coupled to the DC voltage source, the first electrode and the second electrode. The control unit controls the converter such that the first electrode and the second electrode apply a DC voltage to the object to be tested.

Another embodiment of the present invention provides a biosensing method, which is applicable to a sensing unit and a biosensor. The sensing unit houses a sample to be tested and has a first electrode and a second electrode. The biosensor is coupled to the sensing unit and has a converter. The method includes: applying a DC voltage to the object to be tested; after a first predetermined time; transmitting, by the converter, the first electrode and the second electrode to apply a pair of DC voltages to the object to be tested a reverse voltage of the same magnitude; after a second predetermined time, a current value is obtained, and the concentration of the sample to be tested is estimated according to the current value, and the blood volume ratio of the current value is less than The current value for a predetermined period of time.

Another embodiment of the present invention provides a biosensing method, which is applicable to a sensing unit and a biosensor. The sensing unit houses a sample to be tested and has a first electrode and a second electrode. The biosensor is coupled to the sensing unit and has a converter. The method includes: applying a DC voltage to the test object; after a first predetermined time, measuring a first current value; and transmitting, by the converter, the first electrode and the second electrode to be tested Applying a pair of reverse voltages that are DC voltages and of the same magnitude; and after a second predetermined time, measuring a second current value because the second current value is greater than the blood volume ratio of the first current value Differently, a blood cell volume ratio of the sample to be tested may be estimated according to the first current value and the second current value.

Another embodiment of the present invention provides a biosensing method, which is applicable to a sensing unit and a biosensor. The sensing unit has a reaction chamber, a reagent, a first electrode and a second electrode. The biosensor has a converter. The method comprises: taking a sample to be tested into the reaction cavity, and reacting the sample to be tested with the reaction reagent; applying a DC voltage to the sample to be tested during a constant stabilization period, and measuring a first current value; the first electrode and the second electrode are applied to the object to be tested by applying a reverse voltage corresponding to a DC voltage; and in a transition period, the test is to be tested The sample is measured by a second current value; after the reverse voltage is applied for a predetermined time, the third current value is measured for the sample to be tested; A blood value is different from the influence of the blood volume ratio, and a blood cell volume ratio of the sample to be tested is estimated according to the first current value and the third current value.

The above and other technical contents, features and advantages of the present invention will be apparent from the following detailed description of the preferred embodiments. The directional terms mentioned in the following embodiments, such as up, down, left, right, front or back, etc., are only directions referring to the additional drawings. Therefore, the directional terminology used is for the purpose of illustration and not limitation.

An embodiment of the present invention provides a simple biosensor, sensing unit, and blood volume ratio measurement technology, which reduces the hematocrit ratio by means of compensation to a general disposable biosensor. Interference. The method is characterized in that the sample to be tested is first introduced into a reaction chamber containing at least two reaction electrodes and a reaction reagent by capillary suction. Then, a DC voltage lasting for a few seconds is applied to the two sensing electrodes, and an operational amplifier and an analog-to-digital converter are used to read the reaction signals in the sensing unit, and a first current value is obtained at different time points. And a second current value. Then, using a converter (or switching device), the polarities of the two sensing electrodes are instantaneously and mutually switched, and another reverse voltage lasting for several seconds is applied, and then the same group of operational amplifiers and analog-to-digital converters are transmitted. The reaction signal is read and a third current value is measured. Wherein the DC voltage and the reverse voltage are two voltages that are opposite. Using the third current value to be different from the blood volume ratio received by the first current value, estimating the blood cell volume ratio by the first current value and the third current value, and then using the estimated blood cell volume ratio to the second The current value is corrected for the current value, and a biosensing parameter, such as a blood glucose level, is estimated based on the corrected second current value. In another embodiment, the first current value and the third current value may be measured only, and the estimated blood volume ratio is used to correct the current of the third current value, and according to the corrected The third current value is used to estimate a biosensing parameter, such as a blood glucose level. In another embodiment, the third current value may be measured only, and a bio-sensing parameter, such as a blood glucose level, may be directly estimated based on the third current value.

1 is a schematic diagram of an embodiment of a biosensor and a sensing unit in accordance with the present invention. The biosensor includes a converter 12, an operational amplifier 13, an analog digital converter 14, and a control unit 15. The sensing unit 11 includes a first electrode 16, a second electrode 17, and a reaction chamber 18. In this embodiment, the first electrode 16 is coupled to the DC voltage source V ₁ and the second electrode 17 is coupled to a ground potential GND. That is, there is a potential difference V ₁ between the first electrode 16 and the second electrode 17. The converter 12 is coupled to a positive input terminal and a negative input terminal of the operational amplifier 13 , and the first electrode 16 is coupled to the negative input terminal or the positive input terminal of the operational amplifier 13 according to a control signal of the control unit 15 . The second electrode 17 is coupled to the positive input terminal or the negative input terminal of the operational amplifier 13 . That is, the first electrode 16 and the second electrode 17 are respectively connected to two different input terminals of the operational amplifier 13. The reaction chamber 18 stores a reaction reagent and is used to accommodate a sample to be tested, such as blood.

When the sample to be tested enters the reaction chamber 18 and is electrochemically reacted with the reagent, the first electrode 16 and the second electrode 17 can apply a DC voltage V ₁ to the sample to be tested, and continue for a first time. After a predetermined time T _A (for example, about 2 to 7 seconds), a first current value I _A and a second current value I _B are respectively measured by the operational amplifier 13 and the analog-to-digital converter 14 (see 2, described later). Next, the control unit 15 then outputs a control signal to the converter 12 so that the first electrode 16 is applied with a DC voltage V ₁ is the reverse of a reverse current to the second electrode of the test specimen 17 The voltage, which has a value of -V ₁ and continues for a second predetermined time (for example, about 0.5 seconds to 5 seconds), is measured and a third current value I _{C is} measured. For a clearer explanation, please refer to Figure 2. Fig. 2 is a schematic diagram of the voltage applied to the biosensor and the sensing unit of Fig. 1 and the measured current. In Fig. 2, the DC voltage V ₁ is applied to the test object _first , and at this time, it can be found that the current value flowing through the test object is gradually lowered and approaches a stable value. Therefore, when measuring the first current value I _A , it must be obtained as early as possible in the steady state time interval. In FIG. 2, when the current value _A measurement time T I _A, T _B and then at the time point of time, measure the current value I _B. It should be noted that the time point T _B is before the time point when the aforementioned applied DC voltage V _{1 is} converted into the reverse voltage -V ₁ . In another embodiment, the current value I _B can also be measured after the voltage is converted, that is, at the reverse voltage -V ₁ (not shown). Next, when the third current value I _C is measured at the time point T _C , it is acquired as much as possible in the transition state time interval. In the second diagram and the present embodiment, the applied voltage is changed from the DC voltage V ₁ to the reverse voltage -V ₁ at the 7th second, so that the time point T _C is, for example, at the 8th second. Measure the current value I _C . In this embodiment, the closer the time point C is to the time point of the voltage transition, the better; in other words, the current value I _C is measured immediately after the voltage conversion, which can be better for the correction of the current current correction and the hematocrit ratio. effect.

After obtaining the first current value I _A , the second current value I _B and the third current value I _C , the first current value I _A is first divided by the third current value I _{C to} obtain a ratio R (R=I _A / I _C ). Then, by plotting the ratio R and the hematocrit ratio (HCT), a linear equation HCT=kR+h exhibiting an inverse relationship as shown in FIG. 3, wherein k and h are parameters, can be obtained. In other embodiments, a comparison table between the R value and the hematocrit ratio may be established, and the value of the hematocrit ratio may be obtained by using a look-up table.

Since the aforementioned R value has a linear relationship with the HCT value, the HCT value can be estimated by measuring the ratio R (R = I _A / I _C ) of the first current value I _A and the third current value I _C . Taking this estimated 40% of the HCT value as the center point, it can be estimated that for every 1% increase in HCT value, the measured current value is reduced by 1.11% (as shown in Fig. 4). Thus, we can first value to a second current I _B is compensated, the compensated second current value I _B ^'as follows:

I _B '=I _B /(1+(HCT-40%)*1.11)

By introducing the aforementioned blood cell volume ratio formula (HCT=kR+h), the following formula can be obtained.

I _B '=I _B /(1+((k*I _A /I _C +h)-40%)*1.11)

Figure 5 is a comparison of the second current value I _{B that} has not been corrected and the second current value I _B ' that has been corrected. It can be seen from Fig. 5 that after the feedback of the aforementioned hematocrit ratio, the disturbance (Bias) due to the hematocrit ratio is significantly reduced.

On the other hand, since the first current value, the second current value, and the third current value measured by the foregoing various methods have different degrees of influence on the blood volume ratio, different organisms can be evaluated according to different measurement values. Sensing parameters such as blood glucose levels. Please refer to Figure 6. Figure 6 is a schematic diagram of voltage and measurement current applied to a biosensor and a sensing unit. An embodiment of the biosensor used in Fig. 6 is one of the biosensors shown in Fig. 1. In Fig. 6, the DC voltage V ₁ is applied to the test object _first , and at this time, it can be found that the current value flowing through the test object is gradually lowered and approaches a stable value. Therefore, when measuring the current value I _A , it must be obtained as early as possible in the steady state time interval. In Fig. 6, the current value I _A is measured at the 3rd second after the application of the DC voltage V ₁ , and then, after a certain time, the current value I _B is measured. It should be noted that the time point at which the current value I _B is measured is preferably before the time point when the aforementioned applied DC voltage V ₁ is converted to the reverse voltage -V ₁ . In another embodiment, the current value I _B can also be measured after the voltage is converted, that is, measured at the reverse voltage -V ₁ (not shown). In the present embodiment, the current value I _B is measured at the 7th second after the application of the DC voltage V ₁ .

Then, the current value I _C is measured after another predetermined time. The measurement of the current value I _C should be taken as far as possible within the transition state time interval. In the embodiment of Fig. 6, the applied voltage is changed from the DC voltage V ₁ to the reverse voltage -V ₁ at the 7th second, so the time point at which the current value I _C is measured can be selected. The current value I _C is measured at 8 seconds. In the present embodiment, the time point at which the current value I _C is measured is closer to the time point of the voltage transition. In other words, when the current value I _C is measured immediately after the voltage is converted, it is possible to have a better effect on the correction of the current correction and the hematocrit ratio.

Fig. 7 is a graph showing the drift rate of the current value I _A and the current value I _C at different hematocrit ratios. The schematic diagram of Fig. 7 is a result of detection based on a sample of 80 mg/dL of glucose (or blood glucose). It can be seen from Fig. 7 that the smaller the hematocrit ratio, the higher the drift rate of the current value I _A and the current value I _C . In order to reduce the influence of the drift rate, the ratio R (R = I _A / I _C ) can be obtained first by the above method. The current value I _{B is} then corrected to reduce the interference due to the hematocrit ratio, and a biosensing parameter, such as a blood glucose level, is estimated based on the corrected current value I _B .

The above is only the preferred embodiment of the present invention, and the scope of the invention is not limited thereto, that is, the simple equivalent changes and modifications made by the scope of the invention and the description of the invention are All remain within the scope of the invention patent. 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.

11. . . Sensing unit

12. . . converter

13. . . Operational Amplifier

14. . . Analog digital converter

15. . . control unit

16. . . First electrode

17. . . Second electrode

18. . . Reaction chamber

I _A . . . First current

I _B . . . Second current

I _C . . . Third current

T _A , T _B , T _C . . . Time point

1 is a schematic diagram of an embodiment of a biosensor and a sensing unit in accordance with the present invention.

Fig. 2 is a schematic diagram of the voltage applied to the biosensor and the sensing unit of Fig. 1 and the measured current.

Figure 3 is a plot of R value versus blood cell volume ratio.

Figure 4 is a plot of blood cell volume ratio versus current.

Figure 5 is a comparison of the second current value I _{B that} has not been corrected and the second current value I _B ' that has been corrected.

Figure 6 is a schematic diagram of voltage and measurement current applied to a biosensor and a sensing unit.

Fig. 7 is a graph showing the drift rate of the current value I _A and the current value I _C at different hematocrit ratios.

11. . . Sensing unit

12. . . converter

13. . . Operational Amplifier

14. . . Analog digital converter

15. . . control unit

16. . . First electrode

17. . . Second electrode

18. . . Reaction chamber

Claims (16)

A biosensor is used to cooperate with a sensing unit. The sensing unit includes a first electrode, a second electrode, and a reaction cavity for accommodating a sample to be tested. The biosensor is coupled to the DC voltage. Source and include:
a control unit; and a converter coupled to the DC voltage source, the first electrode and the second electrode; the control unit controls the converter to cause the first electrode and the second electrode to be tested Apply a DC voltage. The biosensor of claim 1, wherein the DC voltage source comprises:
a first end is initially coupled to the first electrode; and a second end is initially coupled to the second electrode. The biosensor of claim 2, wherein the converter couples the first electrode to the second end, the second electrode is coupled to the first end, the electrode and the second The electrode applies a pair of DC voltages to the object to be tested as a reverse voltage. A biosensor as described in claim 1 is for sensing a blood glucose level. The biosensor according to claim 1, further comprising an operational amplifier for sensing and amplifying a current of the object to be tested. The biosensor of claim 5, further comprising an analog-to-digital converter for converting an output signal of the operational amplifier into a digital signal. A biosensing method is applied to a sensing unit and a biosensor, the sensing unit accommodating a sample to be tested and having a first electrode and a second electrode, the biosensor and the sensing unit Connected and has a converter, the method comprising:
Applying a DC voltage to the sample to be tested;
After a first predetermined time, measuring a first current value;
Transmitting, by the converter, the first electrode and the second electrode to apply a pair of reverse voltages corresponding to a DC voltage to the object to be tested; and after a second predetermined time, measuring a second current value, and according to The first current value and the second current value estimate a blood cell volume ratio of the sample to be tested. The biosensing method described in claim 7 of the patent application further includes:
The first current value or the second current value is corrected according to the blood cell volume ratio to estimate a bio-sensing parameter of the sample to be tested. The biosensing method described in claim 7 of the patent application further includes:
Calculating a third current value before applying the reverse voltage to the sample to be tested;
Correcting the third current value according to the blood cell volume ratio; and estimating a bio-sensing parameter of the sample to be tested according to the corrected third current value. The biosensing method described in claim 7 of the patent application further includes:
When the reverse voltage is applied to the sample to be tested, a third current value is simultaneously measured;
Correcting the third current value according to the blood cell volume ratio; and estimating a bio-sensing parameter of the sample to be tested according to the corrected third current value. The biosensing method described in claim 7 of the patent application further includes:
Measuring a third current value before measuring the second current value;
Correcting the third current value according to the blood cell volume ratio; and estimating a bio-sensing parameter of the sample to be tested according to the corrected third current value. A biosensing method is applied to a sensing unit and a biosensor, the sensing unit has a reaction chamber, a reaction reagent, a first electrode and a second electrode, and the biosensor and the sense The measuring unit is connected and has a converter, the method comprising:
Taking a sample to be tested into the reaction chamber, and reacting the sample to be tested with the reaction reagent;
During a constant stabilization period, a DC voltage is applied to the sample to be tested, and a first current value is measured;
Applying, by the converter, the first electrode and the second electrode to apply a pair of reverse voltages corresponding to a DC voltage to the object to be tested;
During a conversion period, a second current value is obtained for the sample to be tested;
After the reverse voltage is applied for a predetermined period of time, the third current value is measured for the sample to be tested; and the to-be-tested is estimated according to the first current value and the third current value. The ratio of the volume of a blood cell. The biosensing method according to claim 12, further comprising:
And correcting the second current value according to the blood cell volume ratio; and estimating a bio-sensing parameter of the sample to be tested according to the corrected second current value. The biosensing method of claim 13, wherein the biosensing parameter is a blood glucose level. The biosensing method according to claim 12, further comprising:
A ratio of the first current value to the third current value is obtained; and the blood cell volume ratio is estimated based on the ratio. A biosensing method is applied to a sensing unit and a biosensor, the sensing unit accommodating a sample to be tested and having a first electrode and a second electrode, the biosensor and the sensing unit Connected and has a converter, the method comprising:
Applying a DC voltage to the sample to be tested;
After a first predetermined time, the first electrode and the second electrode are applied to the object to be tested by applying a pair of reverse voltages of a DC voltage and a same amount; and at a second predetermined time Thereafter, a current value is measured, and the concentration of the sample to be tested is estimated based on the current value.