KR100545129B1 - Urine glucose measuring apparatus - Google Patents

Abstract

The urine glucose measuring apparatus according to the present invention includes a urine glucose sensor configured to output a first signal generated in response to a glucose component and an interference component in urine and a second signal generated in response to an interference component; A signal detector for differentially amplifying the first signal and the second signal and outputting a third signal; A control unit for converting the third signal into a concentration value of glucose and outputting it as a fourth signal; And a display unit for displaying the concentration of glucose according to the fourth signal. In addition, the urine glucose measurement apparatus according to the present invention, a radio transmitter for modulating and transmitting the fourth signal to a radio signal; And a wireless receiver for receiving, demodulating and outputting a wireless signal. Here, the wireless signal may be transmitted and received by a protocol according to the infrared communication standard. The urine glucose sensor may use glycosylase and an organic or inorganic metal compound as an electron transfer medium to oxidize glucose. According to the present invention, by supplementing the inconvenience of the conventional invasive blood glucose measurement method and the disadvantage of the urine glucose test method using the colorimeter, the general public can easily measure the diabetes level non-invasive and quantitative.

Description

Urine glucose measuring apparatus

1 is a block diagram illustrating a urine glucose measurement apparatus according to an embodiment of the present invention.

2A and 2B are schematic views of the urine glucose sensor shown in FIG. 1.

3 is a schematic diagram illustrating a reaction process of the urine glucose sensor illustrated in FIG. 1.

4 is a schematic view for explaining a preferred embodiment of the electrode manufacturing process of the urine glucose sensor shown in FIG.

Fig. 5A is a model diagram of the amperometric method using a two-electrode system.

5B is a model diagram of the amperometric method using a three-electrode system.

FIG. 6 is a graph measured by an oscilloscope of a current output waveform according to the glucose concentration of the signal detector illustrated in FIG. 1.

7 is a schematic diagram for explaining a preferred embodiment of a wireless communication protocol according to the present invention.

8 is a graph showing comparative analysis results by linear regression analysis.

Figure 9 is a graph showing the residual distribution for the YSI of the urine glucose measuring apparatus according to the present invention.

FIG. 10 is a histogram of the residual distribution shown in FIG. 9.

11 is a graph showing the results of performing the Anderson Daring Normality Test.

The present invention relates to a urine glucose measurement apparatus.

Diabetes mellitus is one of many chronic diseases in recent years, which is difficult to cure and has many problems for the patient and family as well as the society due to various side effects and complications if the health treatment according to the therapeutic prescription is not performed regularly every day. Results in.

Recently, there is a need to periodically measure the amount of glucose (Glucose) to diagnose and prevent diabetes. The blood glucose level measured by the general public at home or at work is the basic data for diagnosing and managing diabetes in daily life, and the measured blood glucose level is recorded as data and shown to the doctor during the examination. Therefore, it is very important to continuously check for diabetes and monitor the state of glucose concentration.

Conventional self blood glucose meters are classified into invasive and colorimetric methods. Invasive methods use a small instrument, such as a lancet, to pierce a portion of the body to collect blood invasively to measure blood glucose levels. The colorimetric method measures blood glucose by reading a strip of reagent that changes color depending on the amount of blood glucose contained in the urine.

However, such a conventional self blood glucose meter has the following inconvenience to continuously check and monitor the glucose level.

First, the invasive approach involves pain in the patient because of the need for bodily blood.

Second, the colorimetric method using the urine strip has a limitation in quantitatively indicating the change in color due to the inaccuracy of sample transport, pretreatment, urine volume, reaction time and color development time.

Therefore, the technical problem to be achieved by the present invention is to provide a urine glucose measuring apparatus that can measure the sugar level in a non-invasive and quantitative manner.

In order to achieve the above technical problem, the urine glucose measuring apparatus according to the present invention, a urine glucose sensor for outputting a first signal generated in response to the glucose component and the interference component in the urine, and a second signal generated in response to the interference component; A signal detector configured to differentially amplify the first signal and the second signal to output a third signal; A controller which converts the third signal into a concentration value of glucose and outputs the fourth signal; And a display unit which displays the concentration of glucose by the fourth signal.

The urine glucose measuring apparatus may include: a radio transmitter for modulating and transmitting the fourth signal into a radio signal; And a wireless receiver configured to receive the demodulated signal and output the demodulated signal. The display unit may display the demodulated signal. Here, the wireless signal may be transmitted and received by a protocol according to the infrared communication standard.

The urine glucose sensor is used to oxidize glucose to hexaaminerucenium (III) chloride, potassium ferricyanide, potassium ferrocyanide, dimethyl ferrocene, ferricinium, ferrocene monocarboxylic acid, 7,7,8,8,- Tetracyanoquinomimethane, tetrathiafubarene, nikerocene, N-methyl asidinium, tetrathiatetracene, N-methylphenazinium, hydroquinone, 3-dimethylaminobenzoic acid, 3-methyl-2-benzo Thiozolinonehydrazone, 2-methoxy-4-arylphenol, 4-aminoantipyrine, dimethylaniline, 4-aminoantipyrene, 4-methoxynaphthol, 3,3`, 5,5`-tetramethylbenzidine, 2,2-azino-di- [3-ethyl-benzthiazoline solfonate], o-diazinidine, o-toluidine, 2,4-dichlorophenol, 4-aminophenazone, benzidine, prussian blue Electron transfer media may be used wherein the electrons are selected from the group consisting of compounds.

Hereinafter, the structure and operation of a urine glucose measuring apparatus according to an embodiment of the present invention will be described in detail with reference to the accompanying drawings.

The present invention supplements the inconvenience of the conventional invasive blood glucose measurement method and the shortcomings of the urine glucose test method using a colorimeter, and relates to a urine glucose measuring device that can easily measure and manage their diabetes degree quantitatively.

In the urine glucose measuring apparatus according to the present invention, the urine glucose is measured using an amount of current output differently according to the concentration of glucose contained in the urine deposited on the urine glucose measuring sensor.

1 is a block diagram illustrating a urine glucose measuring apparatus according to an exemplary embodiment of the present invention, which includes a urine glucose sensor 100, a signal detector 102, a controller 104, a display unit 106, and a wireless transmitter 108. , The wireless receiver 110, the diabetes management unit 112 is provided.

The urine glucose sensor 100 connected to a predetermined power source outputs a first current signal generated in response to a glucose component and an interference component included in urine, and a second current signal generated in response to only an interference component. Here, the interference component is an interference component in urine glucose measurement such as uric acid. When the difference between the first current signal and the second current signal is obtained by applying the differential amplifier method to the current output value of the urine glucose sensor 100, only the concentration of pure glucose contained in the urine can be detected.

The signal detector 102 differentially amplifies the first current signal and the second current signal and outputs a third signal. As a result, the third signal corresponds to glucose concentration. The signal detector 102 may differentially amplify the current signal output from the urine glucose sensor 100, convert the current signal into a voltage signal, remove the noise from the converted voltage signal, and output the third signal. To this end, the signal detector 102 may include a current-voltage converter (not shown), a differential amplifier (not shown), an analog filter unit (not shown), and an amplifier (not shown). The current-voltage converter (not shown) converts the first current signal and the second current signal output from the urine glucose sensor 100 into a first voltage signal and a second voltage signal. The differential amplifier unit differentially amplifies and outputs the first and second voltage signals converted into voltages. An analog filter unit (not shown) may be implemented as a low pass filter to remove noise from the differentially amplified output. An amplifier (not shown) amplifies the signal from which the noise is removed at a predetermined amplification rate and outputs the signal as a third signal.

The controller 104 converts the third signal into a glucose concentration value and outputs the fourth signal as a fourth signal including urine glucose data. The conversion equation may be in the form of Equation 1 below.

는 뇨당 센서(100)의 특성에 따라 소정 값으로 결정될 수 있다. 제어부(104)는 제3 신호를 뇨당 데이터로 환산하기 위하여, 아날로그-디지털 변환부(A/D converter)를 구비할 수 있다. 제4 신호에는 당뇨데이터 측정된 시간 정보가 포함될 수 있다. 시간 정보는 당뇨 데이터의 관리를 위하여 이용될 수 있다.here

May be determined to a predetermined value according to the characteristics of the urine glucose sensor 100. The controller 104 may include an analog-to-digital converter (A / D converter) to convert the third signal into urine glucose data. The fourth signal may include time information of diabetes data measured. The time information can be used for management of diabetes data.

The display unit 106 displays the concentration of glucose in response to the fourth signal. The display unit 106 may be implemented by a liquid crystal display (LCD) or the like.

The radio transmitter 108 modulates the fourth signal output from the controller 104 into a radio signal such as a radio frequency (RF) or an infrared signal (Infra-Red, IR) and transmits the modulated signal to the outside.

The wireless receiver 110 receives a high frequency signal or an infrared signal from the wireless transmitter 106 and demodulates it.

The diabetes management unit 112 receives the demodulated signal from the wireless receiver 108 and manages it. For effective diabetes management, the diabetes management unit 112 performs efficient management of diabetes from the measured diabetes data, including a diabetes management program, and for this purpose, the display unit 116 implemented by the storage unit 114 and the LCD. It may be further provided. Here, the wireless receiver 108 and the diabetic management unit 112 may be integrated into one device by a personal computer (PC) in which a diabetes management program is embedded.

Hereinafter, the components of the urine glucose measuring apparatus shown in FIG. 1 will be described in more detail.

2A and 2B are schematic views of the urine glucose sensor 100 shown in FIG. 1. Referring to the drawings, the urine glucose sensor 100 includes a reference electrode 200 in the center portion, a first working electrode 202 and a second working electrode 208 at both edges, and a dielectric on a polyester film 211. Membrane 212. Urine may be dropped on the first working electrode 202 and the second working electrode 208 or may form a capillary structure 206 on the outside to reach the working electrode and the reference electrode (secondary electrode). An enzyme that reacts to both glucose and an interference component is printed on the urine glucose sensing unit 204 of the first electrode, and an enzyme that does not react to glucose is printed on the urine glucose sensing unit 210 of the second electrode. Therefore, the first working electrode 202 connected to the predetermined power source may output the first current signal described above, that is, the current in response to the glucose component and the interference component. In addition, the second working electrode 208 connected to a predetermined power source may output a current in response only to the aforementioned second current signal, that is, the interference component. By applying the differential amplifier method to the current output value, the difference between the first current signal of the first working electrode 202 and the second current signal of the second working electrode 208 is obtained, the concentration of pure glucose contained in the urine sample Only can be detected quantitatively.

3 is a schematic view illustrating a reaction process of the urine glucose sensor 100 shown in FIG. 1. The urine glucose sensor 100 according to the present invention may use a glycosylase and an organic or inorganic metal compound as an electron transfer medium to oxidize glucose. The urine glucose sensor 100 oxidizes glucose, hexaamineminerium (III) chloride: [Ru (NH ₃ ) ₆ ] Cl ₃ ) or potassium ferricyanide, potassium ferrocyanide. , Dimethyl ferrocene, ferricinium, ferrocene monocarboxylic acid, 7,7,8,8, -tetracyanoquinomimethane, tetrathiafubarene, nichelocene, N-methylasidinium, tetrathiatetracene , N-methylphenazinium, hydroquinone, 3-dimethylaminobenzoic acid, 3-methyl-2-benzothiozononone hydrazone, 2-methoxy-4-arylphenol, 4-aminoantipyrine, dimethylaniline, 4-amino Antipyrene, 4-methoxynaphthol, 3,3 ′, 5,5′-tetramethylbenzidine, 2,2-azino-di- [3-ethyl-benzthiazoline solfonate], o-diazinidine, o -A mixed electron capable of forming a redox pair such as toluidine, 2,4-dichlorophenol, 4-aminophenazone, benzidine, and prussian blue is selected from the group consisting of compounds It can be used as a transfer medium.

The urine glucose sensor 100 immobilizes glucose oxidase (GOD) and an electron transfer medium, preferably with a low oxidation potential, on the surface of the porous thin film. The urine glucose sensor 100 according to the present invention immobilizes glucose oxidase directly on the electrode surface. In addition, nuxaaminerucenium (III) chloride can be used as a preferred material because it can be measured at a lower potential than conventional electron transfer mediators, thereby minimizing the influence of interference materials. The urine glucose sensor 100 according to the present invention has the advantage of being able to introduce a constant amount of sample within a short time due to capillary action, as well as excellent reproducibility between electrodes, easy handling, and mass production at a low price. .

The electron transport media used in conventional glucose sensors mostly use fat-soluble ferrocene and water-soluble potassium ferricyanide, which are ascorbic acid, acetoaminenophen, uric acid, It is oxidized at similar potentials as the same interference material. Therefore, there is a problem that can not completely remove the interference in the urine. In addition, in the conventional glucose sensor, the error of the sample amount affects the measurement result. In order to compensate for this problem, the urine glucose sensor 100 according to the present invention introduces a sample using a capillary phenomenon.

4 is a schematic view for explaining a preferred embodiment of the electrode manufacturing process of the urine glucose sensor 100 shown in FIG.

Carbon paste and silver paste may be used as the electrode material in the manufacture of the urine glucose center 100, and an insulation paste (SCR-505G) and a curing agent may be used. Using a screen printer, a carbon dough electrode can be produced by printing a carbon dough on a polyester film.

First, an electrode layer (conduction layer), which is an electrical connection portion, is printed on a polyester film (step S400). For example, the silver (Ag) electrode layer is printed by printing with a silver paste on the polyester film and then curing for 5 minutes at 140 degrees Celsius.

After step S400, the working electrode is printed using carbon paste (step S402). For example, a working electrode is printed using carbon paste on the silver (Ag) electrode and cured for 15 minutes at 140 degrees Celsius.

After the step S402, a dielectric layer is printed leaving a capillary path on the electrode, and then enzyme is immobilized (step S404), and an external protective substrate is adhered thereto (step S406). Both the glucose and the interference component react with the immobilized enzyme, but only with the interference component other than the electrode to which the glycosylase is not immobilized. The output current values of the first electrode and the second electrode of the urine glucose sensor vary according to the nature of the enzyme that does or does not react to glucose. The urine glucose sensor 100 according to the present invention immobilizes glucose oxidase (GOD) and an electron transfer medium on a porous thin film, and quantitatively detects the concentration of glucose contained in a urine sample by an amperometric method. do.

As a method of measuring the concentration of glucose contained in the urine sample using the urine glucose sensor 100, for example, an amperometric method may be used. FIG. 5A is a schematic diagram of an amperometric method using a two-electrode system, and FIG. 5B is a schematic diagram of a current method using a three-electrode system.

Considering the energy change due to chemical change, the energy change due to the entry and exit of a substance is called the chemical potential 'μ'. This is the thermodynamic potential introduced by Gibbs. Here, if the free energy (Gibbs energy) of the single phase is G and the number of moles of the chemical species i of the system is n _i , the amount of G change corresponding to the change of n _i corresponds to the chemical potential μ, Can be represented as:

The chemical potential μ _i of this system is generated when the temperature (T) and pressure (P) are constant and the number of moles of chemical species i is reversibly changed when the concentration N of all substances other than chemical species i is kept constant. Corresponds to a change in free energy. Relational expression of Fig concentration of species present in solution, i C _i μ _i and its thermodynamic potential is equal to the following equation (3).

Where μ _i ^o is the standard chemical potential and R is the gas constant.

In order to measure the electrode potential in solution using the change in free energy generated by reversibly changing the number of moles of chemical species i, the potential difference between two points should be measured using two electrodes. The measuring electrode is called a working electrode (WE), and another electrode must be connected thereto to measure the potential difference. 5A is a model diagram of a two-electrode system that is most widely used when measuring a potential difference. Here, in order for the cell voltage V to be equal to the electromotive force E, an equilibrium condition of the current i ≒ 0 must be established. For this purpose, the reference electrode (Reference Electrode, Ref) should be used to select the electrode with stable potential. In this way, the potential difference should be measured in an equilibrium state where the actual current between the working electrode WE and the reference electrode Ref can be almost ignored. The potential difference measured at this time corresponds to an electromotive force between the two electrodes, and under this condition (i ≒ 0), the voltage drop due to the internal resistance component between the electrodes can be ignored.

When an external voltage is applied between the electrodes, a ohmic voltage drop (IR _cell ) occurs between the electrodes so that the reference electrode Ref potential is out of the equilibrium value. To avoid this error, the three-electrode system shown in FIG. 5B may be used in electrochemical measurements. In the three-electrode system, the cell current flows between the operation electrode WE and the counter electrode CE and hardly flows between the operation electrode WE and the reference electrode Ref. The potential difference between the operation electrode WE and the reference electrode Ref can be measured accurately regardless of the voltage value flowing by the electrode reaction.

FIG. 6 is a graph measuring the current output waveform of the signal detector 102 according to the glucose concentration shown in FIG. 1 by an oscilloscope. The horizontal axis represents the time axis and the vertical axis represents the magnitude of the output current. The signal detector 102 differentially amplifies the first current signal and the second current signal and outputs a third signal. As a result, the third signal corresponds to glucose concentration. The signal detector 102 may differentially amplify the current signal output from the urine glucose sensor 100, convert the current signal into a voltage signal, remove the noise from the converted voltage signal, and output the third signal. Referring to FIG. 6, it can be seen that the higher the concentration of glucose is, the higher the output current value of the signal detector 102 is, and the change in the current value according to the glucose concentration is stabilized with time.

7 is a schematic diagram for explaining a preferred embodiment of a wireless communication protocol according to the present invention. Wireless communication between the wireless transmitter 108 and the wireless receiver 110 shown in FIG. 1 may be performed by an infrared data association (Infrared Data Association, IrDA). Accordingly, the wireless transmitter 108 shown in FIG. 1 transmits the fourth signal to the wireless receiver 110 according to the protocol shown in FIG. 7. The data communication protocol by IrDA shown in FIG. 7 is based on 4 bytes of continuous transmission. That is, a total of 10 bits of the start bit, the stop bit, and the data bit are sent four times in a single byte, so the total bit of the normal transmission is 40 bits. The upper four bits of the first byte of data to be transmitted are control codes, the lower four bits of the first byte, the eight bits of the second byte, and the upper four bits of the third byte are defined as data blocks. Also, the value of the data block is based on sending only decimal values. The fourth byte that is sent last sends "0AAh" as the exit code. Only when this exit code "0AAh" is transmitted is considered normal communication. This serial communication method converts the data in the memory of the urine glucose meter into a serial signal and sends or receives it to the home medical system, which is the main system.

Hereinafter, the results of the performance evaluation of the urine glucose measurement apparatus according to an embodiment of the present invention will be described as follows. In the evaluation, a solution containing glucose components of any concentration in urine was used as an experimental solution. In addition, YSI Inc., a standard equipment for glucose component analysis, The reliability of the urine glucose measuring apparatus according to the present invention was evaluated through comparative analysis with the STAT Plus Glucose Analyzer (hereinafter referred to as "YSI"). Comparative analysis was performed by linear regression method.

8 is a graph showing comparative analysis results by linear regression analysis.

As shown in FIG. 8, the regression equation of the urine glucose measuring device according to the present invention and the Glucose Analyzer of YSI were derived as shown in Equation 4 below.

The result of the regression equation according to Equation 4 has a standard error of 2.8582 and a minimum mean square value of 99.5%.

9 is a graph showing the distribution of the residual (%) for the YSI of the urine glucose measuring apparatus according to the present invention, it can be seen that the deviation factor (deviation factor distribution) is less than 10%. This results in a residual distribution of ± 5% in the criteria issued by the American Diabetes Association (ADA) (ADA Consensus statement, "self-monitoring of blood glucose", Diabetes Care, Vol. 55, pp1127-1135, 1994). Compared to what we are defining, it is very satisfactory.

In order to evaluate the validity of the regression analysis, a histogram of the residuals was obtained and an Anderson Daring Normality Test was performed.

FIG. 10 is a histogram of the residual distribution shown in FIG. 9. Referring to FIG. 10, the result of the histogram of the residuals is similar to the Gaussian distribution, indicating that the regression analysis is reliable.

FIG. 11 is a graph illustrating a result of performing the Anderson Daring Normality Test, where P-Value = 0.058. This value satisfies the reference value of 0.05 or more.

As described above, according to the urine glucose measuring apparatus of the present invention, the inconvenience of the conventional invasive blood glucose measurement method and the disadvantages of the urine glucose test method using the colorimeter, the general public easily non-invasive and quantitatively diabetic It can be measured.

The present invention is not limited to what has been described above and illustrated in the drawings, and of course, more modifications and variations are possible to those skilled in the art within the scope of the following claims.

Claims (4)

A urine glucose sensor for outputting a first signal generated in response to an interference component of glucose and uric acid contained in urine and a second signal generated in response to only the interference component; A signal detector configured to differentially amplify the first signal and the second signal to output a third signal; A controller which converts the third signal into a concentration value of glucose and outputs the fourth signal; And And a display unit for displaying the concentration of glucose in response to the fourth signal. According to claim 1, A radio transmitter for modulating and transmitting the fourth signal into a radio signal; And And a wireless receiver for receiving the demodulated signal and outputting the demodulated signal. And the display unit displays the demodulated signal. The method of claim 2, wherein the wireless signal, Urine glucose measurement apparatus characterized in that the transmission and reception by a protocol according to the infrared communication standard. The method of claim 1, wherein the urine glucose sensor, Hexaaminerucenium (III) chloride, potassium ferricyanide, potassium ferrocyanide, dimethyl ferrocene, ferricinium, ferrocene monocarboxylic acid, 7,7,8,8, -tetracyanoquinodi Methane, tetrathiafubarene, nikerocene, N-methylacidinium, tetrathiatetracene, N-methylphenazinium, hydroquinone, 3-dimethylaminobenzoic acid, 3-methyl-2-benzothiorizonononhydrazone , 2-methoxy-4-arylphenol, 4-aminoantipyrine, dimethylaniline, 4-aminoantipyrene, 4-methoxynaphthol, 3,3`, 5,5`-tetramethylbenzidine, 2,2-azino Mixed electrons of -di- [3-ethyl-benzthiazoline solphonate], o-diazinidine, o-toluidine, 2,4-dichlorophenol, 4-aminophenazone, benzidine, and prussian blue A device for measuring urine glucose, characterized by using an electron transfer medium selected from the group.

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