A method and system for calibrating sweat glucose concentration

Abstract

The present application relates to the technical field of human chemical signal detection, and provides a sweat glucose concentration calibration method, which comprises the following steps: step 1: obtaining basic data of a sweat glucose detection device, a sweat pH value and a sweat glucose concentration; step 2: respectively calibrating a sweat secretion rate and sensor sensitivity based on the sweat pH value to realize calibrated response current; and step 3: constructing a calibration formula, inputting the basic data, the sweat pH value, the sweat glucose concentration, the calibrated response current and the sensor sensitivity into the calibration formula to obtain a calibrated sweat glucose concentration. The present application calibrates the sweat glucose concentration by using the sweat-borne marker pH, effectively solves the problems of lower concentration of sweat blood glucose and more concentration detection interference, and better realizes the recognition of blood glucose chemical signals.

Description

Technical Field

[0001] This invention relates to the field of human chemical signal detection technology, and in particular to a method and system for calibrating the concentration of glucose in sweat. Background Technology

[0002] Human chemical signals can provide more reference for identifying human health status, but most chemical signal extraction methods rely on invasive blood extraction, making real-time continuous monitoring impossible. Body fluids, as metabolic products, contain numerous identifiable markers that can indicate current health status, such as sweat glucose and sweat pH. Patent CN219089303U proposes a wearable flexible patch for detecting sweat glucose and pH, but this patch is limited to sweat collection and independent detection of glucose and pH; whether the detection results correlate with blood glucose requires further investigation. Patent CN117362884A also describes the detection of sweat glucose, but it does not explore whether the detection results correlate with blood glucose.

[0003] Furthermore, while sweat glucose can be detected in sweat, its excretion is subject to various interferences, such as reabsorption by the distal ducts of the sweat glands and variations in sweat volume. Therefore, obtaining sweat glucose concentrations, which are highly correlated with blood glucose levels, and using sweat glucose as a substitute for blood glucose for continuous monitoring, is a much-needed technology for diabetic patients and is of significant research value. Summary of the Invention

[0004] The purpose of this invention is to provide a method for calibrating the concentration of glucose in sweat. By using pH, a marker naturally present in sweat, to calibrate the concentration of glucose in sweat, the method effectively solves the problems of lower concentration of blood glucose in sweat and more interference in concentration detection, and better realizes the identification of blood glucose chemical signals.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for calibrating the glucose concentration in sweat, comprising: Step 1: Obtain basic data from the sweat glucose detection device, including sweat pH value and sweat glucose concentration; Step 2: Based on the sweat pH value, calibrate the sweat secretion rate and sensor sensitivity to achieve the calibration response current; Step 3: Construct the calibration formula by inputting the basic data, sweat pH value, sweat glucose concentration, calibrated response current and sensor sensitivity into the calibration formula to obtain the calibrated sweat glucose concentration.

[0006] Furthermore, the basic data of the sweat glucose detection device includes: sensor sensitivity, response current I of the sweat glucose detection device, and no-load current. , the permeability constant k and the constant b.

[0007] Furthermore, the process of calibrating sweat secretion rate based on sweat pH value includes: expressing pH value as sweat secretion rate, as shown in the following formula: ;in, This is a function of sweat secretion rate under different pH conditions at different times.

[0008] Furthermore, the process of calibrating sensor sensitivity based on sweat pH value includes: obtaining the current changes caused by glucose drop experiments in PBS solutions at different pH values, confirming the sensor sensitivity at different pH values ​​based on the current changes, and completing the sensor sensitivity calibration; the specific formula is as follows: ;in, This is a sensor sensitivity function under time and pH conditions.

[0009] Furthermore, the relationship between the response current and the sensor sensitivity is expressed as follows: ;in, For sensor sensitivity, The concentration of glucose in sweat. This is the no-load current.

[0010] Furthermore, the calibration formula is as follows: ; The no-load current, osmotic constant k, and constant b are obtained by fitting the initial two fingertip blood glucose values ​​and their device response current.

[0011] This invention also provides a calibration system for sweat glucose concentration, comprising: a data acquisition module for acquiring basic data of a sweat glucose detection device, sweat pH value, and sweat glucose concentration; a pH value calibration module for calibrating sweat secretion rate and sensor sensitivity based on sweat pH value to achieve calibration response current; and a sweat glucose concentration calibration module for constructing a calibration formula by inputting the basic data, sweat pH value, sweat glucose concentration, calibrated response current, and sensor sensitivity into the calibration formula to obtain the calibrated sweat glucose concentration.

[0012] By adopting the above technical solution, the present invention has the following beneficial effects: This invention uses pH, a marker naturally present in sweat, to calibrate the glucose concentration in sweat, effectively solving the problems of lower blood glucose concentration and greater interference in concentration detection, and achieving the identification of blood glucose chemical signals. Attached Figure Description

[0013] Figure 1A graph showing the relationship between sweat pH and sweat secretion rate; Figure 2 A graph showing the relationship between sweat pH and sensor sensitivity. Figure 2 In this diagram, A represents a bar chart and B represents a line graph. Figure 3 The changes in sweat pH value at different times, sweat secretion rate calculated from sweat pH value, and sensor sensitivity; Figure 4 The current values ​​detected by the device at different times and the fingertip blood glucose ( Figure 4 The gray curve in the image represents the current value at different times, and the red dot represents the fingertip blood glucose level. Figure 5 Blood glucose values ​​predicted by calibration at different times and by uncalibrated current response induced by sweat glucose (for different time periods). Figure 5 The left side of the image shows the overall blood glucose values ​​predicted at different time periods, while the right side shows a magnified view of the blood glucose levels from two selected fingertip blood glucose samples used for initial correction. The gray curve in the image represents the blood glucose values ​​predicted by the uncalibrated current response caused by sweat glucose, the black curve represents the blood glucose values ​​predicted by the calibrated current response caused by sweat glucose, and the red dots represent the fingertip blood glucose levels. Detailed Implementation

[0014] This invention provides a method for calibrating the concentration of glucose in sweat by using pH, a marker naturally present in sweat, to calibrate the concentration of glucose in sweat.

[0015] First, common substances like cortisol and ethanol enter sweat through the lipid bilayer of cells. This transcellular diffusion means that the concentration in sweat is strongly correlated with its concentration in the blood. Glucose, on the other hand, diffuses into sweat through the intercellular spaces. Cells are tightly bound by more than 40 proteins, which selectively filter and dilute analytes. This dilution mechanism leads to an inverse relationship between sweat glucose concentration and sweat production rate. Furthermore, since the acidification level of sweat within the sweat gland duct is correlated with sweat pH, the sweat secretion rate can also be expressed through sweat pH. Second, the activity of glucose oxidase is affected by pH, thus influencing sensor sensitivity. Therefore, through repeated experiments, the relationship between pH and sensor sensitivity can be established, allowing for further calibration of sweat glucose concentration.

[0016] Glucose diffuses into sweat via the paracellular space. Therefore, a flux-based approach is used to quantify the process of glucose moving from blood to sweat. The glucose flux is calculated as (formula below): the product of sweat glucose concentration and sweat secretion rate. This glucose flux represents the number of glucose molecules diffused per unit time via the paracellular pathway. In this formula... Indicates glucose flux. Indicates the concentration of glucose in sweat. This indicates the rate of sweat secretion.

[0017] Based on Fick's diffusion law, the physical diffusion model was upgraded to a physiological transport model, resulting in the extended Fick's law (formula below). In this extended Fick's law, " "The concentration gradient-driven diffusion term of the original Fick's diffusion law has been retained." This represents glucose flux driven by a non-concentration gradient, serving as a personalized calibration parameter.

[0018] The extended Fick's law described in this invention indicates the concentration gradient between glucose flux and blood and sweat. The proportions, or osmotic constants (k) and (b), explain other factors that affect glucose flux.

[0019] The concentration of glucose in sweat is much lower than that in blood or interstitial fluid; therefore, the concentration gradient can be simplified as follows: .in This indicates the glucose concentration in blood / interstitial fluid.

[0020] Based on the above three formulas, we can conclude that: .

[0021] In wearable sweat glucose detection devices, the relationship between the device response current and sensor sensitivity is as follows: Therefore, we can conclude that... In this formula, Indicates sensor sensitivity; This represents the response current, the current value detected by the device, which is the change in current caused by the concentration of glucose. This indicates the no-load current (no-load current can cause system errors).

[0022] Based on the above, it can be concluded that in the process of calibrating sweat glucose concentration, only the response current needs to be known. No-load current Sensor sensitivity sweat secretion rate The permeability constants k and b are sufficient. , This can be obtained from the device's response.

[0023] Sweat secretion rate is calibrated based on sweat pH value, with pH value expressed as sweat secretion rate. The relationship between pH and sweat secretion rate is as follows: Figure 1 The calibration function relationships are as follows: , Indicates the rate of sweat secretion. This represents a function of sweat secretion rate under different pH conditions at different times.

[0024] Furthermore, during the calibration process, the sweat secretion rate varied at different pH values; when the pH was between 4.5 and 6.0, When the pH is 6.0-7.0 When the pH is 7.0-8.0, That is, the pH value of sweat was obtained. .

[0025] Based on the principle that "the activity of glucose oxidase is affected by pH, thus affecting the sensitivity of the sensor," pH is used to calibrate the sensor sensitivity. Glucose drop experiments were conducted in PBS solutions with different pH values. The current change caused by the glucose concentration was calculated to obtain the sensor sensitivity at different pH values, thereby completing the sensor sensitivity calibration. The calibration function relationship is as follows: , Indicates sensor sensitivity. This represents the sensor sensitivity function at different pH values.

[0026] Furthermore, That is, to obtain the pH value of sweat as an expression. .

[0027] In summary, the calibration formula for sweat glucose concentration can be obtained as follows: .

[0028] In the formula above: The no-load current is obtained by averaging the values ​​of the device running for 10 minutes under zero input conditions; the values ​​of I and pH are obtained by the corresponding device detection; k and b are obtained by fitting the initial two fingertip blood glucose values ​​and their device response current.

[0029] In this invention, the fitting process for k and b is as follows: k is calculated based on the detected pH value. and Then, the initial two fingertip blood glucose values ​​and the device response current were collected and substituted into... The formula yields a system of two linear equations in two variables, from which the values ​​of k and b can be calculated.

[0030] Subjects wore sensors that could collect pH and sweat glucose levels, obtaining the current value I caused by changes in pH and glucose. The pH value was then substituted into... and The sweat secretion rate was calculated separately. and sensor sensitivity ,get Figure 3 .

[0031] The device detects the current value I (e.g., the response of sweat glucose) to the test. Figure 4 Then, combining A and B obtained by the two-point method, the blood glucose value predicted by the current response caused by sweat glucose before calibration is calculated according to "I*A+B"; then, the sensitivity S and sweat secretion rate V are calculated from the obtained pH, and the result is calculated according to "(I*V / S)*A+B" (where I is equivalent to I-I0, and V is equivalent to I-I0). S is equivalent to A is equivalent to 1 / k, and B is equivalent to -b / k; that is, the formula is as described above. The calibration formula is used to obtain the calibrated blood glucose value predicted by the current response caused by sweat glucose (e.g., ...). Figure 5 ).

[0032] Specifically, in this invention, the time points and blood glucose values ​​collected (as shown in Table 1) were randomly selected. The first two were used as initial calibration points (i.e., 8.4 mM at 08:50 and 7.7 mM at 09:10). At the same time, the gray curve current value at 09:20 after 30 minutes was found to be -18.00167 uA, sensitivity 20.7 uA / mM, and sweat secretion rate 0.02407 μl / min, and the gray curve current value at 09:40 was found to be -14.44989 uA, sensitivity 20.7 uA / mM, and sweat secretion rate 0.02467 μl / min. Then, using the two-point method, the parameters obtained above are substituted into the calculation formula to obtain a set of two linear equations in two variables: 8.4mM=(-18.00167*0.02407 / 20.7)*A+B, 7.7mM=(-14.44989*0.02467 / 20.7)*A+B. Finally, the value of A is calculated to be -188.62, and the value of B is 4.452.

[0033] The R-value for the uncalibrated blood glucose curve was 0.83, while the R-value for the calibrated blood glucose curve was 0.90, indicating an improved correlation.

[0034] In summary, this invention calibrates sweat glucose concentration using pH, a marker naturally present in sweat. The results before and after calibration demonstrate the effectiveness of this method, indicating that the calibration method achieves the calibration of the correlation between sweat glucose concentration and blood glucose concentration. This also provides strong technical support for sweat glucose detection.

[0035] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for calibrating the concentration of glucose in sweat, characterized in that, include: Step 1: Obtain basic data from the sweat glucose detection device, including sweat pH value and sweat glucose concentration; Step 2: Based on the sweat pH value, calibrate the sweat secretion rate and sensor sensitivity to achieve the calibration response current; Step 3: Construct the calibration formula by inputting the basic data, sweat pH value, sweat glucose concentration, calibrated response current and sensor sensitivity into the calibration formula to obtain the calibrated sweat glucose concentration.

2. The method for calibrating sweat glucose concentration according to claim 1, characterized in that, The basic data of the sweat glucose detection device includes: sensor sensitivity, response current I of the sweat glucose detection device, and no-load current. , the permeability constant k and the constant b.

3. The method for calibrating sweat glucose concentration according to claim 1, characterized in that, The process of calibrating sweat secretion rate based on sweat pH value includes: expressing pH value as sweat secretion rate, as shown in the following formula: ; in, This is a function of sweat secretion rate under different pH conditions at different times.

4. The method for calibrating sweat glucose concentration according to claim 1, characterized in that, The process of calibrating sensor sensitivity based on sweat pH value includes: obtaining the current change caused by glucose drop experiments in PBS solutions with different pH values; confirming the sensor sensitivity at different pH values ​​based on the current change; and completing the sensor sensitivity calibration. The specific formula is as follows: ； in, This represents the sensor sensitivity function under different pH conditions at different times.

5. The method for calibrating sweat glucose concentration according to claim 4, characterized in that, The relationship between the response current and the sensor sensitivity is expressed as follows: ； in, For sensor sensitivity, The concentration of glucose in sweat. This is the no-load current.

6. The method for calibrating the glucose concentration in sweat according to claim 1, characterized in that, The calibration formula is as follows: ; The no-load current, osmotic constant k, and constant b are obtained by fitting the initial two blood glucose values ​​and their device response current.

7. A calibration system for sweat glucose concentration, characterized in that, include: Data acquisition module: used to acquire basic data from the sweat glucose detection device, including sweat pH value and sweat glucose concentration; pH calibration module: Based on the pH value of sweat, the sweat secretion rate and sensor sensitivity are calibrated to achieve the calibration response current; Sweat glucose concentration calibration module: Used to construct calibration formulas. Input basic data, sweat pH value, sweat glucose concentration, calibrated response current and sensor sensitivity into the calibration formula to obtain the calibrated sweat glucose concentration.

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