A miniature wearable blood glucose monitoring device

Abstract

The application discloses a micro wearable blood glucose monitoring device. The device comprises a first part and a second part which are connected in series to form a ring; the first part comprises an integrated Raman probe, the integrated Raman probe comprises two light sources for generating a line spot and a slit; the two light sources are arranged on the two sides of the slit respectively, and the slit emits excitation light to the skin tissue to generate a Raman signal, the slit is provided with a long-pass filter film for filtering Rayleigh scattering, other stray light and spontaneous fluorescence; the device further comprises a miniature spectrometer for performing light splitting and detection of the Raman signal; the second part comprises an information processing unit for driving control of the light source and the miniature spectrometer and micro blood glucose online analysis, a touch display screen for reading and displaying blood glucose values, and a battery module for supplying power to the integrated Raman probe, the information processing unit and the touch display screen; the watchband is provided with a data line for transmitting data and a power line for power supply.

Description

TECHNICAL FIELD

[0001] The present application relates to a blood glucose monitoring device, in particular to a micro wearable blood glucose monitoring device. BACKGROUND

[0002] Diabetes is a chronic disease marked by high blood sugar caused by absolute or relative insulin secretion deficiency and utilization disorders. The main means to prevent diabetes and its complications is for diabetic patients to self-monitor blood glucose. Currently, the main method on the market is invasive fingertip blood sampling detection, which is not only time-consuming and troublesome, but also causes strong pain in patients and is prone to wound infection. CGM minimally invasive blood glucose monitoring greatly reduces the pain, but its service life is relatively short (usually 7-14 days), and long-term use can also cause skin allergy and erosion. The new non-invasive Raman spectroscopy detection technology does not require blood sampling and has no allergy problems. However, the traditional detection system based on Raman spectroscopy has the disadvantages of large volume, complex structure, high cost, and some devices still need invasive calibration, which is not suitable for continuous monitoring at home. SUMMARY

[0003] In order to solve the problems of the prior art, the present application provides a micro wearable blood glucose monitoring device, which has simple structure, small size and low cost, and does not need calibration for non-invasive blood glucose detection.

[0004] The present application provides the following technical scheme: a micro wearable blood glucose monitoring device, comprising a first part and a second part connected in series to form a ring through two watchbands;

[0005] The first part comprises an integrated Raman probe, the integrated Raman probe comprises two light sources for generating a line spot and a slit; the two light sources are respectively arranged on both sides of the slit, and the slit emits excitation light to the skin tissue to excite Raman signals, and the slit has a long-pass filter film for filtering out Rayleigh scattering and other stray light and spontaneous fluorescence; and a miniature spectrometer for splitting and detecting Raman signals;

[0006] The second part comprises an information processing unit for driving control of the light source and the miniature spectrometer and micro blood glucose online analysis, a touch display screen for reading and displaying blood glucose values, and a battery module for supplying power to the integrated Raman probe, the information processing unit and the touch display screen;

[0007] The watchband has a data line for transmitting data and a power line for power supply.

[0008] Further, the light source is a horizontal cavity surface emitting laser (HCSEL) or a vertical cavity surface emitting laser array.

[0009] Further, the central wavelength of the light source is 808-976 nm, and the line width is ≥0.1 nm.

[0010] Further, the width direction of the slit is the direction from one light source to another light source, the width is 25-200um; the thickness direction of the slit is the direction perpendicular to the skin tissue, the thickness is 0.1-2mm; the height direction of the slit is the direction perpendicular to the width and height, the height is 0.6-2mm; the back of the slit is coated with a long-pass filter for filtering out Rayleigh scattering and other scattered light and fluorescent background, the side of the slit close to the skin tissue is the front side, and the other side is the back side.

[0011] Further, the distance between the center of the light source and the center of the slit is 0.5-2mm.

[0012] Further, the slit is an air slit or a solid slit.

[0013] Further, the air slit is manufactured by the following steps:

[0014] First, clean the glass substrate or quartz substrate, then use vacuum deposition or magnetron sputtering process to deposit the light shielding film, the light shielding film is extinction nano film or AR black film; after the deposition of the light shielding film is completed, spin-coating photoresist on the light shielding film, the photoresist is positive or negative, after the coating process is completed, the front baking process is carried out; then enter the photoetching process, ultraviolet light is irradiated on the mask to complete the pattern transfer; after the photoetching process is completed, the developing and hardening process is carried out, then wet etching or dry etching is carried out, the size of the slit is transferred from the mask to the light shielding film, after the stripping process, the slit is cleaned, after the cleaning is completed, the long-pass filter film layer is deposited on the back of the glass substrate or quartz substrate by ion beam process, the whole slit processing process is completed.

[0015] Further, the solid slit is manufactured by the following steps:

[0016] First, the glass or quartz substrate is cleaned. Then, a light-shielding film, either an matte nanofilm or an AR black film, is deposited using vacuum deposition or magnetron sputtering. After the light-shielding film deposition, photoresist, either positive or negative, is spin-coated onto the film. A pre-baking process is then performed after the photoresist coating. Next, the photolithography process begins, where ultraviolet light irradiates the photomask to transfer the pattern. After photolithography, development and hardening processes are performed, followed by wet or dry etching to transfer the slit size from the photomask to the final image. On the light-shielding film, the photoresist on the slit surface is removed, and a high-refractive-index film layer is deposited using electron beam or magnetron sputtering. The material is SiO2, SiN, SiON, or a mixture thereof. The thickness of the high-refractive-index film layer is the thickness of the slit, or greater than the thickness of the slit. After the coating is completed, CMP process is used for polishing to remove excess film layer from the surface. After polishing, cleaning is performed to remove polishing slurry and impurities. After cleaning, ion beam process is used to deposit a long-pass filter film layer on the back of a glass substrate or quartz substrate, completing the entire slit processing process.

[0017] Furthermore, the miniature spectrometer includes a collimating lens, a transmission grating, a converging lens group, and a detector arranged sequentially along the Raman signal propagation direction.

[0018] Furthermore, the micro spectrometer includes a lens and a chip-type micro spectrometer arranged sequentially along the Raman signal propagation direction. The chip-type micro spectrometer includes a wide-bandwidth grating coupler, a tapered waveguide, a first planar waveguide, an array waveguide, a second planar waveguide, an output waveguide array, and an array detector arranged sequentially along the Raman signal propagation direction.

[0019] Furthermore, the coupling structure of the output waveguide array and the array detector includes a direct coupling type arranged in parallel, a reflection coupling type arranged in parallel, and a reflection coupling type arranged in a stepped manner.

[0020] The beneficial effects of this invention are as follows:

[0021] (1) By designing the slit structure and integrating it with the light source, an integrated Raman probe is formed, which is then used to assemble a device. The device is simple in structure, small in size, low in cost, requires no calibration, and performs blood glucose detection non-invasively.

[0022] (2) It will not cause any wounds to the patient, realizes non-invasive real-time monitoring, and is small in size and low in cost. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the overall structure of Embodiment 1 of the present invention;

[0024] Figure 2 This is a schematic diagram of the first part of the structure of Embodiment 1 of the present invention;

[0025] Figure 3 Structure diagram of the light source and the slit of the embodiment 1 of the present application;

[0026] Figure 4 Manufacturing flow chart of the slit of the embodiment 1 of the present application;

[0027] Figure 5 Structure diagram of the overall structure of the embodiment 1 of the present application;

[0028] Figure 6 Manufacturing flow chart of the slit of the embodiment 2 of the present application;

[0029] Figure 7 Structure diagram of the first part of the embodiment 3 of the present application;

[0030] Figure 8 Structure diagram of the chip-type micro spectrometer of the embodiment 3 of the present application;

[0031] Figure 9 Structure diagram of the mounting mode of the output waveguide and the array detector of the embodiment 3 of the present application, wherein (a) is a direct coupling type in parallel arrangement, (b) is a reflection coupling type in parallel arrangement, and (c) is a reflection coupling type in stepped arrangement;

[0032] Figure 10 Flow chart of the regression model establishment of the use method of the micro wearable blood glucose monitoring device of the embodiment 4 of the present application;

[0033] Figure 11 Flow chart of the spectrum and processing of the use method of the micro wearable blood glucose monitoring device of the embodiment 4 of the present application;

[0034] Figure 12 Test flow chart of the use method of the micro wearable blood glucose monitoring device of the embodiment 4 of the present application. DETAILED DESCRIPTION

[0035] In order to further explain the technical means and effects adopted by the present application to achieve the predetermined application purposes, the specific embodiments, structures, features and effects according to the present application are described in detail as follows in combination with the drawings and preferred embodiments.

[0036] Through the design of the slit structure and the integration of the slit structure and the light source, an integrated Raman probe is formed, and then a device is composed, which has simple structure, small volume, low cost, no calibration and non-invasive blood glucose detection.

[0037] The embodiments of the present application are further described in the following multiple embodiments.

[0038] Embodiment 1

[0039] As Figures 1-2A micro wearable blood glucose monitoring device, comprising a first part and a second part formed into a ring by two straps 104 in series;

[0040] The first part comprises an integrated Raman probe, which comprises two light sources 101 for generating a line spot and a slit 102; the two light sources 101 are respectively arranged on both sides of the slit 102, and the slit 102 is used for emitting excitation light to the skin tissue 105 to excite Raman signals; the slit 102 is provided with a long-pass filter 305 for filtering out Rayleigh scattering and other stray light and autofluorescence; and the micro spectrometer 103 is used for splitting and detecting the Raman signals.

[0041] The second part comprises an information processing unit 106 for driving control of the light source 101 and the micro spectrometer 103 and micro blood glucose online analysis, a touch display screen 107 for reading and displaying blood glucose values, and a battery module 108 for supplying power to the integrated Raman probe, the information processing unit 106 and the touch display screen 107;

[0042] The strap 104 is provided with a data line for transmitting data and a power line for power supply.

[0043] The light source 101 is a horizontal cavity surface emitting laser, and in some embodiments, a vertical cavity surface emitting laser array can also be used.

[0044] The central wavelength of the light source 101 is 830 nm, and in some embodiments, any value between 808 nm and 976 nm can also be used, such as 808 nm, 850 nm, 905 nm, 940 nm, 976 nm, etc.; the line width of the embodiment is 0.1 nm, and any value greater than 0.1 nm can also be used.

[0045] The width direction of the slit 102 is the direction from one light source 101 to the other light source 101, and the width is 100 um, and in some embodiments, any value between 25 um and 200 um can also be used, such as 200 um, 150 um, 50 um, 25 um, etc.; the thickness direction of the slit 102 is perpendicular to the skin tissue 105, and the thickness is 0.5 mm, and in some embodiments, any value between 0.1 mm and 2 mm can also be used, such as 2 mm, 1.5 mm, 1.2 mm, 0.3 mm, 0.2 mm, 0.1 mm; the height direction of the slit 102 is perpendicular to the width and height at the same time, and the height is 1.5 mm, and in some embodiments, any value between 0.6 mm and 2 mm can also be used, such as 2 mm, 1.2 mm, 1 mm, 0.896 mm, 0.6 mm; the back of the slit 102 is coated with a long-pass filter 305 for filtering out Rayleigh scattering and other stray light and fluorescence background; the side of the slit 102 close to the skin tissue is the front side, and the other side is the back side.

[0046] As Figure 3 the distance between the center of the light source and the center of the slit is 0.5mm, in some embodiments, any value between 0.5mm and 2mm can also be adopted, such as 1mm, 1.5mm, 2mm, etc.

[0047] As Figure 4 the slit 102 in the embodiment is a solid slit, which is manufactured by the following steps:

[0048] First, clean the quartz substrate 301, and then deposit the light shielding film 302 by vacuum deposition process, in some embodiments, magnetron sputtering can also be adopted; the light shielding film 302 is a light extinction nano film, in some embodiments, AR black film and other non-transparent materials can also be adopted, using SiO2+MgF2coating film material, using 70%:30% co-evaporation ratio, at 100°C, the evaporation rate is 1.5nm / s and 1nm / s respectively, depositing 200nm at a vacuum degree of 10⁻ 3 Pa, in some embodiments, the vacuum degree can also be 10⁻ 5Any value between 10-3 Pa and 10-2 Pa, the deposition thickness can also be 150 nm-300 nm; after the deposition of the light shielding film 302 is completed, spin coating photoresist 303 is performed on the light shielding film 302, the photoresist 303 is positive photoresist, the thickness of the photoresist is 2 um, in some embodiments, it can also be 1-5 um, the spin coating speed is 2000 rpm, in some embodiments, it can also be 1500-3000 rpm, in some embodiments, negative photoresist can also be used; after the coating process is completed, the pre-baking process is performed; then the photolithography process is entered, ultraviolet light is irradiated on the mask 304 to complete the pattern transfer, the slit process parameters on the mask 304 are 100x1500 um, other values can also be used as needed; after the photolithography process is completed, the development and hardening processes are performed; then dry etching is performed to make a 100 um light transmission groove (i.e. the width of the slit) on the light shielding film 302, in some embodiments, it can also be 25-200 um, the dry etching adopts reactive ion etching (IRE), and the etching is completed after about 1.5 min, the etching of the 200 nm extinction nano film is completed, the etching time is optimized according to the characteristics of different extinction nano films and other AR black film non-transparent materials, in some embodiments, wet etching can also be used; the size of the slit 301 is transferred from the mask 304 to the light shielding film 302, and the photoresist 303 on the surface of the slit 102 is removed; using electron beam process, a high refractive index film layer 306 is deposited on the light transmission groove and the light shielding film 302, in some embodiments, magnetron sputtering can also be used, the material is SiO2, in some embodiments, SiO2, SIN, SION and mixtures thereof can also be used, and the refractive index is preferably n=1.547; the thickness of the high refractive index film layer 306 is the thickness of the slit 102, in some embodiments, it can also be greater than the thickness of the slit 102; after the film deposition is completed, the CMP process is used for grinding to remove the high refractive index film layer 306 on the light shielding film 302, and the high refractive index film layer 306 in the light transmission groove is reserved, but it should be noted that the nano extinction film should not be damaged by grinding; after the grinding, cleaning is performed to remove the grinding liquid and impurities, and after the cleaning is completed, the long-pass filter film layer 305 is deposited on the back of the quartz substrate by using ion beam process, this process uses commercial film deposition process, 830 nm long-pass filter process is used, in some embodiments, 785 nm-1064 nm long-pass filter process can also be used, and the processing of the entire slit 102 is completed.

[0049] The above preparation method is a common technical means in the art.

[0050] Embodiment 2

[0051] As Figure 5 In this embodiment, the micro wearable blood glucose monitoring device, the micro spectrometer 103 includes a collimating lens 404, a transmission grating 405, a converging lens group 406 and a detector 407 arranged in sequence along the propagation direction of the Raman signal.

[0052] Two light sources 101 emit linear excitation light at the same time, which passes through the epidermis and excites glucose molecules in the dermis interstitial fluid to generate Raman signals. The Raman signals are received by the slit 102 and filtered to remove other unwanted stray light such as Rayleigh scattering. After collimation by the collimating lens 404, the Raman signals are diffracted by the transmission grating 405, which is a volume holographic grating. In some embodiments, a quartz transmission grating or the like can also be used. After dispersion, the Raman signals are focused onto the detector 407 by the focusing lens group 406. The detector 407 is a near-infrared enhanced CCD. In some embodiments, a near-infrared enhanced CMOS sensor or the like can also be used.

[0053] As Figure 6 The slit 102 in the present embodiment is an air slit, which is manufactured by the following steps:

[0054] First, clean the glass substrate 301, then deposit the light shielding film 302 using a magnetron sputtering process. The light shielding film 302 is an extinction nano film, which is made of SiO2 + MgF2 coating material with a co-evaporation ratio of 70%:30%. The evaporation rate is 1.5 nm / s and 1 nm / s respectively at 100°C, and the vacuum degree is 10⁻ 5 Pa to deposit 200 nm. In some embodiments, the vacuum degree can also be 10⁻ 5Any value between 10-3 Pa, the deposition thickness can also be 150 nm-300 nm; after the deposition of the light shielding film 302 is completed, spin coating photoresist 303 is performed on the light shielding film 302, the thickness of the photoresist is 2 um, in some embodiments, it can also be 1-5 um, the spin coating speed is 2000 rpm, in some embodiments, it can also be 1500-3000 rpm, the photoresist 303 is positive photoresist, in some embodiments, negative photoresist can also be used, after the photoresist coating process is completed, a pre-baking process is performed; then the photolithography process is entered, ultraviolet light is irradiated on the mask 304 to complete pattern transfer, the slit process parameters on the mask 304 are 100x1500 um, other values can also be used as needed; after the photolithography process is completed, development and hardening processes are performed, then dry etching is performed, then dry etching is performed to make a 100 um light transmission groove (i.e. the width of the slit) on the light shielding film 302, in some embodiments, it can also be 25-200 um, dry etching uses reactive ion etching (IRE), etching for about 1.5 min can complete etching of the 200 nm extinction nano film, the etching time is optimized according to the characteristics of different extinction nano films and other AR black film non-transparent materials, in some embodiments, wet etching can also be used, the etching depth is the thickness of the extinction nano film; the size of the slit 102 is transferred from the mask 304 to the light shielding film 302, after the photoresist removal process, the slit 102 is cleaned, after cleaning is completed, ion beam process is used to deposit the long-pass filter film layer 305 on the back of the glass substrate, this process uses a commercial coating process, preferably an 830 nm long-pass filter process, in some embodiments, a 785 nm-1064 nm long-pass filter process can also be used, to complete the entire slit processing process.

[0055] The above preparation method is a common technical means in the art.

[0056] Embodiment 3

[0057] As Figures 7-8 A miniature wearable blood glucose monitoring device, two light sources 101 simultaneously emit linear excitation light, which passes through the epidermis and excites the glucose molecules in the interstitial fluid of the dermis to generate Raman signals, the Raman signals are received by the slit 102 and filtered to remove other unwanted stray light such as Rayleigh scattering, after convergence through the lens 110, the Raman signals are coupled into the waveguide chip through the broadband grating coupler 501, input into the first slab waveguide 503-1 through the tapered waveguide 502, after splitting through the array waveguide 504, the same wavelength light interferes into the output waveguide array 505, and is received by the array detector 506 through the second slab waveguide 503-2. The array detector 506 is a photodiode array, in some embodiments, a linear CCD detector or a CMOS image sensor can also be used.

[0058] AsFigure 9 In the present embodiment, the output waveguide 505 and the array detector 506 are arranged in parallel and are directly coupled, and are mounted by dispensing optical glue; in some embodiments, the output waveguide 505 and the array detector 506 can also be arranged in parallel and are reflectively coupled, as shown in (b) or (c) of FIG. 5A. Figure 9 In the present embodiment, the output waveguide 505 and the array detector 506 are arranged in parallel and are directly coupled, and are mounted by dispensing optical glue; in some embodiments, the output waveguide 505 and the array detector 506 can also be arranged in parallel and are reflectively coupled, as shown in (b) or (c) of FIG. 5A. Figure 9 In the present embodiment, the output waveguide 505 and the array detector 506 are arranged in parallel and are directly coupled, and are mounted by dispensing optical glue; in some embodiments, the output waveguide 505 and the array detector 506 can also be arranged in parallel and are reflectively coupled, as shown in (b) or (c) of FIG. 5A. Figure 9 In the present embodiment, the output waveguide 505 and the array detector 506 are arranged in parallel and are directly coupled, and are mounted by dispensing optical glue; in some embodiments, the output waveguide 505 and the array detector 506 can also be arranged in parallel and are reflectively coupled, as shown in (b) or (c) of FIG. 5A.

[0059] The present application adopts an integrated Raman probe and a semiconductor processing technology, greatly reduces the complexity and volume of the monitoring device, and is convenient for the patient to wear.

[0060] Embodiment 4

[0061] The use method of the micro wearable blood glucose monitoring device is as follows:

[0062] As Figures 10-12 , when the information processing unit 106 performs blood glucose prediction, the blood glucose regression model 604 needs to be established first, that is, the blood glucose label value at the corresponding time needs to be collected at the same time as the spectrum obtained by the device. The blood glucose label value selected in the present scheme is the venous blood glucose value, and can also be the fingertip blood glucose value. The number of collected spectra N and the number of blood glucose label values N need to be one-to-one corresponding in the establishment of the regression model. The number N can be 1000, 2000, 5000, 8000, etc., and 5000 is used in the present embodiment. The established regression model 604 is stored in the information processing unit 106. When the user tests, the spectrum data 601 is collected, and after the spectrum preprocessing 602 and feature selection 603, it is input into the regression model 604 to predict the blood glucose value 607. It should be noted that if the regression model 604 establishment process is not performed on the current device, the regression model 604 establishment process needs to be performed before the blood glucose prediction.

[0063] The regression model 604 establishment mainly includes three steps of collecting spectrum data 601, spectrum preprocessing 602, and feature selection 603. When the blood glucose regression model 604 is established, the blood glucose label value corresponding to the test at the time of obtaining the spectrum needs to be input at the same time. The spectrum preprocessing 602 includes three steps of spectrum intensity normalization 701, spectrum baseline removal 702, and spectrum quality evaluation 703.

[0064] Among them, the spectrum intensity normalization 701 is for any spectrum signal , wherein represents the spectrum intensity corresponding to the mth wave number, and the mean value normalization processing obtains ;

[0065] The low-frequency component of the spectral baseline removal 702 is calculated by a neighbor adjusted mean filtering method is the optimal mean filtering radius centered at the mth wavenumber obtained by statistical analysis of the spectral data obtained from the collected spectral data 601, and let The feature spectrum after removing the baseline is To avoid the minimum value in as the denominator in the subsequent ratio calculation, all feature values can be added by 1.

[0066] The spectral quality evaluation 703 is for the M peak response values in the feature spectrum after removing the baseline Two-by-two combination can generate M·(M-1) / 2 pairs of combinations. For each pair of combinations, the peak response ratio of the combination in the spectral data obtained from the collected spectral data 601 is counted, and the most dense (the smallest interval span) 95% interval is taken as the effective value interval, and whether the peak response ratio of the combination in the current spectrum is located in the effective value interval is recorded. If more than 95% of the M·(M-1) / 2 combination peak response ratios in the current spectrum are located in the corresponding effective value interval, it is considered that the spectrum quality is qualified.

[0067] The feature selection 603 and the regression model 604 establishment process of the embodiment are as follows:

[0068] The feature selection 603 is based on the spectral data obtained from the collected spectral data 601 and the corresponding blood glucose label value, that is, each 1 spectrum and each corresponding blood glucose calibration label form a calibration sample pair, and the total number of pairs is N:

[0069] a. For any one of the M·(M-1) / 2 pairs of peak combinations, the peak response ratio of each historical spectrum after the pretreatment completed by the three steps of 701, 702 and 703 is calculated, and a feature sequence with a length of N is obtained ;

[0070] b. Calculate the Spearman correlation coefficient of the current feature sequence and the sequence of blood glucose label values with the same length N ;

[0071] Repeat steps a and b for all calibration sample pairs to obtain a feature correlation sequence with a length of M·(M-1) / 2 ; Each component C of C j ​​(j=1,2,...,M·(M-1) / 2) is defined: the jth pair of peak response combination, in the N rows and M columns matrix composed of N spectra {X^1,...,X^N} preprocessed by steps 701, 702 and 703, take the ratio of {m j-1 ,m j-2} columns, to form a peak response ratio sequence F (length N), C j is the correlation coefficient of F and the blood glucose label value G (also length N), so the absolute value of the K components selected from C is the highest, and their sequence numbers in the 1,2,...,M·(M-1) / 2 sequence are recorded; j-1 Peak response combination: M peak response values, two-by-two combination can produce M·(M-1) / 2 pairs of combinations, each pair of combinations can be represented by the sequence of two peaks {m j-2 ,m j-1 = 1,2,...,M, m j-2 = 1,2,...,M, m j-1 ≠m j-2 ; Obviously, each peak response combination corresponds to two components of X^ in the output X^ of the spectrum baseline removal 702, and the ratio of the two components is the peak response ratio corresponding to the peak response combination;

[0072] d. Select the K pairs of peak combinations with the highest correlation coefficient absolute value from the correlation sequence C ;

[0073] e. For any one of the K pairs of peak combinations, take the corresponding feature sequence in the collected spectrum as the independent variable, and the sequence of blood glucose label values as the regression target, and calculate the Sigmoid regression parameters by least squares method :

[0074] ;

[0075] f. Write and into a local file to establish a regression model 604.

[0076] The blood glucose prediction process is as follows:

[0077] The user triggers the detection by touching the display screen 107, the information processing unit 106 starts the information processing flow, and collects the spectrum data 802 of the user's wrist. The spectrum data 802 is collected by the same method as the spectrum data 601, the spectrum pre-processing 803 is by the same method as the spectrum pre-processing 602, the feature selection 804 is by the same method as the feature selection 603, and the regression model 805 is the same as the regression model 604. Then, for the current spectrum to be predicted , read the local file outputted by steps d to f in the last subsection, and calculate the peak response ratio of each pair of combination according to the K pairs of peak combination recorded in the file , call the corresponding regression parameters , and obtain the single-feature blood glucose prediction value:

[0078] ;

[0079] Take the average of the K single-feature prediction values as the final blood glucose prediction value, and finally display the blood glucose value on the touch display screen 107.

[0080] The above method is only an example to illustrate the use process of the device of the present application, and those skilled in the art can also use other different processing methods and processes to obtain the blood glucose value. The device hardware of the present application has the ability to execute different processing methods and processes to obtain the blood glucose value.

[0081] The above is only a preferred embodiment of the present application, and does not limit the present application in any form. Although the present application has been disclosed as above with a preferred embodiment, it is not intended to limit the present application. Any person skilled in the art can make some changes or modifications to the above disclosed technical content to obtain equivalent embodiments with equivalent changes, without departing from the technical solution of the present application. Any modification, change, equivalent change and modification of the above embodiment, which does not depart from the technical solution of the present application, is still within the scope of the technical solution of the present application.

Claims

1. A micro-wearable blood glucose monitoring device, characterized by, The first part and the second part are connected in series to form a ring through two watchbands; The first part comprises an integrated Raman probe, the integrated Raman probe comprising two light sources for generating a linear spot and a slit; the two light sources are respectively arranged on the two sides of the slit, and the slit is used for emitting excitation light to skin tissue to generate a Raman signal; the slit is provided with a long-pass filter film for filtering Rayleigh scattering and other stray light and autofluorescence; the slit is also provided with a miniature spectrometer for performing light splitting and detection of the Raman signal; The second part comprises an information processing unit for driving control of the light source and the miniature spectrometer and micro-blood glucose online analysis, a touch display screen for reading and displaying a blood glucose value, and a battery module for supplying power to the integrated Raman probe, the information processing unit and the touch display screen; The watchband is provided with a data line for transmitting data and a power line for power supply; The device is used as follows: When the information processing unit performs blood glucose prediction, a blood glucose regression model needs to be established first, that is, a blood glucose label value at a corresponding moment needs to be collected at the same time as the spectrum is collected by the device, and the blood glucose label value is a venous blood glucose value or a fingertip blood glucose value; the number N of collected spectra and the number N of blood glucose label values need to be one-to-one corresponding; after the regression model is established, the regression model is stored in the information processing unit; when a user tests, spectrum data is collected, and after spectrum pretreatment and feature selection, the spectrum data is input into the regression model to predict the blood glucose value; if the regression model establishment process is not performed on the current device, the regression model establishment process needs to be performed before the blood glucose is predicted; The regression model establishment mainly includes three steps of collecting spectrum data, spectrum pretreatment and feature selection; when the blood glucose regression model is established, the corresponding test blood glucose label value needs to be input at the same time as the spectrum is collected; the spectrum pretreatment includes three steps of spectrum intensity normalization, spectrum baseline removal and spectrum quality evaluation; Wherein, the spectral intensity normalization is for any one spectral signal , wherein represents the spectral intensity corresponding to the mth wave number, and the mean value normalization processing obtains ; The low-frequency component of the spectrum baseline is calculated by a neighbor adjusted mean filtering method is the optimal mean filtering radius centered at the mth wave number obtained by spectrum data statistics, and let be the feature spectrum after removing the baseline. In order to avoid the minimum value in as the denominator in the subsequent ratio calculation, let all feature values plus 1.​​ Spectral quality evaluation for feature spectrum after baseline removal M peaks in the feature spectrum, M·(M-1) / 2 pairs of combinations can be generated by combining two by two, for each pair of combinations, the peak response ratio of the combination in the spectral data obtained by statistical acquisition of spectral data is taken as the effective ratio interval, and whether the peak response ratio of the combination in the current spectrum is located in the effective ratio interval is recorded; if more than 95% of the M·(M-1) / 2 combination peak response ratios in the current spectrum are located in the corresponding effective ratio interval, it is considered that the spectrum quality is qualified; The feature selection and the regression model establishment process are as follows: The feature selection is based on the spectrum data and the corresponding blood glucose label value obtained by collecting spectrum data, that is, each spectrum and each corresponding blood glucose label value form a calibration sample pair, and the total number of pairs is N: a. For any pair in the M*(M-1) / 2 pair peak combination, the peak response ratio of each historical spectrum after the three steps of spectral intensity normalization, spectral baseline removal and spectral quality evaluation is calculated to obtain a feature sequence of length N ; b. computing a current feature sequence a sequence of blood glucose label values of the same length N Spearman's correlation coefficient; c. Repeat step a and step b for all calibration samples to get a sequence of characteristic correlations with length M · (M - 1) / 2 ; each component C of C j (j = 1, 2,..., M · (M - 1) / 2) is defined as: the jth pair of the M · (M - 1) / 2 pairs of peak response combinations, in the N rows and M columns matrix consisting of N spectra {X^1,..., X^N} which are preprocessed by spectral intensity normalization, spectral baseline removal and spectral quality evaluation, take the ratio of {m j-1 ,m j-2} columns to form a sequence of peak response ratio F (length N), C j is the correlation coefficient of F and the blood glucose label value G (length N), so from C, select the K components with the highest absolute value and record their sequence number in the sequence of 1, 2,..., M · (M - 1) / 2; peak response combination: M peak response values, two-by-two combination can produce M · (M - 1) / 2 pairs of combinations, each pair of combinations can be represented by the sequence number of the two peaks {m j-1 ,m j-2}, where j = 1, 2,..., M · (M - 1) / 2, m j-1 = 1, 2,..., M, m j-2 = 1, 2,..., M, m j-1 ≠m j-2 ; each peak response combination corresponds to two components of X^ in the output X^ of the spectral baseline removal 7, the ratio of the two components is the peak response ratio corresponding to the peak response combination; d. selecting K pairs of peak combinations with the highest absolute values of correlation coefficients from the correlation sequence C ; e. For any pair of peaks in the combination, the corresponding sequence of features in the acquired spectrum is the sequence of blood glucose tag values is the regression target, the sigmoid regression parameters are calculated using least squares : ； f. Write and to local file, build regression model; The blood glucose prediction process is as follows: The user detects a trigger by touching the display screen, the information processing unit starts the information processing flow, collects spectral data of the user's wrist, performs spectral preprocessing and feature selection, and uses the regression model to predict the blood glucose value. The local files output by steps d to f are read, the peak response ratio of each pair of combinations is calculated according to the K pairs of peak combinations recorded in the files, the corresponding regression parameters are called, and the single-feature blood glucose prediction value is obtained. The local files output by steps d to f are read, the peak response ratio of each pair of combinations is calculated according to the K pairs of peak combinations recorded in the files, the corresponding regression parameters are called, and the single-feature blood glucose prediction value is obtained. ； K single feature prediction values The mean value is taken as the final blood glucose prediction value, and the blood glucose value is finally displayed on the touch display screen.

2. The apparatus of claim 1, wherein, The light source is a horizontal cavity surface emitting laser or a vertical cavity surface emitting laser array.

3. The apparatus of claim 1, wherein, The central wavelength of the light source is 808-976 nm, and the line width is greater than or equal to 0.1 nm.

4. The apparatus of claim 1, wherein, The width direction of the slit is the direction from one light source to the other light source, and the width is 25-200 um; the thickness direction of the slit is perpendicular to the skin tissue, and the thickness is 0.1-2 mm; the height direction of the slit is perpendicular to the width and the height, and the height is 0.6-2 mm; the back of the slit is coated with a long-pass filter for filtering Rayleigh scattering and other stray light and fluorescence background; one side of the slit close to the skin tissue is the front side, and the other side is the back side.

5. The apparatus of claim 1, wherein, The distance between the center of the light source and the center of the slit is 0.5-2 mm.

6. The apparatus of claim 1, wherein, The slit is an air slit or a solid slit.

7. The apparatus of claim 6, wherein, The air slit is manufactured by the following steps: First, the glass substrate or quartz substrate is cleaned, and then the deposition of the light shielding film is performed; after the deposition of the light shielding film is completed, spin coating photoresist is performed on the light shielding film, and after the coating process is completed, the pre-baking process is performed; then, the photolithography process is entered, and the pattern transfer is completed by irradiating ultraviolet light on the mask; After the photolithography process is completed, the development and hardening processes are performed, then the size of the slit is transferred from the mask to the light shielding film, and after the photoresist removal process, the slit is cleaned, and after the cleaning is completed, the long-pass filter film layer is deposited on the back of the glass substrate or quartz substrate, and the entire slit processing process is completed.

8. The apparatus of claim 6, wherein, The solid slit is manufactured by the following steps: First, the glass substrate or quartz substrate is cleaned, and then the deposition of the light shielding film is performed; after the deposition of the light shielding film is completed, spin coating photoresist is performed on the light shielding film, and after the coating process is completed, the pre-baking process is performed; then, the photolithography process is entered, and the pattern transfer is completed by irradiating ultraviolet light on the mask; After the photolithography process is completed, the development and hardening processes are performed, then the size of the slit is transferred from the mask to the light shielding film, and after the photoresist removal process, the slit is cleaned, and after the cleaning is completed, the long-pass filter film layer is deposited on the back of the glass substrate or quartz substrate, and the entire slit processing process is completed. After the film deposition is completed, the CMP process is used for grinding, and the excess film layer on the surface is removed, and after the grinding, the grinding liquid and impurities are removed by cleaning, and after the cleaning is completed, the long-pass filter film layer is deposited on the back of the glass substrate or quartz substrate, and the entire slit processing process is completed.

9. The apparatus of claim 1, wherein, The micro spectrometer comprises, in sequence along a propagation direction of a Raman signal, a collimating lens, a transmission grating, a converging lens group, and a detector.

10. The apparatus of claim 9, wherein, The detector is a near-infrared enhanced CCD or a near-infrared enhanced CMOS sensor.

11. The apparatus of claim 9, wherein, The transmission grating is a bulk holographic grating or a quartz transmission grating.

12. The apparatus of claim 1, wherein, The micro spectrometer comprises, in sequence along a propagation direction of a Raman signal, a lens and a chip-type micro spectrometer, and the chip-type micro spectrometer comprises, in sequence along the propagation direction of the Raman signal, a wide-bandwidth grating coupler, a tapered waveguide, a first slab waveguide, an array waveguide, a second slab waveguide, an output waveguide array, and an array detector.

13. The apparatus of claim 12, wherein, The coupling structure of the output waveguide array and the array detector comprises direct coupling type in parallel arrangement, reflection coupling type in parallel arrangement, and reflection coupling type in stepped arrangement.

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