Single-pixel non-invasive blood glucose detection device

Abstract

The present invention relates to a single-pixel non-invasive blood glucose detection device. According to one embodiment, a single-pixel non-invasive blood glucose detection device may include: a single sensor pixel, arranged on a first substrate, for attaching to the user's skin; and an alignment device, for aligning the sensor pixel to at least one hair follicle on the user's skin. The non-invasive blood glucose detection device of the present invention uses only a single sensor pixel, and uses an alignment device to align the single sensor pixel to at least one hair follicle, so that non-invasive blood glucose detection can be performed quickly and efficiently.

Description

Technical Field

[0001] The present invention generally relates to the field of blood glucose detection, and more particularly, to a single-pixel non-invasive blood glucose detection device. Background Art

[0002] Diabetes is the most common endocrine metabolic disease in the world. The "Report on the Nutrition and Chronic Disease Status of Chinese Residents (2015)" shows that the prevalence of diabetes among adults over 18 years old is 9.7%. my country has become the undisputed number one country with the highest diabetes prevalence, and the prevalence is increasing year by year.

[0003] Among diabetics, the number of people using traditional invasive blood glucose meters has exceeded 50 million, and the average annual use of blood glucose test strips is about 180 per person, and about 9 billion blood glucose test strips are consumed each year. At present, due to the high pressure of social life, eating well and exercising less, staying up late, excessive smoking and drinking, and ecological pollution, there are a large number of potential diabetes patients among the Chinese people. Therefore, it is of great significance to correctly diagnose and treat diabetes.

[0004] During the diagnosis and treatment period, diabetic patients often need to undergo blood sugar concentration tests so that medical staff can understand the effect of treatment in a timely and clear manner. However, frequent blood draws have many disadvantages, which not only increase the risk of infection, but also cause pain to patients and bring certain pressure to medical staff.

[0005] Therefore, how to achieve non-invasive blood glucose detection has become the direction that researchers are working towards. In order to change this situation, non-invasive methods for measuring blood glucose concentration have been actively studied in recent years, including the use of near-infrared spectroscopy and Raman spectroscopy for blood glucose monitoring. These methods have low spectral signal-to-noise ratios, so the accuracy of measuring blood glucose values ​​using the above methods is low. Summary of the invention

[0006] In order to solve the above technical problems, the present invention provides a single-pixel non-invasive blood glucose detection device to achieve the purpose of non-invasive blood glucose detection.

[0007] According to one aspect of the present application, a single-pixel non-invasive blood glucose detection device is provided, comprising: a single sensor pixel, arranged on a first substrate, for being attached to the skin of a user; and an alignment device, for aligning the sensor pixel with at least one hair follicle on the skin of the user.

[0008] In some embodiments, the alignment device includes an alignment mark formed on the first substrate, and the sensor pixel is located at an alignment center of the alignment mark on the first substrate.

[0009] In some embodiments, the alignment device comprises: a second substrate; and an opening penetrating the second substrate, wherein the alignment device is configured such that when the second substrate is attached to the skin of a user, the opening aligns with and exposes the at least one hair follicle.

[0010] In some embodiments, the alignment device further includes: an alignment mark formed on the second substrate, wherein the opening is located on the second substrate at an alignment center of the alignment mark.

[0011] In some embodiments, the openings have substantially the same shape and size as the sensor pixels.

[0012] In some embodiments, the first substrate and the second substrate are flexible substrates.

[0013] In some embodiments, the first substrate and the second substrate are transparent substrates.

[0014] In some embodiments, the alignment mark includes a colored line portion, a raised line portion, a recessed line portion, a laser etched line portion, a solid line portion, a dashed line portion, or any combination thereof.

[0015] In some embodiments, the alignment mark includes a concentric circle pattern, a cross pattern, a crisscross pattern, a square pattern, a circular pattern, or any combination thereof.

[0016] In some embodiments, the sensor pixel includes: an extraction electrode formed on the first substrate, used to extract glucose through the user's skin by reverse ion osmosis; a detection electrode formed on the first substrate, used to detect the concentration of the extracted glucose by an electrochemical method; and a reaction chamber, used to receive the extracted glucose.

[0017] In some embodiments, the extraction electrode includes an anode and a cathode for forming a reverse ion permeation channel in the user's skin to extract glucose, and wherein the detection electrode includes a reference electrode, a working electrode and a counter electrode for detecting the concentration of the extracted glucose through an electrochemical reaction.

[0018] In some embodiments, the anode comprises Ag, and the cathode, the reference electrode, and the counter electrode each comprise Ag / AgCl.

[0019] In some embodiments, the working electrode includes: a noble metal layer; and catalyst particles attached to a surface of the noble metal layer facing the reaction chamber, for catalyzing a decomposition reaction of hydrogen peroxide.

[0020] In some embodiments, a surface of the noble metal layer facing the reaction chamber is a roughened surface.

[0021] In some embodiments, the noble metal layer comprises a gold layer and the catalyst particles comprise Prussian blue.

[0022] In some embodiments, the working electrode includes: a graphene layer; and catalyst nanoparticles attached to a surface of the graphene layer facing the reaction chamber, for catalyzing a decomposition reaction of hydrogen peroxide.

[0023] In some embodiments, the catalyst nanoparticles include at least one of platinum nanoparticles and gold nanoparticles.

[0024] In some embodiments, the working electrode comprises a transition metal oxide layer.

[0025] In some embodiments, the transition metal oxide layer includes a composite of transition metal oxides.

[0026] In some embodiments, the composite of transition metal oxides includes nickel oxide, tin oxide, and indium oxide.

[0027] In some embodiments, the transition metal oxide layer has a porous structure.

[0028] In some embodiments, the reaction chamber contains a gel.

[0029] In some embodiments, the reaction chamber further contains glucose oxidase for catalyzing the oxidation reaction of the extracted glucose to generate hydrogen peroxide.

[0030] In some embodiments, the reaction chamber further contains an alkaline substance.

[0031] In some embodiments, the cathode and the counter electrode are the same electrode.

[0032] In some embodiments, the working electrode has an area larger than any of the other electrodes.

[0033] In some embodiments, the area of ​​the working electrode is greater than the sum of the areas of the other electrodes.

[0034] In some embodiments, the working electrode occupies a central area of ​​the sensor pixel, and other electrodes are disposed around the working electrode.

[0035] In some embodiments, the reaction chamber at least exposes the working electrode.

[0036] In some embodiments, the reaction chamber exposes the detection electrode.

[0037] In some embodiments, the area of ​​the reaction chamber is smaller than the area occupied by both the extraction electrode and the detection electrode.

[0038] In some embodiments, the sensor pixel is configured such that when attached to the user's skin, the detection electrode covers the at least one hair follicle.

[0039] In some embodiments, the sensor pixel is configured such that when attached to the user's skin, the reaction chamber covers the at least one hair follicle.

[0040] In some embodiments, the area of ​​the sensor pixel is 0.0025 mm 2 Up to 80mm 2 Between, preferably 0.0025mm 2 Up to 30mm 2 between 0.0025 mm and more preferably between 0.0025 mm 2 Up to 10mm 2 between 0.0025 mm and more preferably between 0.0025 mm 2 Up to 3mm 2 Between, more preferably 0.0025mm 2 To 1mm 2 between.

[0041] In some embodiments, the volume of the reaction chamber is less than 20 μL, preferably less than 10 μL, and more preferably less than 2 μL.

[0042] In some embodiments, the thickness of the reaction chamber is between 0.03 mm and 0.4 mm, preferably between 0.05 mm and 0.2 mm.

[0043] In some embodiments, the single-pixel non-invasive blood glucose detection device further includes: a data processing unit for processing the detection signal generated by the sensor pixel to determine the concentration of the extracted glucose.

[0044] In some embodiments, the data processing unit includes: a memory storing a calibration curve defining the relationship between glucose concentration and detection current; a controller determining the glucose concentration corresponding to the detection signal based on the calibration curve; and an output unit for outputting the determined glucose concentration.

[0045] It can be seen from the above technical scheme that the embodiment of the present invention provides a single-pixel non-invasive blood glucose detection device. The single-pixel non-invasive blood glucose detection device aligns the sensor pixel with the hair follicles of the human body through the alignment device, uses the sensor pixel to extract glucose from the human body to the skin surface through reverse iontophoresis and with the help of human hair follicles, and detects the glucose concentration on the human skin surface through electrochemical reaction to obtain a current signal related to blood glucose, thereby obtaining the blood glucose concentration. It can be found from the above workflow that the single-pixel non-invasive blood glucose detection device can detect the blood glucose of the object to be tested without damaging the object to be tested, thereby achieving the purpose of non-invasive blood glucose detection.

[0046] In addition, the single-pixel non-invasive blood glucose detection device uses reverse ion electroosmosis to extract glucose from the skin surface, without damaging the object to be tested, thus achieving the purpose of non-invasiveness. The single-pixel non-invasive blood glucose detection device uses electrochemical reactions to detect glucose, which has specificity and eliminates a lot of interference in the detection process. Therefore, the non-invasive blood glucose meter achieves accurate blood glucose testing without damaging the object to be tested. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0048] Figure 1 This is a schematic diagram of the operation of a single-pixel non-invasive blood glucose detection device according to an embodiment of the present application;

[0049] Figure 2 This is a schematic diagram of the detection principle of a single-pixel non-invasive blood glucose detection device according to an embodiment of the present application;

[0050] Figures 3 to 11 is a schematic structural diagram of an alignment device in a single-pixel non-invasive blood glucose detection device according to some embodiments of the present application;

[0051] Fig.12 is a schematic structural diagram of a sensor pixel according to an embodiment of the present application;

[0052] Fig.13 is a schematic structural diagram of a sensor pixel according to another embodiment of the present application;

[0053] Fig.14A and Fig. 14B is a schematic structural diagram of a single-pixel non-invasive blood glucose detection device according to another embodiment of the present application;

[0054] Fig.15 This is a schematic diagram of wearing a single-pixel non-invasive blood glucose detection device according to an embodiment of the present application.

[0055] Fig.16 is a structural block diagram of a data processing unit according to an embodiment of the present application. DETAILED DESCRIPTION

[0056] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0057] Figure 1 FIG. 1 is a schematic diagram of the operation of a single-pixel non-invasive blood glucose detection device 100 according to an embodiment of the present application. Figure 1 As shown, the single-pixel non-invasive blood glucose detection device 100 includes a substrate 110 , an alignment device 120 , and a sensor pixel 130 .

[0058] The substrate 110 may be a flexible transparent substrate, for example, it may be made of a plastic film such as PET, for supporting the alignment device 120 and the sensor pixels 130 thereon. The alignment device 120 may be various alignment marks, such as a colored line portion, a raised line portion, a recessed line portion, a laser etched line portion, a solid line portion, a dotted line portion, etc., and may have various shapes or patterns, which will be described in further detail below. The alignment device 120 may be formed on the upper surface or the lower surface of the substrate 110, or may be embedded in the substrate 110, as long as it can perform the alignment function described in detail below. The sensor pixels 130 are formed on the surface of the substrate 110 to be attached to the skin, and the sensor pixels 130 are formed on the surface of the substrate 110 to be attached to the skin. Figure 1 It should be noted that Figure 1 1 and 120 are shown separately for clarity, but in reality the sensor pixel 130 may be formed on the lower surface of the substrate 110, and the sensor pixel 130 is located at the alignment center of the alignment device 120. The specific structure of the sensor pixel 130 will be described in detail below. Although not shown, the conductive wiring connected to the sensor pixel 130 may extend on the substrate 110 and may penetrate the substrate 110 and extend on the opposite surface.

[0059] When users use Figure 1As shown, with the assistance of the alignment device 120, the sensor pixel 130 located at the alignment center position of the alignment device 120 can be aligned and attached to the hair follicle 410 on the human skin. In some embodiments, the sensor pixel 130 can have a smaller size, and is therefore referred to as a "pixel" in this article. Generally speaking, the size of the sensor pixel 130 can be roughly equivalent to the size of the hair follicle on the human skin, which will be described in detail below. Since both the hair follicle 410 and the sensor pixel 130 have a smaller size, it may be difficult to align the two. Therefore, in some embodiments of the present invention, an alignment device 120 is provided, which can be an alignment mark in various forms and can be formed into various alignment patterns. The sensor pixel 130 can be located at the center position of the alignment pattern of the alignment device 120. In this way, for people with poor eyesight, such as the elderly, the position of the sensor pixel 130 can be easily determined with the help of the alignment device 120. Furthermore, since the substrate 110 is transparent, the hair follicles 410 can be seen through the substrate 110, and with the assistance of the alignment device 120, the sensor pixels 130 are aligned above the hair follicles 410, so that the sensor pixels 130 are accurately covered on the hair follicles 410. It should be understood that although Figure 1 Only one hair follicle 410 is shown, but there may be two or more hair follicles very close to each other on the skin, in which case the sensor pixel 130 may also cover two or more hair follicles.

[0060] Figure 2 FIG. 1 is a schematic diagram of the detection principle of a single-pixel non-invasive blood glucose detection device according to an embodiment of the present application. Figure 2 As shown, the sensor pixel 130 of the single-pixel non-invasive blood glucose detection device 100 includes an extraction electrode 131 and a detection electrode 133. The extraction electrode 131 is used to extract glucose through the corresponding hair follicle 410 by reverse ion permeation, and the detection electrode 133 is used to detect the concentration of the extracted glucose by an electrochemical method. Figure 2 In the illustrated embodiment, the extraction electrode 131 may include an anode 132 and a cathode 134, which establish a reverse iontophoresis channel in the user's skin, thereby extracting glucose to the skin surface. The anode 132 may be an Ag electrode, and the cathode 134 may be an Ag / AgCl electrode, which includes a mixture of Ag and AgCl. The detection electrode 133 may include a counter electrode 134, a working electrode 136, and a reference electrode 138, which constitute a three-electrode system for an electrochemical reaction, thereby detecting the concentration of glucose extracted to the skin surface by an electrochemical method. The counter electrode 134 and the reference electrode 138 may also be Ag / AgCl electrodes. It should be noted that the electrode 134 serves as both a cathode during extraction and a counter electrode during detection, that is, the cathode and the counter electrode are the same electrode, but it should be understood that in other embodiments, the cathode and the counter electrode may also be separate electrodes.

[0061] The working electrode 136 may include a conductive layer and catalyst particles disposed on the conductive layer. For example, in some embodiments, the working electrode 136 may include a graphene layer conductive layer, and nanoparticles of a noble metal catalyst, such as platinum nanoparticles, gold nanoparticles, etc., may be attached to the surface of the side facing the reaction chamber 135 (described later). Here, the graphene layer may be a single layer of graphene or a multilayer of graphene, which has excellent conductivity and flexibility, and is therefore a preferred material for the working electrode 136, and can achieve perfect adhesion to human skin. In other embodiments, the working electrode 136 may include a noble metal layer such as a gold layer. The gold layer may be formed thinner, so that it also has good flexibility. The working electrode 136 may also include catalyst particles disposed on the surface of the noble metal layer facing the reaction chamber 135. For example, the noble metal layer may be specially treated to have a roughened surface, so that catalyst particles such as Prussian blue can be well attached to the roughened surface of the noble metal layer.

[0062] like Figure 2 As shown, the sensor pixel 130 further includes a reaction chamber 135 disposed below the extraction electrode 131 and the detection electrode 133. The reaction chamber 135 may be a chamber surrounded by an insulating material such as PDMS, which exposes at least the working electrode 136, for example, the detection electrode 133, or for example, both the extraction electrode 131 and the detection electrode 133. Preferably, the reaction chamber 135 exposes the detection electrode 133, but may not expose the extraction electrode 131. As will be described below, a smaller reaction chamber 135 is beneficial for improving detection efficiency. In some embodiments, the area occupied by the reaction chamber 135 may be smaller than the area of ​​the sensor pixel 130, that is, the area occupied by both the extraction electrode 131 and the detection electrode 133. The reaction chamber 135 may have a shape substantially the same as the area covered by the extraction electrode 131 and the detection electrode 133 above, or may have a different shape. The reaction chamber 135 may contain a gel for absorbing glucose extracted through the hair follicle 410, and the absorbed glucose may undergo an electrochemical reaction in the reaction chamber 135.

[0063] In some embodiments, in addition to the gel, the reaction chamber 135 may also include glucose oxidase, which can catalyze the oxidation reaction of glucose to generate hydrogen peroxide, which can be catalytically decomposed by the catalyst nanoparticles on the working electrode 136. During the above electrochemical reaction, a detection current related to the concentration of the extracted glucose is generated, so that the blood sugar concentration in the human body can be determined. Although it is described here that the glucose oxidase is located in the reaction chamber 135, in other embodiments, the particles of glucose oxidase can also be arranged on the surface of the conductive layer of the working electrode 136 together with the catalyst particles, and this variation should also be covered by the scope of the present invention defined by the attached claims.

[0064] In other embodiments, the working electrode 136 may also include a transition metal oxide electrode. The transition metal oxide electrode may include transition metal oxides such as nickel oxide, copper oxide, and the like, and may also include a composite of transition metal oxides, such as a mixture of nickel oxide, tin oxide, and indium oxide. Such a transition metal oxide electrode has a porous structure with a high specific area, and can directly catalyze the electrochemical reaction of glucose. In the sensor pixel 130 using the working electrode 136, glucose oxidase may not be required, so the structure is simpler, and the problem of easy inactivation of glucose oxidase can be solved, and the detection activity can be maintained for a long time, which is conducive to long-term continuous detection. It should be understood that in the present embodiment, the working electrode 136 may also include a substrate for supporting the transition metal oxide, and the substrate may be a transition metal material that has not yet been oxidized. Such a working electrode 136 is preferably used to include OH - In an alkaline environment, an alkaline substance may be contained in the reaction chamber 135 to provide such an alkaline environment.

[0065] like Figure 2As shown, in the human body, glucose in blood vessels and tissue fluid can be exchanged with each other through the reabsorption process and the refiltration process, and their concentrations are basically equal. The traditional non-invasive blood glucose meter extracts glucose through the skin and then detects the extracted glucose. However, it generally takes a long time, such as more than 20 minutes, for the extracted glucose to reach a stable concentration, thereby completing the detection. The inventors have found through research that the transcutaneous extraction channels of human blood glucose include multiple types, typically including transcellular channels, intercellular channels, and hair follicle channels, and the extraction capabilities of different channels vary greatly. Hair follicles, as natural channels that penetrate the stratum corneum, epidermis and dermis of the skin and directly reach the lower cortex, have excellent glucose extraction capabilities, which are far greater than transcellular channels and intercellular channels. Moreover, each hair follicle has basically a similar structure, so the hair follicles in the same area have basically the same glucose extraction capabilities. In view of the above research findings, the non-invasive blood glucose detection device of the present invention is designed to align the sensor pixels 130 with the hair follicles to non-invasively extract and detect blood glucose in the human body.

[0066] On the other hand, the inventors have found that the sensors of conventional non-invasive blood glucose meters are designed to have a large area. When the area of ​​the sensor is large, it is extracted not only through the hair follicles, but also through the transcellular channel and the intercellular channel in an area larger than the hair follicles. The extraction capacity of the transcellular channel and the intercellular channel is much lower than that of the hair follicles, so that the concentration of glucose extracted through the hair follicles is diluted, and it takes a long time to complete the extraction and detection, resulting in low detection efficiency and low detection accuracy. On the contrary, in the present invention, by designing the sensor pixel 130 to have a sufficiently small area, only a single sensor pixel is used, and the single sensor pixel is mainly used for extraction and detection of hair follicles, due to the excellent glucose extraction capacity of the hair follicle channel, glucose extraction and detection can be completed quickly and efficiently, and the interference caused by migration of other paths can be reduced, thereby effectively improving the signal-to-noise ratio of the measurement, greatly improving the detection accuracy, and being comparable to the conventional finger blood detection method. Of course, the area of ​​the sensor pixel 110 cannot be too small, otherwise it cannot cover the hair follicles, and it is not conducive to manufacturing.

[0067] In order to achieve the above objectives, the inventors have carefully designed the sensor pixel 130. Generally speaking, the diameter of a human hair follicle is in the range of 0.02-0.05 mm. In some embodiments, the area of ​​the sensor pixel 130 can be 0.0025 mm. 2 Up to 80mm 2 Between, preferably between 0.0025mm 2 Up to 30mm 2 More preferably, between 0.0025 mm 2 Up to 10mm 2 Between, preferably between 0.0025mm2 Up to 3mm 2 For example, it can be between 0.0025mm 2 To 1mm 2 The inventors have found through experiments that the area of ​​the sensor pixel 130 is between 10 mm 2 When the area of ​​the sensor pixel 130 is reduced to, for example, 1 mm 2 When the area of ​​the sensor pixel 130 is 1 mm, the glucose extraction operation can be completed in less than 1 minute. 2 The following are the most preferred.

[0068] The glucose extraction time is also related to the volume of the reaction chamber 135. In some embodiments of the present invention, the reaction chamber 135 may have an area substantially the same as or smaller than the area occupied by the electrodes above, i.e., the area of ​​the sensor pixel 130, and the thickness (or depth) of the reaction chamber 135 may be between 0.03 mm and 0.4 mm, preferably between 0.05 mm and 0.2 mm. The volume of the reaction chamber 135 may be in the range of less than 20 μL, preferably less than 10 μL, and more preferably less than 2 μL.

[0069] It should also be noted that during detection, the glucose oxidase in the reaction chamber 135 catalyzes the oxidation reaction of glucose to generate hydrogen peroxide, and the working electrode 136 in the detection electrode 133 catalyzes the decomposition reaction of hydrogen peroxide, thereby generating a detection current corresponding to the glucose concentration. Therefore, in some embodiments of the present invention, the reaction chamber 135 is configured to expose the working electrode 136, or preferably expose the detection electrode 133 including the counter electrode 134, the working electrode 136 and the reference electrode 138, or both the extraction electrode 131 and the detection electrode 133 may be exposed. Preferably, the working electrode 136 may be designed to have a larger area than any other electrode, for example, the working electrode 136 may be designed to have an area greater than the sum of the areas of all other electrodes in the sensor pixel. Furthermore, the working electrode 136 may be located in the central area of ​​the sensor pixel 130, and the other electrodes may surround the working electrode 136, and the working electrode 136 may have a contour shape substantially the same as that of the sensor pixel 130. Thus, when the sensor pixel 130 is aligned with the hair follicle 410, the working electrode 136 and the reaction chamber 135 thereunder are aligned with the hair follicle 410, so that glucose extraction and detection can be performed quickly and efficiently.

[0070] Since both the sensor pixel 130 and the hair follicle 410 have a small area, in order to align the sensor pixel 130 to the hair follicle 410, as described above, an alignment device 120 is provided around the sensor pixel 130. On the other hand, the upper surface of the portion of the substrate 110 corresponding to the alignment device 120 can be formed to have a convex lens-like shape, and the lower surface can still be flat to form the sensor pixel 130 and facilitate attachment to the skin surface. In this way, this portion of the transparent substrate 110 has the function of a magnifying glass, which can facilitate the user to observe and align the hair follicle 410.

[0071] The alignment device 120 may include various alignment marks, such as a colored line portion, a raised line portion, a recessed line portion, a laser etched line portion, a solid line portion, a dotted line portion, etc., and may be formed in various shapes or patterns. For example, the alignment device 120 may be formed in a concentric circle pattern, a cross pattern, a crisscross pattern, a square pattern, a circular pattern, and various combinations and variations thereof. Figures 3 to 11 Various examples of alignment devices 120 are shown, it being understood that for clarity, the sensor pixels 130 are not shown, although in reality the sensor pixels 130 are located at the alignment centers of the alignment devices 120 .

[0072] With reference to the accompanying drawings, Figure 3 An example of an alignment device 120 is shown, which includes a cross-shaped alignment mark and a circular pattern surrounding the cross-shaped alignment mark, the circular pattern roughly defining the boundary of the alignment device 120, and the cross-shaped alignment mark defines the alignment center of the alignment device 120. Figure 4 In another example shown, a plurality of concentric circle patterns are used as alignment marks instead of the cross pattern, wherein the smallest circle can surround the perimeter of the sensor pixel 130 and be adjacent thereto; Figure 5 In the example shown, a combination of a cross pattern and a concentric circle pattern is used. Figure 6 The example uses a cross-shaped alignment pattern. Figure 7 The example in adopts a combination of a crisscross pattern and a concentric circle pattern. Figure 8 In the example of , a variation of the cross pattern is used, namely four arrows pointing to the center, and also includes a circular pattern around the central area. Fig. 9 In the example of FIG. 1 , the alignment device 120 includes a rectangular frame as an outer perimeter and a cross-shaped pattern located within the rectangular frame. Fig.10 Examples include a combination of a crisscross pattern and a concentric circle pattern within a rectangular frame. Fig.11 Examples include a combination of a herringbone pattern and a plurality of concentric rectangular frame patterns. It should be understood that the alignment device 120 may also include many other patterns.

[0073] Fig.12FIG. 1 is a schematic diagram of the structure of a sensor pixel 130 according to another embodiment of the present application. Fig.12 As shown, the sensor pixel 130 includes an anode 132, a cathode (counter electrode) 134, a working electrode 136, and a reference electrode 138, each of which is connected to an external circuit via a wiring 137. Figure 2 The examples include the same electrodes, but their layout is different. Figure 2 In the example of , the working electrode 136 is substantially rectangular, the cathode 134 and the reference electrode 138 surround the periphery of the working electrode 136, and the anode 132 is arranged on the outside of the cathode 134 and substantially parallel to the cathode 134. Fig.12 In the example of FIG. 1 , the working electrode 136 has a circular shape, and the anode 132, the cathode 134, and the reference electrode 138 surround the circumference of the working electrode 136. The anode 132 and the cathode 134 may surround a larger portion of the circumference of the working electrode 136 to facilitate glucose extraction, while the reference electrode 138 may only surround a smaller portion of the circumference of the working electrode 136. The advantage of this structure is that the working electrode 136 occupies the central area of ​​the sensor pixel 130 and occupies most of the area of ​​the sensor pixel 130, so that the working electrode 136 and the reaction chamber 135 ( Fig.12 Not shown) is aligned with the hair follicle 410.

[0074] Fig.13 FIG. 1 is a schematic diagram of the structure of a sensor pixel 130 according to another embodiment of the present application. Fig.13 As shown, the sensor pixel 130 includes an anode 132, a cathode (counter electrode) 134, a working electrode 136, and a reference electrode 138. The working electrode 136 is located at the center of the sensor pixel 130 and has a rectangular pattern, and the anode 132, the cathode (counter electrode) 134, and the reference electrode 138 surround the working electrode 136, wherein the anode 132 and the cathode 134 extend along the long side of the working electrode 136 and are located on both sides of the working electrode 136 opposite to each other, and the reference electrode 138 extends along the short side of the working electrode 136.

[0075] Fig.14A and Fig. 14B is a schematic diagram of the structure of a single-pixel non-invasive blood glucose detection device according to another embodiment of the present application, wherein Fig.14A is a top view, Fig. 14B is a side view. Fig.14A and 14BAs shown, the single-pixel non-invasive blood glucose detection device 200 includes a first substrate 210, an alignment device 220, and a sensor pixel 230. The sensor pixel 230 can be arranged on the first substrate 210. The alignment device 220 may include a second substrate 222. The first substrate 210 and the second substrate 222 may be the same substrate as the substrate 110, that is, a transparent flexible substrate. The alignment device 220 may also include an alignment mark 224 formed on the second substrate 222, which defines an alignment center, and an opening 226 penetrating the second substrate 222 is formed at the alignment center. The opening 226 may have a shape and size substantially the same as the sensor pixel 230 to accommodate the sensor pixel 230. When in use, the user may first attach the alignment device 220 to the user's skin, and with the help of the alignment mark 224 of the alignment device 220, align the opening 226 with the hair follicle 410. Since there is no obstruction of the sensor pixel, the user can easily align the opening 226 with the hair follicle 410, for example, the hair follicle 410 may be approximately located at the center of the opening 226. Then, the user can attach the first substrate 210 to the second substrate 222 of the alignment device 220, and position the sensor pixels 230 on the first substrate 210 in the openings 226. In this way, accurate alignment of the sensor pixels 230 and the hair follicles 410 is achieved.

[0076] In some embodiments, the second substrate 222 may not be provided with the alignment mark 224, because the opening 226 itself can be used as an alignment mark. For example, the user can directly align the opening 226 with the hair follicle 410 so that the hair follicle 410 is located at the center of the opening 226.

[0077] In some embodiments, an alignment device, such as the alignment device 120 described above, may also be disposed on the first substrate 210 to assist in determining the position of the sensor pixel 230 and align the sensor pixel 230 into the opening 226 .

[0078] Fig.15 FIG. 1 shows a schematic diagram of wearing a single-pixel non-invasive blood glucose detection device according to an embodiment of the present application. Fig.15 As shown, the aforementioned single-pixel non-invasive blood glucose detection device 100 (200) can be attached to the skin surface of a human body, such as an arm 400, and each electrode of the single-pixel non-invasive blood glucose detection device 100 can be connected to the data processing unit 300 through a wire. It should be understood that the data processing unit 300 can also be regarded as a part of the single-pixel non-invasive blood glucose detection device of the present invention. Fig.15The sensor pixels are shown to be connected to the data processing unit 300 via a wired line, but in other embodiments, the necessary circuits can also be provided on the detection device 100 side to send the signal wirelessly to the data processing unit 300. The data processing unit 300 can be a portable electronic device worn or carried by the user, for example, it can be integrated into the user's mobile phone. In other embodiments, the detection device 100 and the data processing unit 300 can also be integrated together to form a wearable device, which is directly worn on the user's arm 400, for example.

[0079] Fig.16 The structural block diagram of the data processing unit 300 is shown. The data processing unit 300 is used to process the detection signal generated when the detection device 100 detects the extracted glucose to determine the concentration of the extracted glucose. Specifically, the detection signal generated by the detection device 100, such as the detection current, is proportional to the concentration of glucose. The data processing unit 300 may include a memory 310, such as a ROM, EEPROM, flash memory, etc., which can store a calibration curve, which describes the relationship between the glucose concentration and the detection current, which is generally a linear relationship. The data processing unit 300 also includes a controller 320, which can control the glucose extraction and detection operations of the detection device 100, and also determine the glucose concentration corresponding to the detection signal generated by the detection device 100 based on the aforementioned calibration curve, thereby determining the blood glucose concentration of the user. The data processing unit 300 may also include an output unit 330 for outputting the test result, that is, the blood glucose concentration of the user. The output unit 330 may be, for example, a display, a speaker, etc., or a communication unit such as Bluetooth, WiFi, etc. to send the test results to other devices, such as to a hospital's information management system or a patient's doctor's data system via the Internet. In some embodiments, the data processing unit 300 may also include an alarm unit 340. When the blood glucose level exceeds a certain level, the alarm unit 340 may trigger various forms of alarm signals, such as indicator light signals, buzzer signals, etc.

[0080] In summary, the embodiment of the present application provides a single-pixel non-invasive blood glucose detection device. The single-pixel non-invasive blood glucose detection device uses the sensor pixel to extract glucose from the human body to the skin surface through reverse iontophoresis and with the help of human hair follicles, and detects the glucose concentration on the human skin surface through electrochemical reactions to obtain a current signal related to blood glucose, thereby obtaining the blood glucose concentration. Through the above workflow, it can be found that the single-pixel non-invasive blood glucose detection device can detect the blood glucose of the object to be tested without damaging the object to be tested, thereby achieving the purpose of non-invasive blood glucose detection.

[0081] In addition, the single-pixel non-invasive blood glucose detection device uses reverse ion electroosmosis to extract glucose from the skin surface, without damaging the object to be tested, thus achieving the purpose of non-invasiveness. The single-pixel non-invasive blood glucose detection device uses electrochemical reactions to detect glucose, which has specificity and eliminates a lot of interference in the detection process. Therefore, the non-invasive blood glucose meter achieves accurate blood glucose testing without damaging the object to be tested.

[0082] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A single-pixel non-invasive blood glucose detection device, comprising: A first substrate, the first substrate is circular and has an upper surface and a lower surface, the upper surface is formed to have a convex lens-like shape, the lower surface is flat and is used to be attached to the surface of the user's skin, and the first substrate is a transparent flexible substrate; a single sensor pixel, which is circular in shape and disposed on the lower surface of the first substrate, and is used for being attached to the skin of the user; as well as an alignment device, formed on the upper surface, the lower surface or embedded in the first substrate, for aligning and attaching the single sensor pixel to at least one hair follicle on the skin of the user, wherein the alignment device is an alignment mark, the single sensor pixel is located at the alignment center of the alignment mark on the first substrate, wherein the alignment mark includes a colored line portion, a raised line portion, a recessed line portion, a laser etched line portion, a solid line portion, a dotted line portion, or a combination thereof, and the alignment mark is formed as a concentric circle pattern, a cross pattern, a crisscross pattern, a circular pattern, or a combination thereof, Wherein, the sensor pixels include: an extraction electrode formed on the first substrate for extracting glucose through the user's skin by reverse ion osmosis; a detection electrode formed on the first substrate and used for detecting the concentration of the extracted glucose by an electrochemical method; and A reaction chamber for receiving the extracted glucose, The extraction electrode includes an anode and a cathode, which are used to form a reverse ion permeation channel in the user's skin to extract glucose. The detection electrode includes a reference electrode, a working electrode and a counter electrode, which are used to detect the concentration of the extracted glucose through an electrochemical reaction, and the cathode and the counter electrode are the same electrode. The working electrode has a circular shape and occupies the central area of ​​the sensor pixel, the anode, cathode and reference electrode are arranged in a ring around the working electrode, and the area of ​​the anode is larger than the area of ​​the cathode, and the area of ​​the cathode is larger than the area of ​​the reference electrode.

2. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The anode includes Ag, and the cathode, the reference electrode, and the counter electrode each include Ag / AgCl.

3. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The working electrode comprises: a noble metal layer; and Catalyst particles are attached to the surface of the noble metal layer facing the reaction chamber and are used to catalyze the decomposition reaction of hydrogen peroxide.

4. The single-pixel non-invasive blood glucose detection device according to claim 3, wherein: The surface of the noble metal layer facing the reaction chamber is a roughened surface.

5. The single-pixel non-invasive blood glucose detection device according to claim 3, wherein: The noble metal layer includes a gold layer, and the catalyst particles include Prussian blue.

6. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The working electrode comprises: a graphene layer; and Catalyst nanoparticles are attached to the surface of the graphene layer facing the reaction chamber and are used to catalyze the decomposition reaction of hydrogen peroxide.

7. The single-pixel non-invasive blood glucose detection device according to claim 6, wherein: The catalyst nanoparticles include at least one of platinum nanoparticles and gold nanoparticles.

8. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The working electrode includes a transition metal oxide layer.

9. The single-pixel non-invasive blood glucose detection device according to claim 8, wherein: The transition metal oxide layer includes a composite of transition metal oxides.

10. The single-pixel non-invasive blood glucose detection device according to claim 9, wherein: The transition metal oxide composite includes nickel oxide, tin oxide and indium oxide.

11. The single-pixel non-invasive blood glucose detection device according to claim 9, wherein: The transition metal oxide layer has a porous structure.

12. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The reaction chamber contains a gel.

13. The single-pixel non-invasive blood glucose detection device according to claim 12, wherein: The reaction chamber also contains glucose oxidase for catalyzing the oxidation reaction of the extracted glucose to generate hydrogen peroxide.

14. The single-pixel non-invasive blood glucose detection device according to claim 12, wherein: The reaction chamber also contains alkaline substances.

15. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The area of ​​the working electrode is larger than that of any of the other electrodes.

16. The single-pixel non-invasive blood glucose detection device according to claim 15, wherein: The area of ​​the working electrode is greater than the sum of the areas of the other electrodes.

17. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The reaction chamber at least exposes the working electrode.

18. The single-pixel non-invasive blood glucose detection device according to claim 17, wherein: The reaction chamber exposes the detection electrode.

19. The single-pixel non-invasive blood glucose detection device according to claim 18, wherein: The area of ​​the reaction chamber is smaller than the area occupied by both the extraction electrode and the detection electrode.

20. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The sensor pixel is configured such that when attached to the user's skin, the detection electrode covers the at least one hair follicle.

21. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The sensor pixel is configured such that when attached to the user's skin, the reaction chamber covers the at least one hair follicle.

22. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The area of ​​the sensor pixel is 0.0025mm 2 Up to 80mm 2 between.

23. The single-pixel non-invasive blood glucose detection device according to claim 22, wherein: The area of ​​the sensor pixel is 0.0025mm 2 Up to 30mm 2 between.

24. The single-pixel non-invasive blood glucose detection device according to claim 22, wherein: The area of ​​the sensor pixel is 0.0025mm 2 Up to 10mm 2 between.

25. The single-pixel non-invasive blood glucose detection device according to claim 22, wherein: The area of ​​the sensor pixel is 0.0025mm 2 Up to 3mm 2 between.

26. The single-pixel non-invasive blood glucose detection device according to claim 22, wherein: The area of ​​the sensor pixel is 0.0025mm 2 To 1mm 2 between.

27. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The volume of the reaction chamber is less than 20 μL.

28. The single-pixel non-invasive blood glucose detection device according to claim 27, wherein: The volume of the reaction chamber is less than 10 μL.

29. The single-pixel non-invasive blood glucose detection device according to claim 27, wherein: The volume of the reaction chamber is less than 2 μL.

30. The single-pixel non-invasive blood glucose detection device according to claim 1, wherein: The thickness of the reaction chamber is between 0.03 mm and 0.4 mm.

31. The single-pixel non-invasive blood glucose detection device according to claim 30, wherein: The thickness of the reaction chamber is between 0.05 mm and 0.2 mm.

32. The single-pixel non-invasive blood glucose detection device according to claim 1, further comprising: A data processing unit is used to process the detection signals generated by the sensor pixels to determine the concentration of the extracted glucose.

33. The single-pixel non-invasive blood glucose detection device according to claim 32, wherein: The data processing unit comprises: a memory storing a calibration curve defining a relationship between glucose concentration and detection current; a controller, which determines a glucose concentration corresponding to the detection signal based on the calibration curve; and An output unit is used to output the determined glucose concentration.

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