CN-121987832-A - Intelligent colorimetric microneedle patch for monitoring interstitial fluid glucose and preparation method

Abstract

The invention discloses an intelligent colorimetric microneedle patch for instant detection of glucose in interstitial fluid and a system thereof. The integrated device mainly comprises a microneedle array, a colorimetric lateral flow test strip and a medical adhesive patch. Wherein, the microneedle is manufactured by adopting a surface projection micro-stereoscopic photoetching technology and is used for painless skin puncturing and interstitial fluid sample collection. The collected interstitial fluid migrates to a lateral flow test strip loaded with glucose oxidase and horseradish peroxidase to perform biochemical reaction, and a macroscopic color change signal is generated through 3,3', 5' -tetramethyl benzidine. And capturing colorimetric images through an application program of the smart phone and performing RGB color analysis, so that accurate quantitative detection of the glucose concentration can be realized. The invention combines the minimally invasive advantage of the micro-needle and the portable analysis capability of the smart phone, has the characteristics of low cost, simple and convenient operation, rapid detection and easy mass production, and provides a non-invasive and intelligent monitoring solution for daily management of diabetes.

Inventors

• CHEN ZHENCHENG
• LIU CHENGHAO
• LIU ZIANG

Assignees

• 桂林电子科技大学

Dates

Publication Date

20260508

Application Date

20260302

Claims (7)

1. 1. The intelligent colorimetric microneedle integrated patch for monitoring interstitial fluid glucose is characterized by comprising a microneedle array, colorimetric side-flow test strips, an adhesive patch and an intelligent mobile phone matched analysis system, wherein the components are used for cooperatively realizing interstitial fluid collection, glucose reaction detection and quantitative analysis; the microneedle array is of a hollow structure, is prepared by adopting a projection micro-stereoscopic photoetching technology and taking photo-curing resin as a material, and is used for penetrating the skin surface layer to collect interstitial fluid; The colorimetric side-flow test strip is formed by sequentially overlapping and connecting a sample pad, a nitrocellulose membrane and a water absorption pad, wherein the width of the overlapping area is 3mm, the sample pad is loaded with Glucose Oxidase (GOD), the nitrocellulose membrane is loaded with horseradish peroxidase (HRP), and the water absorption pad provides driving force for liquid migration; the medical adhesive plaster is characterized in that the medical adhesive plaster is taken as a substrate, a round liquid drop loading window with the diameter of 4mm and a colorimetric observation window with the diameter of 4mm multiplied by 10mm are arranged on the substrate, a preset fixed window with the diameter of 10mm multiplied by 10mm is arranged at the bottom of the substrate, the microneedle array is fixed in the preset fixed window, and the liquid outlet end is aligned with the liquid drop loading window; the intelligent mobile phone matching analysis system comprises an intelligent mobile phone with a high-definition shooting function and a special image analysis application program, wherein the intelligent mobile phone is used for capturing a color development image of a colorimetric observation window, and the application program is used for realizing quantitative calculation of glucose concentration by analyzing an RGB value of the image.
2. 2. The intelligent colorimetric microneedle patch according to claim 1, wherein the microneedle array has uniform needle number, the size specification can be adjusted according to application requirements, and mechanical property tests prove that the microneedle patch still has no fracture or deformation at a compression rate of 0.5mm/min to 150N, and meets the skin penetration use requirement.
3. 3. A method of preparing the intelligent colorimetric microneedle patch of claim 1, comprising the steps of: (1) Preparation and testing of microneedle arrays: ① Designing a three-dimensional model of the microneedle array by adopting SolidWorks 2023 software; ② Taking photo-curing resin as a printing material, using nanoArch S140,140 projection micro-stereoscopic photoetching system, and carrying out 3D printing on the microneedle array under the irradiation of 405nm UV LED light source; ③ Pasting the microneedle array on a rigid bottom plate, compressing at a speed of 0.5mm/min by a displacement-force analyzer for mechanical test, normalizing at least seven groups of test data by MATLAB software, and screening the microneedle array meeting the requirement of compressive strength; (2) Preparation of colorimetric lateral flow test strips: ① Nitrocellulose membrane treatment, namely immersing untreated nitrocellulose membrane strips in 0.2mg/mL HRP solution for 3 minutes, drying at 37 ℃ for 20 minutes, and cutting into 4mm wide strips by a slitter; ② Sample pad treatment, in which an untreated sample pad is soaked in a GOD solution of 0.5mg/mL for 3 minutes, dried at 37 ℃ for 4 hours, and cut into 10mm multiplied by 10mm gaskets by a slitter; ③ Absorbent pad treatment, cutting the untreated absorbent pad into 10mm x 10mm sheet bodies by a slitter; (3) Assembly of adhesive patches: ① Respectively sticking the treated sample pad and the water absorption pad on two sides of the adhesive bandage, and sticking a nitrocellulose membrane strip across the sample pad and the water absorption pad to ensure that the overlapping areas are 3mm; ② A phi 4mm circular liquid drop loading window is arranged at the position of the adhesive bandage corresponding to the sample pad, and a 4mm multiplied by 10mm colorimetric observation window is arranged at the position corresponding to the nitrocellulose membrane; ③ Adhering the qualified microneedle array in the step (1) into a preset fixed window at the bottom of the adhesive patch, aligning to the droplet loading window, and completing assembly; (4) And configuring a matched system, namely selecting a high-definition shooting smart phone, configuring a special application program with an RGB value analysis function, and establishing a corresponding relation model of RGB values and glucose concentration through glucose standard solution calibration.
4. 4. The method according to claim 3, wherein all cutting operations in the step (2) are performed by a slitter, so that dimensional accuracy of the sample pad, the nitrocellulose membrane strip, and the absorbent pad meets assembly requirements.
5. 5. The method according to claim 3, wherein the concentration range of the glucose standard solution used for calibration in the step (4) is 1-40mmol/L, and the detection error of the application program after calibration is controlled within 1 mmol/L.
6. 6. The smart colorimetric microneedle patch of claim 1, wherein the smart phone is an iPhone 15 Pro and the dedicated image analysis application is capable of capturing a blue colorimetric signal image generated after 3,3', 5' -Tetramethylbenzidine (TMB) is oxidized and performing RGB value analysis.
7. 7. The intelligent colorimetric microneedle patch of claim 1, wherein the sample pad, absorbent pad are purchased from Shanghai Jiejie biotechnology limited, nitrocellulose membrane is purchased from Sartorius AG, adhesive band-aid is purchased from qiang, all materials meeting medical grade standards or analytical purity grade requirements.

Description

Intelligent colorimetric microneedle patch for monitoring interstitial fluid glucose and preparation method Technical Field The invention relates to the technical field of medical instruments and biosensing, in particular to a interstitial fluid glucose instant detection (POCT) system integrating microneedle sampling, colorimetric reaction and intelligent analysis. Background Diabetes is a common chronic metabolic disease. Poor long-term glycemic control can lead to a variety of serious complications that significantly affect the quality of life of the patient. Achieving optimal glycemic management requires periodic monitoring. However, the mainstream detection methods mainly rely on invasive fingertip blood sampling, which is relatively cumbersome and presents a certain risk of infection. Long-term, regular blood glucose monitoring is required, both for patients requiring long-term diabetes management and for healthy people at risk due to bad lifestyle habits. The invasiveness of traditional methods can easily lead to patient conflict, affecting the continuity and effectiveness of routine testing. Therefore, development of painless, convenient glucose detection techniques has become an important research direction for diabetes management. Over the past decade, microneedle technology has received extensive attention and significant progress in the field of glucose monitoring due to its advantages of minimal invasiveness and miniaturization. Research shows that the concentration of metabolites such as glucose in interstitial fluid is highly correlated with the concentration in blood, making interstitial fluid a viable alternative medium for painless sampling by microneedle technology. While microneedle technology presents great potential in point-of-care testing, it still presents considerable challenges in terms of low cost, scalable manufacturing, and rapid, intelligent in-situ testing. At present, many researches adopt 3D printing technology to manufacture the micro-needle, and the micro-needle has the advantages of low mass production cost, high processing precision and good consistency. In addition, the micro needle can be integrated with a colorimetric technology, so that the extracted interstitial fluid is conveyed to a colorimetric area for convenient and visual detection. Although the sensitivity may be relatively limited, combining this approach with smartphone-based quantitative analysis can largely remedy this limitation, meeting the requirements of more stringent detection scenarios. The invention patent with publication number of CN121265819A discloses an Electrochemiluminescence (ECL) MeHA microneedle patch, which utilizes methacryloylated hyaluronic acid (MeHA) to prepare microneedles, and the luminescent reagent is excited by electrochemical signals to realize the detection of biomarkers. Although the electrochemiluminescence technology has higher sensitivity, the system is complex to construct, a precise electrochemical workstation or a complex circuit driving device is usually connected to provide trigger voltage, and the requirements on the conductivity of the microneedle array and the electrode integration process are extremely high. This results in such devices facing limitations such as large instrument volumes, high operating thresholds, and complex manufacturing processes in point of care (POCT) scenarios where home monitoring or resources are limited. In contrast, the colorimetric sensor has the remarkable advantages of intuitiveness, no need of external power supply drive and low cost, and has important scientific research value and clinical significance for overcoming the defects of strong equipment dependence, high cost and the like of the traditional electrochemiluminescence microneedle system and promoting the house-keeping and intellectualization of diabetes management. Disclosure of Invention The invention provides an intelligent colorimetric microneedle patch for monitoring interstitial fluid glucose and a preparation method thereof, which realize painless acquisition of interstitial fluid, rapid colorimetric detection and intelligent quantitative analysis of glucose, solve the problems of strong invasiveness, complex operation, low detection efficiency and the like of the existing detection technology, and provide a convenient and accurate blood glucose monitoring solution for diabetics. The intelligent colorimetric microneedle patch comprises a microneedle array, a colorimetric lateral flow test strip, an adhesive patch and a smart phone image analysis system, wherein each component is used for realizing interstitial fluid collection, glucose reaction detection and quantitative analysis in a cooperative manner, and the specific structure comprises the following components: the micro-needle array is prepared by adopting a hollow structure design and adopting a surface projection micro-stereoscopic photoetching technology, is made of photo-curing resin, has uniform needle nu