3D printed hollow microneedle array resin patch and preparation and application, dynamic blood glucose monitor, dynamic blood glucose concentration monitoring method

Abstract

This invention provides a 3D-printed hollow microneedle array resin patch, its preparation and application, a continuous glucose monitoring device, and a method for dynamic monitoring of blood glucose concentration, belonging to the field of biomedical technology. The hollow microneedle array resin patch of this invention features a "well"-shaped support to ensure the porosity of the perforated microneedles; the design of a hollow conical side opening greatly improves the porosity and microneedle pore volume, effectively increasing the amount of body fluid collected and thus improving detection accuracy. Based on 3D printing technology, the 3D-printed hollow microneedle array resin patch of this invention allows for the determination of basic parameters according to the diameter and height of existing needle sensors, as well as the depth of the stratum corneum and pain nerves, thereby achieving customization of the hollow microneedle combined with the needle sensor structure. It is suitable for needle sensors of different sizes, providing feasibility for microneedles to penetrate subcutaneously for biomarker detection.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to 3D-printed hollow microneedle array resin patches and their preparation and application, dynamic blood glucose monitors, and methods for dynamic monitoring of blood glucose concentration. Background Technology

[0002] Biomonitoring is a primary method for detecting human indicators and obtaining health information. To overcome the cumbersome and limited nature of traditional testing, researchers have proposed point-of-care testing (POCT), currently the most important method. POCT involves testing at or near the patient, continuously providing portable, cost-effective, and readily marketable measurement tools. Among these, to overcome safety concerns, microneedle-based POCT devices have been developed. These devices offer advantages such as minimal invasiveness, painlessness, and convenience for detecting various analytes, attracting considerable research interest and showing great potential in smart healthcare. The widespread application and improved safety of POCT are inseparable from the flexible application and in-depth research of microneedle technology. Thanks to the short and slender shape of microneedles, they can easily penetrate the stratum corneum without touching pain nerves. Combined with drugs or biosensors, this overcomes traditional pain and safety issues, achieving non-invasive and painless drug treatment and analyte detection in bodily fluids. Specially designed microneedles can also monitor the concentration of target substances in bodily fluids in real time, extending the effective time of a single test and avoiding the pain associated with repeated long-term bodily fluid collection. On the other hand, the simple structure, low manufacturing cost, and ease of operation of microneedles also solve the safety hazards of laboratory waste and the problems of environmental pollution and resource waste. They also allow low-income users to afford testing costs and significantly reduce the need for professional supervision in self-diagnosis. Furthermore, research into novel microneedles based on the integration of biosensors, optoelectronics, and wireless communication is conducive to obtaining comprehensive and ubiquitous healthcare solutions. Summary of the Invention

[0003] The purpose of this invention is to provide a 3D-printed hollow microneedle array resin patch, its preparation and application, a dynamic blood glucose monitor, and a method for dynamic blood glucose concentration monitoring. The 3D-printed hollow microneedle array resin patch, combined with a needle-type sensor, can achieve painless and minimally invasive treatment, and can be applied to continuous human blood glucose concentration monitoring to realize smart healthcare.

[0004] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0005] This invention provides a 3D printed hollow microneedle array resin patch, comprising a plurality of structural units; the plurality of structural units are arranged in a square array;

[0006] The structural unit includes a conical hollow side-perforated needle tip 1, a rectangular perforated base 2, and a rectangular cavity support 3; the conical hollow side-perforated needle tip 1, the rectangular perforated base 2, and the rectangular cavity support 3 constitute a hollow microneedle arrangement unit; each hollow microneedle arrangement unit includes a conical hollow side-perforated needle tip, a rectangular perforated base, and a rectangular cavity support; the conical hollow side-perforated needle tip 1 and the rectangular perforated base 2 are aligned on one side of the rectangular cavity support 3; the area defined by four adjacent hollow microneedle arrangement units is a structural unit, and the rectangular cavity supports 3 in a structural unit are arranged in a "well" pattern.

[0007] Preferably, the height of the conical hollow side-opening needle tip 1 is the needle tip height h1, the diameter of the side opening is the needle hole diameter d1, the outer diameter of the bottom of the needle tip is the microneedle bottom diameter d2, and the bottom diameter of the conical hollow part is the hollow cone bottom diameter d3; the opening diameter of the rectangular opening base 2 is the same as the hollow cone bottom diameter d3, the height of the rectangular opening base 2 is the base height h2, and the height of the rectangular cavity support 3 is the support height h3.

[0008] Preferably, the needle tip height h1 = 1.125~3.375mm, the needle hole diameter d1 = 0.385~0.641mm, the microneedle bottom diameter d2 = 2.4mm, the hollow cone bottom diameter d3 = 1.38mm; the base height h2 = 0.5mm; and the support height h3 = 2.5mm.

[0009] Preferably, the material used to prepare the 3D printed hollow microneedle array resin patch is a resin material.

[0010] This invention provides a method for preparing the 3D printed hollow microneedle array resin patch described in the above technical solution, comprising the following steps:

[0011] The resin material is added to the 3D printer, the required 3D printing parameters are adjusted, and photopolymerization 3D printing is performed to obtain a 3D printed hollow microneedle array resin patch.

[0012] Preferably, the resin raw material is HTM140V2 resin material, and the precision of the HTM140V2 resin material is 25-50μm.

[0013] Preferably, the temperature for photopolymerization 3D printing is 25±3℃, and the printing time is 25~35min.

[0014] This invention provides the application of the 3D-printed hollow microneedle array resin patch described in the above-described technical solution, or the 3D-printed hollow microneedle array resin patch prepared by the preparation method described in the above-described technical solution, in a needle-type sensor.

[0015] This invention provides a dynamic blood glucose monitor containing hollow microneedles, comprising a needle-type sensor and a 3D-printed hollow microneedle array resin patch bonded to the needle-type sensor; the 3D-printed hollow microneedle array resin patch is the 3D-printed hollow microneedle array resin patch described in the above technical solution or the 3D-printed hollow microneedle array resin patch prepared by the preparation method described in the above technical solution.

[0016] This invention provides a method for dynamic monitoring of blood glucose concentration, comprising the following steps:

[0017] After diluting the artificial cerebrospinal fluid, a simulated body fluid is obtained;

[0018] The dynamic blood glucose monitor containing hollow microneedles described above is used to measure the blood glucose concentration of the simulated body fluid and obtain a dynamic blood glucose concentration curve.

[0019] This invention provides a 3D-printed hollow microneedle array resin patch. The hollow microneedle array resin patch is designed with a "well"-shaped support to ensure the porosity of the perforated microneedles. The design of the hollow conical side opening method greatly improves the porosity and microneedle pore volume, effectively increasing the amount of body fluid collected and thus improving the detection accuracy.

[0020] The 3D-printed hollow microneedle array resin patch provided by this invention is based on 3D printing technology. It can determine the basic parameters according to the diameter and height of existing needle sensors, as well as the depth of the stratum corneum and pain nerves, thereby realizing the customization of the hollow microneedle combined with the needle sensor structure, so that the hollow microneedle combined with the needle sensor structure meets the requirements of minimally invasive and painless treatment.

[0021] This invention provides a method for preparing the 3D-printed hollow microneedle array resin patch. The invention uses 3D printing technology and can adjust the basic parameters of the hollow microneedle array resin patch according to the length and size of the glucose sensor using 3Dmax software. It designs microneedle array resin patches with different apertures, heights and needle types that conform to the size of the glucose sensor, thereby adapting them to commercial glucose needle sensors and forming a hollow microneedle array resin patch that can be combined with a glucose needle sensor.

[0022] The hollow microneedle array resin patch of this invention is combined with the needle-type sensor of a commercial continuous glucose meter, replacing the disposable guide needle of the original needle-type sensor. This allows it to penetrate the stratum corneum without touching pain nerves, overcoming traditional pain and safety issues. Because the microneedle array resin patch has a hollow structure, it can be combined with different needle-type sensors for detection, providing feasibility for microneedles to penetrate deep into the subcutaneous layer for biomarker detection. Furthermore, it can serve as a guide needle multiple times and can be used continuously, aligning with green and environmentally friendly principles.

[0023] This invention utilizes simulated body fluids to conduct an in vitro blood glucose monitoring simulation experiment, demonstrating the feasibility of combining a hollow microneedle array resin patch with a needle-type sensor for blood glucose monitoring. This lays a solid foundation for the subsequent realization of real-time blood glucose detection and is expected to integrate other sensors such as ethanol and cholesterol into the microneedle array resin patch, transmitting dynamic signals to smart devices, thereby realizing smart healthcare. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the structure of the 3D printed hollow microneedle array resin patch of the present invention;

[0025] Figure 2 This is a comparison diagram of different needle height and aperture scaling transformations based on Example 5;

[0026] Figure 3 A physical image of a combination of microneedle array resin patch and dynamic blood glucose meter needle sensor for measuring blood glucose concentration in artificial cerebrospinal fluid;

[0027] Figure 4 The diagram shows the process and results comparison for real-time monitoring of human blood glucose levels using a continuous glucose meter alone and when a hollow microneedle array resin patch is used in conjunction with a continuous glucose meter. Detailed Implementation

[0028] like Figure 1 As shown, the present invention provides a 3D printed hollow microneedle array resin patch, comprising a plurality of structural units; the plurality of structural units are arranged in a square array;

[0029] The structural unit includes a conical hollow side-perforated needle tip 1, a rectangular perforated base 2, and a rectangular cavity support 3; the conical hollow side-perforated needle tip 1, the rectangular perforated base 2, and the rectangular cavity support 3 constitute a hollow microneedle arrangement unit; each hollow microneedle arrangement unit includes a conical hollow side-perforated needle tip, a rectangular perforated base, and a rectangular cavity support; the conical hollow side-perforated needle tip 1 and the rectangular perforated base 2 are aligned on one side of the rectangular cavity support 3; the area defined by four adjacent hollow microneedle arrangement units is a structural unit, and the rectangular cavity supports 3 in a structural unit are arranged in a "well" pattern.

[0030] The present invention does not impose any special limitation on the specific arrangement of the square array; either 1×1 or 2×2 is acceptable.

[0031] In this invention, such as Figure 1As shown, the height of the conical hollow side-opening needle tip 1 is the needle tip height h1, the diameter of the side opening is the needle hole diameter d1, the outer diameter of the bottom of the needle tip is the microneedle bottom diameter d2, and the bottom diameter of the conical hollow part is the hollow cone bottom diameter d3; the opening diameter of the rectangular opening base 2 is the same as the hollow cone bottom diameter d3, the height of the rectangular opening base 2 is the base height h2; and the height of the rectangular cavity support 3 is the support height h3.

[0032] In this invention, the needle tip height h1 is 1.125–3.375 mm, preferably 1.687–2.812 mm, and 2.25 mm after changing clothes; the needle hole diameter d1 is 0.385–0.641 mm, preferably 0.513 mm; the microneedle bottom diameter d2 is 2.4 mm; the hollow cone bottom diameter d3 is 1.38 mm; the base height h2 is 0.5 mm; and the support height h3 is 2.5 mm.

[0033] The present invention preferably determines the basic parameters of the hollow microneedle array resin patch according to the length and size of the glucose sensor, thereby realizing the customization of the hollow microneedle structure and making the hollow microneedle array resin patch conform to the size of the glucose sensor.

[0034] In this invention, the material used to prepare the 3D printed hollow microneedle array resin patch is preferably a resin material; the resin material is preferably HTM140V2 resin material, and the precision of the HTM140V2 resin material is preferably 25-50μm, which is sourced from EnvisionTEC, Inc., USA.

[0035] This invention provides a method for preparing the 3D printed hollow microneedle array resin patch described in the above technical solution, comprising the following steps:

[0036] The resin material is added to the 3D printer, the required 3D printing parameters are adjusted, and photopolymerization 3D printing is performed to obtain a 3D printed hollow microneedle array resin patch.

[0037] In this invention, unless otherwise specified, all raw materials required for preparation are commercially available products well known to those skilled in the art.

[0038] In this invention, the resin raw material is preferably HTM140V2 resin material, and the HTM140V2 resin material is preferably 25-50μm in precision and is sourced from EnvisionTEC, Inc., USA.

[0039] This invention preferably uses 3ds Max software to draw a model of the hollow microneedle array resin patch based on the different needle tip height, needle hole diameter, microneedle bottom diameter, hollow cone bottom diameter, base height, and support height of the designed hollow microneedle array resin patch. The resulting Max format model file is converted into an STL format file, Materialise Magics is used for model repair, and Refactory RP software is used to slice the STL file. After the slicing and layering are completed, the generated dedicated folder is imported into the 3D printer.

[0040] After importing the generated dedicated folder into the 3D printer, the present invention preferably adds raw material to the 3D printing dedicated material tank, checks whether there are solid residues in the raw material, and after confirming that there are no problems, close the lid of the 3D printer, press and hold the power button to turn on the 3D printer, click "LOAD JOB", select the imported dedicated folder, select layer 26, click "CONNECT", and click "START" to start printing.

[0041] In this invention, the 3D printer is preferably a photopolymer 3D printer from EnvisionTEC GmbH, Germany; the 3D printer's platform size is preferably 46.93×29.38×100mm, the XY resolution is preferably 912×1140px, and it provides a theoretical layer thickness (thickness per layer) of 25-50μm in the z-direction.

[0042] In this invention, the temperature of the photopolymerization 3D printing is preferably 25±3℃, and the printing time is preferably 25 to 35 minutes, more preferably 30 minutes.

[0043] After completing the photopolymerization 3D printing, the present invention preferably removes the obtained resin patch from the object forming platform of the 3D printer, absorbs the residual raw material liquid on the surface, places it in anhydrous ethanol and completely immerses the hollow microneedle array resin patch in anhydrous ethanol, puts it in an ultrasonic cleaner, cleans it for 2-4 minutes, and blows it dry with a high-pressure air gun to obtain the 3D printed hollow microneedle array resin patch.

[0044] This invention provides the application of the 3D-printed hollow microneedle array resin patch described in the above-described technical solution, or the 3D-printed hollow microneedle array resin patch prepared by the preparation method described in the above-described technical solution, in a needle-type sensor.

[0045] This invention provides a dynamic blood glucose monitor containing hollow microneedles, comprising a needle-type sensor and a 3D-printed hollow microneedle array resin patch bonded to the needle-type sensor; the 3D-printed hollow microneedle array resin patch is the 3D-printed hollow microneedle array resin patch described in the above technical solution or the 3D-printed hollow microneedle array resin patch prepared by the preparation method described in the above technical solution.

[0046] The dynamic blood glucose monitor containing hollow microneedles provided by the present invention is preferably an improvement on a commercial dynamic blood glucose monitor. Specifically, the guide pin of the needle sensor in the commercial dynamic blood glucose monitor is replaced by the 3D-printed hollow microneedle array resin patch described in the above technical solution. Specifically, the original guide pin of the needle sensor is removed, and the side of the transmitter with the needle sensor is combined with the bottom of the rectangular cavity support 3, so that the needle sensor passes through the hole of the 3D-printed hollow microneedle array resin patch.

[0047] This invention does not specifically limit the commercial continuous glucose monitoring device; any commercially available instrument known in the art is acceptable. In the embodiments of this invention, it is specifically the Microtech Medical G7-T01 continuous glucose monitoring device.

[0048] This invention provides a method for dynamic monitoring of blood glucose concentration, comprising the following steps:

[0049] After diluting the artificial cerebrospinal fluid, a simulated body fluid is obtained;

[0050] The dynamic blood glucose monitor containing hollow microneedles described above is used to measure the blood glucose concentration of the simulated body fluid and obtain a dynamic blood glucose concentration curve.

[0051] This invention involves diluting artificial cerebrospinal fluid to obtain simulated body fluid; the glucose concentration in the simulated body fluid is preferably 4 mmol / L. Preferably, a small culture dish lid is drilled, artificial cerebrospinal fluid is added to the culture dish, and then deionized water is added for dilution to obtain the simulated body fluid.

[0052] After obtaining the simulated liquid, the present invention uses the dynamic blood glucose monitor containing hollow microneedles described in the above technical solution to measure the blood glucose concentration of the simulated body fluid and obtain a dynamic blood glucose concentration curve.

[0053] In this invention, before modifying the commercial continuous glucose monitor to a continuous glucose monitor containing hollow microneedles, it is preferable to calibrate the commercial continuous glucose monitor. The calibration preferably includes: measuring the glucose concentration of the simulated body fluid using a Yuwell finger-prick glucose meter to obtain a baseline glucose concentration; measuring the glucose concentration of the simulated body fluid using the commercial continuous glucose monitor until the reading stabilizes, and then using the baseline glucose concentration for reading correction. More preferably, the calibration process includes placing the simulated body fluid in a petri dish, inserting a disposable blood glucose test strip into the Yuwell finger-prick glucose meter, absorbing the test solution, and reading the reading as a correction standard value for the continuous glucose monitor result; using the guide needle of the commercial continuous glucose monitor, immersing the needle-type sensor into the simulated body fluid through a small hole, and attaching the needle-type sensor transmitter to the petri dish lid using bottom adhesion; combining the receiver and transmitter of the needle-type sensor, connecting it to a mobile phone via Bluetooth, pairing it on the smart platform detection end, and after the reading stabilizes, first using the correction standard value obtained from the Yuwell finger-prick glucose meter for calibration; and after the reading stabilizes again, dynamically monitoring the glucose concentration in the simulated body fluid.

[0054] After completing the calibration, the present invention improves the commercial continuous glucose monitor into a continuous glucose monitor containing hollow microneedles, and uses the obtained continuous glucose monitor containing hollow microneedles to measure the blood glucose concentration of the simulated body fluid. The present invention does not have any particular limitations on the process of measuring the blood glucose concentration of the simulated body fluid; any process well known in the art can be followed.

[0055] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0056] In the following examples, the resin material is HTM140V2 resin material with a precision of 25μm, sourced from EnvisionTEC, USA;

[0057] The 3D printer is a photopolymer 3D printer from EnvisionTEC GmbH, Germany; the 3D printer's platform dimensions are 46.93×29.38×100mm, the XY resolution is 912×1140px, and it provides a theoretical layer thickness of 25μm in the z-direction.

[0058] The continuous glucose monitor is the Microtech G7-T01 model.

[0059] Table 1. Design parameters of 3D printed hollow microneedle resin patches in Examples 1-9.

[0060]

[0061]

[0062] Example 1

[0063] (1) Based on the parameters of the 3D printed hollow microneedle array resin patch designed in Table 1, the patch model of Example 1 in Table 1 was drawn using 3ds Max (Autodesk). The obtained Max format model file was converted into an STL format file. The model was repaired using Materialise Magics. The STL file was sliced ​​using Refactory RP software. After the slicing and layering were completed, the obtained special folder was imported into the 3D printer.

[0064] (2) Add HTM140V2 resin material to the 3D printing material tank. Use the equipped scraper to check whether there are solid residues in the material. After confirming that there are no residues, cover the 3D printer and press and hold the power button to turn on the 3D printer. Click "LOADJOB", select the special folder imported in step (1), select the 26th layer, click "CONNECT", click "START" to start printing, and perform photocuring 3D printing at room temperature for 30 minutes to obtain microneedle array resin patch.

[0065] (3) Remove the microneedle array resin patch obtained in step (2) from the object forming platform of the 3D printer, absorb the residual raw material liquid on the surface, completely immerse it in anhydrous ethanol, put it into an ultrasonic cleaner, clean it for 3 minutes, and blow it dry with a high-pressure air gun to obtain a clean 3D microneedle array resin patch.

[0066] Example 2

[0067] The only difference from Example 1 is that the patch model of Example 2 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0068] Example 3

[0069] The only difference from Example 1 is that the patch model of Example 3 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0070] Example 4

[0071] The only difference from Example 1 is that the patch model of Example 4 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0072] Example 5

[0073] The only difference from Example 1 is that the patch model of Example 5 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0074] Example 6

[0075] The only difference from Example 1 is that the patch model of Example 6 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0076] Example 7

[0077] The only difference from Example 1 is that the patch model of Example 7 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0078] Example 8

[0079] The only difference from Example 1 is that the patch model of Example 8 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0080] Example 9

[0081] The only difference from Example 1 is that the patch model of Example 9 in Table 1 is drawn; otherwise, it is the same as Example 1.

[0082] Figure 2 The diagram shows a comparison of different needle height and aperture scaling transformations based on Example 5; a is a schematic diagram based on a needle tip height h1 = 2.25 mm; (b to d) are actual images obtained by scaling the needle tip height by 0.75, 1, and 1.25 times, respectively. After combining the needle sensor and the patch, observe whether the sensor needle tip is exposed. The height at which it is not exposed is the most suitable height, which is 2.25 mm.

[0083] Figure 2 The three columns from left to right are actual images obtained by scaling the pinhole diameter d1 = 0.513 mm by 0.75, 1, and 1.25 times respectively, to show that the most suitable pinhole diameter is 0.513 mm.

[0084] Test case

[0085] The hollow-structured microneedle array resin patch prepared in Example 5 was used for simulated in vitro real-time blood glucose monitoring tests in body fluids.

[0086] Artificial cerebrospinal fluid (NMDGaCSF, sterile, Beijing Mairibo Biotechnology Co., Ltd.);

[0087] Drill a hole in the lid of a small culture dish, add artificial cerebrospinal fluid to the culture dish, and then dilute it with deionized water to obtain a glucose concentration of 4 mmol / L in the simulated body fluid.

[0088] The simulated body fluid was placed in a petri dish. A disposable blood glucose test strip was inserted into the Yuwell finger-prick blood glucose meter, the test solution was drawn, and the reading was taken as the calibration standard for the continuous glucose monitoring (CGM) results. Using the CGM's matching guide needle, the needle sensor from the CGM was immersed in the simulated body fluid through a small hole and connected to the transmitter. The needle sensor transmitter was attached to the petri dish lid using bottom adhesion. The receiver of the needle sensor was combined with the transmitter and connected to a mobile phone via Bluetooth. Pairing was performed on the smart platform detection end. After the glucose concentration reading stabilized, the glucose concentration reading was taken. After 24 hours, the glucose concentration measured by the Yuwell finger-prick blood glucose meter was used as the benchmark for calibration. After stabilization again, the real-time glucose concentration was read using the mobile phone to dynamically monitor the glucose concentration in the simulated body fluid.

[0089] like Figure 3 As shown, the original guide pin of the needle sensor is removed, and the bottom of the needle sensor is pasted onto the rectangular cavity support 3 of the hollow microneedle array resin patch. The needle sensor is then passed through the hole of the hollow microneedle array resin patch. The resulting composite sensor is used to measure the blood glucose concentration of the simulated body fluid and obtain a dynamic blood glucose concentration curve.

[0090] The results showed that the average glucose concentration of simulated body fluid measured three times in parallel using the Yuwell finger-prick blood glucose meter was 4.8 mmol / L. The glucose concentration measured in the simulated body fluid using only the glucose sensor in the continuous glucose monitoring system was 4.7 mmol / L, which was close to the result measured by the Yuwell finger-prick blood glucose meter. The glucose concentration measured by combining the hollow microneedle array resin patch with the continuous glucose monitoring system was 4.6 mmol / L. The glucose concentration reading was within the acceptable error range (±0.3 mmol / L, based on the Yuwell finger-prick blood glucose meter), indicating accurate results. The dynamic curve is shown in [Figure number missing]. Figure 4 .

[0091] Figure 4 Figures a to c) show the theoretical flowchart of combining a hollow microneedle array resin patch with a needle sensor of a continuous glucose meter, implanting it into the human epidermis, and then using a mobile phone app to monitor blood glucose concentration in real time; in d), the curve corresponding to the glucose sensor is the curve of glucose concentration change monitored by the needle sensor alone in vitro for a period of time, and the curve corresponding to the glucose sensor combined with the microneedle is the curve of glucose concentration change monitored under the same conditions after the needle sensor and the hollow microneedle array resin patch are combined, indicating that the combination of the hollow microneedle array resin patch and the needle sensor does not affect the needle sensor's monitoring of glucose.

[0092] As can be seen from the above embodiments, the use of the hollow-structured microneedle array resin patch provided by the present invention for simulated in vitro body fluid real-time blood glucose monitoring test results show that the hollow-structured microneedle array resin patch is a customized microneedle array patch with high success rate, efficient body fluid detection, and personalized elastic customization function.

[0093] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A 3D-printed hollow microneedle array resin patch, characterized in that, It includes several structural unit cells; the several structural unit cells are arranged in a square array; The structural unit includes a conical hollow side-perforated needle tip (1), a rectangular perforated base (2), and a rectangular cavity support (3); the conical hollow side-perforated needle tip (1), the rectangular perforated base (2), and the rectangular cavity support (3) constitute a hollow microneedle arrangement unit; each hollow microneedle arrangement unit includes a conical hollow side-perforated needle tip, a rectangular perforated base, and a rectangular cavity support; the conical hollow side-perforated needle tip (1) and the rectangular perforated base (2) are aligned on one side of the rectangular cavity support (3); the area defined by four adjacent hollow microneedle arrangement units is a structural unit, and the rectangular cavity supports (3) in a structural unit are arranged in a "well" pattern; The height of the conical hollow side-opening needle tip (1) is the needle tip height h1, the diameter of the side opening is the needle hole diameter d1, the outer diameter of the bottom of the needle tip is the micro-needle bottom diameter d2, and the bottom diameter of the conical hollow part is the hollow cone bottom diameter d3; the opening diameter of the rectangular opening base (2) is the same as the hollow cone bottom diameter d3, the height of the rectangular opening base (2) is the base height h2; the height of the rectangular cavity support (3) is the support height h3. The needle tip height h1 = 1.125~3.375mm, the needle hole diameter d1 = 0.385~0.641mm, the microneedle bottom diameter d2 = 2.4mm, the hollow cone bottom diameter d3 = 1.38mm; the base height h2 = 0.5mm; the support height h3 = 2.5mm.

2. The 3D printed hollow microneedle array resin patch according to claim 1, characterized in that, The hollow microneedle array resin patch is made of resin material.

3. The method for preparing the 3D printed hollow microneedle array resin patch according to any one of claims 1 to 2, characterized in that, Includes the following steps: The resin material is added to the 3D printer, the required 3D printing parameters are adjusted, and photopolymerization 3D printing is performed to obtain a 3D printed hollow microneedle array resin patch.

4. The preparation method according to claim 3, characterized in that, The resin raw material is HTM140V2 resin material, and the precision of the HTM140V2 resin material is 25-50μm.

5. The preparation method according to claim 3 or 4, characterized in that, The temperature for the photopolymerization 3D printing is 25±3℃, and the printing time is 25~35min.

6. The application of the 3D printed hollow microneedle array resin patch according to any one of claims 1 to 2 or the 3D printed hollow microneedle array resin patch prepared by the preparation method according to any one of claims 3 to 5 in a needle-type sensor.

7. A dynamic blood glucose monitor containing hollow microneedles, characterized in that, The invention includes a needle-type sensor and a 3D-printed hollow microneedle array resin patch bonded to the needle-type sensor; the 3D-printed hollow microneedle array resin patch is the 3D-printed hollow microneedle array resin patch according to any one of claims 1 to 2 or the 3D-printed hollow microneedle array resin patch prepared by the preparation method according to any one of claims 3 to 5.

8. A method for dynamic monitoring of blood glucose concentration, characterized in that, Includes the following steps: After diluting the artificial cerebrospinal fluid, a simulated body fluid is obtained; The blood glucose concentration of the simulated body fluid was measured using the dynamic blood glucose monitor containing hollow microneedles as described in claim 7, and a dynamic blood glucose concentration curve was obtained.

Images