Advances in the Application of 3D Printed Microneedle Biosensor for Continuous Glucose Monitoring
Liu Jun1, Fan Kai1, Yao Danyu1, Gan Kaifeng3, SuChang4, Wang Ling1,2, Xu Mingen1,2*
1(School of Automation, Hangzhou Dianzi University, Hangzhou 310018,China) 2(Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province,Hangzhou 310018,China) 3(Lihuili Hospital Affiliated to Ningbo University,Ningbo 315040, Zhejiang, China) 4(The Children′s Hospital of Zhejiang University School of Medicine,Hangzhou 310051,China)
Abstract:Diabetes is a metabolic disease characterized by chronic hyperglycemia. Continuous glucose monitoring is a crucial component in the management of diabetes. Microneedle technology is an emerging method for blood glucose monitoring, which offers significant advantages such as painless, continuous, and real-time monitoring. Traditional microneedle manufacturing techniques, such as micromolding, have limitations including lower precision and lack of customizability. 3D printing technology, with its high precision, customization, and material versatility, has emerged as a new approach for microneedle fabrication. This review summarized the latest advancements in 3D printed microneedles, covering key technologies, printing principles, printable materials, and medical applications. We discussed the progress of microneedle-based glucose sensors in continuous glucose monitoring, including the underlying principles, microneedle preparation, electrochemical performance characterization, and wearable integration technologies. Finally, this review explored the challenges of 3D printed microneedles, along with future directions for the development of microneedle biosensors.
刘俊, 樊凯, 姚丹语, 干开丰, 苏畅, 王玲, 徐铭恩. 3D打印微针生物传感器用于连续血糖监测的应用进展[J]. 中国生物医学工程学报, 2025, 44(4): 494-501.
Liu Jun, Fan Kai, Yao Danyu, Gan Kaifeng, SuChang, Wang Ling, Xu Mingen. Advances in the Application of 3D Printed Microneedle Biosensor for Continuous Glucose Monitoring. Chinese Journal of Biomedical Engineering, 2025, 44(4): 494-501.
[1] Hao Ying, Li Wei, Zhou Xingli, et al. Microneedles-based transdermal drug delivery systems: a review[J]. Journal of Biomedical Nanotechnology, 2017, 13(12): 1581-1597.
[2] Luzuriaga MA, Berry DR, Reagan JC, et al. Biodegradable 3D printed polymer microneedles for transdermal drug delivery[J]. Lab on a Chip, 2018, 18(8): 1223-1230.
[3] Bhatnagar S, Dave K, Venuganti VVK. Microneedles in the clinic[J]. Journal of Controlled Release, 2017, 260: 164-182.
[4] Chun Yongyao, Tan WWR, Vos MIG, et al. Scar prevention through topical delivery of gelatin-tyramine-siSPARC nanoplex loaded in dissolvable hyaluronic acid microneedle patch across skin barrier[J]. Biomaterials Science, 2022, 10: 3963-3971.
[5] Zhang Xiaopeng, Wang Beibei, Li Wenxuan, et al. In vivo safety assessment, biodistribution and toxicology of polyvinyl alcohol microneedles with 160-day uninterruptedly applications in mice[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2021, 160: 1-8.
[6] Liu Depeng, Yu Bo, Jiang Guohua, et al. Fabrication of composite microneedles integrated with insulin-loaded CaCO3 microparticles and PVP for transdermal delivery in diabetic rats[J].Materials Science and Engineering: C, 2018, 90: 180-188.
[7] Ramadon D, Ulayya F, Qur’ani AS, et al. Combination of dissolving microneedles with nanosuspension and co-grinding for transdermal delivery of ketoprofen[J]. Pharmaceuticals, 2023, 16(3): 378.
[8] Zhu Jixiang, Zhou Xingwu, Kim Hanjun, et al. Gelatin methacryloyl microneedle patches for minimally invasive extraction of skin interstitial fluid[J]. Small, 2020, 16(16): 1905910.
[9] Qin Kang, Gui Yuan, Li Yanchun, et al. Biodegradable microneedle array-mediated transdermal delivery of dimethyloxalylglycine-functionalized zeolitic imidazolate framework-8 nanoparticles for bacteria-infected wound treatment[J]. ACS Applied Materials & Interfaces, 2023, 15: 6338-6353.
[10] Jia Tianshuo, Kuang Dajiang, Qi Zhenzhen, et al. Silk fibroin/chitosan pH-sensitive controlled microneedles[J].Journal of Materials Science, 2023, 58(46):17711-17725.
[11] Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications[J]. Nature Reviews Endocrinology, 2018, 14(2): 88-98.
[12] Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications[J]. Nature Reviews Nephrology, 2020, 16(7): 377-390.
[13] Pavithran AA, Ramamoorthy L, Suryanarayana BS, et al. Comparison of fingertip vs palm site sampling on pain perception, and variation in capillary blood glucose level among patients with diabetes mellitus[J]. Journal of Caring Sciences, 2020, 9: 182.
[14] Mian Z, Hermayer KL, Jenkins A. Continuous glucose monitoring: review of an innovation in diabetes management[J]. The American Journal of the Medical Sciences, 2019, 358: 332-339.
[15] Geelhoed-Duijvestijn P, Vegelyte D, Kownacka A, et al. Performance of the prototype NovioSense noninvasive biosensor for tear glucose in type 1 diabetes[J]. Journal of Diabetes Science and Technology, 2021, 15(6): 1320-1325.
[16] Loh JM, Lim YJL, Tay JT, et al. Design and fabrication of customizable microneedles enabled by 3D printing for biomedical applications[J]. Bioactive Materials, 2024, 32: 222-241.
[17] Yu W, Sun L, Li M, et al. FDM 3D printing and properties of PBS/PLA blends[J]. Polymers, 2023, 15(21): 4305.
[18] Tang Junnan, Wang Jinqiang, Huang Ke, et al. Cardiac cell-integrated microneedle patch for treating myocardial infarction[J]. Science Advances, 2018, 4(11): eaat9365.
[19] Lee JH, Baik JM, Yu YS, et al. Development of a heat labile antibiotic eluting 3D printed scaffold for the treatment of osteomyelitis[J]. Scientific Reports, 2020, 10(1): 7554.
[20] Allen EA, O′Mahony C, Cronin M, et al. Dissolvable microneedle fabrication using piezoelectric dispensing technology[J]. International Journal of Pharmaceutics, 2016, 500: 1-10.
[21] Derakhshandeh H, Aghabaglou F, McCarthy A, et al. A wirelessly controlled smart bandage with 3D‐printed miniaturized needle arrays[J]. Advanced Functional Materials, 2020, 30(13): 1905544.
[22] 张怡心,楚皓文,李翔,等.光固化3D打印微针在透皮给药系统中的研究进展[J].微纳电子技术, 2023, 60(7):979-987.
[23] Tunçel E, Tort S, Han S, et al. Development and in vitro-in vivo evaluation of composite hydrogel-forming microneedles containing diclofenac sodium with box-behnken design using SLA 3D-printed microneedle molds[J]. Drug Delivery and Translational Research, 2024. 15(6):2116-2145.
[24] Shin D, Hyun J. Silk fibroin microneedles fabricated by digital light processing 3D printing[J]. Journal of Industrial and Engineering Chemistry, 2021, 95: 126-133.
[25] Rajesh NU, Coates I, Driskill MM, et al. 3D-printed microarray patches for transdermal applications[J]. JACS Au, 2022, 2(11): 2426-2445.
[26] Szeto B, Aksit A, Valentini C, et al. Novel 3D-printed hollow microneedles facilitate safe, reliable, and informative sampling of perilymph from guinea pigs[J]. Hearing Research, 2021, 400: 108141.
[27] Caudill C, Perry J L, Iliadis K, et al. Transdermal vaccination via 3D-printed microneedles induces potent humoral and cellular immunity[J]. Proceedings of the National Academy of Sciences, 2021, 118(39): e2102595118.
[28] Yang Yuan, Luo Ruizeng, Chao Shengyu, et al. Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation[J]. Nature Communications, 2022, 13(1): 6908.
[29] Chu Huaqing, Xue Jiangtao, Yang Yuan, et al. Advances of Smart Stimulus-Responsive Microneedles in Cancer Treatment[J]. Small Methods, 2023: 2301455.
[30] Vora LK, Sabri AH, McKenna PE, et al. Microneedle-based biosensing[J]. Nature Reviews Bioengineering, 2024, 2: 64-81.
[31] Zhang Baoli, Yang Yuan, Zhao Zeqiang, et al. A gold nanoparticles deposited polymer microneedle enzymatic biosensor for glucose sensing[J]. Electrochimica Acta, 2020, 358: 136917.
[32] Economidou SN, Pissinato Pere CP, Okereke M, et al. Optimisation of design and manufacturing parameters of 3D printed solid microneedles for improved strength, sharpness, and drug delivery[J]. Micromachines, 2021, 12(2): 117.
[33] Takeuchi K, Takama N, Kinoshita R, et al. Flexible and porous microneedles of PDMS for continuous glucose monitoring[J]. Biomedical Microdevices, 2020, 22: 1-12.
[34] Liu Yiqun, Yu Qi, Luo Xiaojin, et al. Continuous monitoring of diabetes with an integrated microneedle biosensing device through 3D printing[J]. Microsystems & Nanoengineering, 2021, 7: 75.
[35] Hui Yue, Yao Yuan, Qian Qilin, et al. Three-dimensional printing of soft hydrogel electronics[J]. Nature Electronics, 2022, 5(12): 893-903.
[36] Huang Xinshuo, Liang Baoming, Huang Shuang, et al. Integrated electronic/fluidic microneedle system for glucose sensing and insulin delivery[J]. Theranostics, 2024, 14: 1662.
[37] Yue Wei, Guo Yunjian, Wu JiaKang, et al. A wireless, battery-free microneedle patch with light-cured swellable hydrogel for minimally-invasive glucose detection[J]. Nano Energy, 2024, 131: 110194.