Research progress on the manufacturing technology of hollow microneedles_Journal of Biomedical Engineering

Authors：

ZHOU Shengshuo ¹ , ZHOU Huajian ¹ , DU Xiaoyu ¹ , YU Ziye ¹ , XU Tongle ¹ , ZHAO Shun ¹ , SU Peiqiang ² , ZHANG Leian ¹ , FU Guangyang ¹ ,  LIU Xuelei ^1,2

1. School of Mechanical Engineering, Shandong University of Technology , Zibo, Shandong 255000, P. R. China;
2. Shandong Huiyu Auto Parts Co., Ltd., Binzhou, Shandong 251702, P. R. China;

Corresponding?author：

Keywords：

Microneedle; Hollow microneedle; Manufacturing technology; Process route; Hollow microneedle material

DOI：

10.7507/1001-5515.202408024

Video：

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Abstract Full text Figures/Tables Video References Cited by

Drug administration via hollow microneedles (HMN) have the advantages of painlessness, avoidance of first-pass effect, capability of sustained infusion, and no need for professional personnel operation. In addition, HMN can also be applied in the fields of body fluid extraction and biosensors, showing broad application prospects. However, traditional manufacturing technologies cannot meet the demand for low-cost mass production of HMN, limiting its widespread application. This paper reviews the main manufacturing technologies used for HMN in recent years, which include photolithography and etching, laser etching, sputtering and electroplating, micro-molding, three-dimensional (3D) printing and drawing lithography. It further analyzes the characteristics and limitations of existing manufacturing technologies and points out that the combination of various manufacturing technologies can improve production efficiency to a certain extent. In addition, this paper looks forward to the future trends of HMN manufacturing technology and proposes possible directions for its development. In conclusion, it is expected that this review can provide new ideas and references for follow-up research.

Citation： ZHOU Shengshuo, ZHOU Huajian, DU Xiaoyu, YU Ziye, XU Tongle, ZHAO Shun, SU Peiqiang, ZHANG Leian, FU Guangyang, LIU Xuelei. Research progress on the manufacturing technology of hollow microneedles. Journal of Biomedical Engineering, 2025, 42(2): 423-430. doi: 10.7507/1001-5515.202408024 Copy

1.	陳鑫, 張永萍, 徐劍, 等. 微針現代研究進展. 亞太傳統醫藥, 2021, 17(7): 210-213.
2.	Zhang X, Zhang W, Wu W, et al. Recent advances in the preparation of microneedle patches for interstitial fluid extraction and analysis. Microchemical Journal, 2023, 195: 109477.
3.	Abd-El-Azim H, Tekko I A, Ali A, et al. Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer. Journal of Controlled Release, 2022, 348: 849-869.
4.	Cheng J, Huang J, Xiang Q, et al. Hollow microneedle microfluidic paper-based chip for biomolecules rapid sampling and detection in interstitial fluid. Anal Chim Acta, 2023, 1255: 341101.
5.	Li H, Wu G, Weng Z, et al. Microneedle-based potentiometric sensing system for continuous monitoring of multiple electrolytes in skin interstitial fluids. ACS Sens, 2021, 6(6): 2181-2190.
6.	Li R, Liu X, Yuan X, et al. Fast customization of hollow microneedle patches for insulin delivery. International Journal of Bioprinting, 2022, 8(2): 553.
7.	Ren Y, Li J, Chen Y, et al. Customized flexible hollow microneedles for psoriasis treatment with reduced-dose drug. Bioeng Transl Med, 2023, 8(4): e10530.
8.	Monou P K, Andriotis E G, Tsongas K, et al. Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives. ACS Biomaterials Science & Engineering, 2023, 9(8): 5072-5083.
9.	Luo X, Yu Q, Liu Y, et al. Closed-loop diabetes minipatch based on a biosensor and an electroosmotic pump on hollow biodegradable microneedles. ACS Sens, 2022, 7(5): 1347-1360.
10.	Chen Y H, Wang F Y, Chan Y S, et al. Biofabricating hollow microneedle array with controllable microstructure for cell transplantation. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2022, 110(9): 1997-2005.
11.	Van Hileghem L, Kushwaha S, Piovesan A, et al. Innovative fabrication of hollow microneedle arrays enabling blood sampling with a self-powered microfluidic patch. Micromachines, 2023, 14(3): 615.
12.	Liu Y, He C, Qiao T, et al. Coral-inspired hollow microneedle patch with smart sensor therapy for wound infection. Advanced Functional Materials, 2024, 34(24): 2314071.
13.	Chinnamani M V, Hanif A, Kannan P K, et al. Soft microfiber-based hollow microneedle array for stretchable microfluidic biosensing patch with negative pressure-driven sampling. Biosensors and Bioelectronics, 2023, 237: 115468.
14.	Wu T, You X, Chen Z. Hollow microneedles on a paper fabricated by standard photolithography for the screening test of prediabetes. Sensors, 2022, 22(11): 4253.
15.	Parrilla M, Detamornrat U, Domínguez-Robles J, et al. Wearable hollow microneedle sensing patches for the transdermal electrochemical monitoring of glucose. Talanta, 2022, 249: 123695.
16.	崔聞宇, 王瑾. 微針技術在經皮給藥系統中應用的研究進展. 微納電子技術, 2023, 60(2): 195-204.
17.	Mighra R, Maiti T K, Bhattacharyya T K. Development of SU-8 hollow microneedles on a silicon substrate with microfluidic interconnects for transdermal drug delivery. Journal of Micromechanics and Microengineering, 2018, 28(10): 105017.
18.	O'Mahony C, Sebastian R, Tjulkins F, et al. Hollow silicon microneedles, fabricated using combined wet and dry etching techniques, for transdermal delivery and diagnostics. Int J Pharm, 2023, 637: 122888.
19.	Datta A, Biswas S, Dhar R, et al. Design and development of a piezoelectric driven micropump integrated with hollow microneedles for precise insulin delivery. Journal of Micromechanics and Microengineering, 2023, 33(7): 075003.
20.	朱錦濤,王華,李鈺策,等.一種制備中空微針陣列的方法: CN201810706922.2. 2018-12-25. [2024-08-15].
21.	Evens T, Van Hileghem L, Dal Dosso F, et al. Producing hollow polymer microneedles using laser ablated molds in an injection molding process. Journal of Micro and Nano Manufacturing, 2021, 9(3): 030902.
22.	Dong C W, Jeon J Y, Kang H M, et al. Tip fabrication methods of hollow metal microneedles. Journal of Mechanical Science and Technology, 2022, 37: 261-269.
23.	Chen Y H, Wang F Y, Chan Y S, et al. Fabrication of hollow microneedle patch with controllable microstructure for cell therapy. SSRN Electronic Journal, 2020. DOI: 10.2139/ssrn.3757907.
24.	劉仁志. 獨特而不可或缺的電鍍技術. 表面工程與再制造, 2022, 22(1): 2-9.
25.	劉龍. 基于MEMS技術的微量采樣/注射金屬微針研究. 上海: 上海交通大學, 2016.
26.	Miller P R, Moorman M, Boehm R D, et al. Fabrication of hollow metal microneedle arrays using a molding and electroplating method. MRS Advances, 2019, 4(24): 1417-1426.
27.	Chen J, Cheng P, Sun Y, et al. A minimally invasive hollow microneedle with a cladding structure: ultra-thin but strong, batch manufacturable. IEEE Trans Biomed Eng, 2019, 66(12): 3480-3485.
28.	Lee D S, Li C G, Ihm C, et al. A three-dimensional and bevel-angled ultrahigh aspect ratio microneedle for minimally invasive and painless blood sampling. Sensors and Actuators B: Chemical, 2018, 255: 384-390.
29.	Liu Y, Yu Q, Ye L, et al. A wearable, minimally-invasive, fully electrochemically-controlled feedback minisystem for diabetes management. Lab on a Chip, 2023, 23(3): 421-436.
30.	Ren Y, Li J, Wang Z, et al. Polyimide (PI) flexible hollow microneedle array prepared based on optimized dual-moulding processes//2021 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers), Orlando: IEEE, 2021: 1452-1455.
31.	Zhou C, Tang H, Zhang L, et al. Hollow microneedle arrays produced by low-cost, high-fidelity replication of hypodermic needle tips for high-dose transdermal drug delivery. Advanced Engineering Materials, 2021, 23(6): 2001355.
32.	張怡心, 楚皓文, 李翔, 等. 光固化3D打印微針在透皮給藥系統中的研究進展. 微納電子技術, 2023, 60(7): 979-987.
33.	Parhi R. Recent advances in 3D printed microneedles and their skin delivery application in the treatment of various diseases. Journal of Drug Delivery Science and Technology, 2023, 84: 104395.
34.	Mathew E, Pitzanti G, Gomes Dos Santos A L, et al. Optimization of printing parameters for digital light processing 3D printing of hollow microneedle arrays. Pharmaceutics, 2021, 13(11): 1837.
35.	熊莎, 賴蓉蓉, 劉紫藝, 等. 微針經皮給藥系統應用于皮膚腫瘤治療的研究進展. 藥學進展, 2022, 46(2): 128-137.
36.	萬姍姍. 基于3D打印技術的微針結構設計和制造工藝研究. 農業裝備與車輛工程, 2023, 61(5): 157-160.
37.	Sarker S, Wang J, Shah S A, et al. Geometric determinants of cell viability for 3d-printed hollow microneedle array-mediated delivery//2024 IEEE 37th International Conference on Micro Electro Mechanical Systems (MEMS), Austin: IEEE, 2024: 429-432.
38.	曾少楓, 劉付春俏, 周柏先, 等. 3D打印技術在透皮給藥系統中應用的研究進展. 中國藥學雜志, 2023, 58(14): 1265-1270.
39.	Sheikh M, Qassem M, Kyriacou P A. Optical detection of lithium therapeutic levels in porcine interstitial fluid collected using a hollow microneedle//2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Glasgow, Scotland: IEEE, 2022: 4257-4260.
40.	Hu Z, Meduri C S, Ingrole R S J, et al. Solid and hollow metallic glass microneedles for transdermal drug-delivery. Applied Physics Letters, 2020, 116(20): 203703.

1. 陳鑫, 張永萍, 徐劍, 等. 微針現代研究進展. 亞太傳統醫藥, 2021, 17(7): 210-213.
2. Zhang X, Zhang W, Wu W, et al. Recent advances in the preparation of microneedle patches for interstitial fluid extraction and analysis. Microchemical Journal, 2023, 195: 109477.
3. Abd-El-Azim H, Tekko I A, Ali A, et al. Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer. Journal of Controlled Release, 2022, 348: 849-869.
4. Cheng J, Huang J, Xiang Q, et al. Hollow microneedle microfluidic paper-based chip for biomolecules rapid sampling and detection in interstitial fluid. Anal Chim Acta, 2023, 1255: 341101.
5. Li H, Wu G, Weng Z, et al. Microneedle-based potentiometric sensing system for continuous monitoring of multiple electrolytes in skin interstitial fluids. ACS Sens, 2021, 6(6): 2181-2190.
6. Li R, Liu X, Yuan X, et al. Fast customization of hollow microneedle patches for insulin delivery. International Journal of Bioprinting, 2022, 8(2): 553.
7. Ren Y, Li J, Chen Y, et al. Customized flexible hollow microneedles for psoriasis treatment with reduced-dose drug. Bioeng Transl Med, 2023, 8(4): e10530.
8. Monou P K, Andriotis E G, Tsongas K, et al. Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives. ACS Biomaterials Science & Engineering, 2023, 9(8): 5072-5083.
9. Luo X, Yu Q, Liu Y, et al. Closed-loop diabetes minipatch based on a biosensor and an electroosmotic pump on hollow biodegradable microneedles. ACS Sens, 2022, 7(5): 1347-1360.
10. Chen Y H, Wang F Y, Chan Y S, et al. Biofabricating hollow microneedle array with controllable microstructure for cell transplantation. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2022, 110(9): 1997-2005.
11. Van Hileghem L, Kushwaha S, Piovesan A, et al. Innovative fabrication of hollow microneedle arrays enabling blood sampling with a self-powered microfluidic patch. Micromachines, 2023, 14(3): 615.
12. Liu Y, He C, Qiao T, et al. Coral-inspired hollow microneedle patch with smart sensor therapy for wound infection. Advanced Functional Materials, 2024, 34(24): 2314071.
13. Chinnamani M V, Hanif A, Kannan P K, et al. Soft microfiber-based hollow microneedle array for stretchable microfluidic biosensing patch with negative pressure-driven sampling. Biosensors and Bioelectronics, 2023, 237: 115468.
14. Wu T, You X, Chen Z. Hollow microneedles on a paper fabricated by standard photolithography for the screening test of prediabetes. Sensors, 2022, 22(11): 4253.
15. Parrilla M, Detamornrat U, Domínguez-Robles J, et al. Wearable hollow microneedle sensing patches for the transdermal electrochemical monitoring of glucose. Talanta, 2022, 249: 123695.
16. 崔聞宇, 王瑾. 微針技術在經皮給藥系統中應用的研究進展. 微納電子技術, 2023, 60(2): 195-204.
17. Mighra R, Maiti T K, Bhattacharyya T K. Development of SU-8 hollow microneedles on a silicon substrate with microfluidic interconnects for transdermal drug delivery. Journal of Micromechanics and Microengineering, 2018, 28(10): 105017.
18. O'Mahony C, Sebastian R, Tjulkins F, et al. Hollow silicon microneedles, fabricated using combined wet and dry etching techniques, for transdermal delivery and diagnostics. Int J Pharm, 2023, 637: 122888.
19. Datta A, Biswas S, Dhar R, et al. Design and development of a piezoelectric driven micropump integrated with hollow microneedles for precise insulin delivery. Journal of Micromechanics and Microengineering, 2023, 33(7): 075003.
20. 朱錦濤,王華,李鈺策,等.一種制備中空微針陣列的方法: CN201810706922.2. 2018-12-25. [2024-08-15].
21. Evens T, Van Hileghem L, Dal Dosso F, et al. Producing hollow polymer microneedles using laser ablated molds in an injection molding process. Journal of Micro and Nano Manufacturing, 2021, 9(3): 030902.
22. Dong C W, Jeon J Y, Kang H M, et al. Tip fabrication methods of hollow metal microneedles. Journal of Mechanical Science and Technology, 2022, 37: 261-269.
23. Chen Y H, Wang F Y, Chan Y S, et al. Fabrication of hollow microneedle patch with controllable microstructure for cell therapy. SSRN Electronic Journal, 2020. DOI: 10.2139/ssrn.3757907.
24. 劉仁志. 獨特而不可或缺的電鍍技術. 表面工程與再制造, 2022, 22(1): 2-9.
25. 劉龍. 基于MEMS技術的微量采樣/注射金屬微針研究. 上海: 上海交通大學, 2016.
26. Miller P R, Moorman M, Boehm R D, et al. Fabrication of hollow metal microneedle arrays using a molding and electroplating method. MRS Advances, 2019, 4(24): 1417-1426.
27. Chen J, Cheng P, Sun Y, et al. A minimally invasive hollow microneedle with a cladding structure: ultra-thin but strong, batch manufacturable. IEEE Trans Biomed Eng, 2019, 66(12): 3480-3485.
28. Lee D S, Li C G, Ihm C, et al. A three-dimensional and bevel-angled ultrahigh aspect ratio microneedle for minimally invasive and painless blood sampling. Sensors and Actuators B: Chemical, 2018, 255: 384-390.
29. Liu Y, Yu Q, Ye L, et al. A wearable, minimally-invasive, fully electrochemically-controlled feedback minisystem for diabetes management. Lab on a Chip, 2023, 23(3): 421-436.
30. Ren Y, Li J, Wang Z, et al. Polyimide (PI) flexible hollow microneedle array prepared based on optimized dual-moulding processes//2021 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers), Orlando: IEEE, 2021: 1452-1455.
31. Zhou C, Tang H, Zhang L, et al. Hollow microneedle arrays produced by low-cost, high-fidelity replication of hypodermic needle tips for high-dose transdermal drug delivery. Advanced Engineering Materials, 2021, 23(6): 2001355.
32. 張怡心, 楚皓文, 李翔, 等. 光固化3D打印微針在透皮給藥系統中的研究進展. 微納電子技術, 2023, 60(7): 979-987.
33. Parhi R. Recent advances in 3D printed microneedles and their skin delivery application in the treatment of various diseases. Journal of Drug Delivery Science and Technology, 2023, 84: 104395.
34. Mathew E, Pitzanti G, Gomes Dos Santos A L, et al. Optimization of printing parameters for digital light processing 3D printing of hollow microneedle arrays. Pharmaceutics, 2021, 13(11): 1837.
35. 熊莎, 賴蓉蓉, 劉紫藝, 等. 微針經皮給藥系統應用于皮膚腫瘤治療的研究進展. 藥學進展, 2022, 46(2): 128-137.
36. 萬姍姍. 基于3D打印技術的微針結構設計和制造工藝研究. 農業裝備與車輛工程, 2023, 61(5): 157-160.
37. Sarker S, Wang J, Shah S A, et al. Geometric determinants of cell viability for 3d-printed hollow microneedle array-mediated delivery//2024 IEEE 37th International Conference on Micro Electro Mechanical Systems (MEMS), Austin: IEEE, 2024: 429-432.
38. 曾少楓, 劉付春俏, 周柏先, 等. 3D打印技術在透皮給藥系統中應用的研究進展. 中國藥學雜志, 2023, 58(14): 1265-1270.
39. Sheikh M, Qassem M, Kyriacou P A. Optical detection of lithium therapeutic levels in porcine interstitial fluid collected using a hollow microneedle//2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Glasgow, Scotland: IEEE, 2022: 4257-4260.
40. Hu Z, Meduri C S, Ingrole R S J, et al. Solid and hollow metallic glass microneedles for transdermal drug-delivery. Applied Physics Letters, 2020, 116(20): 203703.

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