Integrated Lithographic Molding for Microneedle-Based Devices

This paper presents a new fabrication method consisting of lithographically defining multiple layers of high aspect-ratio photoresist onto preprocessed silicon substrates and release of the polymer by the lost mold or sacrificial layer technique, coined by us as lithographic molding. The process methodology was demonstrated fabricating out-of-plane polymeric hollow microneedles. First, the fabrication of needle tips was demonstrated for polymeric microneedles with an outer diameter of 250 mum, through-hole capillaries of 75-mum diameter and a needle shaft length of 430 mum by lithographic processing of SU-8 onto simple v-grooves. Second, the technique was extended to gain more freedom in tip shape design, needle shaft length and use of filling materials. A novel combination of silicon dry and wet etching is introduced that allows highly accurate and repetitive lithographic molding of a complex shape. Both techniques consent to the lithographic integration of microfluidic back plates forming a patch-type device. These microneedle-integrated patches offer a feasible solution for medical applications that demand an easy to use point-of-care sample collector, for example, in blood diagnostics for lithium therapy. Although microchip capillary electrophoresis glass devices were addressed earlier, here, we show for the first time the complete diagnostic method based on microneedles made from SU-8.

[1]  Shankar Chandrasekaran,et al.  Surface micromachined metallic microneedles , 2003 .

[2]  O. Tabata,et al.  A novel fabrication process of 3-D microstructures by double exposure in standard deep X-ray lithography , 2004, 17th IEEE International Conference on Micro Electro Mechanical Systems. Maastricht MEMS 2004 Technical Digest.

[3]  Michael Stangegaard,et al.  Whole genome expression profiling using DNA microarray for determining biocompatibility of polymeric surfaces. , 2006, Molecular bioSystems.

[4]  Tetsuya Miyagishi,et al.  A disposable on-line microsystem for continuous sampling and monitoring of glucose , 2004 .

[5]  Jeung Sang Go,et al.  In-channel 3-D micromesh structures using maskless multi-angle exposures and their microfilter application , 2004 .

[6]  Derrick C. Mancini,et al.  Tapered LIGA HARMs , 2003 .

[7]  G. Kotzar,et al.  Evaluation of MEMS materials of construction for implantable medical devices. , 2002, Biomaterials.

[8]  S. Buttgenbach,et al.  Fabrication of microchannels by laser machining and anisotropic etching of silicon , 1992 .

[9]  D. Reinhoudt,et al.  Surface modification with self-assembled monolayers for nanoscale replication of photoplastic MEMS , 2002 .

[10]  P. Vettiger,et al.  High-aspect-ratio, ultrathick, negative-tone near-uv photoresist for MEMS applications , 1997, Proceedings IEEE The Tenth Annual International Workshop on Micro Electro Mechanical Systems. An Investigation of Micro Structures, Sensors, Actuators, Machines and Robots.

[11]  Hyoung J. Cho,et al.  Microlens fabrication using an etched glass master , 2006 .

[12]  Dorian Liepmann,et al.  Fluid injection through out-of-plane microneedles , 2000, 1st Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.00EX451).

[13]  Ji Won Suk,et al.  Development of Plastic Microneedles for Transdermal Interfacing Using Injection Molding Techniques , 2002 .

[14]  J. Kutter,et al.  Integrating advanced functionality in a microfabricated high-throughput fluorescent-activated cell sorter. , 2003, Lab on a chip.

[15]  Göran Stemme,et al.  Side-opened out-of-plane microneedles for microfluidic transdermal liquid transfer , 2003 .

[16]  Daniel Bertrand,et al.  Buried microchannels in photopolymer for delivering of solutions to neurons in a network , 1998 .

[17]  Gwo-Bin Lee,et al.  A new fabrication process for ultra-thick microfluidic microstructures utilizing SU-8 photoresist , 2002 .

[18]  Peter Vettiger,et al.  High-aspect-ratio, ultrathick, negative-tone near-UV photoresist and its applications for MEMS , 1998 .

[19]  N. D. Rooij,et al.  All-photoplastic, soft cantilever cassette probe for scanning force microscopy , 2000 .

[20]  S. D. Collins,et al.  Microneedle array for transdermal biological fluid extraction and in situ analysis , 2004 .

[21]  R. E. Oosterbroek,et al.  Etching methodologies in -oriented silicon wafers , 2000 .

[22]  Masayoshi Esashi,et al.  Silicon Micromachining , 1998, Digest of Papers. Microprocesses and Nanotechnology'98. 198 International Microprocesses and Nanotechnology Conference (Cat. No.98EX135).

[23]  Jian Zhang,et al.  Polymerization optimization of SU-8 photoresist and its applications in microfluidic systems and MEMS , 2001 .

[24]  Albert P. Pisano,et al.  Silicon-processed microneedles , 1999 .

[25]  Mark G. Allen,et al.  Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Robert C. White,et al.  Fabrication of a fluid encapsulated dermal patch using multilayered SU-8 , 2004 .

[27]  Wei-Keng Lin,et al.  A novel fabrication method of embedded micro-channels by using SU-8 thick-film photoresists , 2003 .

[28]  Jin-Woo Choi,et al.  Disposable smart lab on a chip for point-of-care clinical diagnostics , 2004, Proceedings of the IEEE.

[29]  R. Ghodssi,et al.  Microfluidic systems with on-line UV detection fabricated in photodefinable epoxy , 2001 .

[30]  Jane E. Curtin,et al.  Nanochannel fabrication for chemical sensors , 1997 .

[31]  Miko Elwenspoek,et al.  Advanced sacrificial poly-Si technology for fluidic systems , 2001 .

[32]  H. Baltes,et al.  Photolithography in anisotropically etched grooves , 1996, Proceedings of Ninth International Workshop on Micro Electromechanical Systems.

[33]  R. E. Oosterbroek,et al.  Etching methodologies in <111>-oriented silicon wafers , 2000, Journal of Microelectromechanical Systems.

[34]  S. Kuiper,et al.  Wet and dry etching techniques for the release of sub-micrometre perforated membranes , 2000 .

[35]  K D Wise,et al.  Microfabrication techniques for integrated sensors and microsystems. , 1991, Science.

[36]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[37]  Sung-Keun Lee,et al.  3D microfabrication with inclined/rotated UV lithography , 2004 .

[38]  Regina Luttge,et al.  Silicon micromachined hollow microneedles for transdermal liquid transport , 2003 .

[39]  Michael L. Reed,et al.  Microsystems for drug and gene delivery , 2004, Proceedings of the IEEE.

[40]  D. Liepmann,et al.  In-device enzyme immobilization: wafer-level fabrication of an integrated glucose sensor , 2004 .

[41]  Regina Luttge,et al.  Microchip capillary electrophoresis for point-of-care analysis of lithium. , 2007, Clinical chemistry.

[42]  Miko Elwenspoek,et al.  Guidelines for etching silicon MEMS structures using fluorine high-density plasmas at cryogenic temperatures , 2002 .

[43]  Wouter Olthuis,et al.  Microchip analysis of lithium in blood using moving boundary electrophoresis and zone electrophoresis , 2005, Electrophoresis.