INTRODUCTION TO BIO- MEMS/NEMS 丁卫平电子科学与技术系网址 :http://biomems.ustc.edu.cn 电子邮件 :wpdings@ustc.edu.cn 办公室 : 科技楼东楼 403/416 Outlines 0: It s a small world 1: How do we make small things? 2: Micropatterning of substrates and cells 3: Microfluidics 4: Molecular biology on a chip 5: Cell-based chips for biotechnology 6: BioMEMS for cell biology 7: Tissue microengineering 8: Microfabricated implants and sensors 9: The frontiers of BioMEMS 1
0. It s a small world Dimensions and scaling in biology Size: from our bodies to our molecules Time: from life s origin to enzymatic reactions Energy: from body heat to chemical bonds Electric currents: from electronics to ion channels Complexity Why BioMEMS? A technology that allows us to make small things that are useful for biomedicine 1. How do we make small things? Microfabrication techniques Micropatterning Photolithography Scanning Lithographies Soft Lithography Microstamping ( Microcontact Printing ) Microfluidic Patterning Stencil Patterning Dynamic Substrates Micromachining Micromolding: PDMS, plastics Subtraction: dry/wet etching Addition: deposition/growth 2
1.1. Benefits of microfabrication 1.2. Photolithography 1. Photoresist (photosensitive organic polymer) 2. Selective illumination through mask Positive / Negative photoresist Contact / Projection 3. Dissolution of photoresist 3
Discussion on use of photoresist for patterning biological material Clean room requirements: biological solutions? Substrate requirements: plastic? glass? Compatible with proteins? Compatible with cells? 1.3. 3-D photoresist structures 4
1.4. The SU-8 era Photoplastic SU-8 photosensitized epoxy negative photoresist Depth = 53 µm 750 rpm ~ 50 µm 30 s exp. @ 365 nm 20 min. dev. aspect ratios > 5:1 vertical sidewalls 1.5. Tilted exposure 5
1.6. Biocompatible photoresists 1.7. Maskless Photolithography Laser Writer Raster Scanning of SU8 6
1.8. Maskless Photolithography Digital Micromirror Device Texas Instruments 1.9. Micromachining 1. Photoresist micropattern 2. Chemical etching through photoresist mask dry etching (ion plasma) wet etch (acids, bases, etc.) selectivity is an issue 3. Photoresist stripping 7
1.10. Metal deposition and lift-off 1. Photoresist micropattern 2.a. Blanket deposition of material Metal evaporation Metal sputtering 2.b. Selective growth Electrochemical growth Self-assembly 3. Photoresist lift-off 1.11. Micromachining of a cantilevered tip Si Deposition of Si 3 N 4 Etch of Si 3 N 4 with reactive plasma Etch of Si with HNO 3 /HF Three masks Si 3 N 4 8
1.12. Flexible substrates 1.13. Laser-cut laminated devices 9
Combinatorial Micromixer 4 dilutions of yellow 4 dilutions of blue = 16 outputs 9 Mylar laminates 4 fluidic layers Chris Neils, Lab Chip (2004) 1.14. Laser deposition in-situ 10
1.15. Laser direct writing Micromolding Duroplastic ( thermoset ) polymers Thermoplastic polymers Elastomeric polymers Injection molding Hot embossing Soft Lithography 11
1.16. Photolithography vs. Soft Lithography Soft lithography First paper on microcontact printing First paper on microfluidic patterning Kim, E., Xia, Y., and Whitesides, G.M. Nature 376, 581-584 (1995) 12
1.17. PDMS micromolding 1. Photolithography 2. Pour polymer precursor(s) and cure 3. Peel off and cut 4. Apply 1.17. PDMS micromolding PDMS replica PDMS Photoresist (SU8) master Inexpensive Multiple replicas 30 µm 13
1.18. Structural integrity of PDMS walls 1.17. The magic of PDMS Inexpensive Very elastic and soft Transparent down to 300 nm O CH 3 Si O CH 3 Si O Surface is hydrophobic Self-seals by conformal contact CH 3 CH 3 Inert, but can be oxidized, etched, and derivatized Biocompatible Swells when exposed to solvents High permeability to gases and fluids Expands a lot with temperature 14
Soft lithography: Microcontact printing Material is added where stamp contacts surface 1. Ink Poly-dimethylsiloxane (PDMS) (transparent rubber) 2. Transfer Microcontact printing 15
1.20. Selective inking of a flat stamp Soft Lithography: Microfluidic Patterning 1. Fill Material is added where stamp does not contact the surface Inlet fabrication? Seal? Filling method? Uniformity of filling? Types of solutions? microchannels 2. Remove microchannels Immobilization of material? Procedure for removal of microchannels? 16
1.21. Micromolding in capillaries (MIMIC) 1.22. Microfluidically-patterned polyurethane 3D structures 17
Microfluidic patterning for BioMEMS Science 276, 779 (1997) microchannels filled by capillarity 1.23. Stopped-flow lithography 18
1.24. Railed microfluidic fabrication 1.25. Lock-release microfluidic lithography 19
1.26. Lock-release microfluidic lithography 1.27. Fabrication of PDMS stencils 20
1.28. Fabrication of PDMS stencils by exclusion molding 1.29. Tunable micromolding 21
1.30. Molding of PDMS from liquid patterns Traditional photolithography is limited to 2-D 1. Homogeneous photoresist thickness 2. Mask only has 2 levels of opacity 3. Developing is homogeneous 22
1.31. Microfluidic photomasks for grayscale photolithography 1.32. Agarose stamps 23
1.33. Depositing and etching of posts and wells using agarose stamps 1.34. Nanoscale lithography Also: scanning beam deposition: Energetic particles (electrons, ions, photons) break bonds in gas or liquid, resulting in solid remains 24
1.35. Mesoscale self-assembly 25