introduction to bio- mems/nems
TRANSCRIPT
INTRODUCTION TO BIO-
MEMS/NEMS
丁卫平 副教授、博士生导师 电子科学与技术系
电子邮件:[email protected]
电话:18056099696
实验室:科技楼东楼 403/409/416
Dr. Ding’s Course
When: 1st to 9th week, Tuesday (6,7)
Where:
Lectures: 3A110;
Experiments: East Tech. Lab Bldg. (Dr. Ding’s Lab Rm 403/409/416)
Assignments and Grading:
Total points: 50+5
Class participation (30%): 8+2
Presentation (10%): 1
Final report (10%): 1
Experiments (+5%): 1
Presentation:
PPT (review articles)
Textbook:
《Introduction to BioMEMS》Albert; Folch CRC Press 2012-07-08
Reference books:
1.《BioMEMS (microsystems)》Gerald
Urban Springer,2006
2.《微纳加工科学原理》唐天同、王兆宏 编
著,电子工业出版社,2010
3.《图解微流控芯片实验室》林炳承、秦建华
编著,科学出版社,2008
Great Expectations Student Learning Goals Know the state of the art of BioMEMS (lectures)
Learn to design/operate from scratch a microfluidic device (labs)
Be able to comprehend a text from the BioMEMS literature (assignments)
Experiment Goals
Photomask design (computer)
Photolithography
Soft lithography
Microfluidic gradient
Quantitative analysis (microscopy, image processing)
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
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 (模板构图)
Dynamic Substrates
Micromachining
Micromolding: PDMS, plastics
Subtraction: dry/wet etching
Addition: deposition/growth
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
Section 2: How do we make small things?
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
Section 2: How do we make small things?
Depth = 53 µm
• photosensitized
epoxy
• negative photoresist
• 750 rpm ~ 50 µm
• 30 s exp. @ 365 nm
• 20 min. dev.
• aspect ratios > 5:1
• vertical sidewalls
Photoplastic “SU-8”
1.4. The SU-8 era
1.5. Tilted exposure
1.6. Biocompatible photoresists
1.7. Maskless Photolithography
Laser Writer
• Raster Scanning of SU8
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”
Section 2: How do we make small things?
1. Photoresist micropattern
2.a. “Blanket” deposition of material
• Metal evaporation
• Metal sputtering
3. Photoresist “lift-off”
2.b. Selective growth
• Electrochemical growth
• Self-assembly
1.10. Metal deposition and lift-off
Section 2: How do we make small things?
• Deposition of Si3N4
• Etch of Si3N4 with reactive plasma
• Etch of Si with HNO3/HF
• Three masks
Si3N4
Si
1.11. Micromachining of a
cantilevered tip
Section 2: How do we make small things?
1.12. Flexible substrates
1.13. Laser-cut laminated devices
1.14. Laser deposition in-situ
1.15. Laser direct writing
Micromolding
• Duroplastic
(“thermoset”)
polymers
• Thermoplastic
polymers
• Elastomeric
polymers
• Injection molding • Hot embossing • Soft Lithography
1.16. Photolithography vs.
Soft Lithography
Soft lithography
Section 2: How do we make small things?
First paper on microcontact printing
First paper on microfluidic patterning
Kim, E., Xia, Y., and Whitesides, G.M. Nature 376, 581-584 (1995)
Section 2: How do we make small things?
1. Photolithography 2. Pour polymer precursor(s)
and cure
3. Peel off and cut 4. Apply
1.17. PDMS micromolding
Section 2: How do we make small things?
Photoresist (SU8) master
30 µm
PDMS replica
PDMS
• Multiple replicas
• Inexpensive
1.17. PDMS micromolding
Section 2: How do we make small things?
Inexpensive
Very elastic and soft
Transparent down to 300 nm
Surface is hydrophobic
Self-seals by conformal contact
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
Si
O OO
Si
CH3
CH3
CH3
CH3
1.17. The magic of PDMS
1.18. Structural integrity of PDMS walls
Section 2: How do we make small things?
Soft lithography: Microcontact printing
1. Ink
2. Transfer
Poly-dimethylsiloxane (PDMS) (transparent rubber)
Material is added where stamp contacts surface
Section 2: How do we make small things?
Microcontact printing
1.20. Selective inking of a flat stamp
Section 2: How do we make small things?
Soft Lithography: Microfluidic Patterning
1. Fill
2. Remove microchannels
microchannels
Material is added where stamp does not contact the surface
• Inlet fabrication?
• Seal?
• Filling method?
• Uniformity of filling?
• Types of solutions?
• Immobilization of material?
• Procedure for removal of microchannels?
1.21. Micromolding in capillaries (MIMIC)
1.22. Microfluidically-patterned
polyurethane 3D structures
Section 2: How do we make small things?
Microfluidic patterning for BioMEMS
Science 276, 779 (1997)
microchannels filled by capillarity
1.23. Stopped-flow lithography
1.24. Railed microfluidic fabrication
1.25. Lock-release microfluidic lithography
1.26. Lock-release microfluidic lithography
1.27. Fabrication of PDMS stencils
1.28. Fabrication of PDMS stencils by
exclusion molding
1.29. Tunable micromolding
1.30. Molding of PDMS from liquid patterns
Section 2: How do we make small things?
Traditional photolithography is limited to 2-D
1. Homogeneous photoresist
thickness
2. Mask only has 2 levels of
opacity
3. Developing is homogeneous
1.31. Microfluidic photomasks for
grayscale photolithography
1.32. Agarose stamps(琼脂糖模板)
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
1.35. Mesoscale self-assembly