1. INTRODUCTION TO BIO-MEMS/NEMS
丁卫平 副教授、博士生导师
电子科学与技术系
电话：
实验室：科技楼东楼 403/409/416

2. Dr. Ding’s Course
When: 1st to 9th week, Tuesday (6,7) Where: Lectures: 3A109; Experiments: East Tech. Lab Bldg. (Dr. Ding’s Lab Rm ) 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), 9 groups (4x9), 10 min/group, 9th week Textbook: 《Introduction to BioMEMS》Albert; Folch CRC Press
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

3. Great Expectations Student Learning Goals Experiment 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)

4. 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

5. 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”

6. 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

7. 1.1. Benefits of microfabrication

8. 1.2. Photolithography Photoresist (photosensitive organic polymer)
2. Selective illumination through mask
Positive / Negative photoresist
Contact / Projection
3. Dissolution of photoresist

9. Discussion on use of photoresist for patterning biological material
Clean room requirements: biological solutions?
Substrate requirements: plastic? glass?
Compatible with proteins?
Compatible with cells?

10. 1.3. 3-D photoresist structures

11. 1.4. The SU-8 era Photoplastic “SU-8” Depth = 53 µm
photosensitized epoxy
negative photoresist
750 rpm ~ 50 µm
30 s 365 nm
20 min. dev.
aspect ratios > 5:1
vertical sidewalls
Depth = 53 µm

12. 1.5. Tilted exposure

13. 1.6. Biocompatible photoresists

14. 1.7. Maskless Photolithography
Laser Writer
Raster Scanning of SU8

15. 1.8. Maskless Photolithography
Digital Micromirror Device
Texas Instruments

16. 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”

17. 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”

18. 1.11. Micromachining of a cantilevered tip
Deposition of Si3N4
Etch of Si3N4 with reactive plasma
Etch of Si with HNO3/HF
Three masks Si
Si3N4

19. 1.12. Flexible substrates

20. 1.13. Laser-cut laminated devices

21. 1.14. Laser deposition in-situ

22. 1.15. Laser direct writing

23. Micromolding Duroplastic (“thermoset”) polymers Thermoplastic polymers
Elastomeric polymers
Injection molding
Hot embossing
Soft Lithography

24. 1.16. Photolithography vs.
Soft Lithography
Soft lithography

25. First paper on microcontact printing
First paper on microfluidic patterning
Kim, E., Xia, Y., and Whitesides, G.M. Nature 376, (1995)

26. 1.17. PDMS micromolding 2. Pour polymer precursor(s) and cure
1. Photolithography
3. Peel off and cut
4. Apply

27. 1.17. PDMS micromolding PDMS replica PDMS Photoresist (SU8) master
Inexpensive
Multiple replicas

28. 1.17. The magic of PDMS 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

29. 1.18. Structural integrity of PDMS walls

30. Soft lithography: Microcontact printing
Material is added where stamp contacts surface
Poly-dimethylsiloxane (PDMS)
(transparent rubber)
1. Ink
2. Transfer

31. Microcontact printing

32. 1.20. Selective inking of a flat stamp

33. Soft Lithography: Microfluidic Patterning
Material is added where stamp
does not contact the surface
microchannels
1. Fill
Inlet fabrication?
Seal?
Filling method?
Uniformity of filling?
Types of solutions?
2. Remove microchannels
Immobilization of material?
Procedure for removal of microchannels?

34. 1.21. Micromolding in capillaries (MIMIC)

35. 1.22. Microfluidically-patterned polyurethane 3D structures

36. Microfluidic patterning for BioMEMS
Science 276, 779 (1997)
microchannels filled by capillarity

37. 1.23. Stopped-flow lithography

38. 1.24. Railed microfluidic fabrication

39. 1.25. Lock-release microfluidic lithography

40. 1.26. Lock-release microfluidic lithography

41. 1.27. Fabrication of PDMS stencils

42. 1.28. Fabrication of PDMS stencils by exclusion molding

43. 1.29. Tunable micromolding

44. 1.30. Molding of PDMS from liquid patterns

45. Traditional photolithography is limited to 2-D
Homogeneous photoresist thickness
2. Mask only has 2 levels of opacity
3. Developing is homogeneous

46. 1.31. Microfluidic photomasks for grayscale photolithography

47. 1.32. Agarose stamps（琼脂糖模板）

48. 1.33. Depositing and etching of posts and wells using agarose stamps

49. 1.34. Nanoscale lithography
Also: scanning beam deposition:
Energetic particles (electrons, ions, photons) break bonds in gas or liquid, resulting in solid remains

50. 1.35. Mesoscale self-assembly