1. BME 273 Senior Design Project Group 25 “MEMs in the Market”

2. Problem Drug companies demand a MEMs device that allows mobile, On-Chip drug testing, but at this point, that demand has not been met

3. Business Strategy Objective: Developing a strategy to market this BioMEMS device to major drug companies Customer: Major drug development and drug delivery companies

4. Market Potential Worldwide MEMS market estimate (in billions of $) 2003 3.85 2004 4.5 2005 5.4 2006 6.2 2007 7 (in billions of $) 2003 3.85 2004 4.5 2005 5.4 2006 6.2 2007 7 Source: Yole Development 2005 forecast MEMS markets by sector Automotive 41% Telecom 29% Bio-med 16% Military 3% Other 11% Source: Peripheral Research Corp, Santa Barbara, Calif. Microfluidics/LOC revenue forecasts 2004-2012

5. Corporate Environment Microfluidics/LOC competitive market share, 2004

6. Market Drivers Cost efficiency Currently, $400-800 million and 10 years per drug Currently, $400-800 million and 10 years per drug Reduced sample size  Lowers cost by decreasing reagent and labor usage Reduced sample size  Lowers cost by decreasing reagent and labor usage <$1 per BioMEMS chip <$1 per BioMEMS chip Scale up the number of cell cultures per experiment Higher speed  faster experiments Higher speed  faster experiments Greater control and modularity Portable experimentation Portable experimentation Reduction of human error Reduction of human error

7. Market Barriers Government regulation of medical devices Class I device regulated by FDA Class I device regulated by FDA Lack of a BioMEMS technological standard Replacing old systems with new technologies Reluctance from conservative pharm. companies Reluctance from conservative pharm. companies Scaling up production of prototypes Many possible manufacturing problems Many possible manufacturing problems

8. Device Construction Objective: Our primary objective is to create a MEMs On-Chip dual cell culture device at the pico-liter volume scale that allows for automated cell culturing and sensing for the testing of drugs and other perfused substances.

9. Goals Primary goal: Create two cell cultures, each 720 pico-liter volumes, on one chip according to previous specifications Create two cell cultures, each 720 pico-liter volumes, on one chip according to previous specifications Show that these cell cultures allow for cells to retain life during experiments Show that these cell cultures allow for cells to retain life during experiments Secondary goals: Create On-Chip sensors that allow us to sense the metabolism/response of cells to different stimuli (i.e., drugs) Create On-Chip sensors that allow us to sense the metabolism/response of cells to different stimuli (i.e., drugs)

10. Solution Original Dual cell design with two waste channels to allow independent experiments Dual pressure gauges to allow closure of entrance and exit channels for cell capturing Checkerboard cell culture to capture cells in troughs

11. Solution This is the mask for the primary experiment. Alterations to original drawing due to channel flow restrictions and MEMS practicality Dimensions: Cell culture Cell culture 600 nm x 600 nm Perfusion Channels Perfusion ChannelsMaximum 30 nm Minimum 10 nm

12. Solution Continued These are the pressure values that will be placed on the layer above the channels to allow for air pressure to shut off specified channels on demand Fabricated separately onto a different layer

13. Products thus far Mask delivered Primary device created Next step: Show cell viability

14. Devices Used

15. Solution Secondary Design:

16. Solution Experimental Methods: Load cells into device Begin perfusion Wait 24 hrs., 48 hrs., etc. At different times periods test cell viability via fluorescence Test fluorescence via imaging

17. Materials Polydimethlysiloxane (PDMS) Negative Resist (SU-8) Silicon Wafers MEMS laboratory 8 mm masks Platinum (working electrodes) Silver (reference Ag/AgCl electrodes)

18. Fabrication Steps Lay down SU-8 on silicon wafer, expose using mask, and develop lower region for cell insertion and perfusion. Cast PDMS replica of master Lay down SU-8 on silicon wafer, expose using mask, and develop upper region for pneumatic control of cell insertion channels. Cast PDMS replica of master and then lay over top of lower region

19. References Fabrication of miniature Clark oxygen sensor integrated with microstructure Ching-Chou Wu, Tomoyuki Yasukawa, Hitoshi Shiku, Tomokazu Matsue Ching-Chou Wu, Tomoyuki Yasukawa, Hitoshi Shiku, Tomokazu Matsue A BioMEMS Review: MEMS Technology for Physiologically Integrated Devices AMY C. RICHARDS GRAYSON, REBECCA S. SHAWGO, AUDREY M. JOHNSON, NOLAN T. FLYNN, YAWEN LI, MICHAEL J. CIMA, AND ROBERT LANGER AMY C. RICHARDS GRAYSON, REBECCA S. SHAWGO, AUDREY M. JOHNSON, NOLAN T. FLYNN, YAWEN LI, MICHAEL J. CIMA, AND ROBERT LANGER Bouchaud, Jeremie. “BioMEMS: high potential but also highly challenging.” Wicht Technology Consulting, Munich. 21 February 2006. Clark, Lauren. “BioMEMS: Mini Medical Devices with Major Market Potential.” MIT Deshpande Center Ignition Forum. 8 December 2003. http://web.mit.edu/deshpandecenter http://web.mit.edu/deshpandecenter Allan, Roger. “BioMEMS Making Huge Inroads Into Medical Market.” Electronic Design. 16 June 2003. http://www.elecdesign.com/Articles/Index.cfm?AD=1&AD=1&ArticleID=50 50 http://www.elecdesign.com/Articles/Index.cfm?AD=1&AD=1&ArticleID=50 50 http://www.elecdesign.com/Articles/Index.cfm?AD=1&AD=1&ArticleID=50 50 Brown, Chappell. “Chip Makers Looking at BioMEMS.” EE Times Online. 27 March 2003. http://www.eet.com/story/OEG20030327S0019 http://www.eet.com/story/OEG20030327S0019