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

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

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

Market Potential Worldwide MEMS market estimate (in billions of $) (in billions of $) 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

Corporate Environment Microfluidics/LOC competitive market share, 2004

Market Drivers Cost efficiency Currently, $ million and 10 years per drug Currently, $ 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

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

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.

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)

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

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

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

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

Devices Used

Solution Secondary Design:

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

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

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

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 Clark, Lauren. “BioMEMS: Mini Medical Devices with Major Market Potential.” MIT Deshpande Center Ignition Forum. 8 December Allan, Roger. “BioMEMS Making Huge Inroads Into Medical Market.” Electronic Design. 16 June Brown, Chappell. “Chip Makers Looking at BioMEMS.” EE Times Online. 27 March