BME 273BME 273Senior Design ProjectSenior Design Project

Group 25Group 25“MEMs in the Market”“MEMs in the Market”

ProblemProblem

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

Business StrategyBusiness Strategy

ObjectiveObjective: Developing a strategy to : Developing a strategy to market this BioMEMS device to major market this BioMEMS device to major drug companiesdrug companies

CustomerCustomer: Major drug development : Major drug development and drug delivery companies and drug delivery companies

Market PotentialMarket Potential

Worldwide MEMS market estimateWorldwide MEMS market estimate

         (in billions of $)(in billions of $)                                         2003    3.852003    3.85                     2004    4.52004    4.5                     2005    5.42005    5.4                     2006    6.22006    6.2                     2007    72007    7

Source: Yole DevelopmentSource: 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

Corporate EnvironmentCorporate Environment

Microfluidics/LOC competitive market share, 2004

Market DriversMarket Drivers

Cost efficiencyCost efficiency Currently, $400-800 million and 10 years per drugCurrently, $400-800 million and 10 years per drug Reduced sample size Reduced sample size Lowers cost by decreasing Lowers cost by decreasing

reagent and labor usagereagent and labor usage <$1 per BioMEMS chip<$1 per BioMEMS chip

Scale up the number of cell cultures per Scale up the number of cell cultures per experimentexperiment Higher speed Higher speed faster experiments faster experiments

Greater control and modularity Greater control and modularity Portable experimentation Portable experimentation Reduction of human errorReduction of human error

Market BarriersMarket Barriers

Government regulation of medical devicesGovernment regulation of medical devices Class I device regulated by FDAClass I device regulated by FDA

Lack of a BioMEMS technological Lack of a BioMEMS technological standardstandardReplacing old systems with new Replacing old systems with new technologies technologies Reluctance from conservative pharm. Reluctance from conservative pharm.

companiescompanies

Scaling up production of prototypesScaling up production of prototypes Many possible manufacturing problemsMany possible manufacturing problems

Device ConstructionDevice Construction

ObjectiveObjective: Our primary objective is to create a : Our primary objective is to create a MEMs On-Chip dual cell culture device at the MEMs On-Chip dual cell culture device at the

pico-liter volume scale that allows for pico-liter volume scale that allows for automated cell culturing and sensing for the automated cell culturing and sensing for the

testing of drugs and other perfused testing of drugs and other perfused substances.substances.

GoalsGoals

Primary goal:Primary goal: Create two cell cultures, each 720 pico-liter Create two cell cultures, each 720 pico-liter

volumes, on one chip according to previous volumes, on one chip according to previous specificationsspecifications

Show that these cell cultures allow for cells to Show that these cell cultures allow for cells to retain life during experimentsretain life during experiments

Secondary goals:Secondary goals: Create On-Chip sensors that allow us to Create On-Chip sensors that allow us to

sense the metabolism/response of cells to sense the metabolism/response of cells to different stimuli (i.e., drugs)different stimuli (i.e., drugs)

Solution OriginalSolution Original

Dual cell design Dual cell design with two waste with two waste channels to allow channels to allow independent independent experimentsexperimentsDual pressure Dual pressure gauges to allow gauges to allow closure of closure of entrance and exit entrance and exit channels for cell channels for cell capturingcapturingCheckerboard Checkerboard cell culture to cell culture to capture cells in capture cells in troughstroughs

SolutionSolution

This is the mask for the This is the mask for the primary experiment. primary experiment. Alterations to original Alterations to original drawing due to channel drawing due to channel flow restrictions and flow restrictions and MEMS practicalityMEMS practicality

Dimensions:Dimensions: Cell culture Cell culture

600 nm x 600 nm600 nm x 600 nm Perfusion ChannelsPerfusion Channels

MaximumMaximum30 nm30 nm

MinimumMinimum10 nm10 nm

Solution ContinuedSolution Continued

These are the pressure These are the pressure values that will be placed on values that will be placed on the layer above the channels the layer above the channels to allow for air pressure to to allow for air pressure to shut off specified channels on shut off specified channels on demanddemand

Fabricated separately onto a Fabricated separately onto a different layerdifferent layer

Products thus farProducts thus far

Mask deliveredMask delivered

Primary device Primary device createdcreated

Next step: Show cell Next step: Show cell viabilityviability

Devices UsedDevices Used

SolutionSolution

Secondary Design:Secondary Design:

SolutionSolution

Experimental Methods:Experimental Methods:

Load cells into deviceLoad cells into device

Begin perfusionBegin perfusion

Wait 24 hrs., 48 hrs., etc.Wait 24 hrs., 48 hrs., etc.

At different times periods test cell viability At different times periods test cell viability via fluorescencevia fluorescence

Test fluorescence via imagingTest fluorescence via imaging

MaterialsMaterials

Polydimethlysiloxane (PDMS)Polydimethlysiloxane (PDMS)

Negative Resist (SU-8)Negative Resist (SU-8)

Silicon WafersSilicon Wafers

MEMS laboratoryMEMS laboratory

8 mm masks8 mm masks

Platinum (working electrodes)Platinum (working electrodes)

Silver (reference Ag/AgCl electrodes)Silver (reference Ag/AgCl electrodes)

Fabrication StepsFabrication Steps

Lay down SU-8 on silicon wafer, expose using Lay down SU-8 on silicon wafer, expose using mask, and develop lower region for cell insertion mask, and develop lower region for cell insertion and perfusion.and perfusion.

Cast PDMS replica of masterCast PDMS replica of master

Lay down SU-8 on silicon wafer, expose using Lay down SU-8 on silicon wafer, expose using mask, and develop upper region for pneumatic mask, and develop upper region for pneumatic control of cell insertion channels.control of cell insertion channels.

Cast PDMS replica of master and then lay over Cast PDMS replica of master and then lay over top of lower regiontop of lower region

ReferencesReferencesFabrication of miniature Clark oxygen sensor integrated with Fabrication of miniature Clark oxygen sensor integrated with microstructuremicrostructure

Ching-Chou Wu, Tomoyuki Yasukawa, Hitoshi Shiku, Tomokazu MatsueChing-Chou Wu, Tomoyuki Yasukawa, Hitoshi Shiku, Tomokazu MatsueA BioMEMS Review: MEMS Technology for Physiologically Integrated A BioMEMS Review: MEMS Technology for Physiologically Integrated DevicesDevices

AMY C. RICHARDS GRAYSON, REBECCA S. SHAWGO, AUDREY M. AMY C. RICHARDS GRAYSON, REBECCA S. SHAWGO, AUDREY M. JOHNSON, NOLAN T. FLYNN, YAWEN LI, MICHAEL J. CIMA, AND JOHNSON, NOLAN T. FLYNN, YAWEN LI, MICHAEL J. CIMA, AND ROBERT LANGERROBERT LANGER

Bouchaud, Jeremie. “BioMEMS: high potential but also highly Bouchaud, Jeremie. “BioMEMS: high potential but also highly challenging.” Wicht Technology Consulting, Munich. 21 February 2006.challenging.” Wicht Technology Consulting, Munich. 21 February 2006.Clark, Lauren. “BioMEMS: Mini Medical Devices with Major Market Clark, Lauren. “BioMEMS: Mini Medical Devices with Major Market Potential.” MIT Deshpande Center Ignition Forum. 8 December 2003. Potential.” MIT Deshpande Center Ignition Forum. 8 December 2003. http://http://web.mit.edu/deshpandecenterweb.mit.edu/deshpandecenter Allan, Roger. “BioMEMS Making Huge Inroads Into Medical Market.” Allan, Roger. “BioMEMS Making Huge Inroads Into Medical Market.” Electronic DesignElectronic Design. 16 June 2003. . 16 June 2003. http://http://www.elecdesign.com/Articles/Index.cfm?ADwww.elecdesign.com/Articles/Index.cfm?AD=1&AD=1&ArticleID=5050=1&AD=1&ArticleID=5050 Brown, Chappell. “Chip Makers Looking at BioMEMS.” Brown, Chappell. “Chip Makers Looking at BioMEMS.” EE Times EE Times OnlineOnline. 27 March 2003. . 27 March 2003. http://www.eet.com/story/OEG20030327S0019http://www.eet.com/story/OEG20030327S0019