1. MEMS in the Market – Design and Market Analysis MEMS in the Market – Design and Market Analysis Ryan Dempsey, Peter Shanahan, John Richardson, Rachel Weaver, Charles Bloom Advisors: Franz Baudenbacher, Ph.D. 1 ; Raghav Venkataraman; Paul King, Ph.D. 1 1 Department of Biomedical Engineering, Vanderbilt University, Nashville, TN Background BioMEMS Cell Culture Device Fabrication Release and Bind GLASS PDMS PDMS Casting and Curing PDMS SILICON Exposed and Developed Photoresist SILICON Spin Photoresist onto Silicon Wafer SILICON PHOTORESIST Device Testing Market Barriers The NPV of our project is $6,612,618 for the period between 2001 and 2010. Therefore, we should accept the project because it is profitable. Project Valuation Objectives Future Directions Market & Demand Cost Savings The market for our BioMEMS device includes companies involved in one of two related industries: (1) major drug manufacturing, and (2) drug delivery. Major pharmaceutical companies spend an average of $802 million and 10 to 15 years researching and developing a drug to come to the market The following is a list of our device’s primary design innovation factors that improve on the most current designs: Circular wells to allow user-friendly cell insertion and perfusion Dual-chambers to allow independent experiments on a single chip Disposable and low per-unit cost Unit cost of our device is approximately $3 per chip (beginning in 2008). The market potential for lab-on-chip (LOC) devices used in drug development and delivery is massive! United States Microfluidics/LOC revenue forecasts 2004-2012 Current Method Establish screening goal of 100 active compounds. Order any 100,000 compounds. (Internal inventory or vendor.) Screen 100,000 compounds to identify active compounds. Expect 100 hits with present hit rate of 0.001. (100,000 compounds) x (.001) = 100 hits CURRENT HTS COSTS FOR THIS ASSAY: (# of compounds screened) x (cost per compound) = 100,000 x $1.50 = $150,000 Total cost: $150,000 Number of Hits: 100 Order any 10,000 compounds. (Internal inventory or vendor.) Screen 10,000 compounds to identify active compounds. Our BioMEMS Device Establish screening goal of 100 active compounds. Expect 100 hits with present hit rate of 0.01. (10,000 compounds) x (.01) = 100 hits ASSAY COSTS USING OUR DEVICE: (# of compounds screened) x (cost per compound) = 10,000 x $5.00 = $50,000 Total cost: $50,000 Number of Hits: 100 Total cost using current HTS method = $ 150,000 Total cost using our bioMEMS device = $ 50,000 TOTAL SAVINGS FOR ONE ASSAY = $ 100,000 The most significant barriers to market entry include: Interfacing concerns: nano- versus macro- Lack of silicon flexibility Replacing old systems with new technologies Lack of BioMEMS technological standard Government regulation (Class I device) Our device increases cost savings by… Increasing the hit rate of discovered compounds Reducing # of ordered compounds for testing Reducing reagent cost Our device has great potential in the market Market share is anyone’s “game” Cell-scaled beads can correctly perfuse The future of our device’s design will be in bio-sensing. We can now pass our project on to future design groups to add bio-sensors to our design Corporate Environment The market is young and fragmented The top five companies account for approximately 48% of the total LOC market in 2004. Caliper, Cephoid, Agilent, Combimatrix, and Nanogen Inc. Initially, our forecast market share = 1% CompanyLOC Device Name(s)Market Share Public/Private Caliper Life Sciences LabChip17%Public CepheidSmartCycler; GeneXpert10%Private Agilent Technologies HPLC Chip; 2100 Bioanalyzer; 5100 Automated LOC 9%Public CombiMatrix Corp. CustomArray7%Public Nanogen, Inc.NanoChip5%Public 1.Technology Design and fabricate dual cell culture micro-electro-mechanical system (MEMS) device in order to allow for multiple experiments on single chip Design enclosure in order to allow gas permeability to simulate in-vivo environment Design the device to be capable of allowing both nutrient and drug perfusion via different pathways in order to provide drug testing capabilities Design device with pneumatic valves in order to prevent cellular relocation Device should hold pico-liter volumes and have channel diameters >30 microns Design device to be low cost and disposable 2.Business To create a business proposal in order to market our technology to venture capitalists Large scale bioreactor for experimenation Micro-sized BioMEMS device for experimentation Courtesy of Raghav Venkataraman Advantages over conventional Petri dish Higher cell-to-volume ratio MEMS devices can have on-chip sensors unlike Petri dishes Allows detection of cell metabolism changes more accurately due to more sensitive detectors for smaller concentration changes Advantages over conventional bioreactors Conventional bioreactors require large amounts of physical laboratory space which MEMS devices do not Substantially lower cost Reduced experimentation setup time Reduced sensing time of metabolic activity from smaller volumes Spin SU-8 photoresist onto silicon wafer Pre-Bake SU-8 Expose using mask below with UV light “Post-Exposure” bake Develop SU-8 photoresist Hard Bake Cast and cure PDMS on master Remove PDMS device from master Bind upper pneumatic PDMS layer to lower cell culture PDMS layer using bake Punch insertion holes for fluidics channels in PDMS device Seal entire PDMS device to glass slide using plasma oxidation AutoCad drawings of actual masks used for fabrication with the device on left and pneumatic valves on right. Biological MicroElectroMechanical Systems (BioMEMS) MEMS devices are micro-sized devices used in a wide variety of applications from automobiles to cell culturing in order to provide sensor and cultures at a reduced size Bio-MEMS devices are designed to use very small volumes which translates to significantly fewer supplies for experimentation The significantly fewer supplies and the low cost of actual devices has potential to substantially cut costs Micro-beads A diluted solution of beads was mixed using water The solution was then drawn into a syringe The syringe was connected to plastic tubing lines which were then connected to the device inlet ports Following this the bead solution was run through the device in order to check for structural integrity and to assure that none of the fluidic lines were sealed to the underlying glass slide Image of beads flowing through device taken through Zeiss microscope and digital camera Device Dimensions Integration of multiple sensors to the cell culture area for rigorous analysis of cell metabolism and reaction to drug Oxygen sensor pH sensor CO2 sensor Lactate sensor Glucose sensor Schematic above shows future direction of device. Courtesy of Dr. Baudenbacher Cell culture = 600 x 600 um Perfusion channels Maximum = 200 microns Minimum = 100 microns Current drug development costs Markets for microfluidic devices