Miniaturized Silicon Nanowire System for the In Vivo Diagnosis of Disease R. Myers, L. Rivera, Y. He, Z. Li and J. Villalba

Technical Need 46% of all cancer patients are diagnosed when cancer has reached an advanced stage Current cancer diagnostic techniques are invasive and expensive Similar Available Technology: Miriam by Miroculus In vitro detection of disease through blood samples Drawbacks: long diagnostic time, high price ($500 per device) and size

Technical Approach Task 1: Biomarker Screening If Benchmark Biomarker fails Task 2: Nanowire Distribution If Miniaturization fails Risk Mitigation Task 3: Miniaturization Task 4: In Vitro Testing

Task 1: Biomarker Screening Select benchmark biomarker based on: Sensitivity Specificity Size of biomarker- aptamer-cross- linker complex FDA approved biomarkers from Polanski M., Anderson Leigh N., “A List of Candidate Cancer Biomarkers for Targeted Proteomics”, Biomarker Insights, Volume 1, Pages 1-48 (2007)

Task 2: Nanowire Distribution Manufacture systems by varying manufacturing conditions for CVD and thermal evaporation Test for sensitivity and specificity Goal: Determine optimal surface area to nanowire distribution ratio Aptamer-Biomarker binding by lock-and-key mechanism from De Vico L. et al, “Quantifying signal changes in nano-wire based biosensors”, Nanoscale, Volume 3, Pages 706-717 (2011)

Task 3: Miniaturization Determine safe implant size range Scale down current systems based on optimal surface area to nanowire distribution ratio Re-evaluate project based on results Silicon Nanowire between source and drain from Hsu S., Tsai C., Hsu W., Lu F., He J., Cheng K., Hsieh S., Wang H., Sun Y. and Tu L., “Fabrication of Silicon Nanowires Field Effect Transistors for Biosensor Applications”, Bioengineering Conference (NEBEC) 2012 38th Annual Northeast, Pages 5-6 (2012)

Task 4: In Vitro Testing Test sensitivity to ensure proper functionality of miniaturized system Ensure that miniaturized system will: Be resistant to clogging Allow filtration by biomarker size Ensure laminar flow Maintain mechanical and conductive integrity Microfluidic channel for silicon nanowire biosensor from Leydent M.T., Schuman C., Sharf T., Kevek J., Remcho V.T. and Minot E.D., “Fabrication and Characterization of Carbon Nanotube Field-Effect Transistor Biosensors”, Organic Semiconductors in Sensors and Bioelectronics III, Conference Volume 7779 (2010)

Project Timeline

Project Cost and Deliverables Research plan and outcomes will be presented and updated at the end of each task Will provide a working prototype of a miniaturized silicon nanowire biosensor to monitor biomarker levels in blood plasma Prototype will be ready for integration into applications for In Vivo testing Project cost distribution. Total estimated cost for 4-year research project is $1,295,682

Social and Economic Impact Will allow for focus of resources on treatment instead of diagnosis Early diagnosis system save thousands of lives and up to $16 billion in healthcare costs within the first five years Opportunities for project growth by partnerships with medical research teams and insurance providers

There is no time to waste! Early diagnostic procedures save lives and save money!