Microtechnologies for biodetection and diagnostics Peter Lillehoj, Ph.D. November 27, 2012

Introduction to MEMS Micro-electrical-mechanical systems Started in mid-late 1980’s Typical component size: 1-100s µm www.eee.metu.edu http://biopoets.berkeley.edu http://joebrownmems.com

BioMEMS Manipulate, analyze or process biological samples Improved performance over conventional technologies S. Sia Lab, Columbia University http://www.smartsheet.com L. Lee Lab, UC Berkeley http://www.dolomite-microfluidics.com

Microfabrication Etching Patterning Molding PDMS Si wafer Deposition

Microfluidic systems: cell trapping & lysis Buffer flow rate Trapping efficiency % Buffer flow rate (µL/min) 0 µL/min 10 µL/min 15 µL/min C. Wu, P. B. Lillehoj, et al., Biotechnology Journal, 2011

Microfluidic systems: cell sorting Sample inlet Sheath flow inlet R1 R3 R2 Separation region C1 C2 C3 P1 P2 P3 S1 S2 P. B. Lillehoj, et al., Lab on a Chip, 2010

Biosensing I: capturing Contact pads Sensors Alignment mark Targeting domain Peptides C Binding domain Au sensor

Biosensing II: detecting P. aerugionsa S. mutans E1 E2 E3 E4 E1 E2 E3 E4 P. B. Lillehoj, et al., Proc. Of 6th IEEE NANOMED 2012

Lab-on-a-chip Inlet 1 Outlet Mixer Capillary Pump Sensor Inlet 2 Fluids are autonomously driven within channels via capillary pumping Detection is carried out using a highly-sensitive rapid electrochemical sensor P. B. Lillehoj, et al., Lab on a Chip, 2010

Electrochemical detection: w/ target current time TMB TMB

Electrochemical detection: w/o target current time TMB TMB

BoNT detection results BoNT/A Specificity BoNT/A Detection Limit BoNT/A could be detected at concentrations down to 5 ng/mL with high specificity The entire detection process only requires 2 loading steps and can be completed within 20 min

Cell phone diagnostics Highly portable Cell phones contain a visual display, electrical interface and power source Widely accessible >75% of the world are mobile subscribers3 www.wired.com www.dipity.com/tickr/ www.mobiledia.com 3http://www.grandchallenges.org/

Summary & Conclusions Microtechnologies enables for the development of next-generation systems