Considerable effort has recently been directed toward the miniaturization of quantitative-polymerase-chain-reaction [QPCR] instrumentation in an effort to reduce both cost and form factor for point-of-care applications. Notable gains have been made in shrinking the required volumes of PCR reagents, but resultant prototypes retain their bench-top form factor either due to heavy heating plates or cumbersome optical sensing instrumentation. In this thesis, we describe the use of complementary-metal-oxide semiconductor (CMOS) integrated circuit (IC) technology to produce a fully integrated qPCR lab-on-chip. Exploiting a 0.35-µm high-voltage CMOS process, the IC contains all of the key components for performing qPCR. Integrated resistive heaters and temperature sensors regulate the surface temperature of the chip to 0.45°C. Electrowetting-on-dielectric microfluidic pixels are actively driven from the chip surface, allowing for droplet generation and transport down to volumes of less than 1.2 nanoliters. Integrated single-photon avalanche diodes [SPAD] are used for fluorescent monitoring of the reaction, allowing for the quantification of target DNA with more than four-orders-of-magnitude of dynamic range with sensitivities down to a single copy per droplet. Using this device, reliable and sensitive real-time proof-of-concept detection of Staphylococcus aureus (S. aureus) is demonstrated.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/D8HX1B0H |
| Date | January 2014 |
| Creators | Norian, Haig |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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