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Issue 20, 2014
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An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics

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Abstract

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. Considerable 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 paper, 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 an accuracy of 0.45 °C. Electrowetting-on-dielectric microfluidics are actively driven from the chip surface, allowing for droplet generation and transport down to volumes less than 1.2 nanoliter. Integrated single-photon avalanche diodes (SPADs) 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 and 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.

Graphical abstract: An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics

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Supplementary files

Article information


Submitted
14 Apr 2014
Accepted
15 Aug 2014
First published
15 Aug 2014

Lab Chip, 2014,14, 4076-4084
Article type
Paper
Author version available

An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics

H. Norian, R. M. Field, I. Kymissis and K. L. Shepard, Lab Chip, 2014, 14, 4076
DOI: 10.1039/C4LC00443D

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