A Fully Integrated Cmos Fluorescence Biochip For Multiplex Polymerase Chain-Reaction (Pcr) Processes

Integration and miniaturization of bio-molecular detection systems into electronic biosensors and lab-on-chip platforms is of great importance. One widely recognized application area for such devices is nucleic acid (DNA and RNA) detection, specifically, nucleic acid amplification testing (NAAT), which relies on enzymatic processes such as polymerase chain reaction (PCR) to increase the copy number of target sequences and detecting them spectroscopically [1,2]. Here, we present a fully integrated CMOS DNA biosensor array (biochip) for clinical NAAT capable of performing multiplex (parallel) PCR in one -40μL reaction chamber using on-chip thermo-cycling (±4°C sec-1 heat/cool rate), real-time amplicon-probe hybridization detection (up to target 1000 unique sequences), and solid-phase (surface) melt-curve analysis from 40 to 90°C with 0.3°C resolution. The detection modality is continuous-wave fluorescence with an effective pass-band to stop-band optical density (OD) of -3.6 using an inverse fluorophore assay [3] that requires no labeling, or sandwich probes [4] in the reaction mix. Unlike electro-analytical biochips [5], the transducer surface as well as surface chemistries of this system, are chemically and thermally stable and do not degrade during PCR thermo-cycling.