This invention is a novel approach to performing DNA sequencing-by-synthesis methodology that is anticipated to make DNA sequencing routine, highly accurate and affordable.
The approach is a silicon-based field effect nanoscale sensor array using a sequence-by-synthesis methodology. PCR is performed locally in each pixel through the use of recently developed methods for heating fluid using a silicon field effect sensor, and then the amplified molecules in the pixel are detected in a label-free electrical manner where the added charge during the synthesis process is detected using the same thin-film SOI transistor.
Cost is significantly reduced since the nucleotides do not need a fluorescent label, there is no need for gel electrophoresis, and the entire machinery of optical signal processing is unnecessary. In addition, since the silicon field effect sensors when used in a nanoscale dimension can be very sensitive and detect the charge from just a few molecules, it is quite feasible that the PCR amplification can be utilized with very few cycles. Reduction of PCR cycling would reduce the usage of costly reagents. The information retrieval can be scaled and the information obtained per unit time is maximized.