An automated hand-held CMOS-based instrument for hand-held mutation detection via electrophoresis

Lab-on-chip technology has tremendous potential for point-of-care and in-field medical diagnostics, but the uptake of such technologies is hampered by the high cost and large size of the instrumentation conventionally required. In the present work we demonstrate an instrument that fully automates sample preparation, enzymatic digestion and electrophoresis to implement DNA sizing and restriction fragment length polymorphism analysis for mutation detection. The instrument is largely based on a single CMOS chip, notably for fluorescence detection and high voltage generation, and can be operated in an off-the-shelf mode using low-cost pre-packaged polymeric microfluidic chips. We demonstrate the automated detection of the C282Y single nucleotide mutation in the HFE gene that underlies hereditary haemochromatosis. The system is currently in a portable form factor and could be implemented in a hand-held format. In higher volumes of manufacture, the remainder of the instrument could be moved to the CMOS chip, enabling a single chip instrument that could be housed within an inexpensive, thumb-sized device.