Microelectronic photosensors for genetic diagnostic microsystems

Ultra-sensitive miniaturized and economical photosensors are a key issue for analytical systems in genetic diagnostics, in particular for microchip systems for fast DNA fragment and protein analysis and separation. The planar Silicon Single-Photon Avalanche Diodes (SPAD) introduced and developed in this laboratory have various advantages over other high-sensitivity detectors currently employed (Photo-Multiplier Tubes PMT, Single-Photon Counting Modules SPCM, high-quality CCD, etc.). They are smaller, rugged and reliable and operate with low voltage and low power dissipation. They are fabricated at low cost and high yield with technology compatible with integrated circuits and monolithic detector arrays. A high-performance and truly miniaturized photon-counting module is obtained by associating a patented integrated Active Quenching Circuits (i-AQC) to a SPAD. The feasibility of chip electrophoresis systems with SPADs had been previously demonstrated with a preliminary set-up based on a microscope. A new, compact and versatile analytical instrument is here presented. It includes a laser diode for fluorescence excitation; compact input and output optical systems; a separation chip with controlled temperature and controlled high-voltage supplies; two SPAD sensors with associated i-AQC for dual-wavelength operation. The operation is fully automated under PC control. Sensitivity better than 10pM with injection volume 50pL is achieved in the separation of CY5 DNA labeled fragments.