Abstract
For future fully integrated sensing applications, a CMOS sensor will be required. New CMOS photon counting sensors have recently become available and these devices provide high quantum efficiency, photon counting sensitivity, low power and new devices in arrays and with on-chip electronics. In biological applications, photon counting is focused on the detection of low intensity fluorescence signals from fluorophores conjugated to proteins or nucleic acid biomarkers from fluorescent proteins. We describe the development of a novel microtitre plate reader format, or bioassay platform that incorporates arrays of photon counting detectors for multiple parallel readout and data acquisition. Using Pyrex wafers, we have designed and fabricated custom-made reaction wells using Pyrex and deep ion trench etched silicon, which produce optically clear structures to facilitate fluorescence detection in biological samples volumes of 2 nL to 2 μL. For initial verification of the system, a new photon counting detector from SensL is used to determine the effectiveness of the wells as the bioassay platform. The compact unit consists of a fibre coupled silicon photon counting sensor, thermoelectric cooler, thermoelectric controller, active quenching circuit, power supplies, and an USB interface to the operating software. Included in the module is a counter with time binning capability. Sensitivity increases of more than two orders of magnitude in fluorescence detection are expected over commercially available instruments. This system demonstrates that a miniaturized, low cost solution is possible for fluorescence bioassay detection, which can be used to meet growing demands in the in vitro diagnostics and Point of Care markets.
Published Version
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