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Parallel single molecule detection with a fully integrated single-photon 2x2 CMOS detector array.

Research paper by Michael M Gösch, Alexandre A Serov, Tiemo T Anhut, Theo T Lasser, Alexis A Rochas, Pierre-André PA Besse, Radivoje S RS Popovic, Hans H Blom, Rudolf R Rigler

Indexed on: 28 Sep '04Published on: 28 Sep '04Published in: Journal of biomedical optics



Abstract

We present parallel single molecule detection (SMD) and fluorescence correlation spectroscopy (FCS) experiments with a fully integrated complementary metal oxide semiconductor (CMOS) single-photon 2x2 detector array. Multifocal excitation is achieved with a diffractive optical element (DOE). Special emphasis is placed on parallelization of the total system. The performance of the novel single-photon CMOS detector is investigated and compared to a state-of-the-art single-photon detecting module [having an actively quenched avalanche photodiode (APD)] by measurements on free diffusing molecules at different concentrations. Despite the order of magnitude lower detection efficiency of the CMOS detector compared to the state-of-the-art single-photon detecting module, we achieve single molecule sensitivity and reliably determine molecule concentrations. In addition, the CMOS detector performance for the determination of the fraction of slowly diffusing molecules in a primer solution (two-component analysis) is demonstrated. The potential of this new technique for high-throughput confocal-detection-based systems is discussed.