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

Michael Gösch1, Alexandre Serov, Tiemo Anhut

  • 1Karolinska Institute, Department of Medical Biochemistry and Biophysics, S-171 77 Stockholm, Sweden.

Journal of Biomedical Optics
|September 28, 2004
PubMed
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We developed a parallel single molecule detection system using a novel complementary metal oxide semiconductor (CMOS) detector. This system achieves single molecule sensitivity and concentration determination, even with lower detection efficiency.

Area of Science:

  • Optoelectronics
  • Spectroscopy
  • Biophysics

Background:

  • Single molecule detection (SMD) and fluorescence correlation spectroscopy (FCS) are crucial for analyzing molecular dynamics.
  • Current systems often rely on bulky and expensive components, limiting high-throughput applications.

Purpose of the Study:

  • To present a fully integrated, parallelized SMD and FCS system utilizing a novel complementary metal oxide semiconductor (CMOS) single-photon detector array.
  • To evaluate the performance of this new CMOS detector against a state-of-the-art avalanche photodiode (APD) module.

Main Methods:

  • Utilized a 2x2 CMOS single-photon detector array for parallel detection.
  • Employed a diffractive optical element (DOE) for multifocal excitation.
  • Conducted experiments on free-diffusing molecules at various concentrations to assess performance.

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Main Results:

  • Achieved single molecule sensitivity and reliable concentration determination with the CMOS detector, despite lower detection efficiency compared to APD modules.
  • Demonstrated the CMOS detector's capability for two-component analysis to determine fractions of slowly diffusing molecules.
  • Successfully parallelized the entire system for enhanced throughput.

Conclusions:

  • The novel CMOS single-photon detector enables efficient parallel SMD and FCS.
  • This technology holds significant potential for developing high-throughput confocal detection systems.
  • The system offers a promising alternative for sensitive molecular analysis in various scientific fields.