Silicon Photon-Counting Avalanche Diodes for Single-Molecule Fluorescence Spectroscopy

Xavier Michalet, Antonino Ingargiola, Ryan A. Colyer, Giuseppe Scalia, Shimon Weiss, Piera Maccagnani, Angelo Gulinatti, Ivan Rech, Massimo Ghioni

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry, and biophysics. The basic feature of this technique is to excite and collect light from a very small volume and work in a low concentration regime resulting in rare burst-like events corresponding to the transit of a single molecule. Detecting photon bursts is a challenging task: the small number of emitted photons in each burst calls for high detector sensitivity. Bursts are very brief, requiring detectors with fast response time and capable of sustaining high count rates. Finally, many bursts need to be accumulated to achieve proper statistical accuracy, resulting in long measurement time unless parallelization strategies are implemented to speed up data acquisition. In this paper, we will show that silicon single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection. We will review the key SPAD parameters and highlight the issues to be addressed in their design, fabrication, and operation. After surveying the state-of-the-art SPAD technologies, we will describe our recent progress toward increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of this approach is illustrated with single-molecule Förster resonance energy transfer measurements.

Original languageEnglish
Article number6861975
JournalIEEE Journal of Selected Topics in Quantum Electronics
Volume20
Issue number6
DOIs
StatePublished - 1 Nov 2014
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Awards 5R01 GM095904 (UCLA and Politecnico di Milano) and 5R01 GM069709 (UCLA), and by UCLA-DOE Institute for Genomics and Proteomics, under grant DE-FC02- 02ER63421 (UCLA). Conflict of interest statement: S. Weiss discloses equity in Nesher Technologies and intellectual property used in the research reported here. The work at UCLA was conducted in Dr. Weiss’s Laboratory. M. Ghioni discloses equity in Micro Photon Devices S.r.l. (MPD). No resources or personnel from MPD were involved in this work. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, National Science Foundation or Department of Energy.

Publisher Copyright:
© 1995-2012 IEEE.

Keywords

  • FCS
  • FRET
  • Fluorescence
  • Single-molecule
  • detector array
  • single-photon avalanche diode

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