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2011, Optics Letters
Philosophical Transactions of the Royal Society B: Biological Sciences
Development of new photon-counting detectors for single-molecule fluorescence microscopy2013 •
Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences. Currently, two types of detectors best fulfil the needs of each approach: single-photon-counting avalanche diodes (SPADs) for point-like detection, and electron-multiplying charge-coupled devices (EMCCDs) for wide field detection. However, there is room for improvements in both cases. The first configuration suffers from low throughput owing to the analysis of data from a single location. The second, on the other hand, is limited to relatively low frame rates and loses the benefit of single-photon-counting approaches. During the past few years, new developments in point-like and wide field detectors have started addressing some of these issues. Here, we describe our recent progresses towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. We also discuss our development of large area photon-counting cameras achieving subnanosecond resolution for fluorescence lifetime imaging applications at the single-molecule level.
2012 •
Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences.
2014 •
We present the architecture and three applications of the largest resolution image sensor based on single-photon avalanche diodes (SPADs) published to date. The sensor, fabricated in a high-voltage CMOS process, has a resolution of 512 × 128 pixels and a pitch of 24 μm. The fill-factor of 5% can be increased to 30% with the use of microlenses. For precise control of the exposure and for time-resolved imaging, we use fast global gating signals to define exposure windows as small as 4 ns. The uniformity of the gate edges location is ∼140 ps (FWHM) over the whole array, while in-pixel digital counting enables frame rates as high as 156 kfps. Currently, our camera is used as a highly sensitive sensor with high temporal resolution, for applications ranging from fluorescence lifetime measurements to fluorescence correlation spectroscopy and generation of true random numbers.
IEEE Journal of Selected Topics in Quantum Electronics
100 000 Frames/s 64 × 32 Single-Photon Detector Array for 2-D Imaging and 3-D Ranging2014 •
Daniel Durini, D. Bronzi, Danilo Bronzi, Federica Villa, S. Weyers
IEEE J. Select. Topics Quantum Electron.
Silicon photon counting avalanche diodes for single-molecule fluorescence spectroscopySolution-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.
2013 •
IEEE Transactions on Electron Devices
SPAD Image Sensor With Analog Counting Pixel for Time-Resolved Fluorescence Detection2000 •
IEEE Journal of Selected Topics in Quantum Electronics
16-Channel Module Based on a Monolithic Array of Single-Photon Detectors and 10-ps Time-to-Digital Converters2014 •
Conference on Ultrasensitive and Single-Molecule Detection Technologies
A space- and time-resolved single-photon counting detector for fluorescence microscopy and spectroscopy - art. no. 60920M2006 •
Applied Spectroscopy
Fluorescence Rejection in Resonance Raman Spectroscopy Using a Picosecond-Gated Intensified Charge-Coupled Device Camera2007 •
IEEE Journal of Selected Topics in Quantum Electronics
CMOS Imager With 1024 SPADs and TDCs for Single-Photon Timing and 3-D Time-of-Flight2014 •
IEEE Journal of Selected Topics in Quantum Electronics
A Single-Photon Avalanche Camera for Fluorescence Lifetime Imaging Microscopy and Correlation Spectroscopy2014 •
Ieee Photonics Journal
SPAD Smart Pixel for Time-of-Flight and Time-Correlated Single-Photon Counting Measurements2012 •
Astrobiology
Raman Spectroscopic Techniques for Planetary Exploration: Detecting Microorganisms through Minerals2015 •
Advances in Photodiodes
Avalanche Photodiodes in Submicron CMOS Technologies for High-Sensitivity Imaging2011 •
Advances in Photosynthesis and Respiration
(Sub)-Picosecond Spectral Evolution of Fluorescence Studied with a Synchroscan Streak-Camera System and Target Analysis2008 •
IEEE Journal of Solid-State Circuits
A 128 <formula formulatype="inline"><tex Notation="TeX">$\times$</tex> </formula> 128 Single-Photon Image Sensor With Column-Level 10-Bit Time-to-Digital Converter Array2000 •
Journal of the American Society of Echocardiography
Quantitative assessment of mechanical prosthetic valve area by 3-dimensional transesophageal echocardiography2001 •
Review of Scientific Instruments
Effective suppression of fluorescence light in Raman measurements using ultrafast time gated charge coupled device camera2004 •
Multiphoton Microscopy in the Biomedical Sciences IV
<title>Fluorescence light suppression in Raman spectroscopy using ultrafast time-gated CCD camera</title>2004 •
8Th International Workshop on Laser Ranging Instrumentation
Station report on the Goddard Space Flight Center (GSFC) 1.2 meter telescope facility1993 •
2010 •
Ground-based and Airborne Instrumentation for Astronomy
<title>QuantEYE: a quantum optics instrument for extremely large telescopes</title>2006 •
2008 •
IEEE Transactions on Geoscience and Remote Sensing
Standoff sensing of bioaerosols using intensified range-gated spectral analysis of laser-induced fluorescence2000 •
Applied Spectroscopy
Fast-Gated Intensified Charge-Coupled Device Camera to Record Time-Resolved Fluorescence Spectra of Tryptophan2004 •
2010 •
IEEE Transactions on Electron Devices
Scaleable Single-Photon Avalanche Diode Structures in Nanometer CMOS Technology2000 •
2006 •
Journal of Raman Spectroscopy
Time resolved Raman spectroscopy for depth analysis of multi-layered mineral samples2013 •
2010 •
IEEE Journal of Selected Topics in Quantum Electronics
InP-Based Single-Photon Detectors and Geiger-Mode APD Arrays for Quantum Communications Applications2015 •
Storage and Retrieval for Image and Video Databases
A Single Photon Avalanche Diode Array Fabricated in 0.35µm CMOS and based on anEvent-Driven Readout for TCSPC Experiments2000 •
2009 •
Progress in Biomedical Optics and Imaging
Multi-dimensional fluorescence lifetime measurements2007 •
Multiphoton Microscopy in the Biomedical Sciences VIII
<title>Multi-dimensional fluorescence lifetime measurements</title>2008 •