Synonymous codon usage regulates translation initiation.

Nonoptimal synonymous codons repress gene expression, but the underlying mechanisms are poorly understood. We and others have previously shown that nonoptimal codons slow translation elongation speeds and thereby trigger messenger RNA (mRNA) degradation. Nevertheless, transcript levels are often insufficient to explain protein levels, suggesting additional mechanisms by which codon usage regulates gene expression.

Phylodynamics of a regional SARS-CoV-2 rapid spreading event in Colorado in late 2020.

Since the initial reported discovery of SARS-CoV-2 in late 2019, genomic surveillance has been an important tool to understand its transmission and evolution. Here, we sought to describe the underlying regional phylodynamics before and during a rapid spreading event that was documented by surveillance protocols of the United States Air Force Academy (USAFA) in late October-November of 2020. We used replicate long-read sequencing on Colorado SARS-CoV-2 genomes collected July through November 2020 at the University of Colorado Anschutz Medical campus in Aurora and the United States Air Force Academy in Colorado Springs.

A quantum-enhanced wide-field phase imager.

Quantum techniques can be used to enhance the signal-to-noise ratio in optical imaging. Leveraging the latest advances in single-photon avalanche diode array cameras and multiphoton detection techniques, here, we introduce a supersensitive phase imager, which uses space-polarization hyperentanglement to operate over a large field of view without the need of scanning operation. We show quantum-enhanced imaging of birefringent and nonbirefringent phase samples over large areas, with sensitivity improvements over equivalent classical measurements carried out with equal number of photons.

Real-time multispectral fluorescence lifetime imaging using Single Photon Avalanche Diode arrays.

Autofluorescence spectroscopy has emerged in recent years as a powerful tool to report label-free contrast between normal and diseased tissues, both in vivo and ex vivo. We report the development of an instrument employing Single Photon Avalanche Diode (SPAD) arrays to realize real-time multispectral autofluorescence lifetime imaging at a macroscopic scale using handheld single-point fibre optic probes, under bright background conditions. At the detection end, the fluorescence signal is passed through a transmission grating and both spectral and temporal information are encoded in the SPAD array.

Imaging Cherenkov photon emissions in radiotherapy with a Geiger-mode gated quanta image sensor.

The emission of Cherenkov photons from human and animal tissue can be observed during clinical x-ray or particle beam irradiation. However, imaging this weak emission with the necessary single-photon sensitivity in the clinical room is challenging because of milliwatt-level ambient room lighting and the presence of stray high-energy radiation. In this Letter, we demonstrate, to the best of our knowledge, the first Cherenkov imaging with a time-gated quanta image sensor employing a large single-photon avalanche diode (SPAD) array.

Functional Fluorescence Microscopy Imaging: Quantitative Scanning-Free Confocal Fluorescence Microscopy for the Characterization of Fast Dynamic Processes in Live Cells.

Functional fluorescence microscopy imaging (fFMI), a time-resolved (21 μs/frame) confocal fluorescence microscopy imaging technique without scanning, is developed for quantitative characterization of fast reaction-transport processes in solution and in live cells. The method is based on massively parallel fluorescence correlation spectroscopy (FCS). Simultaneous excitation of fluorescent molecules in multiple spots in the focal plane is achieved using a diffractive optical element (DOE).

Multispectral Depth-Resolved Fluorescence Lifetime Spectroscopy Using SPAD Array Detectors and Fiber Probes.

Single Photon Avalanche Diode (SPAD) arrays are increasingly exploited and have demonstrated potential in biochemical and biomedical research, both for imaging and single-point spectroscopy applications. In this study, we explore the application of SPADs together with fiber-optic-based delivery and collection geometry to realize fast and simultaneous single-point time-, spectral-, and depth-resolved fluorescence measurements at 375 nm excitation light. Spectral information is encoded across the columns of the array through grating-based dispersion, while depth information is encoded across the rows thanks to a linear arrangement of probe collecting fibers.

Multichannel low power time-to-digital converter card with 21 ps precision and full scale range up to 10 μs.

We present a Time-to-Digital Converter (TDC) card with a compact form factor, suitable for multichannel timing instruments or for integration into more complex systems. The TDC Card provides 10 ps timing resolution over the whole measurement range, which is selectable from 160 ns up to 10 μs, reaching 21 ps rms precision, 1.25% LSB rms differential nonlinearity, up to 3 Mconversion/s with 400 mW power consumption.

Time-resolved double-slit interference pattern measurement with entangled photons.

The double-slit experiment strikingly demonstrates the wave-particle duality of quantum objects. In this famous experiment, particles pass one-by-one through a pair of slits and are detected on a distant screen. A distinct wave-like pattern emerges after many discrete particle impacts as if each particle is passing through both slits and interfering with itself.

Low-noise low-jitter 32-pixels CMOS single-photon avalanche diodes array for single-photon counting from 300 nm to 900 nm.

We developed a single-photon counting multichannel detection system, based on a monolithic linear array of 32 CMOS SPADs (Complementary Metal-Oxide-Semiconductor Single-Photon Avalanche Diodes). All channels achieve a timing resolution of 100 ps (full-width at half maximum) and a photon detection efficiency of 50% at 400 nm. Dark count rate is very low even at room temperature, being about 125 counts/s for 50 μm active area diameter SPADs.

Single-photon pulsed-light indirect time-of-flight 3D ranging.

"Indirect" time-of-flight is one technique to obtain depth-resolved images through active illumination that is becoming more popular in the recent years. Several methods and light timing patterns are used nowadays, aimed at improving measurement precision with smarter algorithms, while using less and less light power. Purpose of this work is to present an indirect time-of-flight imaging camera based on pulsed-light active illumination and a 32 × 32 single-photon avalanche diode array with an improved illumination timing pattern, able to increase depth resolution and to reach single-photon level sensitivity.

10 ps resolution, 160 ns full scale range and less than 1.5% differential non-linearity time-to-digital converter module for high performance timing measurements.

We present a compact high performance time-to-digital converter (TDC) module that provides 10 ps timing resolution, 160 ns dynamic range and a differential non-linearity better than 1.5% LSB(rms). The TDC can be operated either as a general-purpose time-interval measurement device, when receiving external START and STOP pulses, or in photon-timing mode, when employing the on-chip SPAD (single photon avalanche diode) detector for detecting photons and time-tagging them.

New photon-counting detectors for single-molecule fluorescence spectroscopy and imaging.

Solution-based single-molecule fluorescence spectroscopy is a powerful new experimental approach with applications in all fields of natural sciences. Two typical geometries can be used for these experiments: point-like and widefield excitation and detection. In point-like geometries, the basic concept is to excite and collect light from a very small volume (typically femtoliter) and work in a concentration regime resulting in rare burst-like events corresponding to the transit of a single-molecule.

Ultra high-throughput single molecule spectroscopy with a 1024 pixel SPAD.

Single-molecule spectroscopy is a powerful approach to measuring molecular properties such as size, brightness, conformation, and binding constants. Due to the low concentrations in the single-molecule regime, measurements with good statistical accuracy require long acquisition times. Previously we showed a factor of 8 improvement in acquisition speed using a custom-CMOS 8x1 SPAD array.

Sub-Rayleigh imaging via N-photon detection.

The Rayleigh diffraction bound sets the minimum separation for two point objects to be distinguishable in a conventional imaging system. We demonstrate sub-Rayleigh resolution by scanning a focused beam--in an arbitrary, object-covering pattern that is unknown to the imager--and using N-photon photodetection implemented with a single-photon avalanche detector array. Experiments show resolution improvement by a factor ∼(N-N(max))(½) beyond the Rayleigh bound, where N(max) is the maximum average detected photon number in the image, in good agreement with theory.

High-throughput single-molecule fluorescence spectroscopy using parallel detection.

Solution-based single-molecule fluorescence spectroscopy is a powerful new experimental approach with applications in all fields of natural sciences. The basic concept of this technique is to excite and collect light from a very small volume (typically femtoliter) and work in a concentration regime resulting in rare burst-like events corresponding to the transit of a single-molecule. Those events are accumulated over time to achieve proper statistical accuracy.

Variable-load quenching circuit for single-photon avalanche diodes.

We present a compact 50 microm x 100 microm cell for single-photon detection, based on a new circuitry monolithically integrated together with a 20 microm-diameter CMOS Single-Photon Avalanche Diode (SPAD). The detector quenching relies on a novel mechanism based on starving the avalanche current till quenching through a variable-load (VLQC, Variable- Load Quenching Circuit). Fabricated in a standard 0.

Fully-integrated CMOS single photon counter.

Traditionally, Single Photon Avalanche Diodes (SPADs) are fabricated using dedicated processes that require additional technological steps when compared to standard CMOS. Instead, this paper presents the design of SPADs that attain good performances, by using a standard high-voltage CMOS process. The detector is monolithically integrated together with an Active Quenching Circuit (iAQC), a counter, and a serial communication interface.

Single-photon imaging at 20,000 frames/s.

A complete two-dimensional imaging system based on a silicon monolithic array of 60 single-photon counters is presented. The fabricated solid-state array is rugged and operates at low voltages. Detection efficiency is higher than 40% in the visible range, and cross talk among 50 microm pixels is lower than 10(-4).

Complete single-photon counting and timing module in a microchip.

A complete module for single-photon counting and timing is demonstrated in a single chip. Features comparable with or better than commercially available macroscopic modules are obtained by integration of an active-quenching and active-reset circuit in complementary metal-oxide semiconductor technology together with a single-photon avalanche diode (SPAD). The integrated SPAD has a 12-microm-diameter sensitive area and operates with an overvoltage above breakdown adjustable up to 20 V.