A Method to Correct the Temporal Drift of Single-Photon Detectors Based on Asynchronous Quantum Ghost Imaging.

Single-photon detection and timing has attracted increasing interest in recent years due to their necessity in the field of quantum sensing and the advantages of single-quanta detection in the field of low-level light imaging. While simple bucket detectors are mature enough for commercial applications, more complex imaging detectors are still a field of research comprising mostly prototype-level detectors. A major problem in these detectors is the implementation of in-pixel timing circuitry, especially for two-dimensional imagers. One of the most promising approaches is the use of voltage-controlled ring resonators in every pixel. Each of these runs independently based on a voltage supplied by a global reference. However, this yields the problem that the supply voltage can change across the chip which, in turn, changes the period of the ring resonator. Due to additional parasitic effects, this problem can worsen with increasing measurement time, leading to drift in the timing information. We present here a method to identify and correct such temporal drifts in single-photon detectors based on asynchronous quantum ghost imaging. We also show the effect of this correction on recent quantum ghost imaging (QGI) measurement from our group.

Multi-Channel Gating Chip in 0.18 µm High-Voltage CMOS for Quantum Applications.

A gating circuit for a photonic quantum simulator is introduced. The gating circuit uses a large excess bias voltage of up to 9.9 V and an integrated single-photon avalanche diode (SPAD). Nine channels are monolithically implemented in an application-specific integrated circuit (ASIC) including nine SPADs using 0.18 µm high-voltage CMOS technology. The gating circuit achieves rise and fall times of 480 ps and 280 ps, respectively, and a minimum full-width-at-half-maximum pulse width of 1.26 ns. Thanks to a fast and sensitive comparator, a detection threshold for avalanche events of less than 100 mV is possible. The power consumption of all nine channels is about 250 mW in total. This gating chip is used to characterize the integrated SPADs. A photon detection probability of around 50% at 9.9 V excess bias and for a wavelength of 635 nm is found.

Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.

Significance: Fluorescence guidance is used clinically by surgeons to visualize anatomical and/or physiological phenomena in the surgical field that are difficult or impossible to detect by the naked eye. Such phenomena include tissue perfusion or molecular phenotypic information about the disease being resected. Conventional fluorescence-guided surgery relies on long, microsecond scale laser pulses to excite fluorescent probes. However, this technique only provides two-dimensional information; crucial depth information, such as the location of malignancy below the tissue surface, is not provided. Aim: We developed a depth sensing imaging technique using light detection and ranging (LiDAR) time-of-flight (TOF) technology to sense the depth of target tissue while overcoming the influence of tissue optical properties and fluorescent probe concentration. Approach: The technology is based on a large-format (512×512 pixel), binary, gated, single-photon avalanche diode (SPAD) sensor with an 18 ps time-gate step, synchronized with a picosecond pulsed laser. The fast response of the sensor was developed and tested for its ability to quantify fluorescent inclusions at depth and optical properties in tissue-like phantoms through analytical model fitting of the fast temporal remission data. Results: After calibration and algorithmic extraction of the data, the SPAD LiDAR technique allowed for sub-mm resolution depth sensing of fluorescent inclusions embedded in tissue-like phantoms, up to a maximum of 5 mm in depth. The approach provides robust depth sensing even in the presence of variable tissue optical properties and separates the effects of fluorescence depth from absorption and scattering variations. Conclusions: LiDAR TOF fluorescence imaging using an SPAD camera provides both fluorescence intensity images and the temporal profile of fluorescence, which can be used to determine the depth at which the signal is emitted over a wide field of view. The proposed tool enables fluorescence imaging at a higher depth in tissue and with higher spatial precision than standard, steady-state fluorescence imaging tools, such as intensity-based near-infrared fluorescence imaging, optical coherence tomography, Raman spectroscopy, or confocal microscopy. Integration of this technique into a standard surgical tool could enable rapid, more accurate estimation of resection boundaries, thereby improving the surgeon's efficacy and efficiency, and ultimately improving patient outcomes.

A time-correlated single photon counting SPAD array camera with a bespoke data-processing algorithm for lightsheet fluorescence lifetime imaging (FLIM) and FLIM videos.

A wide-field microscope with epi-fluorescence and selective plane illumination was combined with a single-photon avalanche diode (SPAD) array camera to enable live-cell fluorescence lifetime imaging (FLIM) using time-correlated single-photon counting (TCSPC). The camera sensor comprised of 192 × 128 pixels, each integrating a single SPAD and a time-to-digital converter. Jointly, they produced a stream of single-photon images of photon arrival times with ≈ 38 ps accuracy. The photon arrival times were subject to systematic delays and nonlinearities, which were corrected by a Monte-Carlo algorithm. The SPAD camera was then applied to FLIM where histogramming the resulting photon arrival times in each pixel resulted in decays compatible with common data processing pipelines for fluorescence lifetime analysis. The capabilities of the TCSPC camera-based FLIM microscope were demonstrated by imaging living unicellular photosynthetic algae and artificial lipid vesicles. Epi-fluorescence illumination enabled rapid fluorescence lifetime imaging of living cells and selective-plane illumination enabled 3-dimensional FLIM of stationary samples.

Multiplexed near infrared fluorescence lifetime imaging in turbid media.

Significance: Fluorescence lifetime imaging (FLI) plays a pivotal role in enhancing our understanding of biological systems, providing a valuable tool for non-invasive exploration of biomolecular and cellular dynamics, both in vitro and in vivo. Its ability to selectively target and multiplex various entities, alongside heightened sensitivity and specificity, offers rapid and cost-effective insights. Aim: Our aim is to investigate the multiplexing capabilities of near-infrared (NIR) FLI within a scattering medium that mimics biological tissues. We strive to develop a comprehensive understanding of FLI's potential for multiplexing diverse targets within a complex, tissue-like environment. Approach: We introduce an innovative Monte Carlo (MC) simulation approach that accurately describes the scattering behavior of fluorescent photons within turbid media. Applying phasor analyses, we enable the multiplexing of distinct targets within a single FLI image. Leveraging the state-of-the-art single-photon avalanche diode (SPAD) time-gated camera, SPAD512S, we conduct experimental wide-field FLI in the NIR regime. Results: Our study demonstrates the successful multiplexing of dual targets within a single FLI image, reaching a depth of 1 cm within tissue-like phantoms. Through our novel MC simulation approach and phasor analyses, we showcase the effectiveness of our methodology in overcoming the challenges posed by scattering media. Conclusions: This research underscores the potential of NIR FLI for multiplexing applications in complex biological environments. By combining advanced simulation techniques with cutting-edge experimental tools, we introduce significant results in the non-invasive exploration of biomolecular dynamics, to advance the field of FLI research.