The marriage of coherent Raman scattering imaging and advanced computational tools.

Coherent Raman scattering microscopy can provide high-contrast tissue and single-cell images based on the inherent molecular vibrations of the sample. However, conventional techniques face a three-way trade-off between Raman spectral bandwidth, imaging speed, and image fidelity. Although currently challenging to address via optical design, this trade-off can be overcome via emerging computational tools such as compressive sensing and machine learning.

Long-term effects of Pfizer-BioNTech COVID-19 vaccinations on platelets.

There is a global concern about the safety of COVID-19 vaccines associated with platelet function. However, their long-term effects on overall platelet activity remain poorly understood. Here we address this problem by image-based single-cell profiling and temporal monitoring of circulating platelet aggregates in the blood of healthy human subjects, before and after they received multiple Pfizer-BioNTech (BNT162b2) vaccine doses over a time span of nearly 1 year. Results show no significant or persisting platelet aggregation trends following the vaccine doses, indicating that any effects of vaccinations on platelet turnover, platelet activation, platelet aggregation, and platelet-leukocyte interaction was insignificant.

Massive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19.

A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis of the big image data shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, respiratory condition, and vascular endothelial dysfunction level of COVID-19 patients.

Sagnac-enhanced impulsive stimulated Raman scattering for highly sensitive low-frequency Raman spectroscopy.

The "fingerprint" (500-1800 cm-1) and "high-frequency" (2400-4000 cm-1) regions in Raman spectroscopy are commonly used for label-free chemical analysis, while the "low-frequency" region (<200 cm-1) is often overlooked, despite containing rich information. This is largely due to the challenge of measuring weak Raman signals that are obscured by strong Rayleigh scattering. Here we propose and experimentally demonstrate Sagnac-enhanced impulsive stimulated Raman scattering (SE-ISRS), a filter-free method for time-domain Raman spectroscopy that overcomes the challenge and provides low-frequency Raman spectra at all probe frequencies. Using SE-ISRS for simultaneous low-frequency and fingerprint region measurements, we demonstrate a >5× enhancement of the signal-to-noise ratio compared to conventional ISRS spectroscopy.