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High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads

In serology, each sample is typically tested individually, one antigen at a time. This is costly and time consuming. Serology techniques should ideally allow recurrent measurements in parallel in small sample volumes and be inexpensive and fast. Here we show that mass cytometry can be used to scale up multiplexed serology testing by leveraging polystyrene beads uniformly loaded with combinations of stable isotopes. We generated 18,480 unique isotopically barcoded beads to simultaneously detect, in a single tube with 924 serum samples, the levels of immunoglobulins G and M against 19 proteins from SARS-CoV-2 (a total of 36,960 tests in 400 nl of sample volume and 30 μl of reaction volume). As a rapid, high-throughput and cost-effective technique, serology by mass cytometry may contribute to the effective management of public health emergencies originating from infectious diseases.

Frequency shift caused by nonuniform field and boundary relaxation in magnetic resonance and comagnetometers

In magnetic resonance experiments, it is widely recognized that a nonuniform magnetic field can lead to an increase in the resonance line width, as well as a reduction in sensitivity and spectral resolution. However, a nonuniform magnetic field can also cause shifts in resonance frequency, which has received far less attention. In this work, we investigate the frequency shift caused by boundary relaxation and nonuniform magnetic field with arbitrary spatial distribution. We find that this frequency shift is spin-species dependent, implying a systematic error in NMR gyroscopes and comagnetometers. The first order correction to this systematic error is proportional to the difference of boundary relaxation rate, and dominates for small cells. In contrast, the third and higher order corrections arise from the difference of gyromagnetic ratios of spin species, and dominates for large cells. This insight helps understanding the unexplained isotope shifts in recent NMR gyroscopes and new physics searching experiments that utilize comagnetometers. Finally, we propose a tool for wall interaction research based on the frequency shift’s dependency on boundary relaxation.

Elucidating reactive sugar-intermediates by mass spectrometry

The stereoselective introduction of glycosidic bonds is one of the greatest challenges in carbohydrate chemistry. A key aspect of controlling glycan synthesis is the glycosylation reaction in which the glycosidic linkages are formed. The outcome is governed by a reactive sugar intermediate – the glycosyl cation. Glycosyl cations are highly unstable and short-lived, making them difficult to study using established analytical tools. However, mass-spectrometry-based techniques are perfectly suited to unravel the structure of glycosyl cations in the gas phase. The main approach involves isolating the reactive intermediate, free from external influences such as solvents and promoters. Isolation of the cations allows examining their structure by integrating orthogonal spectrometric and spectroscopic technologies. In this perspective, recent achievements in gas-phase research on glycosyl cations are highlighted. It provides an overview of the spectroscopic techniques used to probe the glycosyl cations and methods for interpreting their spectra. The connections between gas-phase data and mechanisms in solution synthesis are explored, given that glycosylation reactions are typically performed in solution.

Visible-to-THz near-field nanoscopy

Optical microscopy has a key role in research, development and quality control across a wide range of scientific, technological and medical fields. However, diffraction limits the spatial resolution of conventional optical instruments to about half the illumination wavelength. A technique that surpasses the diffraction limit in the wide spectral range between visible and terahertz frequencies is scattering-type scanning near-field optical microscopy (s-SNOM). The basis of s-SNOM is an atomic force microscope in which the tip is illuminated with light from the visible to the terahertz spectral range. By recording the elastically tip-scattered light while scanning the sample below the tip, s-SNOM yields near-field optical images with a remarkable resolution of 10 nm, simultaneously with the standard atomic force microscopic topography image. This resolution is independent of the illumination wavelength, rendering s-SNOM a versatile nanoimaging and nanospectroscopy technique for fundamental and applied studies of materials, structures and phenomena. This Review presents an overview of the fundamental principles governing the measurement and interpretation of near-field contrasts and discusses key applications of s-SNOM. We also showcase emerging developments that enable s-SNOM to operate under various environmental conditions, including cryogenic temperatures, electric and magnetic fields, electrical currents, strain and liquid environments. All these recent developments broaden the applicability of s-SNOMs for exploring fundamental solid-state and quantum phenomena, biological matter, catalytic reactions and more.

Optical sorting: past, present and future

Optical sorting combines optical tweezers with diverse techniques, including optical spectrum, artificial intelligence (AI) and immunoassay, to endow unprecedented capabilities in particle sorting. In comparison to other methods such as microfluidics, acoustics and electrophoresis, optical sorting offers appreciable advantages in nanoscale precision, high resolution, non-invasiveness, and is becoming increasingly indispensable in fields of biophysics, chemistry, and materials science. This review aims to offer a comprehensive overview of the history, development, and perspectives of various optical sorting techniques, categorised as passive and active sorting methods. To begin, we elucidate the fundamental physics and attributes of both conventional and exotic optical forces. We then explore sorting capabilities of active optical sorting, which fuses optical tweezers with a diversity of techniques, including Raman spectroscopy and machine learning. Afterwards, we reveal the essential roles played by deterministic light fields, configured with lens systems or metasurfaces, in the passive sorting of particles based on their varying sizes and shapes, sorting resolutions and speeds. We conclude with our vision of the most promising and futuristic directions, including AI-facilitated ultrafast and bio-morphology-selective sorting. It can be envisioned that optical sorting will inevitably become a revolutionary tool in scientific research and practical biomedical applications.

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