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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.
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.
Grover’s algorithm in a four-qubit silicon processor above the fault-tolerant threshold
Spin qubits in silicon are strong contenders for the realization of a practical quantum computer, having demonstrated single- and two-qubit gates with fidelities above the fault-tolerant threshold, and entanglement of three qubits. However, maintaining high-fidelity operations while increasing the qubit count remains challenging and therefore only two-qubit algorithms have been executed. Here we utilize a four-qubit silicon processor with all control fidelities above the fault-tolerant threshold and demonstrate a three-qubit Grover’s search algorithm with a ~95% probability of finding the marked state. Our processor is made of three phosphorus atoms precision-patterned into isotopically pure silicon, which localise one electron. The long coherence times of the qubits enable single-qubit fidelities above 99.9% for all qubits. Moreover, the efficient single-pulse multi-qubit operations enabled by the electron–nuclear hyperfine interaction facilitate controlled-Z gates between all pairs of nuclear spins with fidelities above 99% when using the electron as an ancilla. These control fidelities, combined with high-fidelity non-demolition readout of all nuclear spins, allow the creation of a three-qubit Greenberger–Horne–Zeilinger state with 96.2% fidelity. Looking ahead, coupling neighbouring nuclear spin registers, as the one shown here, via electron–electron exchange may enable larger, fault-tolerant quantum processors.
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