A class of large cell-like extracellular vesicles
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Rapid brain tumor classification from sparse epigenomic data
Although the intraoperative molecular diagnosis of the approximately 100 known brain tumor entities described to date has been a goal of neuropathology for the past decade, achieving this within a clinically relevant timeframe of under 1 h after biopsy collection remains elusive. Advances in third-generation sequencing have brought this goal closer, but established machine learning techniques rely on computationally intensive methods, making them impractical for live diagnostic workflows in clinical applications. Here we present MethyLYZR, a naive Bayesian framework enabling fully tractable, live classification of cancer epigenomes. For evaluation, we used nanopore sequencing to classify over 200 brain tumor samples, including 10 sequenced in a clinical setting next to the operating room, achieving highly accurate results within 15 min of sequencing. MethyLYZR can be run in parallel with an ongoing nanopore experiment with negligible computational overhead. Therefore, the only limiting factors for even faster time to results are DNA extraction time and the nanopore sequencer’s maximum parallel throughput. Although more evidence from prospective studies is needed, our study suggests the potential applicability of MethyLYZR for live molecular classification of nervous system malignancies using nanopore sequencing not only for the neurosurgical intraoperative use case but also for other oncologic indications and the classification of tumors from cell-free DNA in liquid biopsies.
Coupling of cell shape, matrix and tissue dynamics ensures embryonic patterning robustness
Tissue patterning coordinates morphogenesis, cell dynamics and fate specification. Understanding how precision in patterning is robustly achieved despite inherent developmental variability during mammalian embryogenesis remains a challenge. Here, based on cell dynamics quantification and simulation, we show how salt-and-pepper epiblast and primitive endoderm (PrE) cells pattern the inner cell mass of mouse blastocysts. Coupling cell fate and dynamics, PrE cells form apical polarity-dependent actin protrusions required for RAC1-dependent migration towards the surface of the fluid cavity, where PrE cells are trapped due to decreased tension. Concomitantly, PrE cells deposit an extracellular matrix gradient, presumably breaking the tissue-level symmetry and collectively guiding their own migration. Tissue size perturbations of mouse embryos and their comparison with monkey and human blastocysts further demonstrate that the fixed proportion of PrE/epiblast cells is optimal with respect to embryo size and tissue geometry and, despite variability, ensures patterning robustness during early mammalian development.
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.
Universal relations and bounds for fluctuations in quasistatic small heat engines
The efficiency of any heat engine, defined as the ratio of average work output to heat input, is bounded by Carnot’s celebrated result. However, this measure is insufficient to characterize the properties of miniaturized heat engines carrying non-negligible fluctuations, and a study of higher-order statistics of their energy exchanges is required. Here, we generalize Carnot’s result for reversible cycles to arbitrary order moment of the work and heat fluctuations. Our results show that, in the quasistatic limit, higher-order statistics of a small engine’s energetics depend solely on the ratio between the temperatures of the thermal baths. We further prove that our result for the second moment gives universal bounds for the ratio between the variances of work and heat for quasistatic cycles. We test this theory with our previous experimental results of a Brownian Carnot engine and observe the consistency between them, even beyond the quasistatic regime. Our results can be exploited in the design of thermal nanomachines to reduce their fluctuations of work output without marginalizing its average value and efficiency.
Collective quantum enhancement in critical quantum sensing
Critical systems represent a valuable resource in quantum sensing and metrology. Critical quantum sensing (CQS) protocols can be realized using finite-component phase transitions, where criticality arises from the rescaling of system parameters rather than the thermodynamic limit. Here, we show that a collective quantum advantage can be achieved in a multipartite CQS protocol using a chain of parametrically coupled critical resonators in the weak-nonlinearity limit. We derive analytical solutions for the low-energy spectrum of this unconventional quantum many-body system, which is composed of locally critical elements. We then assess the scaling of the quantum Fisher information with respect to fundamental resources. We demonstrate that the coupled chain outperforms an equivalent ensemble of independent critical sensors, achieving quadratic scaling in the number of resonators. Finally, we show that even with finite Kerr nonlinearity or Markovian dissipation, the critical chain retains its advantage, making it relevant for implementing quantum sensors with current microwave superconducting technologies.
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