Annual review of analytical chemistry (Palo Alto, Calif.)最新文献

Vibrational circular dichroism (VCD) is an established chiroptical technique that probes molecular handedness via differential IR absorption of left- and right-circularly polarized light. Quantum cascade lasers (QCLs) have revitalized VCD spectroscopy by delivering high-power, narrowband mid-IR sources that, combined with polarization-modulation strategies, have dramatically improved VCD sensitivity and speed-enabling imaging that was not previously attainable. We review the instrumental design of QCL-based VCD imaging and demonstrate its application to spatially resolved chiral biosensing. By mapping VCD signals with micrometer resolution, one can detect and differentiate protein secondary structures, monitor enantiomeric purity in pharmaceutical compounds, and visualize pathological tissue features without labels. We discuss practical challenges-including cell-window birefringence, polarization-sensitive detection, and data processing-and propose optimized configurations for robust imaging. Finally, we outline future directions for QCL-VCD systems and their integration with nonlinear chiroptical techniques, highlighting the potential of QCL-VCD imaging to transform chiral analysis in biological and clinical contexts.

Diagnostics are central to pandemic preparedness, guiding surveillance, clinical care, and public health response. The COVID-19 pandemic exposed limitations in diagnostic infrastructure but also accelerated innovation across assay types, created accessible testing mechanisms, and demonstrated the value of public-private partnerships. This review outlines the critical roles diagnostics play across pandemic phases, from early detection to post recovery surveillance. We review the current diagnostic landscape for pandemic priority pathogens and unmet needs and challenges and examine recent advances in analytical technologies, including isothermal amplification, CRISPR-based methods, alternative sample types, and novel platforms, with a focus on their potential for rapid deployment and field use. We also explore the emergence of diagnostic accelerators and biorepositories that support assay validation and global test availability. For analytical chemists, pandemic preparedness presents a call to action: to develop, validate, and translate innovative tools that can adapt to meet urgent diagnostic needs during future health emergencies.

The rapid and continued development of mass spectrometry-based technologies has significantly increased the capability to study and characterize lipids while providing new insight into the complex roles of lipids throughout biology. These capabilities have included the ability to quantify, structurally characterize (including resolving isomers that pose significant challenges to lipidomics), and spatially map lipids within numerous complex organisms, revealing new capabilities in emerging areas such as single-cell analysis. With these rapid developments, several challenges have emerged, such as accurate lipid identification, incorrect and overinterpretation of mass spectrometry data and structural assignments, and the need for improved analytical and bioinformatics tools to understand lipidomics data at the pathway and systems levels. This review critically assesses analytical technologies used for lipidomics studies, along with current challenges and technological developments driving the field forward. By highlighting these challenges, and possible avenues to address them, this review emphasizes the excitement for the future of lipidomics and the need for continued development of analytical tools to enhance our understanding lipid biology.

Gas-phase ion-ion reactions lead to well-defined changes in mass and charge that are readily detected via mass spectrometry. They have unusually large cross sections, which allow for rates on the order of 1-1,000 s-1 and, as a result, enable a variety of analytically useful measurements. Such applications rely on one or more of a variety of reaction mechanisms, such as proton transfer, electron transfer, metal ion transfer, and selective covalent bond formation. Electrodynamic ion traps make excellent reaction vessels for ion-ion reactions due to their ability to trap one or both polarities of ions, thereby allowing reactions to proceed with high reactant to product conversion. Understanding the underlying phenomena of ion-ion reactions, as well as the conditions under which they proceed, is essential to designing future experiments. This tutorial review summarizes the underlying phenomena of gas-phase ion-ion reactions and related practical considerations needed to optimize these reactions in an electrodynamic ion trap.

Advances in protein sequencing and analysis are poised to transform proteomics through an ability to link sequence, structure, and function at scale, thereby accelerating biological discovery and biomedical innovation. However, interrogating proteins is uniquely challenging because they cannot be amplified, are composed of complex chemical structures, and exist across a vast landscape of proteoforms. Techniques such as mass spectrometry typically drive large-scale proteomics studies; however, a new generation of technologies is pushing the boundaries, promising new features such as de novo, single-molecule, and/or higher-throughput sequencing and analysis. While many strategies are still in an early stage, a few modalities, such as fluorosequencing, single-molecule sequencing, digital proteomics mapping, and nanopore-based protein sequencing, have now reached or are thought to be nearing commercial implementation. In this review, we evaluate the mechanisms, current progress, and remaining challenges of these technologies while also highlighting how recent innovations are converging toward a new generation of proteomic technologies.

Metabolic function plays a key role in our understanding of both biological and pathophysiological processes. Metabolism is a complex combination of intrinsic processes and environmental cues across a heterogeneous mix of cell types. To investigate metabolism, stable isotope tracing is a versatile approach to assess metabolism across scales, including in cultured cells, animal models, and humans. From the first tracing studies over a century ago, the development and utility of these studies have gone hand-in-hand with technological advances in detecting these labeled atoms, particularly with mass spectrometry. In this review, we describe the instrumentation used to measure isotopically labeled metabolites and approaches to analyze and interpret stable isotope tracing data, and discuss current challenges and opportunities for discovery with these methods.

Extracellular vesicles (EVs) are membrane-bound vesicles that mediate intercellular communication and have gained significant interest as potential biomarker sources and therapeutic agents. This review summarizes the most recent advances in EV analysis, including an overview of EV biology, current approaches for EV isolation and enrichment, and emerging technologies for EV detection, with a particular focus on single-EV analysis. We also examine the integration of artificial intelligence into EV research. This review provides a broad perspective into the landscape of EV analysis and highlights potential future directions in this rapidly evolving field to improve the analytical rigor and translational potential of EV-based diagnostics and therapeutics.

Mental health disorders, such as depression, represent a growing global challenge. Depression is difficult to diagnose and treat. These difficulties stem from an insufficient understanding of the underlying mechanisms of the disorder. It is incredibly challenging to improve diagnostic and therapeutic approaches without a clear understanding of depression pathology. Neurotransmitters are low in concentration and fluctuate rapidly, making them difficult to investigate. Progress in methods to study the brain has uncovered clues to the pathology of depression and antidepressant mechanisms. In this review, we first describe the three medical hypotheses of depression: the monoamine, plasticity, and inflammation theories. We highlight key analytical methods that have been employed in depression studies. Lastly, we show how these investigations have advanced our knowledge of depression mechanisms and treatment strategies. Thus, via this review, we present the status quo of how chemical measurements are guiding our understanding of the chemical underpinnings of depression and pointing the community toward new antidepressant treatment targets.

Autonomous systems integrating machine learning (ML) and laboratory automation are transforming synthetic chemistry by enabling closed-loop experimentation and discovery. In this review, we examine the state-of-the-art in autonomous systems for organic synthesis, with a focus on the components, configurations, and ML algorithms that enable automated reaction planning, execution, and optimization. We survey representative systems that span applications from reaction discovery to molecular optimization, comparing flow and batch configurations and identifying trends in system design. Emphasis is placed on the critical bottlenecks of purification and analytical measurement, particularly structural elucidation of unexpected products-areas that currently constrain autonomous platforms. We describe recent advances in chromatographic method development, structural elucidation from mass spectrometry and nuclear magnetic resonance, and novel ML-based approaches to quantify complex mixtures without calibration. By focusing on enabling technologies in chemical analysis, we identify opportunities for ML and automation to expand beyond domain-specific platforms and accelerate the pace of synthetic discovery.

Single-cell proteomics (scP) is a crucial complement to transcriptomics, offering deeper insight into cellular heterogeneity, disease mechanisms, and therapeutic vulnerabilities in samples such as 2D cell culture, 3D models, and patient tissue. While transcriptomics enables high-throughput gene expression characterization, RNA levels frequently do not correlate with protein levels even in the same cell. Furthermore, protein isoforms, posttranslational modifications, and complexes are missed by transcriptomic analyses. This review explores modern scP technologies, including flow and mass cytometry, single-cell mass spectrometry, immunohistochemistry, cyclic imaging, and imaging mass cytometry applied to both dissociated and spatially preserved samples. We emphasize applying these techniques to organ-on-a-chip, organoids, spheroids, and intact tissues, highlighting advances in spatial resolution and multiplexing. We also discuss the trade-offs between throughput, spatial fidelity, and protein selectivity across platforms. Finally, we identify key measurement gaps, suggesting future directions toward spatially resolved scP clinical translation.