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Cited by 14Mass Spectrometry Techniques and ApplicationsMetabolomics and Mass Spectrometry StudiesAdvanced Proteomics Techniques and Applications

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Twenty-Five Years of High-Throughput Screening of Biological Samples with Mass Spectrometry: Current Platforms and Emerging Methods

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Smith, Rachel, Brookes, Catherine, Morris, Michael, Barran, Perdita·2025·Analytical Chemistry
DOI 10.1021/acs.analchem.5c02331

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Abstract

Robust high-throughput screening (HTS) approaches for discovering new chemical entities are desirable for research and translation. Applications for which high-throughput (HT) methods are particularly required also include the screening of potential therapeutics for drug discovery and development, profiling of biofluids for disease biomarker discovery, and clinical diagnostics. Complementing the demand for HTS from specific application areas are substantial technological advancements in the fields of automation, microfluidics, and ambient ionization that facilitate highly automated and sophisticated analytical workflows. The time period spanning 2000-2025 has witnessed a significant expansion in the mass spectrometry (MS) capabilities and technology. This has included novel ionization approaches that can achieve rapid analysis with minimal solvent and sample consumption, while retaining high sensitivity and specificity in the absence of chromatography. Despite the demand for HTS methods and the well-documented analytical capabilities of MS, optical methods dominate as the HTS detection methods of choice. This perspective provides an overview of the evolution of HTS-MS over the last 25 years, focusing on emerging approaches that also provide efficient and sustainable workflows that compete with optical detection. Additionally, this perspective will highlight challenges in the field that may hinder widespread adoption and consider lessons from the COVID-19 pandemic, as well as the impact of sustainability on the future of HTS-MS and analytical chemistry.

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Metadata

Authors
Smith, R., Brookes, C., Morris, M., & Barran, P.
Affiliations
  • University of Manchester (GB)
  • Bristol-Myers Squibb (United Kingdom) (GB)
Corresponding author
Barran, Perdita
ORCID
Venue
Analytical Chemistry
Publisher
American Chemical Society (ACS)
Published
2025-10-09
Volume
97
Issue
41
Pages
22457-22474
ISSN
  • 0003-2700 (ISSN-L)
  • 1520-6882
DOI
10.1021/acs.analchem.5c02331
OpenAlex
W4414992610
Cited by
14
References
5
Citations by year
2026: 14
FWCI
1.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Analytical Chemistry (publishedVersion)
  • ChemRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, cc-by-nc-nd)
Funders
Engineering and Physical Sciences Research Council
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
high-throughput screening, mass spectrometry, ambient ionization, microfluidics, drug discovery, biomarker discovery, clinical diagnostics, green analytical chemistry
MeSH terms
COVID-19, SARS-CoV-2, Humans, Mass Spectrometry, Tandem Mass Spectrometry, Drug Discovery, High-Throughput Screening Assays

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