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Label-free detection of biomolecules using inductively coupled plasma mass spectrometry (ICP-MS)

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Abstract

Bioassays using inductively coupled plasma mass spectrometry (ICP-MS) have gained increasing attention because of the high sensitivity of ICP-MS and the various strategies of labeling biomolecules with detectable metal tags. The classic strategy to tag the target biomolecules is through direct antibody-antigen interaction and DNA hybridization, and requires the separation of the bound from the unbound tags. Label-free ICP-MS techniques for biomolecular assays do not require direct labeling: they generate detectable metal ions indirectly from specific biomolecular reactions, such as enzymatic cleavage. Here, we highlight the development of three main strategies of label-free ICP-MS assays for biomolecules: (1) enzymatic cleavage of metal-labeled substrates, (2) release of immobilized metal ions from the DNA backbone, and (3) nucleic acid amplification-assisted aggregation and release of metal tags to achieve amplified detection. We briefly describe the fundamental basis of these label-free ICP-MS assays and discuss the benefits and drawbacks of various designs. Future research is needed to reduce non-specific adsorption and minimize background and interference. Analytical innovations are also required to confront challenges faced by in vivo applications.

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Funding

This work was partially supported by the National Key Research and Development Program of China (2022YFF0710200), the National Natural Science Foundation of China (22074127, 22193053), the Science and Technology Projects of Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) (HRTP-[2022]-13), and the Natural Sciences and Engineering Research Council of Canada (RGPIN-2018–06913).

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  1. Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada

    Jianyu Hu & X. Chris Le

  2. Department of Chemistry and the MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China

    Xiaowen Yan

  3. Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen, 361005, China

    Xiaowen Yan

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  1. Jianyu Hu
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Published in the topical collection Elemental Mass Spectrometry for Bioanalysis with guest editors Jörg Bettmer, Mario Corte-Rodríguez, and Márcia Foster Mesko.

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Hu, J., Yan, X. & Chris Le, X. Label-free detection of biomolecules using inductively coupled plasma mass spectrometry (ICP-MS). Anal Bioanal Chem 416, 2625–2640 (2024). https://doi.org/10.1007/s00216-023-05106-7

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