Unlocking the potential of microfluidics in mass spectrometry-based immunopeptidomics for tumor antigen discovery

作者：Charlotte Stutzmann, Jiaxi Peng, Zhaoguan Wu, Christopher J. Savoie, Isabelle Sirois, Pierre Thibault, Aaron R. Wheeler, Étienne Caron · 发表于：Cell Reports Methods · 年份：2023 · DOI：10.1016/j.crmeth.2023.100511 · 被引用次数：30 · 研究领域：Biosensors and Analytical Detection、Advanced biosensing and bioanalysis techniques、Innovative Microfluidic and Catalytic Techniques Innovation

The identification of tumor-specific antigens (TSAs) is critical for developing effective cancer immunotherapies. Mass spectrometry (MS)-based immunopeptidomics has emerged as a powerful tool for identifying TSAs as physical molecules. However, current immunopeptidomics platforms face challenges in measuring low-abundance TSAs in a precise, sensitive, and reproducible manner from small needle-tissue biopsies (<1 mg). Inspired by recent advances in single-cell proteomics, microfluidics technology offers a promising solution to these limitations by providing improved isolation of human leukocyte antigen (HLA)-associated peptides with higher sensitivity. In this context, we highlight the challenges in sample preparation and the rationale for developing microfluidics technology in immunopeptidomics. Additionally, we provide an overview of promising microfluidic methods, including microchip pillar arrays, valved-based systems, droplet microfluidics, and digital microfluidics, and discuss the latest research on their application in MS-based immunopeptidomics and single-cell proteomics.