PMID- 37426761 OWN - NLM STAT- MEDLINE DCOM- 20230711 LR - 20230718 IS - 2667-2375 (Electronic) IS - 2667-2375 (Linking) VI - 3 IP - 6 DP - 2023 Jun 26 TI - Unlocking the potential of microfluidics in mass spectrometry-based immunopeptidomics for tumor antigen discovery. PG - 100511 LID - 10.1016/j.crmeth.2023.100511 [doi] LID - 100511 AB - 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. CI - (c) 2023 The Author(s). FAU - Stutzmann, Charlotte AU - Stutzmann C AD - CHU Sainte Justine Research Center, Montreal, QC, Canada. FAU - Peng, Jiaxi AU - Peng J AD - Department of Chemistry, University of Toronto, Toronto, ON, Canada. FAU - Wu, Zhaoguan AU - Wu Z AD - CHU Sainte Justine Research Center, Montreal, QC, Canada. FAU - Savoie, Christopher AU - Savoie C AD - CHU Sainte Justine Research Center, Montreal, QC, Canada. FAU - Sirois, Isabelle AU - Sirois I AD - CHU Sainte Justine Research Center, Montreal, QC, Canada. FAU - Thibault, Pierre AU - Thibault P AD - Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada. AD - Department of Chemistry, University of Montreal, Montreal, QC, Canada. FAU - Wheeler, Aaron R AU - Wheeler AR AD - Department of Chemistry, University of Toronto, Toronto, ON, Canada. AD - Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada. AD - Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada. FAU - Caron, Etienne AU - Caron E AD - CHU Sainte Justine Research Center, Montreal, QC, Canada. AD - Department of Pathology and Cellular Biology, University of Montreal, Montreal, QC, Canada. LA - eng GR - 174924/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230626 PL - United States TA - Cell Rep Methods JT - Cell reports methods JID - 9918227360606676 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (HLA Antigens) RN - 0 (Antigens, Neoplasm) SB - IM MH - Humans MH - *Microfluidics MH - Mass Spectrometry/methods MH - Histocompatibility Antigens Class I MH - HLA Antigens MH - Antigens, Neoplasm MH - *Neoplasms PMC - PMC10326451 OTO - NOTNLM OT - HLA OT - MHC OT - immunopeptidomics OT - mass spectrometry OT - microfluidics OT - peptide OT - single-cell proteomics COIS- The authors declare no competing interests. EDAT- 2023/07/10 06:42 MHDA- 2023/07/11 06:42 PMCR- 2023/06/26 CRDT- 2023/07/10 05:15 PHST- 2023/07/11 06:42 [medline] PHST- 2023/07/10 06:42 [pubmed] PHST- 2023/07/10 05:15 [entrez] PHST- 2023/06/26 00:00 [pmc-release] AID - S2667-2375(23)00140-6 [pii] AID - 100511 [pii] AID - 10.1016/j.crmeth.2023.100511 [doi] PST - epublish SO - Cell Rep Methods. 2023 Jun 26;3(6):100511. doi: 10.1016/j.crmeth.2023.100511. eCollection 2023 Jun 26.