title: Detecting Low-Abundance Molecules at Single-Cell Level by Repeated Ion Accumulation in Ion Trap Mass Spectrometer.
abstract: Low-abundance metabolites or proteins in single-cell samples are usually undetectable by mass spectrometry (MS) due to the limited amount of substances in single cells. This limitation inspired us to further enhance the sensitivity of commercial mass spectrometers. Herein, we developed a technique named repeated ion accumulation by ion trap MS, which is capable of enhancing the sensitivity by selectively and repeatedly accumulating ions in a linear ion trap for up to 25 cycles. The increase in MS sensitivity was positively correlated with the number of repeated cycles. When ions were repeatedly accumulated for 25 cycles, the sensitivity of adenosine triphosphate detection was increased by 22-fold within 1.8 s. Our technique could stably detect low-abundance ions, especially MSnions, at the single-cell level, such as 5-methylcytosine hydrolyzed from sample equivalent to ∼0.2 MCF7 cell. The strategy presented in this study offers the possibility to aid single-cell analysis by enhancing MS detection sensitivity.
authors.affiliation: Beijing Key Laboratory for Microanalytical Methods, Instrumentation, Department of Chemistry, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Si
authors.affiliation: Beijing Key Laboratory for Microanalytical Methods, Instrumentation, Department of Chemistry, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Xingchuang
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Beijing Key Laboratory for Microanalytical Methods, Instrumentation, Department of Chemistry, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Sichun
authors.identifier: 0000-0001-8927-2376
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory for Microanalytical Methods, Instrumentation, Department of Chemistry, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Fang
authors.affiliation: Beijing Key Laboratory for Microanalytical Methods, Instrumentation, Department of Chemistry, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis* / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000032:analysis* / Q000737:chemistry; D000809:Angiotensins / Q000032:analysis / Q000737:chemistry; D002110:Caffeine / Q000032:analysis / Q000737:chemistry; D006801:Humans; D000068877:Imatinib Mesylate / Q000032:analysis / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D061986:MCF-7 Cells; D059010:Single-Cell Analysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000809:Angiotensins; D007477:Ions; D002110:Caffeine; D044503:5-Methylcytosine; D000068877:Imatinib Mesylate; D000255:Adenosine Triphosphate