Affiliation:
1. Single‐Cell Center CAS Key Laboratory of Biofuels Shandong Key Laboratory of Energy Genetics Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao 266101 China
2. Shandong Energy Institute Qingdao 266101 China
3. Qingdao New Energy Shandong Laboratory Qingdao 266101 China
4. College of Life Science University of Chinese Academy of Sciences Beijing 100049 China
5. College of Information Science & Engineering Ocean University of China Qingdao 266100 China
6. Qingdao Single‐Cell Biotech. Co., Ltd Qingdao 266100 China
Abstract
AbstractA full‐spectrum spontaneous single‐cell Raman spectrum (fs‐SCRS) captures the metabolic phenome for a given cellular state of the cell in a label‐free, landscape‐like manner. Herein a positive dielectrophoresis induced deterministic lateral displacement‐based Raman flow cytometry (pDEP‐DLD‐RFC) is established. This robust flow cytometry platform utilizes a periodical positive dielectrophoresis induced deterministic lateral displacement (pDEP‐DLD) force that is exerted to focus and trap fast‐moving single cells in a wide channel, which enables efficient fs‐SCRS acquisition and extended stable running time. It automatically produces deeply sampled, heterogeneity‐resolved, and highly reproducible ramanomes for isogenic cell populations of yeast, microalgae, bacteria, and human cancers, which support biosynthetic process dissection, antimicrobial susceptibility profiling, and cell‐type classification. Moreover, when coupled with intra‐ramanome correlation analysis, it reveals state‐ and cell‐type‐specific metabolic heterogeneity and metabolite‐conversion networks. The throughput of ≈30–2700 events min−1 for profiling both nonresonance and resonance marker bands in a fs‐SCRS, plus the >5 h stable running time, represent the highest performance among reported spontaneous Raman flow cytometry (RFC) systems. Therefore, pDEP‐DLD‐RFC is a valuable new tool for label‐free, noninvasive, and high‐throughput profiling of single‐cell metabolic phenomes.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Natural Science Foundation of Shandong Province
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
6 articles.
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