Label-free and quantitative dry mass monitoring for single cells during in situ culture

Ya Su, Rongxin Fu, Wenli Du, Han Yang, Li Ma, Xianbo Luo, Ruliang Wang, Xue Lin, Xiangyu Jin, Xiaohui Shan, Wenqi Lv, Guoliang Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Quantitative measurement of single cells can provide in-depth information about cell mor-phology and metabolism. However, current live-cell imaging techniques have a lack of quantitative detection ability. Herein, we proposed a label-free and quantitative multichannel wide-field interferometric imaging (MWII) technique with femtogram dry mass sensitivity to monitor single-cell metabolism long-term in situ culture. We demonstrated that MWII could reveal the intrinsic status of cells despite fluctuating culture conditions with 3.48 nm optical path difference sensitivity, 0.97 fg dry mass sensitivity and 2.4% average maximum relative change (maximum change/average) in dry mass. Utilizing the MWII system, different intrinsic cell growth characteristics of dry mass between HeLa cells and Human Cervical Epithelial Cells (HCerEpiC) were studied. The dry mass of HeLa cells consistently increased before the M phase, whereas that of HCerEpiC increased and then decreased. The maximum growth rate of HeLa cells was 11.7% higher than that of HCerEpiC. Fur-thermore, HeLa cells were treated with Gemcitabine to reveal the relationship between single-cell heterogeneity and chemotherapeutic efficacy. The results show that cells with higher nuclear dry mass and nuclear density standard deviations were more likely to survive the chemotherapy. In conclusion, MWII was presented as a technique for single-cell dry mass quantitative measurement, which had significant potential applications for cell growth dynamics research, cell subtype analy-sis, cell health characterization, medication guidance and adjuvant drug development.

Original languageEnglish
Article number1635
JournalCells
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 2021
Externally publishedYes

Keywords

  • Dry mass measurement
  • Label-free imaging
  • Long-term cell monitoring
  • Quantitive inter-ferometry

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