Terahertz refractive phenotype of living cells

Guangxu Zhang; Yadi Wang; Jiang Qian; Yue Wang; Xueling Li; Junhong Lü

doi:10.3389/fbioe.2022.1105249

Terahertz refractive phenotype of living cells

Front Bioeng Biotechnol. 2023 Jan 10:10:1105249. doi: 10.3389/fbioe.2022.1105249. eCollection 2022.

Authors

Guangxu Zhang^{1

2

3}, Yadi Wang^{2

4}, Jiang Qian^{1

2

3}, Yue Wang^{1

2

3}, Xueling Li^{2

5}, Junhong Lü^{1

2

4

5

6}

Affiliations

¹ Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China.
² Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ School of Pharmacy, Binzhou Medical University, Yantai, China.
⁵ Shanghai University of Medicine and Health Sciences, Shanghai, China.
⁶ Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.

Abstract

Cellular refractive index is a vital phenotypic parameter for understanding the cell functional activities. So far, there remains technical challenges to obtain refractive index of viable cells at the terahertz frequency in which contains rich information closely related to their physiological status. Here we introduce a label-free optical platform for interrogating cellular phenotypes to measure the refractive index of living cells in near-physiological environments by using terahertz spectroscopy with the combination of cellular encapsulation in a confined solution droplet. The key technical feature with cells encapsulated in aqueous droplets allows for keeping cellular viability while eliminating the strong adsorption of solvent water to terahertz signal. The obtained high signal-to-noise ratio enables to differentiate different cell types (e.g., E. coli, stem cell and cancer cell) and their states under stress conditions. The integrating of terahertz spectroscopy to droplet microfluidic further realizes automated and high-through sample preparation and detection, providing a practical toolkit for potential application in cellular health evaluation and phenotypic drug discovery.

Keywords: droplet microfluidic; living cells; refractive index; terahertz spectroscopy; water droplet.

Grants and funding

This work was supported by NSAF Joint Fund of National Natural Science Foundation of China (U2230110), Shandong Provincial Natural Science Foundation (ZR2021QC029), the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (JNL-2022021B), Shanghai International Science & Technology Cooperation Program (22490714400), Yantai Region and College Integration Development Project (2021XDRHXMPT28), and the National Defense Science and Technology Innovation Special Zone.