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J Biophotonics. 2019 Apr;12(4):e201800291. doi: 10.1002/jbio.201800291. Epub 2018 Dec 13.

Integration of diffraction phase microscopy and Raman imaging for label-free morpho-molecular assessment of live cells.

Author information

1
Connecticut Children's Innovation Center, University of Connecticut School of Medicine, Farmington, Connecticut.
2
Department of Chemistry, Laser Biomedical Research Center, George R. Harrison Spectroscopy Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts.
3
Laser Metrology and Biomedicine Lab, Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
4
Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
5
The Johns Hopkins University School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
6
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland.
7
Department of Otolaryngology, Stanford University, Palo Alto, California.
8
Department of Surgery, Connecticut Children's Medical Center, Harford, Connecticut.

Abstract

Label-free quantitative imaging is highly desirable for studying live cells by extracting pathophysiological information without perturbing cell functions. Here, we demonstrate a novel label-free multimodal optical imaging system with the capability of providing comprehensive morphological and molecular attributes of live cells. Our morpho-molecular microscopy (3M) system draws on the combined strength of quantitative phase microscopy (QPM) and Raman microscopy to probe the morphological features and molecular fingerprinting characteristics of each cell under observation. While the commonr-path geometry of our QPM system allows for highly sensitive phase measurement, the Raman microscopy is equipped with dual excitation wavelengths and utilizes the same detection and dispersion system, making it a distinctive multi-wavelength system with a small footprint. We demonstrate the applicability of the 3M system by investigating nucleated and nonnucleated cells. This integrated label-free platform has a promising potential in preclinical research, as well as in clinical diagnosis in the near future.

KEYWORDS:

Raman spectroscopy; cellular imaging; label-free imaging; quantitative phase microscopy

PMID:
30421505
PMCID:
PMC6447451
[Available on 2019-10-01]
DOI:
10.1002/jbio.201800291

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