Optical‐mechanical signatures of cancer cells based on fluctuation profiles measured by interferometry

Abstract

We propose to establish a cancer biomarker based on the unique optical-mechanical signatures of cancer cells measured in a noncontact, label-free manner by optical interferometry. Using wide-field interferometric phase microscopy (IPM), implemented by a portable, off-axis, common-path and low-coherence interferometric module, we quantitatively measured the time-dependent, nanometer-scale optical thickness fluctuation maps of live cells in vitro. We found that cancer cells fluctuate significantly more than healthy cells, and that metastatic cancer cells fluctuate significantly more than primary cancer cells. Atomic force microscopy (AFM) measurements validated the results. Our study shows the potential of IPM as a simple clinical tool for aiding in diagnosis and monitoring of cancer.

Noncontact optical sensor for bone fracture diagnostics

“…The broken bone has a different response than a non-broken bone due to the following reasons: (1) the inner part of the bone is softer than the outer part of the bone. As it is shown in Refs [24][25][26][27], softer materials have the ability to better transmit vibrations. (2) When the bone is cracked or broken, a new edge is created at the broken bone spot.…”

Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

“…Central to these techniques are theories that link biological structure to experimentally controlled electromagnetic wave interactions. These strategies include light scattering spectroscopy, 4,5 angle-resolved low coherence interferometry, 6,7 Raman spectroscopy, 8,9 diffuse optical spectroscopy, 10 partial wave spectroscopic (PWS) microscopy, 11,12 low-coherence enhanced backscattering, 12,13 quantitative phase microscopy, [14][15][16] and noninterferometric quantitative phase microscopy (NIQPM). 17 Cellular level observations of cancerous cells enabled by these technologies include an increase in subcellular constituent size, 4,5,7,13,14,17,18 changes in density, 7,14,17,18 alterations of the organization of this density to a more inhomogeneous state, 12,14,18 alterations in cellular metabolism, 10 and changes in biochemical composition 8 including higher concentrations of nuclear acids.…”

“…22,23 Using a novel optical approach combining quantitative phase microscopy and PWS microscopy, we quantified nanoscale and microscale cellular density properties including nanoscale nuclear disorder strength, and at the micron scale: nuclear and cytoplasmic area, dry mass content, mean dry mass density, and shape metrics of the dry mass density histogram including the median, mode, min, max, skew, and kurtosis. Similar multiparameter approaches have been previously utilized to characterize phase distortions in tissue sections, 14 red blood cells, 24 phase fluctuations observed in waves transmitted through cells, 16 and in the context of monitoring the cell cycle through phase-derived parameters. 25 Our approach is the first to investigate the interdependence of these parameters.…”

Characterization of dormant and active human cancer cells by quantitative phase imaging

“…More broadly viewed, the quantitative, label-free, and ease-of-use advantages of this method may have important clinical applications (37)(38)(39)(40)(41)(42), including characterizing the heterogeneous cell populations in human osteosarcoma tumors. Combined with clinical biomarker staining, one can envision that the percentages of angiogenic and non-angiogenic cells could be quantified using QPI, providing potentially useful information to pathologists as they evaluate the neovascularization of tumors being studied.…”