Raman-based identification of circulating tumor cells for cancer diagnosis

Abstract

Circulating tumor cells (CTCs) that can be extracted from body fluids offer new prospects in cancer diagnostics. An overview about our recent achievements is presented to use Raman-based methodologies to distinguish cancer cells from normal blood cells. In a first approach, a microfluidic chip was developed to collect Raman spectra from optically trapped cells. Whereas sensitivities and specificities were promising, the throughput was not compatible with the expected low number of CTCs per million white blood cells. A second strategy immobilized up to 200,000 cells onto a microhole array made of silicon nitride. Rapid microscopic screening can be applied to pre-select a subset of cells from which Raman spectra are collected for specific CTC identification. As this approach is compatible with living cells and Raman spectroscopy with 785 nm excitation is non-destructive, a robotic arm can select positively identified CTCs for in-depth biochemical assessment. Finally, an in vivo approach directly collects CTCs from the blood stream. This way reduces the cell number to a manageable size that is subjected to Raman spectroscopy for cell typing and enumeration. An integrated acquisition mode was introduced to further increase the throughput and robustness of single cell classification.