Advances in optical technologies for rare cell detection and characterization.

Scanning cytometry enables detection of circulating tumor cells without enrichment, minimizing potential loss of sensitivity due to variable expression of enrichment targets; however, some approaches lack specificity without imaging to identify false positives. High fidelity imaging enables identification of CTCs using morphological considerations and semi-quantitative measurement of biomarker expression for predicting targeted therapy but often lacks speed needed for the large number of mononuclear blood cells. A hybrid approach of first scanning a sample at high speed and high numerical aperture to locate CTCs followed by high resolution imaging of a small number of objects reduces the time needed for high resolution imaging without loss of detection sensitivity.