A multi-mode imager

Conventionally, the acquisition of bright-field images and fluorescence images using the same device has required an imager equipped with a mechanical movement, able to mechanically interchange filters in-between a sample stage and an imaging element, dependent on whether a bright-field or a fluorescence exposure is being made. The present application discusses a multi-mode imager (30) comprising a bright-field light source (32) and a first excitation light source (34) for exciting fluorescent dyes in a biopsy sample (31). An optical filter arrangement (36, 36a, 36b, 36c) is provided enabling the multi-mode scanning of the biopsy without the need to use a mechanism for interchanging filters

Sequencing of human genomes extracted from single cancer cells isolated in a valveless microfluidic device

Sequencing the genomes of individual cells enables the direct determination of genetic heterogeneity amongst cells within a population. We have developed an injection-moulded valveless microfluidic device in which single cells from colorectal cancer derived cell lines (LS174T, LS180 and RKO) and fresh colorectal tumors have been individually trapped, their genomes extracted and prepared for sequencing using multiple displacement amplification (MDA). Ninety nine percent of the DNA sequences obtained mapped to a reference human genome, indicating that there was effectively no contamination of these samples from non-human sources. In addition, most of the reads are correctly paired, with a low percentage of singletons (0.17 ± 0.06%) and we obtain genome coverages approaching 90%. To achieve this high quality, our device design and process shows that amplification can be conducted in microliter volumes as long as the lysis is in sub-nanoliter volumes. Our data thus demonstrates that high quality whole genome sequencing of single cells can be achieved using a relatively simple, inexpensive and scalable device. Detection of genetic heterogeneity at the single cell level, as we have demonstrated for freshly obtained single cancer cells, could soon become available as a clinical tool to precisely match treatment with the properties of a patient's own tumor