Colorimetric histology using plasmonically active microscope slides

The human eye can distinguish as many as10,000 different colours but is far less sensitive to variations in intensity', meaning that colour is highly desirable when interpreting images. However, most biological samples are essentially transparent, and nearly invisible when viewed using a standard optical microscope(2). It istherefore highly desirable to be able to produce coloured images without needing to add any stains or dyes, which can alter the sample properties. Here we demonstrate that colorimetric histology images can be generated using full-sized plasmonically active microscope slides. These slidestranslate subtle changes in the dielectric constant into striking colour contrast when samples are placed upon them. We demonstrate the biomedical potential of thistechnique, which we term histoplasmonics, by distinguishing neoplastic cells from normal breast epithelium during the earliest stages of tumorigenesis in the mouse MMTV-PyMT mammary tumour model. We then apply this method to human diagnostictissue and validate its utility in distinguishing normal epithelium, usual ductal hyperplasia, and early-stage breast cancer (ductal carcinoma in situ). The colorimetric output of the image pixels is compared to conventional histopathology. The results we report here support the hypothesis that histoplasmonics can be used as a novel alternative or adjunct to general staining. The widespread availability of this technique and its incorporation into standard laboratory workflows may prove transformative for applications extending well beyond tissue diagnostics. This work also highlights opportunities for improvements to digital pathology that have yet to be explored.

Automated summary

This study demonstrates the generation of colorimetric histology images using full-sized plasmonically active microscope slides. These slides translate subtle changes in dielectric constant into striking color contrast when samples are placed on them. The biomedical potential of this technique is shown by distinguishing neoplastic cells from normal breast epithelium in mouse models and in human diagnostic tissue. Comparing the colorimetric output with conventional histopathology shows the potential for histoplasmonics as an alternative or adjunct to staining.