Colorimetric histology using plasmonically active microscope slides

Eugeniu Balaur, Sandra O’ Toole, Alex J. Spurling, G. Bruce Mann, Belinda Yeo, Kate Harvey, Catherine Sadatnajafi, Eric Hanssen, Jacqueline Orian, Keith A. Nugent, Belinda S. Parker () and Brian Abbey ()
Additional contact information
Eugeniu Balaur: La Trobe University
Sandra O’ Toole: Royal Prince Alfred Hospital
Alex J. Spurling: Peter MacCallum Cancer Centre
G. Bruce Mann: The Royal Melbourne Hospital, The University of Melbourne
Belinda Yeo: Olivia Newton‐John Cancer Research Institute
Kate Harvey: Garvan Institute of Medical Research
Catherine Sadatnajafi: La Trobe University
Eric Hanssen: Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
Jacqueline Orian: La Trobe University
Keith A. Nugent: La Trobe University
Belinda S. Parker: Peter MacCallum Cancer Centre
Brian Abbey: La Trobe University

Nature, 2021, vol. 598, issue 7879, 65-71

Abstract: Abstract The human eye can distinguish as many as 10,000 different colours but is far less sensitive to variations in intensity1, 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 microscope2. It is therefore 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 slides translate subtle changes in the dielectric constant into striking colour contrast when samples are placed upon them. We demonstrate the biomedical potential of this technique, 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 diagnostic tissue 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.

Date: 2021
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DOI: 10.1038/s41586-021-03835-2

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