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Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues

BACKGROUND: Technologies for quick and label-free diagnosis of malignancies from breast tissues have the potential to be a significant adjunct to routine diagnostics. The biophysical phenotypes of breast tissues, such as its electrical, thermal, and mechanical properties (ETM), have the potential to...

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Autores principales: G. K., Anil Vishnu, Gogoi, Gayatri, Kachappilly, Midhun C., Rangarajan, Annapoorni, Pandya, Hardik J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644568/
https://www.ncbi.nlm.nih.gov/pubmed/37957665
http://dx.doi.org/10.1186/s13036-023-00388-y
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author G. K., Anil Vishnu
Gogoi, Gayatri
Kachappilly, Midhun C.
Rangarajan, Annapoorni
Pandya, Hardik J.
author_facet G. K., Anil Vishnu
Gogoi, Gayatri
Kachappilly, Midhun C.
Rangarajan, Annapoorni
Pandya, Hardik J.
author_sort G. K., Anil Vishnu
collection PubMed
description BACKGROUND: Technologies for quick and label-free diagnosis of malignancies from breast tissues have the potential to be a significant adjunct to routine diagnostics. The biophysical phenotypes of breast tissues, such as its electrical, thermal, and mechanical properties (ETM), have the potential to serve as novel markers to differentiate between normal, benign, and malignant tissue. RESULTS: We report a system-of-biochips (SoB) integrated into a semi-automated mechatronic system that can characterize breast biopsy tissues using electro-thermo-mechanical sensing. The SoB, fabricated on silicon using microfabrication techniques, can measure the electrical impedance (Z), thermal conductivity (K), mechanical stiffness (k), and viscoelastic stress relaxation (%R) of the samples. The key sensing elements of the biochips include interdigitated electrodes, resistance temperature detectors, microheaters, and a micromachined diaphragm with piezoresistive bridges. Multi-modal ETM measurements performed on formalin-fixed tumour and adjacent normal breast biopsy samples from N = 14 subjects were able to differentiate between invasive ductal carcinoma (malignant), fibroadenoma (benign), and adjacent normal (healthy) tissues with a root mean square error of 0.2419 using a Gaussian process classifier. Carcinoma tissues were observed to have the highest mean impedance (110018.8 ± 20293.8 Ω) and stiffness (0.076 ± 0.009 kNm(−1)) and the lowest thermal conductivity (0.189 ± 0.019 Wm(−1) K(−1)) amongst the three groups, while the fibroadenoma samples had the highest percentage relaxation in normalized load (47.8 ± 5.12%). CONCLUSIONS: The work presents a novel strategy to characterize the multi-modal biophysical phenotype of breast biopsy tissues to aid in cancer diagnosis from small-sized tumour samples. The methodology envisions to supplement the existing technology gap in the analysis of breast tissue samples in the pathology laboratories to aid the diagnostic workflow. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13036-023-00388-y.
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spelling pubmed-106445682023-11-13 Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues G. K., Anil Vishnu Gogoi, Gayatri Kachappilly, Midhun C. Rangarajan, Annapoorni Pandya, Hardik J. J Biol Eng Research BACKGROUND: Technologies for quick and label-free diagnosis of malignancies from breast tissues have the potential to be a significant adjunct to routine diagnostics. The biophysical phenotypes of breast tissues, such as its electrical, thermal, and mechanical properties (ETM), have the potential to serve as novel markers to differentiate between normal, benign, and malignant tissue. RESULTS: We report a system-of-biochips (SoB) integrated into a semi-automated mechatronic system that can characterize breast biopsy tissues using electro-thermo-mechanical sensing. The SoB, fabricated on silicon using microfabrication techniques, can measure the electrical impedance (Z), thermal conductivity (K), mechanical stiffness (k), and viscoelastic stress relaxation (%R) of the samples. The key sensing elements of the biochips include interdigitated electrodes, resistance temperature detectors, microheaters, and a micromachined diaphragm with piezoresistive bridges. Multi-modal ETM measurements performed on formalin-fixed tumour and adjacent normal breast biopsy samples from N = 14 subjects were able to differentiate between invasive ductal carcinoma (malignant), fibroadenoma (benign), and adjacent normal (healthy) tissues with a root mean square error of 0.2419 using a Gaussian process classifier. Carcinoma tissues were observed to have the highest mean impedance (110018.8 ± 20293.8 Ω) and stiffness (0.076 ± 0.009 kNm(−1)) and the lowest thermal conductivity (0.189 ± 0.019 Wm(−1) K(−1)) amongst the three groups, while the fibroadenoma samples had the highest percentage relaxation in normalized load (47.8 ± 5.12%). CONCLUSIONS: The work presents a novel strategy to characterize the multi-modal biophysical phenotype of breast biopsy tissues to aid in cancer diagnosis from small-sized tumour samples. The methodology envisions to supplement the existing technology gap in the analysis of breast tissue samples in the pathology laboratories to aid the diagnostic workflow. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13036-023-00388-y. BioMed Central 2023-11-13 /pmc/articles/PMC10644568/ /pubmed/37957665 http://dx.doi.org/10.1186/s13036-023-00388-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
G. K., Anil Vishnu
Gogoi, Gayatri
Kachappilly, Midhun C.
Rangarajan, Annapoorni
Pandya, Hardik J.
Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues
title Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues
title_full Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues
title_fullStr Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues
title_full_unstemmed Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues
title_short Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues
title_sort label-free multimodal electro-thermo-mechanical (etm) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644568/
https://www.ncbi.nlm.nih.gov/pubmed/37957665
http://dx.doi.org/10.1186/s13036-023-00388-y
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