Solid Plasmonic Substrates for Breast Cancer Detection by Means of SERS Analysis of Blood Plasma.

Gabriela Fabiola Știufiuc,Nicolae Leopold,Romulus Tetean,Rareș Ionuț Știufiuc,Bogdan Culic,Ioana Pavel,Mihail Buse,Radu Mărginean,Constantin Mihai Lucaciu,Gabriela Morar-Bolba,Valentin Toma

doi:10.3390/nano10061212

Abstract

Surface enhanced Raman spectroscopy (SERS) represents a promising technique in providing specific molecular information that could have a major impact in biomedical applications, such as early cancer detection. SERS requires the presence of a suitable plasmonic substrate that can generate enhanced and reproducible diagnostic relevant spectra. In this paper, we propose a new approach for the synthesis of such a substrate, by using concentrated silver nanoparticles purified using the Tangential Flow Filtration method. The capacity of our substrates to generate reproducible and enhanced Raman signals, in a manner that can allow cancer detection by means of Multivariate Analysis (MVA) of Surface Enhanced Raman (SER) spectra, has been tested on blood plasma samples collected from 35 healthy donors and 29 breast cancer patients. All the spectra were analyzed by a combined Principal Component-Linear Discriminant Analysis. Our results facilitated the discrimination between healthy donors and breast cancer patients with 90% sensitivity, 89% specificity and 89% accuracy. This is a direct consequence of substrates’ ability to generate diagnostic relevant spectral information by performing SERS measurements on pristine blood plasma samples. Our results suggest that this type of solid substrate could be employed for the detection of other types of cancer or other diseases by means of MVA-SERS procedure.

Highlights

Nowadays, screening for known cancer biomarkers is considered to be one of the most successful strategies for cancer prevention, diagnosis and/or improvement of survival rate [1,2], as opposed to traditional cancer screening methods which do not consistently provide the desirable results
This challenge exists for all types of cancer, but according to recent reports [7] there is a strong belief that surface enhanced Raman spectroscopy (SERS)-based strategies could bring a major improvement in this area, that is beneficial, for researchers, but most importantly for patients
By removing the chemical by-products produced during the synthesis process, the tangential flow filtration (TFF) allowed a better interaction of the small plasmatic biomolecules with the plasmonic substrate

Summary

Introduction

Nowadays, screening for known cancer biomarkers is considered to be one of the most successful strategies for cancer prevention, diagnosis and/or improvement of survival rate [1,2], as opposed to traditional cancer screening methods which do not consistently provide the desirable results. As breast cancer (BC) is the leading cause of death related to neoplastic disease in women worldwide [6], an alternative screening method with substantial benefits is urgently needed. This challenge exists for all types of cancer, but according to recent reports [7] there is a strong belief that surface enhanced Raman spectroscopy (SERS)-based strategies could bring a major improvement in this area, that is beneficial, for researchers, but most importantly for patients. The three aforementioned criteria are often met by optical analytical approaches, out of which vibrational spectroscopy techniques have the greatest advantage in providing “molecular fingerprints” of complex biological mixtures with no need for extrinsic labeling [10]

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Conclusion