<p>Filter-Membrane-Based Ultrafiltration Coupled with Surface-Enhanced Raman Spectroscopy for Potential Differentiation of Benign and Malignant Thyroid Tumors from Blood Plasma</p>

Abstract

The objective of this study is to evaluate the performance and feasibility of surface-enhanced Raman spectroscopy coupled with a filter membrane and advanced multivariate data analysis on identifying and differentiating benign and malignant thyroid tumors from blood plasma. Patients and Methods: We proposed a membrane filter SERS technology for the differentiation between benign thyroid tumor and thyroid cancer. That is to say, by using filter membranes with optimal pore size, the blood plasma samples from thyroid tumor patients were pretreated with the macromolecular proteins being filtered out prior to SERS measurement. The SERS spectra of blood plasma ultrafiltrate obtained using filter membranes from 102 patients with thyroid tumors (70 thyroid cancers and 32 benign thyroid tumors) were then analyzed and compared. Two multivariate statistical analyses, principal component analysis-linear discriminate analysis (PCA-LDA) and Lasso-partial least squaresdiscriminant analysis (Lasso-PLS-DA), were performed on the SERS spectral data after background subtraction and normalization, as well as the first derivative processing, to analyze and compare the differential diagnosis of benign thyroid tumors and thyroid cancer. Results: SERS measurements were performed in blood plasma acquired from a total of 102 thyroid tumor patients (benign thyroid tumor N=32; thyroid cancer N=70). By using filter membranes, the macromolecular proteins in blood plasma were effectively filtered out to yield high-quality SERS spectra. 84.3% discrimination accuracy between benign and malignant thyroid tumor was achieved using PCA-LDA method, while Lasso-PLS-DA yields a discrimination accuracy of 90.2%. Conclusion: Our results demonstrate that SERS spectroscopy, coupled with ultrafiltration and multivariate analysis has the potential of providing a non-invasive, rapid, and objective detection and differentiation of benign and malignant thyroid tumors.

Clinical applications of infrared and Raman spectroscopy in the fields of cancer and infectious diseases

“…Diagnostic sensitivities of 89% and 86%, and corresponding specificities of 71% and 79%, were achieved, using either 785 or 633 nm, respectively. Liang et al [81] employed SERS for differentiation of benign (n ¼ 30) and malignant (n ¼ 70) thyroid tumors from blood plasma which had been subjected to ultrafiltration, resulting in 90% discrimination accuracy.…”

Metabolic Profile Characterization of Different Thyroid Nodules Using FTIR Spectroscopy: A Review

“…Nevertheless, over the past few years, the metabolomics approach in terms of thyroid diagnosis has shown an enormous evolution, which is due, in part, to the application of several analytical techniques that allow the study of the complete set of small biomolecules that make up a biological sample. The main metabolomics techniques that have mostly been adopted in the thyroid, in an attempt to identify biomarkers, classify the thyroid cancer, facilitate an earlier diagnosis and prevent the development and invasion at the systemic level of the cancer itself, are Mass Spectrometry (MS) [53][54][55], Nuclear Magnetic Resonance (NMR) [53,56,57], Raman Spectroscopy [58][59][60] and Fourier Transform Infrared (FTIR) Spectroscopy [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79]. This increase in the number of studies is attributed to the greater availability of improved and accurate metabolomics techniques that exist and also due to the development of appropriate statistical tools that are able to handle the huge amount of data resulting from the samples under analysis [80].…”

Highly Efficient Blood Protein Analysis Using Membrane Purification Technique and Super-Hydrophobic SERS Platform for Precise Screening and Staging of Nasopharyngeal Carcinoma

“…In particular, label-free SERS, which can directly detect bioanalytes after adsorption onto a nanostructured gold or silver surface, is a convenient and cost-effective approach that, in contrast to label-based SERS strategies, does not require complicated sample preparation or expensive Raman tags [ 13 , 14 ]. Recently, label-free blood SERS analysis has blossomed into an area of intensive research for cancer diagnosis, and it has been shown to be of significant clinical value for nasopharyngeal [ 15 ], gastric [ 16 ], thyroid [ 17 ], prostate [ 18 ], lung [ 19 ], and breast cancers [ 20 ]. A label-free blood SERS method for NPC detection has also been applied by our group to analyze and identify the different tumor (T) stages.…”