Surface Plasmon Resonance for Biomarker Detection: Advances in Non-invasive Cancer Diagnosis

Abstract

Biomarker-based cancer analysis has great potential to lead to a better understanding of disease at the molecular level and to improve early diagnosis and monitoring. Unlike conventional tissue biopsy, liquid biopsy allows the detection of a large variety of circulating biomarkers, such as microRNA (miRNA), exosomes, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and proteins, in an easily accessible and minimally invasive way. In this review, we describe and evaluate the relevance and applicability of surface plasmon resonance (SPR) and localized SPR (LSPR)-based platforms for the detection of different classes of cancer biomarkers in liquid biopsy samples. Firstly, we critically discuss unsolved problems and issues in capturing and analyzing biomarkers. Secondly, we highlight current challenges which need to be resolved in applying SPR biosensors into clinical practice. Then, we mainly focus on applications of SPR-based platforms that process a patient sample aiming to detect and quantify biomarkers as a minimally invasive liquid biopsy tool for cancer patients appearing over the last 5 years. Finally, we describe the analytical performances of selected SPR biosensor assays and their significant advantages in terms of high sensitivity and specificity as well as accuracy and workflow simplicity.

Analytical techniques for multiplex analysis of protein biomarkers

“…Plasmonic immunosensors based on the localized surface plasmon resonance (LSPR) [146,149] and immunoassays based on potentiometric measurements with immuno-field effect transistors (immunoFETs) [150,151] are promising technologies for label-free sensing offering ultralow sensitivities (fM), cost-effectiveness and the possibility for ultra-high multiplexing combining several sensors with the concept of micro-arrays (immobilization of molecular libraries) [152,153]. These characteristics of transducers like plasmonic biosensors or immunoFETs make them excellent candidates for early detection of cancerbiomarkers and POC diagnostics [154][155][156]. However, most of the nanotechnology-based devices are still at the stage of 'proof of concept.'…”

Exosomes as a promising diagnostic tool in head and neck squamous cell carcinoma?

“…This procedure is not only an invasive method, but it also shows the disadvantage that the anatomical location of some oncogenic mutations is not always accessible by tissue biopsy. Another disadvantage is that the tissue extraction may cause an expansion of the metastatic lesion [23] . In addition, it is time-consuming since several surgeries are needed to follow up on tumor progression, making it more expensive [9] .…”

Liquid biopsies in myeloid malignancies

“…As exosomes content depends on the physiological state of the cell, the cargo and abundance of tumor derived exosomes generally reflects the stage of the tumor, rendering diagnostic value in LB for early tumor detection [153][154][155] . Even though exosomes are not being used in clinical practice, the potential of these vesicles for diagnosis is highlighted by the 71 clinical trials studies focused on exosomes of cancer patients (according to www.clinicalTrials.gov accessed on 12 September 2019), accompanied by the development of platforms for tumor derived exosomes detection in complex samples (e.g., surface plasmon resonance for exosome biomarkers detection [156] , microfluidic chip for ovarian cancer diagnosis [157] , or a platform with superparamagnetic conjunctions and molecular beacons targeting urinary exosomes for prostate cancer diagnosis [158] ). Nevertheless, several sensitive and specific exosomal biomarkers were already suggested for early diagnosis of ovarian cancer (over-expression of miR-200a, miR-200b, and miR200c in patient's serum exosomes) [159][160][161] , non-small cell lung cancer (enrichment of Leucine-rich a2-glycoprotein 1 in exosomes of patients urine and MALAT-1 in patient's blood) [162][163][164] , colon cancer (overexpression of miR-1246 and miR-23a in patient's serum exosomes) [165,166] , or pancreatic ductal adenocarcinoma (presence of glypican-1 in patient's serum) [167,168] .…”