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Review
. 2021 Nov 12;11(11):449.
doi: 10.3390/bios11110449.

Multiplexed Liquid Biopsy and Tumor Imaging Using Surface-Enhanced Raman Scattering

Francesco Dell'Olio  1
Affiliations
Review

Multiplexed Liquid Biopsy and Tumor Imaging Using Surface-Enhanced Raman Scattering

Francesco Dell'Olio. Biosensors (Basel). .

Abstract

The recent improvements in diagnosis enabled by advances in liquid biopsy and oncological imaging significantly better cancer care. Both these complementary approaches, which are used for early tumor detection, characterization, and monitoring, can benefit from applying techniques based on surface-enhanced Raman scattering (SERS). With a detection sensitivity at the single-molecule level, SERS spectroscopy is widely used in cell and molecular biology, and its capability for the in vitro detection of several types of cancer biomarkers is well established. In the last few years, several intriguing SERS applications have emerged, including in vivo imaging for tumor targeting and the monitoring of drug release. In this paper, selected recent developments and trends in SERS applications in the field of liquid biopsy and tumor imaging are critically reviewed, with a special emphasis on results that demonstrate the clinical utility of SERS.

Keywords: biophotonics; biosensing; nanoplasmonics; oncology; surface-enhanced Raman scattering.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of SERS substrates. (A) Au bowtie nanoantenna array deposited on a Si3N4 membrane. (B) Graphene-encapsulated AuNPs on Si substrate. (C) Array of Si dimer nanoantennas: SEM image of the array of nanostructures, SEM top-view and lateral-view images of a single nanoantenna. (D) Gold nanostars with different spike morphologies. SEM: scanning electron microscopy. TEM: transmission electron microscopy. Reproduced with permission from [7,8,9]. Copyright 2015, Springer. Copyright 2015, Nature Publishing Group. Copyright 2014, Royal Society of Chemistry.
Figure 2
Figure 2
SERS-active NPs of various shapes used in CTC detection: spherical gold nanoparticles (AuNPs), gold nanorods (AuNRs), and gold nanostars (AuNSs). These NPs possess a strong SERS signal due to the modification of 4-mercaptobenzoic acid (4-MBA), which is the Raman reporter molecule. rBSA: reductive bovine serum albumin, which reduces nonspecific catching or uptake by healthy cells in the blood. FA: folic acid, targeted ligand. Reproduced with permission from [33]. Copyright 2016, American Chemical Society.
Figure 3
Figure 3
Multicolor SERS analysis of MCF-7 cells in blood: (1) a single MCF-7 cell among white blood cells; (2) a single MCF-7 cell in whole (unprocessed) blood; (3) white blood cells only. Reproduced with permission from [37]. Copyright 2016, Nature Publishing Group.
Figure 4
Figure 4
SERS-based sandwich immunoassay for the phenotypic profiling of cancer-derived small extracellular vesicles. (A) Nanotag preparation. (B) SERS nanotags and magnetic beads used for the molecular phenotype profiling of CD63-positive extracellular vesicles (EVs). Reproduced with permission from [46]. Copyright 2020, American Chemical Society.
Figure 5
Figure 5
Schematic illustration of the use of a SERS-based method for the early diagnosis and prognosis of hepatocellular carcinoma. Reproduced with permission from [68]. Copyright 2021, American Chemical Society.
Figure 6
Figure 6
SERS-based assay for the simultaneous detection of f-PSA and c-PSA. MGITC and XRITC are the Raman reporter molecules. MGITC: malachite green isothiocyanate. XRITC: X-rhodamine-5-(and-6)-isothiocyanate. Reproduced with permission from [73]. Copyright 2017, American Chemical Society.
Figure 7
Figure 7
SERS NPs and their application in oncological SERS imaging. (a) Typical sandwich structure of SERS NPs. (b) SERS NPs functionalization. Operating principle of SERS imaging: (c) topical administration of SERS NPs, (d) systemic administration of SERS NPs, (e) imaging, and (f) demultiplexing. Reproduced with permission from [79]. Copyright 2016, IEEE.
Figure 8
Figure 8
Typical experimental setup operating at NIR for SERS NP imaging in tissues. Reproduced with permission from [79]. Copyright 2016, IEEE.
Figure 9
Figure 9
Imaging strategy based on MPR NPs. Gd: gadolinium. Reproduced with permission from Ref. [91]. Copyright 2016, Nature Publishing Group.
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