Multiplex SERS Phenotyping of Single Cancer Cells in Microdroplets

Abstract

In the context of personalized medicine, the analysis of single cells is key in order to understand the origin and evolution of cancer to provide an accurate prognosis. Microfluidics and microdroplets are increasingly used for the handling and understanding of the behavior of single cells, as they offer the perfect isolated environment. However, due to the small volumes handled, it is necessary to couple this technology with an ultrasensitive detection technique. Herein, surface‐enhanced Raman scattering (SERS) spectroscopy and droplet microfluidics are combined toward the multiplex phenotypic analysis of single cancer cells. For this, cancer cells are labeled with different SERS tags that recognize membrane proteins and encapsulated individually in microdroplets. Afterward, single cells within microdroplets are imaged by SERS spectroscopy. To the best of the authors’ knowledge, this is the first time that a multiplex phenotypic SERS analysis of single cells in microdroplets is shown. This integrated optofluidic platform paves the way toward the multiplex and automated characterization of cell populations in cancer patients.

Microfluidics for disease diagnostics based on surface-enhanced raman scattering detection

“…Oliveria et al developed a SERS-based microfluidic sensor capable of multiplex phenotype analysis of single cancer cells (Fig. 7 ) [ 53 ]. Cancer cells labeled with different SERS nanotags capable of recognizing membrane proteins were individually encapsulated in microdroplets.…”

“…The proportions of elements in this figure are not accurately represented to scale. Reprinted with permission from [ 53 ]. Copyright 2023 Wiley-VCH Verlag GmbH & Co …”

Current and Emerging Techniques for Diagnosis and MRD Detection in AML: A Comprehensive Narrative Review

“…On the distinction of different cell populations, Teixeira et al demonstrated the potential of the SERS technique to detect the profiles of different cell types (malignant and non-malignant) and to distinguish them based on spectral differences [214]. In a recent study, Oliveira et al demonstrated the multiplex phenotyping of single cancer cells using SERS probes [215]. Furthermore, the possibility to detect DNA mutations using SERS was also demonstrated.…”

True One Cell Chemical Analysis in Cancer Research: A Review

“…In a TOC study conducted by Yang et al 105-106 protein copies were detected per cell using MALDI MS (with a spatial resolution of 50 um) combined with a microfluidic approach for sample preparation, a combination coined "MIMAS" (Microfluidic assay combined with MALDI Mass Spectrometry). This study and another past work allowed Yang et al to develop a method that does not require fluorescent-based method for detecting highly abundant proteins from a cell [74][75][76]. In this study isotope-labeled peptides were used as internal standards to quantify the presence of protein Bcl-2, known to be a key regulator in cell apoptosis [74].…”