Three-Dimensional Plasmonic Trap Array for Ultrasensitive Surface-Enhanced Raman Scattering Analysis of Single Cells

Abstract

Single-cell analysis provides an important strategy to evaluate cellular heterogeneity. Although surface-enhanced Raman scattering (SERS) has been considered as a promising label-free technique for single-cell analysis, it remains at the early stage for characterizing the extracellular metabolites of single cells. Herein, we developed a convenient, flexible, and straightforward three-dimensional (3D) plasmonic trap array for simultaneously compartmentalizing and sensitively detecting single-cell metabolites. The 3D trap was spontaneously self-formed by an interfacial-energy-driven process when a liquid droplet was covered with an immiscible oil liquid (polydimethylsiloxane, PDMS). When a droplet of pure AgNO solution was immersed into PDMS, Ag ions were automatically reduced by the residual Si-H groups in PDMS. Snowflake-like nanoparticles of Ag could be formed on the inner surface of the 3D traps by tuning the concentration of Ag salt precursors and then assembled to flower-like microstructures, endowing the traps with remarkable plasmon enhancement. The established 3D traps exhibited considerably enhanced surface plasmon resonance signals for Raman reporting, and a low detection limit at the aM level was achieved for p-aminothiophenol. Moreover, these 3D traps can serve as an efficient tool for single-cell SERS measurement. As a proof-of-concept, dipicolinic acid, a common biomarker of bacterial spores, was successfully detected from a single cell. The presented approach provides a versatile tool for label-free and sensitive detection of single-cell environments.

Plasmonic tweezers: for nanoscale optical trapping and beyond

“…In another example, three-dimensional plasmonic microstructures have remarkable plasmon enhancement at different positions in space, particularly for nonisotropic microstructures, which might enable spatial trapping. In 2018, Yao et al developed a flexible, label-free and straightforward method for preparing a three-dimensional plasmonic trap array for simultaneous compartmentalization and measurement of single-cell secretions 137 . This principle provides a versatile tool for label-free and sensitive detection, particularly for homogeneous samples.…”

“…Thus, it is easy to design three-dimensional structures for trapping. Recently, Yang developed a simple three-dimensional plasmonic trap array that led to considerably enhanced Raman signals, capable of operating at the attomolar level for trapping and sensitive detection of single-cell metabolites 137 . Furthermore, owing to optimizations based on novel graphene materials 261 , two excitation lasers with different wavelengths 243 , and cone-shaped sharp metal tips 296 , improved trapping and Raman signal enhancement have been demonstrated.…”

Recent Advances in Plasmonic Nanostructures Applied for Label‐free Single‐cell Analysis

“…As a result, this sensing platform was suitable for characterization of neuronal differentiation with minimal false positive signals. Besides, single-cell metabolites could be detected by a flexible three-dimensional (3D) plasmonic trap array covered by snowflake-like AgNPs (Figure 5b) [29]. The high density of hot spots on the surfaced of obtained trap array can improve the enhancement factor (EF) up to 1.1 × 10 7 .…”

Dynamic Liquid Surface Enhanced Raman Scattering Platform Based on Soft Tubular Microfluidics for Label-Free Cell Detection

“…Several cell detection techniques including DNA sequencing, immunofluorescence, flow cytometry, and spectroscopy have been developed. Recently, surface enhanced Raman scattering (SERS) has been considered as a popular and promising cell detection method due to its strong signal intensity, biocompatibility, and abundant information for biological samples . For example, Dugandžić et al measured SERS of macrophages in glassware for the detection of vulnerable atherosclerotic plaques .…”

“…Recently, surface enhanced Raman scattering (SERS) has been considered as a popular and promising cell detection method due to its strong signal intensity, 6 biocompatibility, 7 and abundant information for biological samples. 8 For example, Dugandzǐćet al measured SERS of macrophages in glassware for the detection of vulnerable atherosclerotic plaques. 9 Zhang et al researched several tumor cells, immortalized cells, and clinical cancer cells by using the silver film substrate SERS.…”