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Updated: Mar 21, 2026

Optical Trapping of Plasmonic Nanoparticles for In Situ Surface-Enhanced Raman Spectroscopy Characterizations
Published on: June 23, 2022
Highly stable SERS pH nanoprobes produced by co-solvent controlled AuNP aggregation
Haoran Wei1, Marjorie R Willner1, Linsey C Marr1
1Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, VA, USA. pvikes@vt.edu and Institute for Critical Technology and Applied Science (ICTAS) Center for Sustainable Nanotechnology (VTSuN), Virginia Tech, Blacksburg, VA, USA and NSF-EPA Center for the Environmental Implications of Nanotechnology (CEINT), Duke University, Durham, NC, USA.
Researchers developed a simple method using water:ethanol mixtures to create gold nanoparticle (AuNP) surface-enhanced Raman spectroscopy (SERS) nanoprobes. These probes offer stable, sensitive pH detection in complex biological samples, including cancer cells.
Area of Science:
- Nanotechnology
- Spectroscopy
- Biomedical Engineering
Background:
- Surface-enhanced Raman spectroscopy (SERS) nanoprobes are crucial for high-sensitivity molecular detection.
- Producing SERS nanoprobes with high signal intensity requires controlled aggregation of gold nanoparticles (AuNPs) into multimers.
- Existing methods for AuNP multimer production can lack reproducibility and control over aggregation.
Purpose of the Study:
- To develop a simple, controllable, and reproducible method for producing AuNP-based SERS nanoprobes.
- To create pH-sensitive nanoprobes with enhanced colloidal stability for use in complex biological environments.
- To demonstrate the utility of these nanoprobes for intracellular pH mapping in cancer cells.
Main Methods:
- AuNP monomers were aggregated in water:ethanol co-solvents with controlled ratios and incubation times.
- Aggregation was halted using thiolated poly(ethylene glycol) to ensure steric stability.
- The resulting AuNP multimers were functionalized and characterized for pH sensing capabilities.
Main Results:
- Controlled aggregation of AuNPs was achieved by adjusting water:ethanol ratios and 4-mercaptobenzoic acid (4-MBA) concentration.
- The produced pH nanoprobes demonstrated excellent colloidal stability in high ionic strength and complex samples.
- A single AuNP dimer was sufficient for detectable SERS signal, and probes accurately mapped intracellular pH (5-7) in human prostate cancer cells (PC-3).
Conclusions:
- A novel, efficient water:ethanol co-solvent method allows for systematic control over AuNP aggregation for SERS nanoprobe production.
- The developed pH nanoprobes exhibit high sensitivity, stability, and reproducibility, outperforming previous probes.
- This co-solvent approach offers a powerful strategy for fabricating SERS tags and nanoprobes for diverse applications.

