title: A highly sensitive nanoscale pH-sensor using Au nanoparticles linked by a multifunctional Raman-active reporter molecule.
abstract: Chemical sensing on the nanoscale has been breaking new ground since the discovery of surface enhanced Raman scattering (SERS). For nanoparticles, controlled particle aggregation is necessary to achieve the largest SERS enhancements. Therefore, aggregating agents such as salts or linker molecules are used in conjunction with chemically sensitive reporters in order to develop robust environmentally sensitive SERS probes. While salt-induced colloidal nanosphere aggregates have produced robust SERS signals, their variability in aggregate size contributes significantly to poor SERS signal reproducibility, which can complicate their use in in vitro cellular studies. Such systems often also lack reproducibility in spectral measurements between different nanoparticle clusters. Preaggregation of colloids via linkers followed by surface functionalization with reporter molecules results in the linker occupying valuable SERS hotspot volume which could otherwise be utilized by additional reporter molecules. Ideally, both functionalities should be obtained from a single molecule. Here, we report the use of 3,5-dimercaptobenzoic acid, a single multifunctional molecule that creates SERS hotspots via the controlled aggregation of nanoparticles, and also reports pH values. We show that 3,5-dimercaptobenzoic acid bound to Au nanospheres results in an excellent pH nanoprobe, producing very robust, and highly reproducible SERS signals that can report pH across the entire physiological range with excellent pH resolution. To demonstrate the efficacy of our novel pH reporters, these probes were also used to image both the particle and pH distribution in the cytoplasm of human induced pluripotent stem cells (hiPSCs).
authors.affiliation: NSF Center for Biophotonics Science and Technology, University of California, Davis, Sacramento, California 95817, USA.
authors.forename: Latevi S
authors.initials: LS
authors.lastname: Lawson
authors.forename: James W
authors.initials: JW
authors.lastname: Chan
authors.forename: Thomas
authors.initials: T
authors.lastname: Huser
mesh_terms: D019817:Benzoic Acid / Q000138:chemical synthesis / Q000737:chemistry; D002454:Cell Differentiation; D003600:Cytosol / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D007834:Lasers; D053768:Metal Nanoparticles / Q000737:chemistry*; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D013059:Spectrum Analysis, Raman
chemical_list: D015335:Molecular Probes; D006046:Gold; D019817:Benzoic Acid