title: Functionalized plasmonic nanostructure arrays for direct and accurate mapping extracellular pH of living cells in complex media using SERS.
abstract: The extracellular pH (pHe) of living cells is one of the major factors that influence cell behaviors including cycle progression, migration, and proliferation, as well as metastasis and invasion of tumor cells. Thus, accurate sensing and mapping of the pHe is still a critical yet challenging task in the study of pHe-dependent cell behaviors. In this work, we present a method to map pHe of living cells based on surface-enhanced Raman spectroscopy (SERS). We immobilized a pH probe molecule, 4-mercaptobenzoic acid (4-MBA), on a gold quasi three-dimensional plasmonic nanostructure array (Q3D-PNA) to enable an exceptionally sensitive and reproducible pH measurement. We prudentially investigated the influences of cations and complexity of detecting solutions on the responses of 4-MBA SERS spectra to pH variations to ensure the accuracy. Herein, a normal cell line (NIH/3T3) and a tumor cell line (HepG2) were cultured on the 4-MBA modified SERS substrates. Localized pHe was detected and mapped with good spatial resolution and pH sensitivity showing pHe domains on both cells. Moreover, the averaged pHe of tumor cells was shown to be more acidic compared with that of normal cells.
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: David Galvan
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Hsiang-Chieh
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA. Electronic address: qyu@u.washington.edu.
authors.forename: Qiuming
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000818:Animals; D003470:Culture Media; D045604:Extracellular Fluid / Q000737:chemistry*; D006046:Gold; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods*; D020349:Surface Plasmon Resonance / Q000379:methods*; D013499:Surface Properties
chemical_list: D003470:Culture Media; D006046:Gold
keywords: Extracellular pH; Mapping; Surface-enhanced Raman scattering; Tumor cell