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There is much interest in using nanosensors to monitor biologically relevant species such as glucose, or cellular pH, as these often become dysregulated in diseases such as cancer. This information is often inaccessible at depth in biological tissue, due to the highly scattering nature of tissue. Here we show that gold nanoparticles labeled with pH-sensitive reporter molecules can monitor pH at depth in biological tissues. This was achieved using deep Raman spectroscopy (spatially offset Raman and transmission Raman) in combination with surface-enhanced Raman spectroscopy, allowing chemical information to be retrieved significantly deeper than conventional Raman spectroscopy permits. Combining these approaches with chemometrics enabled pH changes to be monitored with an error of ±∼0.1 pH units noninvasively through 22 mm of soft tissue. This development opens the opportunity for the next generation of light-based medical diagnostic methods, such as monitoring of cancers, known to significantly alter pH levels.

Original publication





Analytical chemistry

Publication Date





10984 - 10987


Biomedical Physics, School of Physics and Astronomy, College of Engineering, Mathematics and Physical Sciences , University of Exeter , Exeter , EX4 4QL , United Kingdom.


Muscle, Skeletal, Animals, Swine, Humans, Gold, Benzoates, Sulfhydryl Compounds, Spectrum Analysis, Raman, Sensitivity and Specificity, Hydrogen-Ion Concentration, Surface Properties, Meat, Metal Nanoparticles