Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 diff...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 106; no. 32; pp. 13511 - 13516
Main Authors Zavaleta, Cristina L, Smith, Bryan R, Walton, Ian, Doering, William, Davis, Glenn, Shojaei, Borzoyeh, Natan, Michael J, Gambhir, Sanjiv S
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 11.08.2009
National Acad Sciences
Subjects
Animals
Biological Sciences
Biomarkers
Female
image analysis
Imaging
Imaging, Three-Dimensional - methods
Injections, Intravenous
Injections, Subcutaneous
Liver
Liver - metabolism
Mice
Mice, Nude
Microscopes
Molecular imaging
Multiplexing
Nanoparticles
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Quantum dots
Quantum flavor
Raman scattering
Raman spectroscopy
Rodents
Spectroscopy
Spectrum analysis
Spectrum Analysis, Raman
Studies
Surface Properties
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Summary:Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 different types of surface enhanced Raman scattering (SERS) nanoparticles in a living mouse after s.c. injection. Based on these spectral results, we simultaneously injected the five most intense and spectrally unique SERS nanoparticles i.v. to image their natural accumulation in the liver. All five types of SERS nanoparticles were successfully identified and spectrally separated using our optimized noninvasive Raman imaging system. In addition, we were able to linearly correlate Raman signal with SERS concentration after injecting four spectrally unique SERS nanoparticles either s.c. (R² = 0.998) or i.v. (R² = 0.992). These results show great potential for multiplexed imaging in living subjects in cases in which several targeted SERS probes could offer better detection of multiple biomarkers associated with a specific disease.
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Edited by Stuart M. Lindsay, Arizona State University, Tempe, AZ, and accepted by the Editorial Board June 10, 2009
Author contributions: C.L.Z., B.R.S., and S.S.G. designed research; C.L.Z. and B.R.S. performed research; I.W., W.D., G.D., and M.J.N. contributed new reagents/analytic tools; C.L.Z., B.R.S., I.W., and B.S. analyzed data; and C.L.Z., B.R.S., I.W., M.J.N., and S.S.G. wrote the paper.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.0813327106