title: High-sensitivity, real-time, ratiometric imaging of surface-enhanced Raman scattering nanoparticles with a clinically translatable Raman endoscope device.
abstract: Topical application and quantification of targeted, surface-enhanced Raman scattering (SERS) nanoparticles offer a new technique that has the potential for early detection of epithelial cancers of hollow organs. Although less toxic than intravenous delivery, the additional washing required to remove unbound nanoparticles cannot necessarily eliminate nonspecific pooling. Therefore, we developed a real-time, ratiometric imaging technique to determine the relative concentrations of at least two spectrally unique nanoparticle types, where one serves as a nontargeted control. This approach improves the specific detection of bound, targeted nanoparticles by adjusting for working distance and for any nonspecific accumulation following washing. We engineered hardware and software to acquire SERS signals and ratios in real time and display them via a graphical user interface. We report quantitative, ratiometric imaging with nanoparticles at pM and sub-pM concentrations and at varying working distances, up to 50 mm. Additionally, we discuss optimization of a Raman endoscope by evaluating the effects of lens material and fiber coating on background noise, and theoretically modeling and simulating collection efficiency at various working distances. This work will enable the development of a clinically translatable, noncontact Raman endoscope capable of rapidly scanning large, topographically complex tissue surfaces for small and otherwise hard to detect lesions.
authors.affiliation: Stanford University, Department of Mechanical Engineering, Stanford, California 94305gStanford University, Molecular Imaging Program at Stanford, Stanford, California 94305.
authors.forename: Ellis
authors.initials: E
authors.lastname: Garai
authors.forename: Steven
authors.initials: S
authors.lastname: Sensarn
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Zavaleta
authors.forename: Dominique
authors.initials: D
authors.lastname: Van de Sompel
authors.forename: Nathan O
authors.initials: NO
authors.lastname: Loewke
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mandella
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
mesh_terms: D000465:Algorithms; D003106:Colon / Q000737:chemistry; D003198:Computer Simulation; D019723:Endoscopes; D004867:Equipment Design; D006801:Humans; D057230:Limit of Detection; D053758:Nanoparticles / Q000737:chemistry*; D055100:Optical Fibers; D025341:Principal Component Analysis; D012815:Signal Processing, Computer-Assisted; D013059:Spectrum Analysis, Raman / Q000295:instrumentation* / Q000379:methods*