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A real-time clinical endoscopic system for intraluminal, multiplexed imaging of surface-enhanced Raman scattering nanoparticles.

Garai E, Sensarn S, Zavaleta CL, Loewke NO, Rogalla S, Mandella MJ, Felt SA, Friedland S, Liu JT, Gambhir SS, Contag CH - PLoS ONE (2015)

Bottom Line: This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present.Human and swine studies have demonstrated the speed and simplicity of this technique.This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Stanford University, Stanford, California, United States of America; Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California, United States of America.

ABSTRACT
The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to improve early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the design and in vivo demonstration of a miniature, non-contact, opto-electro-mechanical Raman device as an accessory to clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present. Human and swine studies have demonstrated the speed and simplicity of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential to improve diagnosis and to guide therapy by enabling sensitive quantitative molecular detection of small and otherwise hard-to-detect lesions in the context of white-light endoscopy.

No MeSH data available.


Related in: MedlinePlus

Ex-vivo porcine colon multiplexing study.(a) Porcine colon was initially laid flat. Various cocktails of SERS nanoparticles were injected superficially at 6 different sites. (b) The tissue was placed on a flexible sheath and then rolled to re-form the lumen of the colon, which was then scanned with the device. (c) Images of signal intensities of S493, S440, S482, and S420 shown in 2D. (d) Ratiometric images of the tissue samples shown in 2D. ROIs used for analysis are shown. (e) Average of ratiometric values for each of the respective SERS flavors in each tissue-sample ROI from (d). Error bars are standard errors of the mean.
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pone.0123185.g005: Ex-vivo porcine colon multiplexing study.(a) Porcine colon was initially laid flat. Various cocktails of SERS nanoparticles were injected superficially at 6 different sites. (b) The tissue was placed on a flexible sheath and then rolled to re-form the lumen of the colon, which was then scanned with the device. (c) Images of signal intensities of S493, S440, S482, and S420 shown in 2D. (d) Ratiometric images of the tissue samples shown in 2D. ROIs used for analysis are shown. (e) Average of ratiometric values for each of the respective SERS flavors in each tissue-sample ROI from (d). Error bars are standard errors of the mean.

Mentions: To demonstrate multiplexing capabilities with a tissue model that better resembles the clinical case, excised porcine colon tissue was used. Here, a variety of SERS solutions were injected superficially (Fig 5a) (see S1 File for more details). The signal intensity for the equimolar mixture injections was relatively constant among the four flavors, while at the stepwise mixture injection sites the signal intensity increased linearly for the more concentrated flavors (Fig 5c). This is made apparent by visualizing the ratiometric images, where all flavors are quantified relative to one of the NP flavors: S493 (Fig 5d). Here, S493 is designated as the non-specific control flavor; thus, the quantities displayed in the ratiometric image are: Ratiometric Value = [(Flavor Value)/(S493 Value)– 1]. Values greater than zero indicate locations where the specific SERS flavors are located in greater abundance than the non-specific flavor. Variations in tissue topography and imperfect centering of the device within the colon lumen can also be accounted for and normalized by using this ratiometric algorithm [9]. The quantified results from the 6 injection sites are shown in Fig 5e.


A real-time clinical endoscopic system for intraluminal, multiplexed imaging of surface-enhanced Raman scattering nanoparticles.

Garai E, Sensarn S, Zavaleta CL, Loewke NO, Rogalla S, Mandella MJ, Felt SA, Friedland S, Liu JT, Gambhir SS, Contag CH - PLoS ONE (2015)

Ex-vivo porcine colon multiplexing study.(a) Porcine colon was initially laid flat. Various cocktails of SERS nanoparticles were injected superficially at 6 different sites. (b) The tissue was placed on a flexible sheath and then rolled to re-form the lumen of the colon, which was then scanned with the device. (c) Images of signal intensities of S493, S440, S482, and S420 shown in 2D. (d) Ratiometric images of the tissue samples shown in 2D. ROIs used for analysis are shown. (e) Average of ratiometric values for each of the respective SERS flavors in each tissue-sample ROI from (d). Error bars are standard errors of the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414592&req=5

pone.0123185.g005: Ex-vivo porcine colon multiplexing study.(a) Porcine colon was initially laid flat. Various cocktails of SERS nanoparticles were injected superficially at 6 different sites. (b) The tissue was placed on a flexible sheath and then rolled to re-form the lumen of the colon, which was then scanned with the device. (c) Images of signal intensities of S493, S440, S482, and S420 shown in 2D. (d) Ratiometric images of the tissue samples shown in 2D. ROIs used for analysis are shown. (e) Average of ratiometric values for each of the respective SERS flavors in each tissue-sample ROI from (d). Error bars are standard errors of the mean.
Mentions: To demonstrate multiplexing capabilities with a tissue model that better resembles the clinical case, excised porcine colon tissue was used. Here, a variety of SERS solutions were injected superficially (Fig 5a) (see S1 File for more details). The signal intensity for the equimolar mixture injections was relatively constant among the four flavors, while at the stepwise mixture injection sites the signal intensity increased linearly for the more concentrated flavors (Fig 5c). This is made apparent by visualizing the ratiometric images, where all flavors are quantified relative to one of the NP flavors: S493 (Fig 5d). Here, S493 is designated as the non-specific control flavor; thus, the quantities displayed in the ratiometric image are: Ratiometric Value = [(Flavor Value)/(S493 Value)– 1]. Values greater than zero indicate locations where the specific SERS flavors are located in greater abundance than the non-specific flavor. Variations in tissue topography and imperfect centering of the device within the colon lumen can also be accounted for and normalized by using this ratiometric algorithm [9]. The quantified results from the 6 injection sites are shown in Fig 5e.

Bottom Line: This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present.Human and swine studies have demonstrated the speed and simplicity of this technique.This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Stanford University, Stanford, California, United States of America; Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California, United States of America.

ABSTRACT
The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to improve early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the design and in vivo demonstration of a miniature, non-contact, opto-electro-mechanical Raman device as an accessory to clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present. Human and swine studies have demonstrated the speed and simplicity of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential to improve diagnosis and to guide therapy by enabling sensitive quantitative molecular detection of small and otherwise hard-to-detect lesions in the context of white-light endoscopy.

No MeSH data available.


Related in: MedlinePlus