Widefield quantitative multiplex surface enhanced Raman scattering imaging<i>in vivo</i>

McVeigh, Patrick Z.; Mallia, Rupananda J.; Veilleux, Israël; Wilson, Brian C.

doi:10.1117/1.jbo.18.4.046011

Cited by 50 publications

(47 citation statements)

References 31 publications

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“…After orally introducing these biomarker-targeted NPs into the esophagus (e.g., by oral gavage or by having the subject ingest a cocktail of NPs), physicians and tumor biologists would be able to obtain a rich set of molecular information to detect cancer cells more accurately during endoscopic procedures and to study the molecular changes associated with tumor progression. Recently, a few studies have reported the multiplexed detection of large panels of nontargeted SERS NPs in live animals and human tissues [18][19][20][21][22][23][24]. Our lab and a few other groups have also developed biomarker-targeted SERS NPs and have demonstrated their specific binding abilities with cancer cells and tissues [25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus

Wang

Khan

Leigh

et al. 2014

Biomed. Opt. Express

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Abstract:The early detection and biological investigation of esophageal cancer would benefit from the development of advanced imaging techniques to screen for the molecular changes that precede and accompany the onset of cancer. Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to improve cancer detection and the investigation of cancer progression through the sensitive and multiplexed phenotyping of cell-surface biomarkers. Here, a miniature endoscope featuring rotational scanning and axial pull back has been developed for 2D spectral imaging of SERS NPs topically applied on the lumenal surface of the rat esophagus. Raman signals from low-pM concentrations of SERS NP mixtures are demultiplexed in real time to accurately calculate the concentration and ratio of the NPs. Ex vivo and in vivo experiments demonstrate the feasibility of topical application and imaging of multiplexed SERS NPs along the entire length of the rat esophagus.

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Section: Introductionmentioning

confidence: 99%

Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus

Wang

Khan

Leigh

et al. 2014

Biomed. Opt. Express

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“…[4][5][6][7][8][9][10][11][12][13] The intensity of a Raman signal bears a linear relationship to the analyte concentrations, therefore, Raman spectroscopy can be used as a quantitative tool in concentration measurements as well. 1,4,5,[14][15][16][17] An ultimate goal in this field is to develop Raman spectroscopy-based techniques for biomedical applications through instrumentation, [18][19][20][21][22] plasmonic substrates, [23][24][25][26][27] devices, 28,29 assays, 30,31 and techniques. 32,33 Raman spectroscopic measurements, like other optical techniques, pose minimal danger from exposure to ionizing radiation due to the low-energy optical radiation exposure.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive glucose sensing by transcutaneous Raman spectroscopy

2015

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Abstract. We present the development of a transcutaneous Raman spectroscopy system and analysis algorithm for noninvasive glucose sensing. The instrument and algorithm were tested in a preclinical study in which a dog model was used. To achieve a robust glucose test system, the blood levels were clamped for periods of up to 45 min. Glucose clamping and rise/fall patterns have been achieved by injecting glucose and insulin into the ear veins of the dog. Venous blood samples were drawn every 5 min and a plasma glucose concentration was obtained and used to maintain the clamps, to build the calibration model, and to evaluate the performance of the system. We evaluated the utility of the simultaneously acquired Raman spectra to be used to determine the plasma glucose values during the 8-h experiment. We obtained prediction errors in the range of ∼1.5 − 2 mM. These were in-line with a best-case theoretical estimate considering the limitations of the signal-to-noise ratio estimates. As expected, the transition regions of the clamp study produced larger predictive errors than the stable regions. This is related to the divergence of the interstitial fluid (ISF) and plasma glucose values during those periods. Two key contributors to error beside the ISF/plasma difference were photobleaching and detector drift. The study demonstrated the potential of Raman spectroscopy in noninvasive applications and provides areas where the technology can be improved in future studies.

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“…Global Raman imaging uses a lower power density for illumination, but for in vivo imaging this is not an issue because ultimately we are limited by the American National Standards Institute's laser safety standards (14). Collecting signal from a narrow spectral band, however, sacrifices the rich spectral fingerprint information, possibly reducing detection sensitivity and making both multiplexing and quantification more challenging (13).…”

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confidence: 99%

“…In addition to point scanning, it also is possible to perform direct, or "global," Raman imaging (10) for in vivo applications (12,13), in which a wide area (up to 2 cm 2 ) is illuminated and all spatial points of the image are collected simultaneously on a 2D CCD at a single detection wavelength. Global Raman imaging uses a lower power density for illumination, but for in vivo imaging this is not an issue because ultimately we are limited by the American National Standards Institute's laser safety standards (14).…”

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confidence: 99%

A small animal Raman instrument for rapid, wide-area, spectroscopic imaging

Bohndiek

Wagadarikar

Zavaleta

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

126

118

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Raman spectroscopy, amplified by surface enhanced Raman scattering (SERS) nanoparticles, is a molecular imaging modality with ultra-high sensitivity and the unique ability to multiplex readouts from different molecular targets using a single wavelength of excitation. This approach holds exciting prospects for a range of applications in medicine, including identification and characterization of malignancy during endoscopy and intraoperative image guidance of surgical resection. The development of Raman molecular imaging with SERS nanoparticles is presently limited by long acquisition times, poor spatial resolution, small field of view, and difficulty in animal handling with existing Raman spectroscopy instruments. Our goal is to overcome these limitations by designing a bespoke instrument for Raman molecular imaging in small animals. Here, we present a unique and dedicated small-animal Raman imaging instrument that enables rapid, high-spatial resolution, spectroscopic imaging over a wide field of view (> 6 cm 2 ), with simplified animal handling. Imaging of SERS nanoparticles in small animals demonstrated that this small animal Raman imaging system can detect multiplexed SERS signals in both superficial and deep tissue locations at least an order of magnitude faster than existing systems without compromising sensitivity.R aman spectroscopy is a powerful bioanalytical tool based on the inelastic scattering of photons by molecular bonds; as each bond has a characteristic vibrational energy, the spectrum of Raman scatter peaks provides a unique fingerprint for a given sample. In vivo applications previously were limited by the relatively weak Raman effect (fewer than one event per 10 7 elastic scattering events) and poor depth of penetration (<1 mm). Recently, surface enhanced Raman scattering (SERS) was shown to overcome these limitations, enabling the use of Raman spectroscopy for molecular imaging in small living subjects (1-4).SERS is a plasmonic effect in which molecules adsorbed on a rough metal surface experience a >10 6 -fold increase in Raman scatter intensity (5). The SERS enhancement may be exploited in vivo by coating Raman active molecules onto gold nanoparticles (6), which can be engineered to target specific disease markers (7). Advantages of this approach, as opposed to other optical spectroscopy techniques, include a high sensitivity of detection, a low intrinsic background signal, the environmental and optical stability of nanoparticles, and the ability to multiplex signals from different biological targets (6). Therefore, Raman molecular imaging is not only attractive for studies in small animals, it is also being developed for clinical translation through endoscopy and as an intraoperative imaging approach to guide surgical resection (8,9). Despite the substantial increase in signal afforded by the SERS approach, reports of in vivo Raman imaging using SERS are relatively rare. Expansion of this promising technique currently is limited by the lack of a dedicated Raman spectroscopy instrument speci...

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Widefield quantitative multiplex surface enhanced Raman scattering imagingin vivo

Cited by 50 publications

References 31 publications

Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus

Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus

Noninvasive glucose sensing by transcutaneous Raman spectroscopy

A small animal Raman instrument for rapid, wide-area, spectroscopic imaging

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