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Anal Chem. 2010 Nov 1;82(21):9058-65. doi: 10.1021/ac102058k. Epub 2010 Oct 6.

Hand-held spectroscopic device for in vivo and intraoperative tumor detection: contrast enhancement, detection sensitivity, and tissue penetration.

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  • 1Department of Biomedical Engineering and Chemistry, Emory University and Georgia Institute of Technology, 101 Woodruff Circle Suite 2007, Atlanta, Georgia 30322, United States, Division of Thoracic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, United States, Departments of Biomedical Engineering, Oncology and Radiology, Emory University, 101 Woodruff Circle, Suite 2007, Atlanta, Georgia 30322, United States, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, United States, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, United States, and Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, UA Whitaker Building 4106, Atlanta, Georgia 30332, United States.


Surgery is one of the most effective and widely used procedures in treating human cancers, but a major problem is that the surgeon often fails to remove the entire tumor, leaving behind tumor-positive margins, metastatic lymph nodes, and/or satellite tumor nodules. Here we report the use of a hand-held spectroscopic pen device (termed SpectroPen) and near-infrared contrast agents for intraoperative detection of malignant tumors, based on wavelength-resolved measurements of fluorescence and surface-enhanced Raman scattering (SERS) signals. The SpectroPen utilizes a near-infrared diode laser (emitting at 785 nm) coupled to a compact head unit for light excitation and collection. This pen-shaped device effectively removes silica Raman peaks from the fiber optics and attenuates the reflected excitation light, allowing sensitive analysis of both fluorescence and Raman signals. Its overall performance has been evaluated by using a fluorescent contrast agent (indocyanine green, or ICG) as well as a surface-enhanced Raman scattering (SERS) contrast agent (pegylated colloidal gold). Under in vitro conditions, the detection limits are approximately 2-5 × 10(-11) M for the indocyanine dye and 0.5-1 × 10(-13) M for the SERS contrast agent. Ex vivo tissue penetration data show attenuated but resolvable fluorescence and Raman signals when the contrast agents are buried 5-10 mm deep in fresh animal tissues. In vivo studies using mice bearing bioluminescent 4T1 breast tumors further demonstrate that the tumor borders can be precisely detected preoperatively and intraoperatively, and that the contrast signals are strongly correlated with tumor bioluminescence. After surgery, the SpectroPen device permits further evaluation of both positive and negative tumor margins around the surgical cavity, raising new possibilities for real-time tumor detection and image-guided surgery.

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