Hand-held spectroscopic device for in vivo and intraoperative tumor detection

Contrast enhancement, detection sensitivity, and tissue penetration

Aaron M Mohs, Michael C. Mancini, Sunil Singhal, James M. Provenzale, Brian Leyland-Jones, May D. Wang, Shuming Nie

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9058-9065
Number of pages8
JournalAnalytical Chemistry
Volume82
Issue number21
DOIs
StatePublished - Nov 1 2010

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Tumors
Tissue
Contrast Media
Light pens
Surgery
Raman scattering
Fluorescence
Bearings (structural)
Bioluminescence
Infrared radiation
Gold Colloid
Indocyanine Green
Silicon Dioxide
Fiber optics
Semiconductor lasers
Animals
Coloring Agents
Satellites
Wavelength

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Hand-held spectroscopic device for in vivo and intraoperative tumor detection : Contrast enhancement, detection sensitivity, and tissue penetration. / Mohs, Aaron M; Mancini, Michael C.; Singhal, Sunil; Provenzale, James M.; Leyland-Jones, Brian; Wang, May D.; Nie, Shuming.

In: Analytical Chemistry, Vol. 82, No. 21, 01.11.2010, p. 9058-9065.

Research output: Contribution to journalArticle

Mohs, Aaron M ; Mancini, Michael C. ; Singhal, Sunil ; Provenzale, James M. ; Leyland-Jones, Brian ; Wang, May D. ; Nie, Shuming. / Hand-held spectroscopic device for in vivo and intraoperative tumor detection : Contrast enhancement, detection sensitivity, and tissue penetration. In: Analytical Chemistry. 2010 ; Vol. 82, No. 21. pp. 9058-9065.
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