For toxicology studies on carbon nanotubes or the development of nanotube-based diagnostic or therapeutic agents, it is necessary to monitor the presence of nanotubes inside organisms. Preferred monitoring methods are noninvasive and safe, and can be performed on the laboratory mice commonly used in preclinical research. To advance the in vivo optical detection of single-walled carbon nanotubes (SWCNTs), we have recently developed instrumentation and methodology called spectral triangulation. In this method the specimen is diffusely illuminated by a matrix of light-emitting diodes and the resulting short-wave infrared fluorescence from internal SWCNTs is collected by an optical fiber at or near the animal’s skin. The fluorescence is then transmitted through spectral filters to a cooled InGaAs photon counting detector sensitive to the emitted wavelengths. The high sensitivity of this system allows localized SWCNT deposits of ca. 10^-8 g to be detected through 20 mm of tissue phantom. In addition, by systematically varying the position of the light collector and measuring emission intensities in two wavelength bands, we can deduce the 3D location of the SWCNT deposit by spectral triangulation computations. Here we report refinements to the method and performance tests with live mouse specimens. The current LED excitation matrix emits at a longer wavelength (near 736 nm) to give higher penetration and reduced SWIR autofluorescence. A new specimen holder gently squeezes the mouse against a thin fused silica window, allowing the light collection fiber to translate only in a plane to significantly reduce scan times. Results on sensitivity limits and 3D triangulation accuracy will be presented from tests in which SWCNTs in Matrigel are implanted into mouse ovaries to simulate an antibody-targeted diagnostic application.

References

C.-W.Lin, S. M. Bachilo, M. Vu, K. M. Beckingham, and R. B.Weisman, Spectral Triangulation: a 3D Method for Locating Single-Walled Carbon Nanotubes in vivo, Nanoscale 8, 10348-10357 (2016).

C.-W. Lin and R. B. Weisman, In vivo Detection of Single-Walled Carbon Nanotubes: Progress and Challenges, Nanomedicine 11, 2885-2888 (2016).