Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements

Harald Homulle, F Powolny, PL Stegehuis, J Dijkstra, DU Li, K Homicsko, D. Rimoldi, K. Muehlethaler, JO Prior, R Sinisi, E Dubikovskaya, Edoardo Charbon, C Bruschini

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Abstract

In near infrared fluorescence-guided surgical oncology, it is challenging to distinguish healthy from cancerous tissue. One promising research avenue consists in the analysis of the exogenous fluorophores’ lifetime, which are however in the (sub-)nanosecond range. We have integrated a single-photon pixel array, based on standard CMOS SPADs (single-photon avalanche diodes), in a compact, time-gated measurement system, named FluoCam. In vivo measurements were carried out with indocyanine green (ICG)-modified derivatives targeting the αvβ3 integrin, initially on a genetically engineered mouse model of melanoma injected with ICG conjugated with tetrameric cyclic pentapeptide (ICG−E[c(RGD f K)4]), then on mice carrying tumour xenografts of U87-MG (a human primary glioblastoma cell line) injected with monomeric ICG−c(RGD f K). Measurements on tumor, muscle and tail locations allowed us to demonstrate the feasibility of in vivo lifetime measurements with the FluoCam, to determine the characteristic lifetimes (around 500 ps) and subtle lifetime differences between bound and unbound ICG-modified fluorophores (10% level), as well as to estimate the available photon fluxes under realistic conditions
Original languageEnglish
Pages (from-to)1797-1814
Number of pages18
JournalBiomedical Optics Express
Volume7
Issue number5
DOIs
Publication statusPublished - 11 Apr 2016

Keywords

  • Photon counting
  • Imaging systems
  • Fluorescence microscopy
  • Lifetime-based sensing
  • Medical and biological imaging
  • Photodetectors
  • OA-Fund TU Delft

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    Homulle, H., Powolny, F., Stegehuis, PL., Dijkstra, J., Li, DU., Homicsko, K., Rimoldi, D., Muehlethaler, K., Prior, JO., Sinisi, R., Dubikovskaya, E., Charbon, E., & Bruschini, C. (2016). Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements. Biomedical Optics Express, 7(5), 1797-1814. https://doi.org/10.1364/BOE.7.001797