Quantitative Fluorescence Sensing Through Highly Autofluorescent, Scattering, and Absorbing Media Using Mobile Microscopy
Ceylan Koydemir, Hatice
Troy, Tamara L.
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AbstractCompact and cost-effective systems for in vivo fluorescence and near-infrared imaging in combination with activatable reporters embedded inside the skin to sample interstitial fluid or blood can enable a variety of biomedical applications. However, the strong autofluorescence of human skin creates an obstacle for fluorescence-based sensing. Here we introduce a method for quantitative fluorescence sensing through highly autofluorescent, scattering, and absorbing media. For this, we created a compact and cost-effective fluorescence microscope weighing <40 g and used it to measure various concentrations of a fluorescent dye embedded inside a tissue phantom, which was designed to mimic the optical characteristics of human skin. We used an elliptical Gaussian beam excitation to digitally separate tissue autofluorescence from target fluorescence, although they severely overlap in both space and optical spectrum. Using ∼10-fold less excitation intensity than the safety limit for skin radiation exposure, we successfully quantified the density of the embedded fluorophores by imaging the skin phantom surface and achieved a detection limit of ∼5 × 105 and ∼2.5 × 107 fluorophores within ∼0.01 μL sample volume that is positioned 0.5 and 2 mm below the phantom surface, corresponding to a concentration of 105.9 pg/mL and 5.3 ng/mL, respectively. We also confirmed that this approach can track the spatial misalignments of the mobile microscope with respect to the embedded target fluorescent volume. This wearable microscopy platform might be useful for designing implantable biochemical sensors with the capability of spatial multiplexing to continuously monitor a panel of biomarkers and chronic conditions even at patients’ home.
CitationGöröcs Z, Rivenson Y, Ceylan Koydemir H, Tseng D, Troy TL, et al. (2016) Quantitative Fluorescence Sensing Through Highly Autofluorescent, Scattering, and Absorbing Media Using Mobile Microscopy. ACS Nano 10: 8989–8999. Available: http://dx.doi.org/10.1021/acsnano.6b05129.
SponsorsThis project has been supported by Verily Life Sciences, LLC (formerly known as Google Life Sciences). The Ozcan Research Group at UCLA also acknowledges the support of the Presidential Early Career Award for Scientists and Engineers (PECASE), the Army Research Office (ARO; W911NF-13-1-0419 and W911NF-13-1-0197), the ARO Life Sciences Division, the National Science Foundation (NSF) CBET Division Biophotonics Program, the NSF Emerging Frontiers in Research and Innovation (EFRI) Award, the NSF EAGER Award, NSF INSPIRE Award, NSF Partnerships for Innovation: Building Innovation Capacity (PFI:BIC) Program, Office of Naval Research (ONR), the National Institutes of Health (NIH), the Howard Hughes Medical Institute (HHMI), Vodafone Americas Foundation, and KAUST. This work is based upon research performed in a laboratory renovated by the National Science Foundation under grant no. 0963183, which is an award funded under the American Recovery and Reinvestment Act of 2009 (ARRA). Furthermore, Y.R. is supported by the European Union’s Horizon 2020 research and innovation program under grant agreement no. H2020-MSCA-IF-2014-659595 (MCMQCT).
PublisherAmerican Chemical Society (ACS)