Development of portable and cost-effective optical imaging devices is essential for quantification of molecular bioassays at the point of care (POC). Mobile phone-based microscopy tools have shown great potential as biomedical reader platforms due to their small size, large distribution volume, and constantly improving optical properties. However, the optical detection sensitivity remains a challenge to further improve the diagnostic capabilities of microscopy and sensing devices based on mobile-phones. Here, we demonstrate a simple strategy to enhance the signal intensity of a smartphone fluorescence microscope by approximately an order of magnitude using surface-enhanced fluorescence (SEF) created by a thin silver film. This plasmonics-enhanced smartphone microscopy platform relies on an opto-mechanical attachment based on the Kretschmann configuration, where the sample is placed on a silver-coated glass coverslip and excited by a laser diode from the backside through a glass hemisphere. The fluorescence enhancement effect was systematically optimized by tuning the metal film thickness, spacer distance, excitation angle, and polarization, and experimentally validated by comparison to theoretical simulations. With this mobile device, single fluorescent beads as small as 50 nm and individual quantum dots (ca. 20 nm dia.) were detected. We further quantified the sensitivity limit of this mobile platform to be around 80 fluorophores per diffraction-limited spot by imaging DNA origami based brightness standards labeled with different numbers of fluorophores. We believe that this SEF-based mobile microscopy platform opens up various new opportunities for POC diagnostics and sensing applications in resource-limited-settings.
Qingshan Wei, Guillermo P. Acuna, Seungkyeum Kim, Carolin Vietz, Derek Tseng, Jongjae Chae, Daniel Shir, Wei Luo, Philip Tinnefeld, and Aydogan Ozcan, "Surface-enhanced fluorescence microscopy on a smartphone (Conference Presentation)," Proc. SPIE 10485, Optics and Biophotonics in Low-Resource Settings IV, 104850L (Presented at SPIE BiOS: January 28, 2018; Published: 5 April 2018); https://doi.org/10.1117/12.2289338.5751451091001.
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