Nearly all diseases can be traced back to abnormal mechanotransduction, but few sensors can reliably measure biologically-relevant forces in vivo. Here, we investigate sub-25nm lanthanide-doped upconverting nanoparticles as novel optical force probes, which provide several biocompatible features: sharp emission peaks with near infrared illumination, a high signal-to-noise ratio, and photostability. To increase force sensitivity, we include d-metal doping in the nanoparticles; the d-metal siphons energy from the lanthanide ions with an efficiency that varies with pressure. We synthesize cubic-phase NaYF4: Er3+,Yb3+ nanoparticles doped with 0-5% Mn2+ and compress them in a hydrostatic environment using a diamond anvil cell. When illuminated at 980nm, the nanoparticles show sharp emission peaks centered at wavelengths of 522nm, 545nm, and 660nm. In 20nN increments, up to 700nN, the ratio of the red-to-green peaks in 0% Mn-doped nanoparticles increases by nearly 30%, resulting in a perceived color change from orange to red. In contrast, the 1% Mn-doped samples exhibit little color change but a large 40% decrease in upconversion intensity. In both cases, the red-to-green ratio varies linearly with strain and the optical properties are recoverable upon release. We further use atomic force microscopy to characterize optical responses at lower, pico-Newton to nano-Newton forces. To demonstrate in vivo imaging capabilities, we incubate C. elegans with nanoparticles dispersed in buffer solution (5mg/mL concentration) and image forces involved in digestion using confocal microscopy. Our nanoparticles provide a platform for the first, non-genetically-encoded in vivo force sensors, and we describe routes to increase their sensitivity to the single-pN range.
Alice Lay, Michael Wisser, Yu Lin, Tarun Narayan, Michael Krieg, Ashwin Atre, Miriam Goodman, and Jennifer A. Dionne, "Strain-sensitive upconversion for imaging biological forces
(Conference Presentation)," Proc. SPIE 9930, Biosensing and Nanomedicine IX, 993003 (Presented at SPIE Nanoscience + Engineering: August 28, 2016; Published: 3 November 2016); https://doi.org/10.1117/12.2239540.5164183650001.
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