Conrad Corbella Bagot

A novel force sensor exploiting the interaction between plasmonic nanostructures and upconversion nanoparticles (UCNPs) is reported. The nanosensor is composed of a gold nanodisk and UCNPs separated by a flexible polymer layer. The gold nanodisk is designed to exhibit a plasmon resonance that selectively enhances one of the emission bands of the UCNPs while leaving the other ones largely unaffected. As the nanosensor is compressed or stretched by an external force, the polymer layer thickness changes, modulating the plasmon‐UCNP coupling. The resulting changes in the luminescence intensity provide the basis for sensing. Furthermore, the nanosensor employs ratiometric sensing, which makes it highly robust against any environmental variations. The nanosensors exhibit two orders of magnitude higher responsivity than previously reported UCNP‐based force sensors. They can be prepared as an on‐chip sensor array or in a colloidal solution, making them suitable for a variety of applications in biology and robotics.

Lenses with a tunable focus are highly desirable but remain a challenge. Here, we demonstrate a microwave varifocal meta-lens based on the Alvarez lens principle, consisting of two mechanically movable tri-layer metasurface phase plates with reversed cubic spatial profiles. The manufactured multilayer Alvarez meta-lens enables microwave beam collimation/focusing at frequencies centered at 7.5 GHz, and shows one octave focal length tunability when transversely translating the phase plates by 8 cm. The measurements reveal a gain enhancement up to 15 dB, 3-dB beam width down to 3.5^∘, and relatively broad 3-dB bandwidth of 3 GHz. These advantageous characteristics, along with its simplicity, compactness, and lightweightness, make the demonstrated flat Alvarez meta-lens suitable for deployment in many microwave systems.

In this work, we demonstrate that a photo-cross-linkable conjugate of upconverting nanoparticles and cytosine deaminase can catalyze prodrug conversion specifically at tumor sites in vivo. Non-covalent association of proteins and peptides with cellular surfaces leads to receptor-mediated endocytosis and catabolic degradation. Recently, we showed that covalent attachment of proteins such as affibodies to cell receptors yields extended expression on cell surfaces with preservation of protein function. To adapt this technology for in vivo applications, conjugates were prepared from upconverting nanoparticles and fusion proteins of affibody and cytosine deaminase enzyme (UC-ACD). The affibody allows covalent photo-cross-linking to epidermal growth factor receptors (EGFRs) overexpressed on Caco-2 human colorectal cancer cells under near-infrared (NIR) light. Once bound, the cytosine deaminase portion of the fusion protein converts the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU). NIR covalent photoconjugation of UC-ACD to Caco-2 cells showed 4-fold higher retention than observed with cells that were not irradiated in vitro. Next, athymic mice expressing Caco-2 tumors showed 5-fold greater UC-ACD accumulation in the tumors than either conjugates without the CD enzyme or UC-ACDs in the absence of NIR excitation. With oral administration of 5-FC prodrug, tumors with photoconjugated UC-ACD yielded 2-fold slower growth than control groups, and median mouse survival increased from 28 days to 35 days. These experiments demonstrate that enzyme-decorated nanoparticles can remain viable after a single covalent photoconjugation in vivo, which can in turn localize prodrug conversion to tumor sites for multiple weeks.

Förster resonance energy transfer (FRET)‐based devices have been extensively researched as potential biosensors due to their highly localized responsivity. In particular, dye‐conjugated upconverting nanoparticles (UCNPs) are among the most promising FRET‐based sensor candidates. UCNPs have a multi‐modal emission profile that allows for ratiometric sensing, and by conjugating a biosensitive dye to their surface, this profile can be used to measure localized variations in biological parameters. However, the complex nature of the UCNP energy profile as well as reabsorption of emitted photons must be taken into account in order to properly sense the target parameters. To the authors’ knowledge, no proposed UCNP‐based sensor has accurately taken care of these intricacies. In this article, the authors account for these complexities by creating a FRET‐based sensor that measures pH. This sensor utilizes Thulium (Tm³⁺)‐doped UCNPs and the fluorescent dye fluorescein isothiocyanate (FITC). It is first demonstrated that photon reabsorption is a serious issue for the 475 nm Tm³⁺ emission, thereby limiting its use in FRET‐based sensing. It is then shown that by taking the ratio of the 646 and 800 nm emissions rather than the more popular 475 nm one, it is possible to measure pH exclusively through FRET.