Phase noise matching in resonant metasurfaces for intrinsic sensing stability.

Interferometry offers a precise means of interrogating resonances in dielectric and plasmonic metasurfaces, surpassing spectrometer-imposed resolution limits. However, interferometry implementations often face complexity or instability issues due to heightened sensitivity. Here, we address the necessity for noise compensation and tolerance by harnessing the inherent capabilities of photonic resonances. Our proposed solution, termed "resonant phase noise matching," employs optical referencing to align the phases of equally sensitive, orthogonal components of the same mode. This effectively mitigates drift and noise, facilitating the detection of subtle phase changes induced by a target analyte through spatially selective surface functionalization. Validation of this strategy using Fano resonances in a 2D photonic crystal slab showcases noteworthy phase stability (σ<10-4π). With demonstrated label-free detection of low-molecular-weight proteins at clinically relevant concentrations, resonant phase noise matching presents itself as a potentially valuable strategy for advancing scalable, high-performance sensing technology beyond traditional laboratory settings.

Molecular crowding in single eukaryotic cells: Using cell environment biosensing and single-molecule optical microscopy to probe dependence on extracellular ionic strength, local glucose conditions, and sensor copy number.

The physical and chemical environment inside cells is of fundamental importance to all life but has traditionally been difficult to determine on a subcellular basis. Here we combine cutting-edge genomically integrated FRET biosensing to readout localized molecular crowding in single live yeast cells. Confocal microscopy allows us to build subcellular crowding heatmaps using ratiometric FRET, while whole-cell analysis demonstrates crowding is reduced when yeast is grown in elevated glucose concentrations. Simulations indicate that the cell membrane is largely inaccessible to these sensors and that cytosolic crowding is broadly uniform across each cell over a timescale of seconds. Millisecond single-molecule optical microscopy was used to track molecules and obtain brightness estimates that enabled calculation of crowding sensor copy numbers. The quantification of diffusing molecule trajectories paves the way for correlating subcellular processes and the physicochemical environment of cells under stress.