Vaccines for the COVID-19 pandemic are limited and so effective drugs are needed. The binding affinity of several SARS-CoV-2 variants to human ACE2 receptors was measured using a frequency-locked optical whispering evanescent resonator (FLOWER) system. The advantage of FLOWER is that it is label-free and so drug candidates do not need to be labeled and it is ultra-sensitive so drugs over a wide range of binding affinities can be tested. The dissociation equilibrium constants of spike-RBD wild type as well as two variants, were analyzed and compared. Several drug candidates which inhibit the spike-RBD binding to ACE2, predicted by in-silico simulation, were screened using a competitive binding assay and the corresponding inhibitor constants were measured.
We use a system known as FLOWER (frequency locked optical whispering evanescent resonator) to rapidly detect trace amounts of the chemical warfare agent surrogates DIMP and DMMP. We use sorbent polymer layers covalently bound to the surface of the microtoroid cavity to selectively adsorb target gases. As the target gas diffuses into the polymer layer, a measurable change in the resonance frequency of the toroid occurs. We demonstrate 80 ppt (part per trillion) sensing of DIMP; two orders of magnitude better than what can be achieved using mass spectroscopy.
High Q whispering gallery mode optical resonators are capable of rapid and ultra-sensitive biological detection at attomolar concentrations in under 30 seconds. One main question in the field is how these sensors detect such low concentrations of molecules so quickly. Calculations based on diffusion alone suggest that transport to these sensors should take hours to days. Here, we show using bromothymol blue dye flow visualization methods that transport to a microtoroid optical resonator can take place in seconds. We reconcile these results with finite element simulations.
Accurate measurement of Amyloid-β biomarkers in blood serum has been highly sought after for early detection of Alzheimer’s Disease (AD). However, non-specific binding and low levels of Amyloid-β in blood pose a problem for traditional immunoassays. Here, we propose a lipid-functionalized biosensor for real-time, label-free detection of Amyloid-β by interaction with whispering gallery modes (WGM) of a microtoroid optical resonator. Non-specific binding is reduced by uniform surface coverage of the lipid, and protein-lipid interactions enhance the shift in resonance frequency. The lipid surface functionalization scheme enables increased accuracy and sensitivity of Amyloid-β and potential for blood-based screening of AD.
Whispering-gallery mode (WGM) microtoroid optical resonators have been used for highly sensitive biological and chemical sensing. With the help of auto-balanced detection and data processing techniques, frequency locked optical whispering evanescent resonator (FLOWER) has successfully reduced external noise and achieved detection of single macromolecules. FLOWER, however, can only analyze the size of particles and not their shape. To determine the shape of non-spherical particles interacting with different polarized WGM modes, we built a dual-FLOWER system to perform multi-mode locking. We demonstrate the ability of this system to detect particle shape by detecting gold nanorods and spheres.
Most biosensors rely on immobilized antibodies or aptamers. In contrast, receptor proteins exist naturally in lipid bilayers and are highly specific to small molecules. We use a frequency-locked optical whispering evanescent resonator (FLOWER) system for real-time quantification of rhodopsin incorporation into an artificial lipid membrane and observe photo-induced molecular transformations upon light activation. Our study of proteolipid membrane coated microtoroids for probing the local activity of G-protein coupled receptors was further expanded to kappa-opioid receptors and their endogenous ligand Dynorphin-A. G-protein coupled receptor signaling probed by a microtoroid-proteolipid system will facilitate drug discovery and therapeutic interventions.
Local field enhancement of plasmonic nanoantennas below the diffraction limit plays an important role in a variety of applications, including surface-enhanced Raman scattering, spontaneous emission enhancement, nanolasing, enhanced nonlinear effects and biosensing. Yet due to the radiation and ohmic loss of these nanocavities, their quality factor (Q) is much smaller than a typical optical microcavity Q factor, such as that of a microsphere or microtoroid. Coupling a nanoantenna to an optical microcavity increases the Q of the hybrid plasmonic-photonic system, however, this dramatically degrades the Q of the original microcavity. Here, we propose a judicious hybridization of a plasmonic dark mode of a gold nanoring and whispering gallery mode (WGM) of a microtoroid. It is shown through finite element simulation that the hybridized WGM and dark mode of the proposed plasmonic gold nanoring solves the aforementioned issues in two ways. First, the small radiation loss of the dark mode minimizes Q degradation and allows the system to maintain its ultra-high Q. Second, the nanoring enhances the field on the microcavity’s surface which in turn increases the interaction between, for example, a biomolecular target and the WGM. We have shown that the proposed system generates larger resonance shifts compared to a microcavity loaded with same volume of conventional linear gold nanoantennas . This results in significant enhancement in the system’s sensitivity. We have repeated the same simulations for different materials and volumes.
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