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.
Whispering gallery mode microtoroid optical resonators are one of the most sensitive and rapid optical sensors in existence. These sensors can detect extremely low analyte concentrations down to attomolar levels on the order of seconds. How these sensors have such a rapid response time even at these low concentrations is a question in the field. Here, we show that total analyte arrival and binding time can occur in seconds using flow visualization and finite-element simulations.
Detecting single molecules without labels or capture probes is of great interest for both medical applications and scientific research. Frequency-locked microtoroid optical resonators are capable of label-free single molecule detection, however, this approach requires a priori knowledge of the molecule to be detected as well as surface functionalization of the cavity. Optical frequency microcombs can be a precise source of spectral information on molecules, however, microcombs have not been generated in an aqueous biological sensing environments due to altered dispersion, coupling instability, and reduced quality factor of the resonator. Here we suggest a way toward single-molecule spectroscopy by demonstrating frequency comb generation in water and air at visible wavelengths using a microtoroid optical resonator. Local anomalous dispersion is achieved because of the interaction between different transverse mode families in an overall normal dispersion region. With this approach, the advantageous structure and material of the microtoroid resonator for biosensing is preserved. We believe that in the future this will enable single molecule detection and identification simultaneously in both air and liquid at any wavelength with no labels or capture probes.
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.
Utilization of frequency locking for tracking optical resonances of microresonators is an emergent technique, which has relevance in label-free biosensing, owing to its extremely high sensitivity in detecting adsorption on a microcavity’s surface. In this study, we demonstrate the capabilities of a technique known as FLOWER (Frequency Locked Optical Whispering Evanescent Resonator) in a real-life problem: the detection of human chorionic gonadotropin (hCG) in urine samples. hCG, besides being a hormone secreted during pregnancy, is a performance enhancing agent prone to be abused by athletes, and is routinely investigated in doping laboratories. The gold standard in hCG detection is mass spectrometry. As the lowest limit of detection by mass spectrometry is close to the cut-off value for a positive result, various other measurement techniques such as optical interferometry, photoluminescence, or electrochemical sensors have been used to try to enhance measurement sensitivity. These methods, however, do not show a significant improvement in the limit of detection over mass spectrometry and they mostly have a narrow detection range. In addition, measurement selectivity is another issue. Here, we use microtoroidal optical resonators functionalized with antibodies against hCG, and track their resonances using frequency locking upon analyte infusion. Urine samples from pregnant women were measured using our setup. Our results demonstrate that FLOWER can detect the presence of hCG in a large concentration range from 1 fM to 10 nM.
An imaging lidar system is presented which combines the high speed of a Digital Micromirror Device (DMD) and the higher range of a 1D collimated scanning output. The system employing 1D line object illumination along with DMD placed at focal plane enables flexible optimization of system metrics, such as field of view, angular resolution, maximum range distance and frame rate.
Spatial light modulators (SLMs) that operate in a phase modulation mode enable beam steering with higher diffraction efficiency compared to amplitude modulation mode, thus potentially be used for an efficient beam steering with no moving part. Currently, Twisted Nematic phase SLMs are widely adopted for phase modulation. However, their refresh rate is typically in the range below kilohertz. Recently, a new method for binary and spatial phase modulation using Digital Micromirror Device (DMD) was proposed by a research group in Germany. In the method, complemental self-images of DMD, corresponding to on- and off-pixels, are formed by two auxiliary optics while adding a pi phase shift between two images. The optics function as recycling of light in a coherent manner. The method enables over kilohertz refresh rate and higher diffraction efficiency in binary phase modulation mode to conventional amplitude binary modulation.
As alternatives to the binary phase modulation, we propose and experimentally evaluated high-speed beam steering by DMD based on light recycling. In our experiment, with binary phase modulation mode, system output efficiency reaches 8%. It can be doubled to 16% with light recycling method. Efficiency is still low compared to the reported value of 27% without light recycling. To further increase beam efficiency, system loss was analysed.
A novel method of beam steering, utilizing a mass-produced Digital Micromirror Device (DMD), enables a reliable single chip Light Detection and Ranging (LIDAR) with a large field of view while having minimum moving components. In the single-chip LIDAR, a short-pulsed laser is fired in a synchronous manner to the micromirrors rotation during the transitional state. Since the pulse duration of the laser pulse is substantially short compared to the transitional time of the mirror rotation, virtually the mirror array is frozen in transition at several discrete points, which forms a programmable and blazed grating. The programmable blazed grating efficiently redirects the pulsed light to a single diffraction order among several while employing time of flight measurement. Previously, with a single 905nm nanosecond laser diode and Si avalanche photo diode, a measurement accuracy and rate of <1 cm and 3.34k points/sec, respectively, was demonstrated over a 1m distance range with 48° full field of view and 10 angular resolution. We have also increased the angular resolution by employing multiple laser diodes and a single DMD chip while maintaining a high measurement rate of 3.34k points/s. In addition, we present a pathway to achieve 0.65° resolution with 60° field of view and 23k points/s measurement rate.
A novel Digital Micromirror Device (DMD) based beam steering enables a single chip Light Detection and Ranging (LIDAR) system for discrete scanning points. We present increasing number of scanning point by using multiple laser diodes for Multi-beam and Single-chip DMD-based LIDAR.
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