Abstract: This disclosure describes systems and methods for critical angle reflection (CAR) imaging to quantify molecular binding kinetics on a glass surface in some embodiments. CAR is a label-free method that measures the reflectivity change near a critical angle in response to molecular binding induced refractive index changes on the sensor surface. The sensitivity and dynamic range of CAR is tunable by varying the incident angle of light, which allows for optimizing the measurement for ligands with different sizes in both biomolecular and cell-based studies.

Abstract: Provided herein are methods of determining binding kinetics of a ligand. In some embodiments, the methods include contacting the ligand with a first surface of a substrate, which first surface comprises an electrically conductive coating and a population of receptors connected to the first surface via one or more linker moieties, wherein the receptors bind, or are capable of binding, to the ligand, applying an alternating current electric field to the substrate to induce the receptors to oscillate proximal to the first surface of the substrate, and detecting changes in oscillation amplitudes of the receptors over a duration. Related receptor oscillator array devices, systems and computer readable media are also provided.

Abstract: Provided herein are methods of detecting unlabeled biomolecules. In some embodiments, the methods include disrupting a cell population sufficient to release unlabeled biomolecules from the cell population to produce released biomolecules in which the cell population is disposed on a first inner surface of a chamber that is disposed substantially within a fluidic device and in which the chamber comprises a fluidic material. In some embodiments, the methods also include binding the released biomolecules to a second inner surface of the chamber to produce surface-bound biomolecules, introducing an incident light toward the second inner surface of the chamber concurrent with, and/or after, producing the surface-bound biomolecules, and detecting light scattered by the surface-bound biomolecules over a duration to produce a set of biomolecule imaging data. Related fluidic devices, systems, and computer readable media are also provided.

Abstract: Provided herein are methods of determining molecular binding kinetics on particles, such as magnetic nanoparticles. In some embodiments, the methods include introducing an incident light from a light source toward a sample container that comprises a particle-bound biomolecule-ligand composition comprising a plurality of particle-bound biomolecules and a plurality of ligands that binds, or is capable of binding, to biomolecules of the plurality of particle-bound biomolecules, detecting light scattered from particle-bound biomolecule-ligand complexes in the particle-bound biomolecule-ligand composition over a duration to produce a set of imaging data using the detector, and determining size or volume changes of one or more of the particle-bound biomolecule-ligand complexes during at least a portion of the duration from the set of imaging data to thereby determine the molecular binding kinetics on the particles. Related systems and computer readable media are also provided.

Abstract: Provided herein are methods of tracking molecular dynamics in three dimensions. In some embodiments, the methods include introducing an incident light toward a second surface of a substrate to induce a plasmonic wave at least proximal to a first surface of the substrate. A population of particles is connected to the first surface of the substrate via one or more first biomolecules. In some embodiments, the methods also include detecting a change in position of the particles in the population along at least three dimensions over a duration from a change in intensity of the incident light reflected at an interface of the first surface of the substrate. Related systems and computer readable media are also provided.