Abstract: Provided herein is a method of detecting microorganisms in liquid samples using image features, such as time profiles of object light scattering intensity and time profiles of object position. Related methods, devices, systems, and other aspects are also provided.

Abstract: Provided herein are methods of detecting single molecules that include binding single molecules in a sample solution to a first surface of an optically transparent substrate include the optically transparent substrate is free of a metallic coating. In some embodiments, the methods include irradiating the first surface of the substrate with an incident light having an incident angle selected to achieve total internal reflection of the incident light, thereby scattering light from the first surface and from the single molecules bound to the surface in which a wavelength of the incident light is between 10 nm and 350 ?m and the optically transparent substrate has a refractive index at the wavelength of the incident light exceeding that of the sample solution, and collecting an image that captures interference between evanescent light scattered from the single molecules and the first surface. Systems and additional methods are also provided.

Abstract: Provided herein are methods of assessing the presence of microbes in a liquid sample that include assessing an initial integrated scattering intensity of objects (IC0) in the sample and an integrated scattering intensity of the objects at a time t (ICt) from modified images of the liquid sample, and identifying the sample as comprising microbes for (ICt)/(IC0) above a predefined infection threshold TI. Related systems and other aspects are also provided.

Abstract: Provided herein are systems for the label-free detection of target molecules in samples. The systems include a sensor probe positioned in a sensing region and configured to bind to receptors for the target molecules. The systems also include electrodes configured to expose the sensor probe to an alternating electric field, and a light source optically coupled to the sensor probe and configured to provide light along a length of the sensor probe. In addition, the systems also include a position sensitive photodetector configured to detect a position of light exiting the sensor probe, and a processor configured to assess, based at least in part on the position of the light exiting the sensor probe, an amplitude of oscillation of the sensor at a frequency of the alternating electric field and a direction of a displacement of the sensor. Additional systems and related methods are also provided.

Abstract: Provided herein are methods of assessing the presence of microbes in a liquid sample that include assessing an initial integrated scattering intensity of objects (IC0) in the sample and an integrated scattering intensity of the objects at a time t (ICt) from modified images of the liquid sample, and identifying the sample as comprising microbes for (ICt)/(IC0) above a predefined infection threshold TI. Related systems and other aspects are also provided.

Abstract: The present disclosure provides use of Clostridium ghonii combined with a tumor angiogenesis inhibitor in preparing a pharmaceutical product for treating a tumor. The present disclosure further provides a drug for treating a tumor, where the drug includes active ingredients of Clostridium ghonii and a tumor angiogenesis inhibitor.

Abstract: The present disclosure relates to use of a Clostridium ghonii spore combined with pembrolizumab in cancer treatment. It is found for the first time that the Clostridium ghonii spore combined with pembrolizumab can significantly improve a curative effect of colon cancer and reduce a dose of the pembrolizumab, and thus is efficient and low-toxic. Oncolysis by Clostridium ghonii can affect immunogenicity of a tumor microenvironment (TME) by various ways, converts an immunosuppressive state of the TME into an immune-activated state, adjusts the immunosuppressive TME, and breaks an immune tolerance. An optimal combination of the Clostridium ghonii spore and the pembrolizumab thoroughly removes about 20% of mouse tumor tissues. A benefit range of patients with tumors treated by a PD-1 antibody is expanded. The combination even has an obvious curative effect on patients failed the treatment by the PD-1 antibody.

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: A method for deep learning video microscopy-based antimicrobial susceptibility testing of a bacterial strain in a sample by acquiring image sequences of individual bacterial cells of the bacterial strain in a subject sample before, during, and after exposure to each antibiotic at different concentrations. The image sequences are compressed into static images while preserving essential phenotypic features. Data representing the static images are input into a pre-trained deep learning (DL) model which generates output data; and antimicrobial susceptibility for the bacterial strain is determined from the output data.

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 modulating temperature in detection fields and producing analyte imaging data. In some embodiments, the methods include introducing an incident light toward a second surface of a substrate to induce a plasmonic wave proximal to a first surface of the substrate such that a temperature in a selected heating space within the detection field is substantially uniformly changed to a selected temperature. Additional methods as well as related systems and computer readable media are also provided.

Abstract: Provided herein are methods of detecting exosomes, including unlabeled exosomes. In some embodiments, the methods include disposing a fluidic sample that comprises a plurality of exosomes in a chamber that is positioned at least partially within a fluidic device in which an inner surface of the chamber comprises a first set of exosome binding moieties that are capable of binding the exosomes. In some embodiments, the methods also include binding a portion of the plurality of exosomes to a portion of the first set of exosome binding moieties to produce surface-bound exosomes, introducing an incident light toward the inner surface of the chamber prior to, concurrent with, and/or after, producing the surface-bound exosomes, and detecting light scattered by the surface-bound exosomes to produce a set of exosome imaging data. Related fluidic devices, systems, and computer readable media are also provided.

Abstract: A method for deep learning video microscopy-based antimicrobial susceptibility testing of a bacterial strain in a sample by acquiring image sequences of individual bacterial cells of the bacterial strain in a subject sample before, during, and after exposure to each antibiotic at different concentrations. The image sequences are compressed into static images while preserving essential phenotypic features. Data representing the static images is input into a pre-trained deep learning (DL) model which generates output data; and antimicrobial susceptibility for the bacterial strain is determined from the output data.

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 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 virions connected to the first surface via one or more linker moieties, wherein viral envelopes of the virions display one or more proteins that bind, or are capable of binding, to the ligand, applying an alternating current electric field to the substrate to induce the virions to oscillate proximal to the first surface of the substrate, and detecting changes in oscillation amplitudes of the virions over a duration. Related virion oscillator array 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: Disclosed herein is a system and method for quantitative detection and analysis of molecular binding kinetics of a substance with surface membrane proteins of a biological object, such as a live cell, based on detecting and tracking membrane fluctuation amplitude changes cause by membrane displacement associated with the binding of the substance with the surface membrane proteins. The molecular binding kinetics can be detected with high precision in real time from an optical image of the biological object with a differential detection method.

Abstract: Detecting single bacterial cells in a sample includes collecting, from a sample provided to an imaging apparatus, a multiplicity of images of the sample over a length of time; assessing a trajectory of each bacterial cell in the sample; and assessing, based on the trajectory of each bacterial cell in the sample, a number of bacterial cell divisions that occur in the sample during the length of time.

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.

Abstract: Detecting single molecules includes binding the single molecules to a surface of an optically transparent substrate, irradiating the surface of the substrate with light having an incident angle selected to achieve total reflection of the light, thereby scattering light from the surface and from the single molecules bound to the surface, and collecting light scatted by the surface and by the single molecules bound to the surface to form a series of images. Systems for detecting single molecules include an optically transparent substrate, a means for flowing a sample solution over a surface of the substrate, a light source configured to irradiate the surface, a camera, and a collection optical system configured to collect light scatted by the surface and by the target molecules on the surface to form a series of images on the camera.