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: 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: 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 pm 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 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: A system for detecting target molecules includes a sample well defining a sensing region and two electrode regions, a sensor positioned in the sensing region and sensitized to the target molecules, an electrode positioned in each electrode region and configured to expose the sensor to a frequency-modulated electric field, and a detector configured to detect both an amplitude of oscillation of the sensor at a frequency of the modulated electric field and a direction of a displacement of the sensor. The sensing region defines a channel between the electrodes, and a ratio of a current density at a center of the sensing region to a current density at one of the electrodes is at least 2. The system allows detection of target molecules in a normal ionic strength buffer (e.g., having an ionic strength in a range of about 10 mM to about 1 M).

Abstract: Provided herein are methods of determining antibiotic susceptibility of bacteria. In some embodiments, the methods include obtaining a series of images from partitioned samples over a length of time using a large volume scattering imaging (LVSi) technique to produce a set of image data. In some embodiments, the methods include extracting multiple phenotypic features from individual bacterial cells in the partitioned samples in parallel with one another and detecting one or more phenotypic feature changes associated with bacterial growth and response to the antibiotics in the set of image data over a selected period of time to produce a set of extracted phenotypic features, and passing the set of extracted phenotypic features through a trained machine learning model that predicts the identity and the antibiotic susceptibility of the bacterial cells in the partitioned samples. Related kits, devices, systems, computer readable media, and additional methods are also provided.

Abstract: Provided herein are methods of detecting single-molecule binding kinetics that include contacting a set of single molecules with a surface of an optically transparent substrate and irradiating the surface of the substrate with light having an incident angle selected to achieve total reflection of the light. In some embodiments, the methods include collecting light scattered by the surface and by the subset of the single molecules having the binding association with the surface of the substrate to form a series of raw image data sets, and detecting multiple individual binding and leaving events for the subset of the single molecules having the binding association with the surface of the substrate over one or more selected durations using the series of raw image data sets to produce a detected individual binding and leaving event data set. Systems, computer readable media, and additional methods 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 caused 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: A system for detecting target molecules includes a sample well defining a sensing region and two electrode regions, a sensor positioned in the sensing region and sensitized to the target molecules, an electrode positioned in each electrode region and configured to expose the sensor to a frequency-modulated electric field, and a detector configured to detect both an amplitude of oscillation of the sensor at a frequency of the modulated electric field and a direction of a displacement of the sensor. The sensing region defines a channel between the electrodes, and a ratio of a current density at a center of the sensing region to a current density at one of the electrodes is at least 2. The system allows detection of target molecules in a normal ionic strength buffer (e.g., having an ionic strength in a range of about 10 mM to about 1 M).

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: 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.

Abstract: Provided herein are methods of performing multiplex detection of ligand binding kinetics. In some embodiments, the methods include contacting ligands with an array of nucleic acid barcoded oscillators disposed on a first surface of a substrate that comprises an electrically conductive coating, applying an AC electric field to the substrate sufficient to induce the nucleic acid barcoded oscillators to oscillate proximal to the first surface of the substrate, and detecting changes in oscillation amplitudes of the nucleic acid barcoded oscillators over a duration to produce sets of ligand binding data.

Abstract: The present disclosure relates to the use of DNA-peptide hybrid molecules to detect target molecules in a sample. In some embodiments, the DNA-peptide hybrid molecules comprise target-specific binding peptides which selectively bind to a target molecule. Kits comprising DNA-peptide hybrid molecules 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: A forming device and a preparation method of a graphite crucible are provided. The forming device includes: a support frame, including a base; a male die, disposed on the support frame and far away from the base and movable reciprocally in a vertical direction relative to the support frame; a crucible mouth pressing member, disposed on the support frame, correspondingly disposed on a side of the male die close to the base, movable reciprocally in the vertical direction relative to the support frame, and defining an opening part allowing the male die to pass therethrough; and a female die, disposed on the base and corresponding to the male die, and configured to accommodate crucible paste. The male die, the crucible mouth pressing member and the female die are configured to cooperatively form the crucible paste into the graphite crucible.

Abstract: Provided herein are methods of detecting target molecules. The methods include contacting a sample comprising the target molecule with a substrate that comprises a plurality of capture antibodies, or antigen binding portions thereof, that specifically bind to the target molecule to form captured target molecules, and contacting the captured target molecules with a plurality of detection antibodies, or antigen binding portions thereof, that bind to the captured target molecules to form target molecule complexes. The methods also include taking images of the target molecule complexes to produce imaged target molecule complexes, and quantifying an amount of target molecules in the sample using the imaged target molecule complexes. Additional methods as well as related devices and systems are also provided.

Abstract: Provided herein are methods of quantifying amounts of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) in whole blood samples. The methods include contacting detection antibody-NT-proBNP complexes with a plurality of capture antibodies, or antigen binding portions thereof, that specifically bind to the NT-proBNP molecules of the detection antibody-NT-proBNP complexes to form captured NT-proBNP complexes, and contacting NPs that each comprise a second recognition moiety that binds to the first recognition moiety of the detection antibodies, or antigen binding portions thereof, of the captured NT-proBNP complexes to form captured NP-NT-proBNP complexes. The methods also include taking images of the captured NP-NT-proBNP complexes to produce imaged captured NP-NT-proBNP complexes using a detection mechanism, and quantifying an amount of NT-proBNP in the sample aliquots using the imaged captured NP-NT-proBNP complexes. Additional methods as well as related devices and systems 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 differentiating cell types in a cell population. The methods include removing at least some non-Chimeric Antigen Receptor (CAR)-T cells from a fluidic sample obtained from a subject without centrifuging the fluidic sample to produce a purified fluidic sample. The fluidic sample comprises CAR-T cells and the non-CAR-T cells. The methods also include capturing cells in the purified fluidic sample on a surface that comprises binding moieties that bind at least to the CAR-T cells to produce a captured cell population. In addition, the methods also include distinguishing the CAR-T cells from the non-CAR-T cells in the captured cell population using a trained machine learning model to produce a captured CAR-T cell population data set. Additional methods as well as related devices and systems are also provided.

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.