Abstract: Disclosed herein are nanoparticles that include one or more cyclodextrin moieties crosslinked by a linker. The cyclodextrin moieties can complex therapeutic (e.g., anticancer) agents, and can be used to treat diseases such as cancer.

Abstract: The present disclosure provides bioorthogonal linkers and reagents, including trans-cyclooctene (“TCO”)- and tetrazine (“Tz”)-containing compounds. In a general aspect, the present disclosure provides reagents, conjugates, and bioactive molecules containing a trans-cyclooctene (“TCO”) fragment. Examples of TCO fragments include: Formulae (I) and (II).

Abstract: The present invention, in some aspects, provides methods, reagents, compositions, and kits for the radiolabeling of proteins, for example, of proteins useful for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) (e.g., for diagnostic and therapeutic applications), using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a radioactive agent or molecule to diagnostic or therapeutic peptides or proteins. Compositions comprising sortagged, radiolabeled proteins as well as reagents for generating radiolabeled proteins are also provided. Kits comprising reagents useful for the generation of radiolabeled proteins are provided, as are precursor proteins that comprise a sortase recognition motif.

Abstract: Aspects of the present disclosure provide devices and methods for rapid, quantitative, on-site detection of controlled substances. Devices include a sample processing module and a sensor cartridge, and optionally a detection cradle.

Abstract: Systems, methods, and device can be used to detect target extracellular vesicles (“EVs”). One example of a method includes obtaining a nano-plasmonic array including nanostructures configured to amplify one or more specific wavelengths of electromagnetic radiation, flowing a liquid sample over the nano-plasmonic array, optionally labeling target EVs captured on the nano-plasmonic array with one or more reporter groups, projecting electromagnetic radiation onto the labeled target EVs captured on the nano-plasmonic array, and capturing an image of the target EVs by receiving electromagnetic radiation emitted, scattered, or reflected by the EVs or by reporter groups on the labeled target EVs.

Abstract: Systems, methods, and devices are described herein for detecting and/or monitoring target extracellular vesicles (“EVs”), e.g., to detect and/or monitor cancer treatment, such as breast cancer, in a subject. The methods can include obtaining a nano-plasmonic array including nanostructures configured to amplify one or more specific wavelengths of electromagnetic radiation, flowing a liquid sample over the nano-plasmonic array, optionally labeling target EVs captured on the nano-plasmonic array with one or more reporter groups, projecting electromagnetic radiation onto the labeled target EVs captured on the nano-plasmonic array, and capturing an image of the target EVs by receiving electromagnetic radiation emitted, scattered, or reflected by the labeled target EVs or by reporter groups on the labeled target EVs.

Abstract: The present application provides a compound of Formula (A), or a pharmaceutically acceptable salt thereof, wherein R1, L1, n, L2, m, L3, p, Y2, and Y3 are as described herein. Methods of using the compound of Formula (A) to prepare an antibody conjugate, and methods of using these conjugates for cellular imaging are also described.

Abstract: The present disclosure provides, in some embodiments, devices, methods, and kits for purifying extracellular vesicles (EVs) using size exclusion chromatography in tandem with cation exchange chromatography, which can be referred to as dual-mode chromatography (DMC).

Abstract: The disclosure features systems and methods for measuring and diagnosing target constituents bound to labeling particles in a sample. The systems include a radiation source, a sample holder, a detector configured to obtain one or more diffraction patterns of the sample each including information corresponding to optical properties of sample constituents, and an electronic processor configured to, for each of the one or more diffraction patterns: (a) analyze the diffraction pattern to obtain amplitude information and phase information corresponding to the sample constituents; (b) identify one or more particle-bound target sample constituents based on at least one of the amplitude information and the phase information; and (c) determine an amount of at least one of the particle-bound target sample constituents in the sample based on at least one of the amplitude information and the phase information.

Abstract: Described herein are methods, uses, and kits for droplet-based single cell sequencing of nucleic acids from extracellular vesicles. Specifically, the disclosure provides methods of analyzing protein compositions from individual extracellular vesicles (EVs) from biological samples including pluralities of EVs, the methods comprising labeling the EVs with antibody-DNA conjugates; encapsulating the labeled EVs, barcoded beads, and an extension reagent mix into droplets; within one or more of the droplets, hybridizing the antibody-DNA conjugates with a hybridization region in the barcoded beads; generating RNA from the DNA; synthesizing cDNA from the RNA; amplifying and sequencing the cDNA from one or more individual EVs from the biological sample; and analyzing the sequence of the cDNA from individual EVs to define their protein composition.

Abstract: The present application provides a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein L1, L2, L3, n, m, p, X, T, TR, and D are as described herein. Methods of using of these compounds to treat diseases advantageously treatable by drug D are also described.

Abstract: The present application relates to functionalized 1,2,4,5-tetrazine compounds. The compounds are useful in compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reactions for the rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target.

Abstract: Methods of treating a subject (e.g., a mammalian, preferably human, subject) with cancer, e.g., with melanoma, comprising administering a combination of an inhibitor of the non-canonical NFkB pathway and a checkpoint inhibitor.

Abstract: Target analyte detection devices include a housing having a potentiostat and a microcontroller coupled to the potentiostat. The device also includes a substrate having a plurality of electrodes on a first surface of the substrate. A first set of electrodes of the plurality of electrodes defines a first sample detection region. The substrate is removably attachable to the housing such that the first set of electrodes is coupled to the potentiostat upon attaching the substrate to the housing. The device also includes a magnet assembly couplable to a second surface of the substrate. The magnet assembly includes a magnet positioned in the magnet assembly such that a magnetic field from the magnet extends through the substrate and the first set of electrodes into an area above the first sample detection region upon coupling the magnet assembly to the substrate.

Abstract: The disclosure features systems and methods for measuring and diagnosing target constituents bound to labeling particles in a sample. The systems include a radiation source, a sample holder, a detector configured to obtain one or more diffraction patterns of the sample each including information corresponding to optical properties of sample constituents, and an electronic processor configured to, for each of the one or more diffraction patterns: (a) analyze the diffraction pattern to obtain amplitude information and phase information corresponding to the sample constituents; (b) identify one or more particle-bound target sample constituents based on at least one of the amplitude information and the phase information; and (c) determine an amount of at least one of the particle-bound target sample constituents in the sample based on at least one of the amplitude information and the phase information.

Abstract: This document relates to compounds useful for targeting PARP1. Also provided herein are methods for using such compounds to detect and image cancer cells.

Abstract: In an exemplary method, a sample is provided. The sample contains a polymerase molecule, a receptor molecule containing a fluorophore, and a detector molecule. The detector molecule is configured to, in the presence of a target nucleic acid, inhibit the polymerase molecule from cleaving the fluorophore. A level of fluorescence anisotropy from the sample is detected to determine the absence or presence of the target nucleic acid in the sample.

Abstract: The present invention, in some aspects, provides methods, reagents, compositions, and kits for the radiolabeling of proteins, for example, of proteins useful for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) (e.g., for diagnostic and therapeutic applications), using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a radioactive agent or molecule to diagnostic or therapeutic peptides or proteins. Compositions comprising sortagged, radiolabeled proteins as well as reagents for generating radiolabeled proteins are also provided. Kits comprising reagents useful for the generation of radiolabeled proteins are provided, as are precursor proteins that comprise a sortase recognition motif.

Abstract: Disclosed herein are nanoparticles that include one or more cyclodextrin moieties crosslinked by a linker. The cyclodextrin moieties can complex therapeutic (e.g., anticancer) agents, and can be used to treat diseases such as cancer.

Abstract: Compositions comprising a macrophage-targeted carrier and one or more therapeutic agents that modulate cardiac conductance, and methods of using the same for treating subjects with cardiac rhythm disorders, e.g., bradycardia or tachycardia.