A sensor for liquid biopsy, its method of making, and its method of non-invasive use. The sensor includes a substrate with a surface functionalized with biotinylated antibodies. The biotinylated antibodies are arranged to engage with surface proteins on exosomes associated with malignant cancer cells such as glioma cells.

Provided herein are methods of identifying an inhibitory activity of an exogeneous agent that disrupts binding of a target peptide to a biomolecule using phase separation as in cellulo read-out. Provided herein also are kits for the methods, pharmaceutical compositions comprising the agents screened by the methods, methods of preparing the pharmaceutical composition, and methods of treating a disease or condition in a subject in need thereof by administering the pharmaceutical composition.

The present invention relates to microfluidic fluidic devices, methods and systems for use in identifying epigenetic signatures in a range of sample types, e.g., cells established on a chip (including but not limited to single cell samples, cell populations, cell layers and whole tissues, such as a biopsy), immune cells, cfDNA, exosomes, and the like. More specifically, in some embodiments, a microfluidic chip containing a sample is contacted with a test compound (e.g. DNA altering test compound, an RNA expression altering test compound, etc.) for use in providing a diagnostic epigenetic signature for that type of sample (or cell type) exposed to that specific test compound. In some embodiments, after contact with a test compound, effluent fluids (e.g. fluids exiting the chip that contacted the cells) are derived for testing as a virtual blood draw. In some embodiments, epigenetic signatures include (but are not limited to) identifying specific combinations of modifications of chromosomes and specific modifications of DNA.

The invention relates to a method for analysing an interaction between a first molecule and a second molecule bonded to a particle, including the following steps: contacting the first molecule with the second molecule bonded to the particle under conditions enabling the interaction thereof; applying a predetermined liquid flow to the particle bonded to the second molecule; observing a movement of the particle bonded to the second molecule caused by the applied flow; analysing the interaction according to the movement observed and the applied flow, the particle having a greater hydrodynamic resistance than the first and/or second molecule, and a mass Pclet number of greater than 1. The invention also relates to a device for analysing an interaction between a first molecule and at least one second molecule, as well as to the use of the method or of the device in screening a candidate molecule for developing a drug.

Methods are provided for detecting circulating tumor cells in a mammalian subject. Methods of diagnosing cancer in a mammalian subject are provided. The methods of detection or diagnosis indicate the presence of metastatic cancer or early stage cancer.

A composition comprising a novel Ca.sup.2+-activated, [ATP].sub.i-sensitive nonspecific cation (NC.sub.Ca-ATP) channel is described. The channel is found in mammalian neural cells and exhibits a different sensitivity to block by various adenine nucleotides, and is activated by submicromolar [Ca].sub.i. The NC.sub.Ca-ATP channel is activated under conditions of ATP depletion, which causes severe cell depolarization, followed by cell swelling. The NC.sub.Ca-ATP channel is regulated by a sulfonylurea receptor and is inhibited by sulfonylurea compounds glibenclamide and tolbutamide. Methods employing compositions comprising the NC.sub.Ca-ATP channel to screen for compounds that block the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described. In addition, methods employing compositions comprising the Kir2.3 channel to screen for compounds that open the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described.

This disclosure describes a cell genetically modified to detect ribosome inhibition in the cell and methods involving such a cell. Generally, the genetically-modified cell includes an aminoglycoside-sensitive orthogonal 16S rRNA (O-16S) coding region bearing a mutated anti-Shine-Dalgarno (O-ASD) sequence, a repressor/operator system, and a polynucleotide encoding a detectable reporter under transcriptional control of the repressor/operator system. The repressor/operator system includes a coding region that encodes a transcriptional regulator and having an orthogonal SD (O-SD) sequence complementary to the 16S rRNA O-ASD sequence. The operator sequence, which is repressable by the transcriptional regulator, is operably linked to the polynucleotide encoding a detectable reporter.

The invention relates to isolation of adipocyte-derived exosomes from a biological sample, as well as methods, compositions and kits for detecting an obesity-related disorder, for detecting risk of having an obesity-related disorder, for screening or identifying a therapy for an obesity-related disorder, for screening or identifying a therapeutic agent for an obesity-related disorder, and for treating or preventing an obesity-related disorder.

The invention provides a carrier and a method for obtaining, removing, or detecting extracellular membrane vesicle or virus present in a sample. In particular, the invention provides (a) a carrier (a Tim carrier) on which a protein (a Tim protein), selected from a T-cell immunoglobulin and mucin domain-containing molecule-4 (a Tim-4) protein, a Tim-3 protein, and a Tim-1 protein, is bound; (b) a method for obtaining the extracellular membrane vesicle or the virus in the sample; (c) a method for removing the extracellular membrane vesicle or the virus in the sample; (d) a method for detecting the extracellular membrane vesicle or the virus in the sample; (e) a kit for capturing the extracellular membrane vesicle or the virus, comprising the Tim carrier; and f) a kit for capturing the extracellular membrane vesicle or the virus, comprising a reagent containing the Tim protein and a reagent containing the carrier.

This invention relates to substrates and methods for the visualization of intracellular organelles, such as the lysosome, peroxiosome, nucleus, Endoplasmic Reticulum and Golgi Apparatus, based upon organelle enzyme activity. Such compounds represent a novel combination of chemically distinct enzyme substrates with targeting and detection substrates which are activated by enzyme activity inside target organelles to produce a detectable signal. The organelle targeted enzyme substrates of this invention are designed to provide high fluorescence at lower pH values found in some organelles and can be used for monitoring enzyme activity inside cells at very low concentrations.