Abstract: Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.

Abstract: Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.

Abstract: Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.

Abstract: Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.

Abstract: Automated methods and devices that facilitate iterative staining of biological samples from imaging applications are provided. The methods include the steps of providing a small volume flow cell containing a biological sample, applying a stain to the biological sample, combining at least two precursor reagents to form an activated destaining agent and wherein the activated destaining agent decomposition rate is greater than or similar to the destaining reaction rate, flowing the destaining agent over the biological sample at a flow rate that is greater than the decomposition rate of the activated destaining agent, and releasing the sample from the flow cell wherein the integrity of the sample is intact. The process of staining, combining and flowing may be iteratively repeated.

Abstract: The present invention relates to methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using a benzofuran compound or its radioisotope derivatives. In one embodiment a method of myelin detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the benzofuran compound, or a derivative of the compound, and determining myelination in the subject by detecting binding in the sample. In one embodiment, the invention provides a method of imaging myelinated tissue in a surgical field of mammalian tissue comprising the steps of contacting the surgical site with the benzofuran compound or a radioisotope derivative of the compound, and detecting binding in the surgical site.

Abstract: The present invention relates to methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using a benzofuran compound or its radioisotope derivatives. In one embodiment a method of myelin detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the benzofuran compound, or a derivative of the compound, and determining myelination in the subject by detecting binding in the sample. In one embodiment, the invention provides a method of imaging myelinated tissue in a surgical field of mammalian tissue comprising the steps of contacting the surgical site with the benzofuran compound or a radioisotope derivative of the compound, and detecting binding in the surgical site.

Abstract: A system for analyzing tissue samples, that generally comprises, a storage device for at least temporarily storing one or more images of one or more cells, wherein the images comprise a plurality of channels; and a processor that is adapted to determine the extent to which a biomarker may have translocated from at least one subcellular region to another subcellular region; and then to generate a score corresponding to the extent of translocation.

Abstract: Provided herein are agents that bind to soluble beta-amyloid. Also provided are in vivo and in vitro methods for detecting soluble beta-amyloid in a sample that may include brain tissue.

Abstract: Provided herein are amyloid-binding assays that simulate in situ brain conditions by combining binders with various A-beta species on mammalian brain tissue. In general the amyloid-binding assays comprise the steps of (a) contacting a mammalian brain tissue sample with at least one A-beta species; (b) applying a putative binder to the brain tissue sample; and (c) determining whether the putative binder binds to the A-beta species.

Abstract: Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets, binding at least one fluorescent probe to one or more target present in the sample, and binding at least at least one control probe to one or more target present in the sample. The methods include the steps of observing a signal from the fluorescent probe and a control signal from the control probe and applying to the sample a basic solution containing an oxidizing agent that selectively inactivates the fluorescent probe and not the control probe. The methods further include the steps of binding at least one fluorescent probe to one or more target present in the sample and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.

Abstract: Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets adhered to a solid support, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The method further includes the steps of oxidizing the bound fluorescent probe with a solution containing an oxidizing agent that substantially inactivates the fluorescent probe, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.

Abstract: Provided herein are agents that bind to soluble beta-amyloid. Also provided are in vivo and in vitro methods for detecting soluble beta-amyloid in a sample that may include brain tissue.

Abstract: The present invention relates to methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using a benzofuran compound or its radioisotope derivatives. In one embodiment a method of myelin detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the benzofuran compound, or a derivative of the compound, and determining myelination in the subject by detecting binding in the sample. In one embodiment, the invention provides a method of imaging myelinated tissue in a surgical field of mammalian tissue comprising the steps of contacting the surgical site with the benzofuran compound or a radioisotope derivative of the compound, and detecting binding in the surgical site.

Abstract: Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.

Abstract: Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.

Abstract: Automated methods and devices that facilitate iterative staining of biological samples from imaging applications are provided. The methods include the steps of providing a small volume flow cell containing a biological sample, applying a stain to the biological sample, combining at least two precursor reagents to form an activated destaining agent and wherein the activated destaining agent decomposition rate is greater than or similar to the destaining reaction rate, and flowing the destaining agent over the biological sample at a flow rate that is greater than the decomposition rate of the activated destaining agent. The process of staining, combining and flowing may be iteratively repeated. Also disclosed herein are devices for iterative staining of biological samples comprising a flow cell, in fluid communication with a premixer, wherein the volume capacity of the premixer is smaller than about five times the volume capacity of the flow cell.

Abstract: Agents, methods, and kits for qualitatively or quantitatively determining the presence of soluble A-beta in source of A-beta are provided, wherein the agents comprise the compound of formula III or the compound of formula III labeled with a signal generator.

Abstract: Provided herein are amyloid-binding assays that simulate in situ brain conditions by combining binders with various A-beta species on mammalian brain tissue. In general the amyloid-binding assays comprise the steps of (a) contacting a mammalian brain tissue sample with at least one A-beta species; (b) applying a putative binder to the brain tissue sample; and (c) determining whether the putative binder binds to the A-beta species.

Abstract: Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.