Abstract: Methods and kits for binding and releasing biological targets, comprising, a binder having an environmentally reactive molecular switch that can switch between a high affinity state, to bind the target, to a low affinity state, to release the target. In one embodiment, the binder is a pre-existing chemical sequence, composition, or structural configuration but unknown or unspecified and still viable as a binder for attaching a molecular switch.

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 and kits for binding and releasing biological targets, comprising, a binder comprising an environmentally reactive molecular switch that can switch between a high affinity state, to bind the target, to a low affinity state, to release the target.

Abstract: Novel methods of probing multiple targets in a biological sample are provide whereby the targets are DNA, RNA and protein. The method comprises subjecting the sample to an in situ hybridization reaction using a labeled nucleic acid probe that binds an RNA target, observing a signal, and optionally removing the signal. The method further comprises an antigen retrieval protocol, observing a signal, removing the signal, and optionally applying a protease treatment to access the sample's DNA targets by subjecting the sample to an in situ hybridization reaction using a labeled nucleic acid probe, observing a signal from the labeled DNA targets, and optionally removing the signal.

Abstract: Methods comprising the use of photoactivated chemical bleaching for detecting 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 probe to one or more target present in the sample, and observing a signal from the probe. The method further includes the steps of contacting the sample comprising the bound probe with an electron transfer reagent and irradiating the sample, thereby initiating a photoreaction that substantially inactivates the probe by photoactivated chemical bleaching. The method further includes the steps of binding at least one probe to one or more target present in the sample, and observing a signal from the probe. The process of binding, observing and bleaching may be iteratively repeated.

Abstract: The present invention relates to a method of in vivo optical imaging, of the blood vessels and/or blood pool of a mammalian subject, which comprises an optical imaging contrast agent. The optical imaging agents comprise conjugates of far-red or near-infrared dyes with synthetic polyethyleneglycol (PEG) polymers having a molecular weight in the range 15-45 kDa. Also disclosed are methods of treatment monitoring, methods of diagnosis and medical uses involving the contrast agents.

Abstract: Methods comprising the use of photoactivated chemical bleaching for detecting 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 probe to one or more target present in the sample, and observing a signal from the probe. The method further includes the steps of contacting the sample comprising the bound probe with an electron transfer reagent and irradiating the sample, thereby initiating a photoreaction that substantially inactivates the probe by photoactivated chemical bleaching. The method further includes the steps of binding at least one probe to one or more target present in the sample, and observing a signal from the probe. The process of binding, observing and bleaching may be iteratively repeated.

Abstract: The present teachings provide methods that enable the preparation and purification of radioiodinated vectors without the need for HPLC purification, as well as novel precursors which include biotin-like substituents useful in such methods.

Abstract: Methods comprising the use of photoactivated chemical bleaching for detecting 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 probe to one or more target present in the sample, and observing a signal from the probe. The method further includes the steps of contacting the sample comprising the bound probe with an electron transfer reagent and irradiating the sample, thereby initiating a photoreaction that substantially inactivates the probe by photoactivated chemical bleaching. The method further includes the steps of binding at least one probe to one or more target present in the sample, and observing a signal from the probe. The process of binding, observing and bleaching may be iteratively repeated.

Abstract: The present invention relates to a microbubble complex comprising a microbubble having an outer shell comprising a mixture of native and denatured albumin encapsulating a perfluorocarbon gas, a therapeutic agent, a bifunctional linker having one end attached to the therapeutic agent and the other attached to a ligand and wherein the ligand is bound to the other shell of the microbubble through hydrophobic interactions. Also included are methods for delivering the aforementioned microbubble complex to a tissue target.

Abstract: Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a sample containing multiple targets, binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample, and reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator. The methods include the steps of observing a signal from the fluorescent signal generator and applying to the sample a solution containing an oxidizing agent that substantially inactivates both the fluorescent signal generator and the enzyme. The methods further include the steps of binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample of step, reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator; and observing a signal from the fluorescent signal generator.

Abstract: Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a sample containing multiple targets, binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample, and reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator. The methods include the steps of observing a signal from the fluorescent signal generator and applying to the sample a solution containing an oxidizing agent that substantially inactivates both the fluorescent signal generator and the enzyme. The methods further include the steps of binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample of step, reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator; and observing a signal from the fluorescent signal generator.

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: Disclosed are compounds of formula (I) wherein D1 is a first dye moiety whose fluorescence properties may be modulated so as to be suitable as a donor or an acceptor in an energy transfer arrangement; D2 is a second dye moiety suitable as an acceptor or a donor in an energy transfer arrangement with said first dye; L is a linking group comprises 2-200 linked atoms, wherein said linking group optionally includes an enzyme cleavage site; and M is an enzyme cleavable group chosen to modulate the fluorescence properties of D1. The compounds of formula (I) may be used as reporter molecules for detecting biochemical cleavage events in assays that employ fluorescence resonance energy transfer.

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: A composition includes a first probe, a first initiator component bonded to the first probe, a second probe, and a second initiator component bonded to the second probe. The first probe and the second probe are capable of binding to a single analyte, and the first initiator component and the second initiator component are capable of forming an initiator when present in proximity to each other and when the first probe and the second probe are bonded to the analyte. An associated kit, device, and method are provided.

Abstract: The composition includes a first probe and a first initiator bonded to the first probe. The composition further includes a second probe and a second initiator bonded to the second probe. The first probe and the second probe are capable of binding to a single analyte. An associated kit, device, and method are provided.

Abstract: The present invention relates to a method of in vivo optical imaging, of the margins around tumours, which comprises an optical imaging contrast agent. The optical imaging agents comprise conjugates of near-infrared dyes with synthetic polyethylene glycol (PEG) polymers having a molecular weight in the range 15-45 kDa. Also disclosed are optical imaging contrast agents, pharmaceutical compositions and kits.

Abstract: The invention provides a method for antigen retrieval of a formaldehyde-fixed tissue sample comprising incubating a formaldehyde-fixed tissue sample in a first antigen retrieval solution at a temperature of greater than 90° C., transferring the tissue sample to a second antigen retrieval solution, and incubating the tissue sample in the second antigen retrieval solution at a temperature of greater than 90° C. The invention also provides a kit and sample delivery device for carrying out the method.

Abstract: The invention provides a method for antigen retrieval of a formaldehyde-fixed tissue sample comprising incubating a formaldehyde-fixed tissue sample in a first antigen retrieval solution at a temperature of greater than 90° C., transferring the tissue sample to a second antigen retrieval solution, and incubating the tissue sample in the second antigen retrieval solution at a temperature of greater than 90° C. The invention also provides a kit and sample delivery device for carrying out the method.