Magnetic nanosensor compositions and bioanalytical assays therefor

Abstract

Disclosed are magnetic nanosensors or transducers that permit measurement of a physical parameter in an analyte via magnetic reasonance measurements, in particular of non-agglomerative assays. More particularly, in certain embodiments, the invention relates to designs of nanoparticle reagents and responsive polymer coated magnetic nanoparticles. Additionally provided are methods of use of nanoparticle reagents and responsive polymer coated magnetic nanoparticles for the detection of a stimulus or an analyte with NMR detectors.

Description

FIELD OF THE INVENTION[0001]This invention relates generally to NMR systems with magnetic nanosensors for detection of analytes. More particularly, in certain embodiments, the invention relates to NMR-based analyte detection systems using responsive polymer-coated magnetic nanoparticles and non-agglomerative bioanalytical assays.BACKGROUND OF THE INVENTION[0002]Biocompatible magnetic nanosensors have been designed to detect molecular interactions in biological media. Upon target binding, magnetic nanosensors cause changes in spin-spin relaxation times of neighboring water molecules (or any solvent molecule with free hydrogens) of a sample, which can be detected by classical magnetic resonance (NMR / MRI) techniques. By using nanosensors in a sample, it is possible to detect the presence of an analyte at very low concentration—for example, small molecules, specific DNA, RNA, proteins, carbohydrates, lipids, lipoproteins, organisms, and pathogens (e.g. bacteria, viruses, etc.)—with sens...

AI Technical Summary

Benefits of technology

[0008]Provided methods and compositions exploit the ability of magnetic nanosensors to dephase nuclear spins, hereinafter generally exemplified as protons of water molecules, detectable by nuclear magnetic resonance (NMR) relaxation measurements (e.g., 1 / T2), for sensing and / or measuring an analyte of interest, without aggregation of nanosensors. In principle, T2 relaxivity of water protons dephased by nanosensors can be proportional to the diameter of nanosensors present in a solution and the diffusion time of water protons in the proximity of individual nanosensors. Thus, provided compositions and bioanalytical assays comprise magnetic nanosensors introduced into a sample that may contain a target analyte in order to react with target analyte in a sample in a rapid, and homogeneous reaction. Provided bioanalytical assays include compositions and methods for optimizing the size or responsive size of nanosensors, to enable rapid assay time-to-results, increased sensitivity, and large (e.g., wide) relaxivity (e.g., T2) dynamic range.

Problems solved by technology

Aggregation / disaggregation of nanosensors may not be the optimal method for analyte detection in all assays.

Further, long incubation time may be required for cluster formation due to a two-step kinetic process for aggregation.

Cluster formation has also been shown to limit the dynamic range for certain bioanalytical assays.

Factors that may contribute to limiting dynamic range include the structural instability of clustered aggregates.

In addition, excess aggregation may lead to precipitation of nanosensors out of solution.

Further, imperfect magnetization coupling of nanoparticles with each other, over an extended period of incubation time, may also contribute to a reduction in net magnetization per unit volume of a cluster, making relaxation process less efficient and lowering its magnitude.

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