Magnetic nanosensor compositions and bioanalytical assays therefor

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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.

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.

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 relaxivity dynamic range.

Provided are nanosensors that exploit the ability of magnetic nanoparticles to dephase nuclear spins detectable by NMR, for detection without aggregation of nanoparticles. In particular embodiments, provided nanosensors comprise a nanoparticle having a polymer matrix layer which responds when exposed to an analyte and/or a condition to be detected. A resulting change in nanoparticle size affects dephasing of freely-diffusing water molecules in the vicinity of the nanoparticles, which affects one or more NMR-detectable properties.

In other particular embodiments, provided nanosensors comprise a nanoparticle having a binding agent which is size optimized to provide optimal T2 measurement. A resulting change in nanoparticle size when exposed to an analyte and/or a condition to be detected provides a maximum change in T2.

Additionally provided are particular methods of using provided responsive nanosensor compositions, wherein NMR-detectable properties can be obtained using responsive nanosensor compositions to determine the existence and/or level of a condition and/or analyte of interest in one or more samples. In certain embodiments, comparing obtained NMR-detected properties with a known control (e.g., one or more reference samples, a known control reference measure), may determine the existence and/or level of a condition and/or analyte of interest in one or more samples.

The objects and features of the invention can be better understood with reference to the drawings described below, and the claims. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. In the drawings, like numerals are used to indicate like parts throughout various views.

While the present invention is particularly shown and described herein with reference to specific examples and specific embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.