This disclosure provides compositions and methods for a low-avidity, high-affinity and high-specificity biomolecular interaction that is rapidly reversible under physiological conditions. The methods comprise linking biological targets (such as molecules, proteins, DNA, cells, extracellular vesicles, etc.) with polymers and anti-polymer ligands and a way to reverse their binding using physiologically compatible polymeric compounds. The methods also comprise a way to combine different polymer/anti-polymer systems for orthogonal labeling. The compositions comprise labels including particles (fluorescent, magnetic, dense, etc.) conjugated to polymers or labels conjugated to anti-polymer antibodies. The compositions also comprise biomolecules (proteins, antibodies, DNA, etc.) conjugated to the polymers. These methods and compositions represent a major improvement to the state-of-the-art. They are particularly useful for separation and isolation of biological targets using particles, but have important application to other fields including fluorescent imaging.

The present disclosure is directed to methods for determining the presence and/or amount of norovirus-reactive antibodies in a sample from a subject. The subject may be vaccinated with a norovirus vaccine or infected with a norovirus. The present disclosure further relates to in vitro methods for diagnosing a norovirus infection and determining protection against a norovirus infection in a subject for instance after vaccination with a norovirus vaccine. The present disclosure is further directed to kits for determining norovirus-reactive antibodies in a sample. The present disclosure is further directed to microsphere complexes comprising microspheres coupled to norovirus virus like particles.

The invention relates to methods for conducting binding assays in an assay device that includes one or more storage and use zone. The storage zones of the assay device are configured to house one or more reagents used in an assay conducted in the use zone of the device.

Methods for separating, cells, particles, or other molecules of interest (MOI) from unwanted materials not of interest (MNOI). by forced movement of MOI into certain zones having properties which deter the entry of unwanted materials. MOI are tagged with magnetic particles and moved with a magnetic field through a fluid, or zones, of higher specific gravity that prevents, unwanted less dense materials from entering. Buoyant or other forces are used to remove any unbound material from the complexes with ASG before reading. Readable labels include the magnetic particle tagged complex itself, and other labels such as enzymes, chemiluminescent materials, radioactive isotopes, chromogenic and fluorogenic substrates and other labels may be used. The invention applies to many assays, diagnostic tests, separative procedures and chemical syntheses.

A biomolecular sensor system includes an array of magnetoresistive nanosensors designed for sensing biomolecule-conjugated superparamagnetic nanoparticles. Materials and geometry of each sensor element are designed for optimized sensitivity. The system includes magnetic field generators to apply forces to superparamagnetic nanoparticles for 1) nanoparticle manipulation, 2) sensor magnetic biasing, 3) magnetic pull-off measurement for differentiation against non-specific association, and 4) removal of all particles from the sensor array surface.

For a chemical or biological sensor, which is reusable while maintaining a clean state thereof, and a method for using the same, the present invention provides a reusable chemical or biological sensor and a method for using the same, the reusable chemical or biological sensor comprising: a sensor transducer; a ferromagnetic pattern formed on at least one surface of the sensor transducer; magnetic nanoparticles which can be collected or released in a single layer on the sensor transducer, in directions of first and second magnetic fields applied to the sensor transducer; and a receptor which is fixed on the magnetic nanoparticles and can bind to a target substance to be detected.

A biomolecular sensor system includes an array of magnetoresistive nanosensors designed for sensing biomolecule-conjugated superparamagnetic nanoparticles. Materials and geometry of each sensor element are designed for optimized sensitivity. The system includes magnetic field generators to apply forces to superparamagnetic nanoparticles for 1) nanoparticle manipulation, 2) sensor magnetic biasing, 3) magnetic pull-off measurement for differentiation against non-specific association, and 4) removal of all particles from the sensor array surface.

Methods for separating, in a continuous, multizone fluid medium, cells, particles, or other molecules of interest (MOI) from associated or contaminating unwanted materials not of interest (MNOI). The invention involves forced movement of MOI into certain zones having properties which deter the entry of unwanted materials. Differential movement of MOI and MNOI occurs by active counterforces that move MNOI but not MOI. MOI are tagged with magnetic particles and moved with a magnetic field through a fluid, or zones, of higher specific gravity that prevents, by flotation counterforce, unwanted less dense materials from entering.

Surfaces specifically coated with reactants are reactive with the MOI in the tagged magnetic particle complex and of buoyant or other forces are used to remove any unbound material from the surface before reading. Readable labels, in addition to the magnetic particle tagged complex itself, such as enzymes, fluorophors, chemiluminescent materials, radioactive isotopes, chromogenic and fluorogenic substrates and other labels may be used. In most embodiments, materials of interest are delivered to a special final zone for reading or harvesting. The invention applies to many assays, diagnostic tests, separative procedures and chemical syntheses.

Methods and apparatus are adapted to wash magnetic particles isolated in a vessel. The methods include providing a vessel with wash liquid and a layer of magnetic particles, providing a probe having aspiration capability, positioning a probe tip above the layer of magnetic particles, aspirating at least some of the wash liquid above the layer, positioning the probe tip below the layer, and aspirating at least some of the wash liquid from below the layer of magnetic particles. The suction may be turned off as the probe tip descends past the layer. A novel magnetic particle washing apparatus are disclosed.

Provided herein are methods for detecting and identifying disease-specific biomarkers, such as target antigens associated with infection.