Abstract: Methods for quantitatively determining a binding kinetic parameter of a molecular binding interaction are provided. Aspects of embodiments of the methods include: producing a magnetic sensor device including a magnetic sensor in contact with an assay mixture including a magnetically labeled molecule to produce a detectable molecular binding interaction; obtaining a real-time signal from the magnetic sensor; and quantitatively determining a binding kinetics parameter of the molecular binding interaction from the real-time signal. Also provided are systems and kits configured for use in the methods.

Abstract: A highly specific and versatile surface chemistry for immobilization of amine-terminated probes is disclosed. A bi-layered polymer thin film serves as the platform for coupling the probes, which are preferably oligonucleotides. The process involves sequentially coating a substrate with polyamine and polyacid anhydride. Hydrolyzed polyacid anhydride groups may be converted to non-hydrolyzed groups at about 100° C. prior to probe attachment. The process of coating the substrate requires no harsh chemical pretreatment of substrates such as RCA or Piranha cleaning. In addition, simple thermal activation of the anhydride groups has a low requirement for storage, leading to a long shelf life of modified surfaces. The disclosed surface chemistry is especially compatible with microfabrication processes, and its effective application to magnetic biosensors is demonstrated.

Abstract: A magnetic sensor array including magnetoresistive sensor elements having outputs combined by frequency division multiplexing (FDM) is provided. Each sensor element provides an input to a mixer which provides a distinct frequency shift. Preferably, time division multiplexing is also used to combine sensor element outputs. Each sensor element is typically in proximity to a corresponding sample. The sensor elements are preferably subarrays having row and column addressable sensor element pixels. This arrangement provides multiple sensor pixels for each sample under test. Multiplexing of sensor element outputs advantageously reduces readout time. A modulated external magnetic field is preferably applied during operation, to reduce the effect of 1/f noise on the sensor element signals. The effect of electromagnetic interference (EMI) induced by the magnetic field on sensor element signals is advantageously reduced by the mixing required for FDM.

Abstract: A magnetic tunnel junction having a first electrode separated from a second electrode by a tunneling barrier is provided. The tunneling barrier is a ferromagnetic insulator that provides a spin dependent barrier energy for tunneling. The first electrode includes a ferromagnetic, electrically conductive layer. Electrons emitted from the first electrode toward the tunneling barrier are partially or completely spin-polarized according to the magnetization of the ferromagnetic electrode layer. The electrical resistance of the tunnel junction depends on the relative orientation of the electrode layer magnetization and the tunneling barrier magnetization. Such tunnel junctions are widely applicable to spintronic devices, such as spin valves, magnetic tunnel junctions, spin switches, spin valve transistors, spin filters, and to spintronic applications such as magnetic recording, magnetic random access memory, ultrasensitive magnetic field sensing (including magnetic biosensing), spin injection and spin detection.

Abstract: Magnetic nanoparticles and methods for their use in detecting biological molecules are disclosed. The magnetic nanoparticles can be attached to nucleic acid molecules, which are then captured by a complementary sequence attached to a detector, such as a spin valve detector or a magnetic tunnel junction detector. The detection of the bound magnetic nanoparticle can be achieved with high specificity and sensitivity.

Abstract: A magnetic sifter is adapted for manipulation of biological cells by providing a greater pore density at the edge of the sifter than at the center. Application of an external magnetic field to the sifter causes high magnetic fields and field gradients at the sifter pores. These conditions are suitable for capturing magnetically tagged or labeled cells at the sifter pores. Altering the external magnetic field can provide controlled capture and/or release of magnetically labeled cells from the sifter pores. The purpose of having a greater pore density at the periphery of the sifter than at the center is to provide improved flow rate uniformity through the sifter. Such flow rate uniformity is advantageous for cell quantification.

Abstract: Sensor assay methods for detecting the presence of an analyte in a sample are provided. Aspects of the methods include providing a sensor, e.g., a proximity sensor, in contact with an assay composition that includes a sample and a proximity label. Next, a capture probe configured to bind to the proximity label and the analyte is introduced into the assay composition to produce a labeled analyte. Following capture probe introduction, a signal is obtained from the sensor to detect the presence of the labeled analyte in the sample. Also provided are sensor devices, including hand-held devices, and kits that find use in practicing the subject methods.

Abstract: Double modulation of a magnetoresistive sensor entails modulating both an excitation (e.g., voltage or current) applied to the sensor and a tickling magnetic field applied to the sensor. The excitation and magnetic field are modulated at different frequencies fc and ff, respectively. As a result of the double modulation, the sensor output spectrum includes a carrier tone (CT) at frequency fc and side tones (STs) at frequencies fc±ff. A baseline relation between CT amplitude and ST amplitude is determined (e.g., by measuring CT and ST amplitude while drift occurs in the absence of a sample). During sensor operation, raw ST measurements are corrected using corresponding raw CT measurements to provide corrected ST measurements as the sensor output.

Abstract: Dumbbell-shaped or flower-shaped nanoparticles and a process of forming the same, wherein the process comprises forming a mixture of a nanoparticle with a precursor in a first solvent, wherein the nanoparticle comprises a hydrophobic outer coating; heating the mixture; cooling the mixture to room temperature; modifying the hydrophobic outer coating into a hydrophilic outer coating; precipitating a solid product from the mixture, and dispersing the product in a second solvent. The nanoparticles comprise any of a semiconducting, magnetic, and noble metallic material, wherein the nanoparticles comprise a first portion comprising any of PbSe, PbS, CdSe, CdS, ZnS, Au, Ag, Pd, and Pt, and wherein the precursor comprises any of a cationic, neutral or particulate Au, Ag, Pd, Pt, or transition metal (Fe, Co, Ni) precursors of Fe(CO)5, Co(CO)8, Ni(CO)4 or their analogues. The first and second solvents comprise any of alkanes, arenes, ethers, nitrites, ketones, and chlorinated hydrocarbons.

Abstract: Magnetic nanoparticles and methods for their use in detecting biological molecules are disclosed. The magnetic nanoparticles can be attached to nucleic acid molecules, which are then captured by a complementary sequence attached to a detector, such as a spin valve detector or a magnetic tunnel junction detector. The detection of the bound magnetic nanoparticle can be achieved with high specificity and sensitivity.

Abstract: Embodiments of the present disclosure provide for nanoprobes, methods of imaging, methods of imaging a target, methods of making nanoprobes, and the like.

Abstract: The present invention provides a magnetic sifter that is small in scale, enables three-dimensional flow in a direction normal to the substrate, allows relatively higher capture rates and higher flow rates, and provides a relatively easy method of releasing captured biomolecules. The magnetic sifter includes at least one substrate. Each substrate contains a plurality of slits, each of which extends through the substrate. The sifter also includes a plurality of magnets attached to the bottom surface of the substrate. These magnets are located proximal to the openings of the slits. An electromagnetic source controls the magnitude and direction of magnetic field gradient generated by the magnets. Either one device may be used, or multiple devices may be used in series. In addition, the magnetic sifter may be used in connection with a detection chamber.

Abstract: An inductor structure comprised of a magnetic section and a single turn solenoid. The single turn solenoid to contain within a portion of the magnetic section and circumscribed by the magnetic section.

Abstract: Methods for analyte detection with magnetic sensors are provided. Aspects of the methods include producing a magnetic sensor device having a magnetically labeled analyte from a sample, such as a serum sample, bound to a surface of a magnetic sensor thereof; and obtaining a signal, e.g., a real-time signal, from the magnetic sensor to determine whether the analyte is present in the sample. Also provided are devices, systems and kits that find use in practicing the methods of the invention. The methods, devices, systems and kits of the invention find use in a variety of different applications, including detection of biomarkers, such as disease markers.

Abstract: A method of determining the length of a polynucleotide target is provided. With this method, a target is first hybridized to an array of first probes having different, determined lengths, resulting in the formation of duplexes between the polynucleotide target and the first probes. These duplexes have a single stranded section of target if the target is longer than the first probe it is in a duplex with, and a single stranded section of probe if the target is shorter than the first probe it is in a duplex with. Next, a series of probes is hybridized to the duplexes, breaking apart duplexes in which the target and probe have unequal lengths through the process of branch migration. Thus, the target only remains bound in the duplex if the target and probe are of equal lengths. The length of the polynucleotide target can thereby be determined.

Abstract: Magnetic nanoparticles and methods for their use in detecting biological molecules are disclosed. The magnetic nanoparticles can be attached to nucleic acid molecules, which are then captured by a complementary sequence attached to a detector, such as a spin valve detector or a magnetic tunnel junction detector. The detection of the bound magnetic nanoparticle can be achieved with high specificity and sensitivity.

Abstract: The present invention provides microfluidic devices constructed from four layers. The layers include a rigid substrate layer, a patterned rigid layer having thickness t, a patterned elastomeric layer having thickness greater than t, and a rigid support layer. Microfluidic structures in the devices are defined by the alignment of openings in the patterned rigid layer and the patterned elastomeric layer. The rigid support layer, rigid substrate layer, and patterned rigid layer may be made of any rigid material, including but not limited to plastic or silicon-containing materials, such as glass, quartz, or SiO2-coated materials. Similarly, the patterned elastomeric layer may be made of any elastomeric material, including but not limited to polydimethylsiloxanes, polymethylmethacrylates, perfluoropolyethers, or combinations thereof. Microfluidic devices according to the present invention may include sensors or sensor arrays.

Abstract: The present invention provides a synthetic antiferromagnetic (SAF) nanoparticle. The SAF nanoparticle includes at least two ferromagnetic layers and at least one non-magnetic spacer layer. The spacer layer is situated in between planar surfaces of the ferromagnetic layers. The saturation field of the SAF nanoparticle is tunable by the geometry and composition of the nanoparticle. Preferably, the saturation field can be tuned to be between about 100 Oe and about 10,000 Oe. Also preferably, the SAF nanoparticle has a magnetic moment of at least 800 emu/cm3. In a preferred embodiment, the SAF nanoparticle has at least one of a biomolecule, a recognition moiety, or a molecular coating attached to its surface. The SAF nanoparticle may also have a dye attached to its surface.

Abstract: Dumbbell-shaped or flower-shaped nanoparticles and a process of forming the same, wherein the process comprises forming a mixture of a nanoparticle with a precursor in a first solvent, wherein the nanoparticle comprises a hydrophobic outer coating; heating the mixture; cooling the mixture to room temperature; modifying the hydrophobic outer coating into a hydrophilic outer coating; precipitating a solid product from the mixture, and dispersing the product in a second solvent. The nanoparticles comprise any of a semiconducting, magnetic, and noble metallic material, wherein the nanoparticles comprise a first portion comprising any of PbSe, PbS, CdSe, CdS, ZnS, Au, Ag, Pd, and Pt, and wherein the precursor comprises any of a cationic, neutral or particulate Au, Ag, Pd, Pt, or transition metal (Fe, Co, Ni) precursors of Fe(CO)5, Co(CO)8, Ni(CO)4 or their analogues. The first and second solvents comprise any of alkanes, arenes, ethers, nitrites, ketones, and chlorinated hydrocarbons.

Abstract: A highly specific and versatile surface chemistry for immobilization of amine-terminated probes is disclosed. A bi-layered polymer thin film serves as the platform for coupling the probes, which are preferably oligonucleotides. The process involves sequentially coating a substrate with polyamine and polyacid anhydride. Hydrolyzed polyacid anhydride groups may be converted to non-hydrolyzed groups at about 100° C. prior to probe attachment. The process of coating the substrate requires no harsh chemical pretreatment of substrates such as RCA or Piranha cleaning. In addition, simple thermal activation of the anhydride groups has a low requirement for storage, leading to a long shelf life of modified surfaces. The disclosed surface chemistry is especially compatible with microfabrication processes, and its effective application to magnetic biosensors is demonstrated.