Abstract: Disclosed herein are improved methods and systems for sequencing nucleic acid that exploit the temperature-dependence of the emitted intensity of fluorescent dyes. The temperature of the sequencing reaction is adjusted during each sequencing cycle, and the emission, or lack of emission, of light meeting or exceeding a threshold by the fluorescent dyes at different temperatures, or within different temperature ranges, is used to detect the fluorescent labels of the incorporated dNTPs and thereby sequence the nucleic acid. The disclosed methods enable a determination of the dNTP incorporated at any given site with a reasonable number of chemistry steps without the complex optics necessary for prior-art systems.

Abstract: Disclosed herein are embodiments of single-molecule array sequencing (SMAS) devices and systems. Each sensor of an array of sensors of the SMAS device is capable of detecting labels attached to nucleotides incorporated into a single nucleic acid strand bound to a respective binding site. Each sensor can detect a single label (e.g., fluorescent, magnetic, organometallic, charged molecule, etc.) attached to the incorporated nucleotide. Also disclosed are methods of using SMAS devices and systems for highly-scalable nucleic acid (e.g., DNA) sequencing based on sequencing by synthesis (SBS) of multiple instances of clonally amplified DNA immobilized on such SMAS devices. Also disclosed are error correction methods that mitigate errors (e.g., errant label detections or non-detections) made in sequencing individual nucleic acid strands.

Abstract: Disclosed herein are apparatuses for nucleic acid sequencing using magnetic labels (e.g., magnetic particles) and magnetic sensors. Also disclosed are methods of making and using such apparatuses. An apparatus for nucleic acid sequencing comprises a plurality of magnetic sensors, a plurality of binding areas disposed above the plurality of magnetic sensors, each of the binding areas for holding fluid, and at least one line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor.

Abstract: Disclosed herein are methods and apparatuses for sequencing nucleic acids using a detection device, the detection device comprising a plurality of spin torque oscillators (STOs) and at least one fluidic channel. In some embodiments of a method, a nucleotide precursor is labeled with a magnetic nanoparticle (MNP), and the labeled nucleotide precursor is added to the fluidic channel of the detection device. It is determined whether at least one of the plurality of STOs is generating a signal. Based at least in part on the determination of whether the at least one of the plurality of STOs is generating the signal, it is determined whether the labeled nucleotide precursor has been detected.

Abstract: Disclosed herein are devices, systems, and methods for monitoring single-molecule biological processes using magnetic sensors and magnetic particles (MNP). A MNP is attached to a biopolymer (e.g., a nucleic acid, protein, etc.), and motion of the MNP is detected and/or monitored using a magnetic sensor. Because the MNP is small (e.g., its size is comparable to the size of the molecule being monitored) and is tethered to a biopolymer, changes in the volume of Brownian motion of the MNP in a solution can be monitored to monitor the movement of the MNP and, by inference, the tethered biopolymer. The magnetic sensor is small (e.g., nanoscale or having a size on the order of the sizes of the MNP and the biopolymer) and can be used to detect even small changes in the position of the MNP within the sensing region of the magnetic sensor.

Abstract: Disclosed herein is a detection device comprising sensors with spin torque oscillators (STOs), at least one fluidic channel configured to receive molecules to be detected, and detection circuitry coupled to the sensors. At least some of the molecules to be detected are labeled by magnetic nanoparticles (MNPs). The presence of one or more MNPs in the vicinity of a STO subjected to a bias current changes the oscillation frequency of the STO. The sensors are encapsulated by a material, such as an insulator, separating the sensors from the at least one fluidic channel. A surface of the material provides binding sites for the molecules to be detected. The detection circuitry is configured to detect changes in the oscillation frequencies of the sensors in response to presence or absence of one or more MNPs coupled to one or more binding sites associated with the sensors.

Abstract: Disclosed herein are detection methods that use magnetic nanoparticles (MNPs) to allow molecules to be identified. Embodiments of this disclosure include methods of using magnetic sensors (e.g., magnetoresistive sensors) to detect temperature-dependent magnetic fields (or changes in magnetic fields) emitted by MNPs, and, specifically to distinguish between the presence and absence of magnetic fields emitted, or not emitted, by MNPs at different temperatures selected to take advantage of knowledge of how the MNPs' magnetic properties change with temperature. Embodiments disclosed herein may be used for nucleic acid sequencing, such as deoxyribonucleic acid (DNA) sequencing.

Abstract: Disclosed herein are detection devices, systems, and methods that use magnetic nanoparticles (MNPs) to allow molecules to be identified. Embodiments of this disclosure include magnetic sensors (e.g., magnetoresistive sensors) that can be used to detect temperature-dependent magnetic fields (or changes in magnetic fields) emitted by MNPs, and, specifically to distinguish between the presence and absence of magnetic fields emitted, or not emitted, by MNPs at different temperatures selected to take advantage of knowledge of how the MNPs' magnetic properties change with temperature. Embodiments disclosed herein may be used for nucleic acid sequencing, such as deoxyribonucleic acid (DNA) sequencing.

Abstract: Devices and methods for molecule detection using such devices are disclosed herein. A molecule detection device comprises at least one fluidic channel configured to receive molecules to be detected, a sensor comprising a spin torque oscillator (STO) and encapsulated by a material separating the sensor from the at least one fluidic channel, and detection circuitry coupled to the sensor. At least some of the molecules to be detected are labeled by magnetic nanoparticles (HNPs). A surface of the material provides binding sites for the molecules to be detected. The detection circuitry is configured to detect a frequency or frequency noise of a radio-frequency (RF) signal generated by the STO in response to presence or absence of at least one MNP coupled to one or more binding sites associated with the sensor.

Abstract: Disclosed herein are methods of using detection devices. A detection device comprises a fluidic channel configured to receive a plurality of molecules to be detected, a plurality of temperature sensors, and an insulating material encapsulating the plurality of temperature sensors and providing a barrier between the plurality of temperature sensors and contents of the fluidic channel. A surface of the insulating material within the fluidic channel provides a plurality of sites for binding the plurality of molecules to be detected. Each of the plurality of temperature sensors is configured to detect, in the presence of an alternating magnetic field, a temperature change indicating presence or absence of one or more magnetic nanoparticles (MNPs) coupled to at least one of the plurality of molecules to be detected at a respective subset of the plurality of sites.

Abstract: Disclosed herein are apparatuses for nucleic acid sequencing, and methods of making and using such apparatuses. In some embodiments, the apparatus comprises a magnetic sensor array comprising a plurality of magnetic sensors, each of the plurality of magnetic sensors coupled to at least one address line, and a fluid chamber adjacent to the magnetic sensor array, the fluid chamber having a proximal wall adjacent to the magnetic sensor array.

Abstract: Disclosed herein are detection devices, systems including such detection devices, and methods of using such detection devices. A detection device comprises a fluidic channel configured to receive a plurality of molecules to be detected, a plurality of temperature sensors, and an insulating material encapsulating the plurality of temperature sensors and providing a barrier between the plurality of temperature sensors and contents of the fluidic channel. A surface of the insulating material within the fluidic channel provides a plurality of sites for binding the plurality of molecules to be detected. Each of the plurality of temperature sensors is configured to detect, in the presence of an alternating magnetic field, a temperature change indicating presence or absence of one or more magnetic nanoparticles (MNPs) coupled to at least one of the plurality of molecules to be detected at a respective subset of the plurality of sites.

Abstract: Disclosed herein are improved methods and systems for sequencing nucleic acid that exploit the temperature-dependence of the emitted intensity of fluorescent dyes. The temperature of the sequencing reaction is adjusted during each sequencing cycle, and the emission, or lack of emission, of light meeting or exceeding a threshold by the fluorescent dyes at different temperatures, or within different temperature ranges, is used to detect the fluorescent labels of the incorporated dNTPs and thereby sequence the nucleic acid. The disclosed methods enable a determination of the dNTP incorporated at any given site with a reasonable number of chemistry steps without the complex optics necessary for prior-art systems.

Abstract: Disclosed herein are improved methods and systems for sequencing nucleic acid that exploit the temperature-dependence of the emitted intensity of fluorescent dyes. The temperature of the sequencing reaction is adjusted during each sequencing cycle, and the emission, or lack of emission, of light meeting or exceeding a threshold by the fluorescent dyes at different temperatures, or within different temperature ranges, is used to detect the fluorescent labels of the incorporated dNTPs and thereby sequence the nucleic acid. The disclosed methods enable a determination of the dNTP incorporated at any given site with a reasonable number of chemistry steps without the complex optics necessary for prior-art systems.

Abstract: A method of sensing molecules using a detection device, the detection device comprising a plurality of magnetoresistive (MR) sensors and at least one fluidic channel, comprising adding a plurality of molecules to be detected to the at least one fluidic channel, wherein at least some of the plurality of molecules to be detected are coupled to respective magnetic nanoparticles (MNPs), detecting a characteristic of a magnetic noise of a first MR sensor of the plurality of MR sensors, wherein the characteristic of the magnetic noise is influenced by a presence of one or more MNPs in a vicinity of the first MR sensor, and determining, based on the detected characteristic, whether the first MR sensor detected the presence of one or more MNPs in the vicinity of the first MR sensor.

Abstract: A sensing device comprises a plurality of magnetoresistive (MR) sensors, at least one fluidic channel, and detection circuitry coupled to the MR sensors. Each MR sensor is configured to detect the presence of molecules (e.g., biologic molecules) labeled by magnetic nanoparticles (MNPs). The sensors are encapsulated by an insulating material that protects the sensors from the contents of the at least one fluidic channel. The insulating material has a surface within the fluidic channel that provides sites for binding the molecules to be detected. The detection circuitry is configured to detect (a) a characteristic of magnetic noise of each MR sensor, the characteristic being influenced by a presence or absence of one or more MNPs at each site, or (b) a change in resistance, current, and/or voltage drop of each MR sensor, wherein the change is influenced by the presence or absence of one or more MNPs at each site.

Abstract: Disclosed herein are improved methods and systems for sequencing nucleic acid that exploit the temperature-dependence of the emitted intensity of fluorescent dyes. The temperature of the sequencing reaction is adjusted during each sequencing cycle, and the emission, or lack of emission, of light meeting or exceeding a threshold by the fluorescent dyes at different temperatures, or within different temperature ranges, is used to detect the fluorescent labels of the incorporated dNTPs and thereby sequence the nucleic acid. The disclosed methods enable a determination of the dNTP incorporated at any given site with a reasonable number of chemistry steps without the complex optics necessary for prior-art systems.

Abstract: Disclosed herein are detection devices, systems, and methods that use magnetic nanoparticles (MNPs) to allow molecules to be identified. Embodiments of this disclosure include magnetic sensors (e.g., magnetoresistive sensors) that can be used to detect temperature-dependent magnetic fields (or changes in magnetic fields) emitted by MNPs, and, specifically to distinguish between the presence and absence of magnetic fields emitted, or not emitted, by MNPs at different temperatures selected to take advantage of knowledge of how the MNPs' magnetic properties change with temperature. Embodiments disclosed herein may be used for nucleic acid sequencing, such as deoxyribonucleic acid (DNA) sequencing.

Abstract: A sensing device comprises a plurality of magnetoresistive (MR) sensors, at least one fluidic channel, and detection circuitry coupled to the MR sensors. Each MR sensor is configured to detect the presence of molecules (e.g., biologic molecules) labeled by magnetic nanoparticles (MNPs). The sensors are encapsulated by an insulating material that protects the sensors from the contents of the at least one fluidic channel. The insulating material has a surface within the fluidic channel that provides sites for binding the molecules to be detected. The detection circuitry is configured to detect (a) a characteristic of magnetic noise of each MR sensor, the characteristic being influenced by a presence or absence of one or more MNPs at each site, or (b) a change in resistance, current, and/or voltage drop of each MR sensor, wherein the change is influenced by the presence or absence of one or more MNPs at each site.

Abstract: Disclosed herein is a detection device comprising sensors with spin torque oscillators (STOs), at least one fluidic channel configured to receive molecules to be detected, and detection circuitry coupled to the sensors. At least some of the molecules to be detected are labeled by magnetic nanoparticles (MNPs). The presence of one or more MNPs in the vicinity of a STO subjected to a bias current changes the oscillation frequency of the STO. The sensors are encapsulated by a material, such as an insulator, separating the sensors from the at least one fluidic channel. A surface of the material provides binding sites for the molecules to be detected. The detection circuitry is configured to detect changes in the oscillation frequencies of the sensors in response to presence or absence of one or more MNPs coupled to one or more binding sites associated with the sensors.