Sequencing-by-synthesis (SBS) method is provided that includes providing a detection apparatus that includes an array of magnetically-responsive sensors. Each of the magnetically-responsive sensors is located proximate to a respective designated space to detect a magnetic property therefrom. The detection apparatus also includes a plurality of nucleic acid template strands located within corresponding designated spaces. The method also includes conducting a plurality of SBS events to grow a complementary strand by incorporating nucleotides along each template strand. At least some of the nucleotides are attached to corresponding magnetic particles having respective magnetic properties. Each of the plurality of SBS events includes detecting changes in electrical resistance at the magnetically-responsive sensors caused by the respective magnetic properties of the magnetic particles. The method also includes determining genetic characteristics of the complementary strands based on the detected changes in electrical resistance.

Sequencing-by-synthesis (SBS) method is provided that includes providing a detection apparatus that includes an array of magnetically-responsive sensors. Each of the magnetically-responsive sensors is located proximate to a respective designated space to detect a magnetic property therefrom. The detection apparatus also includes a plurality of nucleic acid template strands located within corresponding designated spaces. The method also includes conducting a plurality of SBS events to grow a complementary strand by incorporating nucleotides along each template strand. At least some of the nucleotides are attached to corresponding magnetic particles having respective magnetic properties. Each of the plurality of SBS events includes detecting changes in electrical resistance at the magnetically-responsive sensors caused by the respective magnetic properties of the magnetic particles. The method also includes determining genetic characteristics of the complementary strands based on the detected changes in electrical resistance.

The invention relates to methods of detecting and/or quantifying analytes in a sample, as well as methods of detecting mutations and/or polymorphisms in nucleic acid molecules. The methods include: providing at least one carrier nucleic acid molecule comprising at least one single-stranded region; providing at least one detection element comprising: at least one fluorophore, at least one fluorescence quencher that quenches spectroscopic detection of the fluorophore; at least one analyte-binding moiety; and at least one nucleic acid moiety that binds to a single stranded region on the carrier nucleic acid molecule; wherein the detection element is configured such that in the absence of the analyte the fluorophore is quenched by the fluorescence quencher and upon analyte binding to the analyte-binding moiety fluorescence is restored; binding these with an analyte to form a complex; translocating the complex through a nanopore via voltage-driven translocation and monitoring time-dependent current response; irradiating the nanopore with radiation that excites the fluorophore and monitoring radiation emissions of the fluorophore over time; and comparing the signals from time-dependent current response and emission over time.

The invention relates to methods of detecting and/or quantifying analytes in a sample, as well as methods of detecting mutations and/or polymorphisms in nucleic acid molecules. The methods include: providing at least one carrier nucleic acid molecule comprising at least one single-stranded region; providing at least one detection element comprising: at least one fluorophore, at least one fluorescence quencher that quenches spectroscopic detection of the fluorophore; at least one analyte-binding moiety; and at least one nucleic acid moiety that binds to a single stranded region on the carrier nucleic acid molecule; wherein the detection element is configured such that in the absence of the analyte the fluorophore is quenched by the fluorescence quencher and upon analyte binding to the analyte-binding moiety fluorescence is restored; binding these with an analyte to form a complex; translocating the complex through a nanopore via voltage-driven translocation and monitoring time-dependent current response; irradiating the nanopore with radiation that excites the fluorophore and monitoring radiation emissions of the fluorophore over time; and comparing the signals from time-dependent current response and emission over time.

Systems and methods of polynucleotide sequencing are provided. Systems and methods optimize control, speed, movement, and/or translocation of a sample (e.g., a polynucleotide) within, through, or at least partially through a nanopore or a type of protein or mutant protein in order to accumulate sufficient time and current blocking information to identify contiguous nucleotides or plurality of nucleotides in a single-stranded area of a polynucleotide.

Systems and methods of polynucleotide sequencing are provided. Systems and methods optimize control, speed, movement, and/or translocation of a sample (e.g., a polynucleotide) within, through, or at least partially through a nanopore or a type of protein or mutant protein in order to accumulate sufficient time and current blocking information to identify contiguous nucleotides or plurality of nucleotides in a single-stranded area of a polynucleotide.

Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

The present disclosure provides devices, systems, and methods for detection of nucleic acids based on CRISPR-Cas editing systems, for example for use in biosurveillance. Disclosed herein are systems and methods utilizing two devices: 1) a point of—need disposable “FET Strip” (enzymatic), and 2) an instrument-operated “FET Multiplexor” (electronic), to provide detection of a nucleic acid for biosurveillance.

The present disclosure provides devices, systems, and methods for detection of nucleic acids based on CRISPR-Cas editing systems, for example for use in biosurveillance. Disclosed herein are systems and methods utilizing two devices: 1) a point of—need disposable “FET Strip” (enzymatic), and 2) an instrument-operated “FET Multiplexor” (electronic), to provide detection of a nucleic acid for biosurveillance.