In some embodiments, a computer-implemented method of determining an identity of one or more monomer subunit residues of a polymer analyte is provided, In some embodiments, a raw current signal generated by using a variable voltage to translocate the polymer analyte through a nanopore. In some embodiments, change points are detected in the raw current signal to determine a series of states, In some embodiments, capacitance compensation is performed on the raw current signal for each state to create an ionic current-vs-voltage curve for each state. In some embodiments, the ionic current-vs-voltage curves is converted to conductance-vs-voltage curves. In some embodiments, filtering is performed for the series of states to create a series of filtered states. In some embodiments, the identity of one or more monomer subunit residues of the polymer analyte is determined based on the series of filtered states.

In some embodiments, a computer-implemented method of determining an identity of one or more monomer subunit residues of a polymer analyte is provided, In some embodiments, a raw current signal generated by using a variable voltage to translocate the polymer analyte through a nanopore. In some embodiments, change points are detected in the raw current signal to determine a series of states, In some embodiments, capacitance compensation is performed on the raw current signal for each state to create an ionic current-vs-voltage curve for each state. In some embodiments, the ionic current-vs-voltage curves is converted to conductance-vs-voltage curves. In some embodiments, filtering is performed for the series of states to create a series of filtered states. In some embodiments, the identity of one or more monomer subunit residues of the polymer analyte is determined based on the series of filtered states.

A Fano resonator device can be used to sequence DNA or other macromolecules. The device includes customized molecular components, informed by computation analysis. Techniques for preparing and using the device also are disclosed. The device can be incorporated in a system that further includes a sample processing component and a flow chamber.

A Fano resonator device can be used to sequence DNA or other macromolecules. The device includes customized molecular components, informed by computation analysis. Techniques for preparing and using the device also are disclosed. The device can be incorporated in a system that further includes a sample processing component and a flow chamber.

Methods of detecting a target nucleic acid sequence analyte are provided in which a crRNA and Cas12 or Cas13 enzyme are contacted to form a non-activated RNP. The non-activated RNP is contacted with a sample containing or suspected of containing the target nucleic acid sequence, and the target nucleic acid sequence and non-activated RNP specifically bind to each other if the target nucleic acid is present in the sample, thereby forming an activated RNP. A reporter nucleic acid is contacted with the activated RNP, and the activated RNP indiscriminately cleaves the reporter nucleic acid, reducing passage of intact, non-cleaved reporter nucleic acid through a nanopore in of a nanopore counting device such that a reduction of resistive pulses is produced which provides a signal representative of presence of the target nucleic acid sequence in the sample.

Methods of detecting a target nucleic acid sequence analyte are provided in which a crRNA and Cas12 or Cas13 enzyme are contacted to form a non-activated RNP. The non-activated RNP is contacted with a sample containing or suspected of containing the target nucleic acid sequence, and the target nucleic acid sequence and non-activated RNP specifically bind to each other if the target nucleic acid is present in the sample, thereby forming an activated RNP. A reporter nucleic acid is contacted with the activated RNP, and the activated RNP indiscriminately cleaves the reporter nucleic acid, reducing passage of intact, non-cleaved reporter nucleic acid through a nanopore in of a nanopore counting device such that a reduction of resistive pulses is produced which provides a signal representative of presence of the target nucleic acid sequence in the sample.

Techniques described herein can apply AC signals with different phases to different groups of nanopore cells in a nanopore sensor chip. When a first group of nanopore cells is in a dark period and is not sampled or minimally sampled by an analog-to-digital converter (ADC) to capture useful data, a second group of nanopore cells is in a bright period during which output signals from the second group of nanopore cells are sampled by the analog-to-digital converter. The reference level setting of the ADC is dynamically changed based on the applied AC signals to fully utilize the dynamic range of the ADC.

Techniques described herein can apply AC signals with different phases to different groups of nanopore cells in a nanopore sensor chip. When a first group of nanopore cells is in a dark period and is not sampled or minimally sampled by an analog-to-digital converter (ADC) to capture useful data, a second group of nanopore cells is in a bright period during which output signals from the second group of nanopore cells are sampled by the analog-to-digital converter. The reference level setting of the ADC is dynamically changed based on the applied AC signals to fully utilize the dynamic range of the ADC.

Sequencing polynucleotides using nanopores is provided herein. A polynucleotide is disposed through a nanopore's aperture such that its 3′ end is on the nanopore's first side and its 5′ end is on the nanopore's second side. On the nanopore's first side, a duplex with the polynucleotide is formed that includes a 3′ end. The duplex is extended on the first side of the nanopore by adding a nucleotide to the 3′ end of the duplex. A first force is applied disposing the 3′ end of the duplex within the aperture, and the nanopore inhibits translocation of the 3′ end of the duplex to the second side of the nanopore. A value of an electrical property of the 3′ end of the duplex and a single-stranded portion of the polynucleotide is measured. The nucleotide at the 3′ end of the duplex is identified using the measured value.

Sequencing polynucleotides using nanopores is provided herein. A polynucleotide is disposed through a nanopore's aperture such that its 3′ end is on the nanopore's first side and its 5′ end is on the nanopore's second side. On the nanopore's first side, a duplex with the polynucleotide is formed that includes a 3′ end. The duplex is extended on the first side of the nanopore by adding a nucleotide to the 3′ end of the duplex. A first force is applied disposing the 3′ end of the duplex within the aperture, and the nanopore inhibits translocation of the 3′ end of the duplex to the second side of the nanopore. A value of an electrical property of the 3′ end of the duplex and a single-stranded portion of the polynucleotide is measured. The nucleotide at the 3′ end of the duplex is identified using the measured value.