Nanopore-based single dna molecule characterization, identification and isolation using speed bumps

A method for sequencing a nucleic acid, the method comprising:

• applying a first electric potential having a first polarity across an array of nanopore detectors, each nanopore detector comprising a pair of electrodes, a membrane disposed between the pair of electrodes, and a nanopore disposed in the membrane;
• threading a plurality of single stranded nucleic acid molecules through the array of nanopore detectors in a first direction based on the first polarity of the applied first electric potential;
• measuring a first electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the first direction;
• applying a second electric potential having a second polarity across the array of nanopore detectors, wherein the second polarity is opposite the first polarity;
• threading the plurality of single stranded nucleic acid molecules through the array of nanopore detectors in a second direction based on the second polarity of the applied second electrical potential, wherein the second direction is opposite the first direction;
• measuring a second electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the second direction;
• applying a third electrical potential across the array of nanopore detectors, wherein the third electrical potential has a polarity that is the same as the polarity of the first electrical potential;
• threading the plurality of single stranded nucleic acid molecules through the array of nanopore detectors in the first direction based on the polarity of the third electrical potential;
• measuring a third electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the first direction as a result of the application of the third electrical potential;
• determining a sequence for each single stranded nucleic acid molecule based on any combination of the first electrical signal, the second electrical signal, and the third electrical signal.

A system for sequencing a nucleic acid molecule, the system comprising:

• an array of nanopore detectors, each nanopore detector comprising a pair of electrodes, a membrane disposed between the pair of electrodes, and a nanopore disposed in the membrane;
• a controller configured to:
• apply a first electric potential having a first polarity across the array of nanopore detectors;
• thread a plurality of single stranded nucleic acid molecules through the array of nanopore detectors in a first direction based on the first polarity of the applied first electric potential;
• measure a first electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the first direction;
• apply a second electric potential having a second polarity across the array of nanopore detectors, wherein the second polarity is opposite the first polarity;
• thread the plurality of single stranded nucleic acid molecules through the array of nanopore detectors in a second direction based on the second polarity of the applied second electrical potential, wherein the second direction is opposite the first direction;
• and
• measure a second electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the second direction;
• and
• a processor configured to determine a sequence for each single stranded nucleic acid molecule based on the first electrical signal and the second electrical signal.

A system for sequencing a nucleic acid molecule, the system comprising:

• an array of nanopore detectors, each nanopore detector comprising a pair of electrodes, a membrane disposed between the pair of electrodes, and a nanopore disposed in the membrane;
• a controller configured to:
• apply a first electric potential having a first polarity across the array of nanopore detectors;
• thread a plurality of single stranded nucleic acid molecules through the array of nanopore detectors in a first direction based on the first polarity of the applied first electric potential;
• measure a first electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the first direction;
• apply a second electric potential having a second polarity across the array of nanopore detectors, wherein the second polarity is opposite the first polarity;
• thread the plurality of single stranded nucleic acid molecules through the array of nanopore detectors in a second direction based on the second polarity of the applied second electrical potential, wherein the second direction is opposite the first direction;
• measure a second electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the second direction;
• apply a third electrical potential across the array of nanopore detectors, wherein the third electrical potential has a polarity that is the same as the polarity of the first electrical potential;
• thread the plurality of single stranded nucleic acid molecules through the array of nanopore detectors in the first direction based on the polarity of the third electrical potential;
• measure a third electrical signal in each nanopore detector as the single stranded nucleic acid molecule is threaded through the nanopore in the first direction as a result of the application of the third electrical potential;
• and
• a processor configured to determine a sequence for each single stranded nucleic acid molecule based on any combination of the first electrical signal, the second electrical signal, and the third electrical signal.