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 Nanopore
detectors are instruments built around
a membrane containing a tiny pore called
an ion channel, just big enough to allow
a single strand of DNA to pass through.
A voltage applied across the membrane
generates an ionic current and pulls the
negatively charged DNA molecules through
the pore. When the DNA molecule blocks
the opening of the nanopore, it causes
a characteristic decrease in the current,
allowing discrimination between individual
DNA molecules. A computer trained by machine-learning
techniques recognizes the signals generated
by different DNA molecules.
The nanopore project at UC Santa Cruz
has pioneered the use of ion channels for the analysis of
single RNA and DNA molecules. Nanopore
technology makes it possible to measure DNA structure and
dynamics with
precision at the angstrom level. Thus, it is possible
to rapidly discriminate between nearly identical strands
of DNA
and investigate
their physical properties. Nanopore technology is well
suited to analysis of the terminal ends of double-stranded
DNA, and
it is amenable to high throughput experiments.
In the future, it may be possible to
develop a durable solid-state or protein-based nanopore device
that would allow the measurement of
several different genomic factors from one cell without amplification:
 gene
expression
single-nucleotide
polymorphisms (SNPs), common, minute variations
in genes that
can
be used to track familial inheritance
point
mutations in single RNA or DNA molecules
Using machine learning tools developed
at UCSC, each molecule could be identified in real time and
in less than 50 milliseconds. Such
a device would have broad clinical
utility in diagnosing inherited traits
such as hearing disorders and drug sensitivity
and in tracking disease progression at the level of single
cells.
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