By Nate Chongsiriwatana —
BioNanomatrix, Inc. recently announced the
issuance
of U.S. Patent No. 7,670,770 for nanochannel arrays that enable
high-throughput
macromolecular analysis.
Previously, single-molecule DNA analysis has
been
limited by the difficulty of linearizing (untangling) and manipulating
intact
native DNA. To address these
limitations, a Princeton University research team, including Dr. Han
Cao, the
founder and chief scientific officer of BioNanomatrix, used a
nanofluidic chip
to untangle and guide individual DNA molecules into an array of
nanochannels. According to Dr. Cao, the founder and chief scientific officer of
BioNanomatrix, "this invention allows for true linear analysis of very
long biomolecules such as native genomic DNA hundreds of thousands of
base
pairs in length without cloning or PCR amplification." This technique,
which is the basis for the company's NanoAnalyzer® system, can be used
for
multiplexed parallel processing applications, such as direct imaging
analysis
of structural variations in a person's genome and DNA mapping and
sequencing.
At the crux of the invention are three
critical
dimensional qualities for nanochannel arrays that enable the
simultaneous
isolation and analysis of a multitude of elongated macromolecules. Specifically, the '770 patent discloses
that: (1) the channels should be sufficiently narrow in order to elongate
and
isolate macromolecules; (2) the channels should be long enough to permit
the
instantaneous observation of the entire elongated macromolecule; and (3)
a high
number of channels should be provided in each array to permit the
simultaneous
observation of a large number of macromolecules.
The lone independent claim of the '770 patent
reads:
1. A method of isolating, imaging, and analyzing, in parallel,
two or
more individual nucleic acid biopolymers, comprising the steps of:
providing a
nanofluidic chip, comprising: a) nanochannel array, comprising: a
surface
having a plurality of parallel nanochannels running along the material
of the surface,
said nanochannels having a trench width of less than about 150
nanometers and a
trench depth of less than 200 nanometers; at least one of the plurality
of
nanochannels being surmounted by sealing material to render such
nanochannels
at least substantially enclosed; at least two of the nanochannels
capable of
admitting a fluid; b) at least one sample reservoir in fluid
communication with
at least two of the nanochannels, said sample reservoir capable of
releasing a
fluid containing at least two nucleic acid biopolymer; providing the at
least
one sample reservoir with at least one fluid, said fluid comprising at
least
two nucleic acid biopolymers; transporting the at least two nucleic acid
biopolymers into the at least two nanochannels to elongate said at least
two
nucleic acid biopolymers, the at least two nucleic acid biopolymers
being
individually confined within the at least two nanochannels such that the
at
least two nucleic acid biopolymer are transported through the at least
two
nanochannels in an unfolded fashion; imaging in parallel at least one
signal
transmitted from the at least two elongated and isolated nucleic acid
biopolymers within the nanochannels; and correlating the signal to at
least one
property of the at least two nucleic acid biopolymers to thereby analyze
the
two or more individual nucleic acid biopolymers.
The specification also discloses methods of
preparing nanochannel arrays and nanofluidic chips, methods of analyzing
macromolecules, such as entire strands of genomic DNA, and systems for
carrying
out these methods.

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