A
new method to identify DNA mutations may shepherd
in an era of small, portable, electronic devices
for the rapid screening and identification of genes
that harbor disease.
Joseph
Wang, director of the Center for Bioelectronics
and Biosensors at the Biodesign Institute at ASU,
led a team that successfully merged efforts in the
fields of biosensors, electronics, and nanotechnology
to fashion nanocrystals that can act as "DNA biosensors" by
electronically recognizing subtle mutations in the
DNA. This creates enormous potential for applications
such as the diagnosis and treatment of genetic diseases,
detection of infectious agents and reliable forensic
analysis.
Wang, who recently was recruited to the Biodesign
Institute and serves a joint appointment as professor
in the chemical and materials department at the Ira
A. Fulton School of Engineering and Department of
Chemistry at ASU, is a renowned expert in nanomaterial-based
biosensors that operate at the scale of a thousand
times smaller than the width of a human hair. He
authored 660 papers and has 12 patents to his credit,
including involvement in the development of the first
noninvasive biosensor for diabetes, the FDA approved
Gluco Watch, which monitors glucose levels through
human sweat.
"The ultimate goal is to make something similar
to a hand-held glucose monitor for future genetic
testing," Wang says. "The electronic detection of
DNA is a thing of beauty. You can make it small,
low-power, inexpensive and robust, creating all sorts
of advantages."
Among
the keys to unearthing the mysteries behind individual
genetic variation and diseases like cancer are
fine differences – single nucleotide polymorphisms,
or "SNPs" – buried within the 3 billion chemical
bases of DNA comprising the human genome. Not every
SNP found will necessarily cause a mutation or determine
our eye or hair color – but, on average, SNPs occur
about once in every 1,000 DNA bases, adding up to
3 million potential individual differences across
the human genome. Wang's method allows for an accurate,
ultra-sensitive, rapid and low-cost identification
of these SNP variants.
"The novelty of the approach is the combination
of the nanocrystal tagging of DNA to create electro-diverse
signatures and combining them with a fast, portable,
low-cost electronic detection," Wang says.
To
achieve the desired results, Wang and his researchers
custom-made several individual nanocrystals, known
as quantum dots, from four heavy metal salts of
lead, cadmium, zinc and copper. Such nanocrystals
were selected owing to their ability to yield distinct
electronic signatures, with four well-resolved
current peaks. Next, the nanocrystals are piggybacked
onto individual DNA bases; these DNA bases – each carrying
a single nanocrystal – bind to a DNA sample and cause
minute electrical current changes in the nanocrystal
that can be measured with an electrode. The individual
base-conjugated nanocrystals are added sequentially
to any DNA sample of interest, generating an electronic "fingerprint" that
rapidly identifies all possible combinations of SNPs
in a single experimental run.
The whole procedure can detect SNPs in as little
as two hours, which represents a vast improvement
over existing laborious and time-consuming DNA detection
methods. Additionally, unlike current technology,
all the steps are carried out at room temperature.
The
approach also is readily adaptable for identifying
protein targets or single virus molecules, which
is what makes it suitable for diagnosing genetic
diseases, detecting infectious agents and providing
reliable forensic analysis. In addition, the technology
is scalable for the so-called "high throughput," or
large-scale DNA sequencing efforts used by many of
today's biotech companies and genomic researchers.
Though Wang is careful to admit that his results
represent just the first preliminary steps for this
new technology, he ultimately envisions a day when
a patient can walk into a doctor's office and have
their DNA checked for diseases, much like at a supermarket
checkout scanner.
"The technology is evolving and we would like to
extend it toward making a practical device," he says.
Wang's results recently were featured as the cover
story of Analytical Chemistry and were published
earlier in the Journal of the American Chemical Society.
The article can be found on the Web at ( http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ja043780a ).
His research was supported through a grant from the
National Science Foundation.
The Biodesign Institute at ASU integrates research
in diverse disciplines including biology, engineering,
medicine, physics, information technology and cognitive
science to accelerate discoveries into beneficial
uses. The institute is pursuing innovations in health
care, national security and environmental sustainability.
For more information, visit ( www.biodesign.asu.edu ).
By Joe Caspermeyer. Caspermeyer, with the Ira A.
Fulton School of Engineering, can be reached at 480-965-8382
or ( joseph.caspermeyer@asu.edu ).
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