novel "Flu Chip" developed at the University of Colorado
at Boulder that can determine the genetic signatures
of specific influenza strains from patient samples
within hours may help world health officials combat
coming epidemics and pandemics.
Tests last month on the new technology by the Centers
for Disease Control and Prevention in Atlanta showed
the CU-Boulder Flu Chip can determine the genetic
make-up of types and subtypes of the flu virus in
about 11 hours, said CU-Boulder Professor Kathy Rowlen
of the chemistry and biochemistry department. Current
methods for characterizing flu subtypes infecting
patients take about four days.
The Flu Chip is expected to be in wide use in laboratories
within a year, said Rowlen, who has led the two-year
CU-Boulder research effort.
Rowlen, who is working on the Flu Chip development
with CU-Boulder chemistry Professor Robert Kuchta
and a team of postdoctoral researchers and students,
said they are conferring with CU's Technology Transfer
Office and plan to make the Flu Chip genetic sequences
freely available to interested researchers.
There currently are less than 200 facilities worldwide
that provide detailed strain analysis of influenza,
said Rowlen. Strain identification is critical for
tracking emerging strains and in determining which
flu strains are most likely to infect people the
following year in order to develop annual, preventative
vaccines, she said.
"This new technology should help provide better
global influenza surveillance by making it easier
for more laboratories to swiftly identify severe
flu strains, which in turn may aid health officials
to stem potential flu epidemics and even pandemics," Rowlen
chip, which can be configured to test for all known
flu virus strains as well as new variant strains,
was evaluated for three primary subtypes of flu
in the October CDC test -- the avian flu strain
H5N1, and two of the most common human flu types
worldwide in recent winters, H1N1 and H3N2. The
chip was more than 90 percent accurate and will
be tested again "side
by side" with standard flu-virus culturing methods
for accuracy and speed at the CDC's Atlanta headquarters
"This was the first time a version of the Flu Chip
was tested outside of our lab, and it exceeded our
expectations," she said. The technology was developed
with a $2 million, five-year grant to CU from the
National Institute of Infectious Diseases.
Flu Chip fits on a microscope slide and contains
an array of microscopic spots, Rowlen said. Genetic
bits of information that are complimentary to known,
individual influenza strains are "spotted" robotically
in an array, where each row of three spots contains
a specific sequence of "capture" DNA. Each spot is
approximately one-hundredth of an inch in diameter.
The microarray is then immersed in a wash of influenza
gene fragments obtained from the fluid of an infected
fragments from the infected fluid bind to specific
DNA segments on the microarray like a key in a
lock, indicating both a match and that the virus
signature is present, she said. The captured RNA
is then labeled with another complimentary sequence
that also contains a fluorescent dye, and such "hits" light
up like a pinball machine when the chip is inserted
into a laser scanner.
The Flu Chip also should be able to recognize mutations
that might occur in avian flu H5N1, which has been
spreading rapidly from bird to bird in Asia, Russia
and parts of Europe, said Kuchta. While the avian
virus does not now spread effectively from person
to person, world health officials are fearful the
strain will mutate and become transmittable between
humans, possibly triggering a worldwide pandemic.
"If an unusual flu subtype surfaces that has characteristics
of both avian and human flu types, we could detect
it rapidly using this technology," Kuchta said.
Standard laboratory culturing techniques by the
CDC and WHO currently take four days to five days
to determine flu strains afflicting patients, said
Kuchta. While commercial tests like rapid antigen
testing can detect influenza in less than an hour,
none provide genetic information about various flu
subtypes, he said.
Rowlen said that within a few years, the technology
could be downsized to fit into a hand-held portable
device the size of a cell phone or PDA and taken
into remote areas around the world to test for lethal
strains of flu.
"We can make it small and simple enough to take
into rural areas in places like the Congo, Cambodia
or Indonesia that may lack lab facilities," she said. "One
of our goals has been to address the needs of developing
nations by providing an inexpensive, field-portable
test kit for respiratory illnesses to the World Health
Organization for global screening of respiratory
said the team hopes to cut down on the 11-hour
virus identification process. "We are now looking
at ways to amplify the fluorescent signal after we
capture the RNA on the microarray, which could shorten
the identification time to just a couple of hours," he
said the Flu Chip could also play a significant
role in alerting government officials to an "engineered" influenza
virus arising from terrorism.
Katrina displayed the vulnerability of the United
States to natural catastrophes, she said. "A
flu pandemic is inevitable since the virus continually
mutates and is naturally spread by migratory birds.
Whether this year or 10 years from now, it is important
to be prepared for such an event."
experts agree that preparations for a flu pandemic
include early identification, vaccine development,
the wide availability of pharmaceuticals and planning
for possible local quarantine events. During the "Spanish
Flu" pandemic of 1918-1919, between 20 million and
40 million people died from influenza in less than
a year and an estimated one-fifth of the world's
population became infected.
The flu chip also could be used to swiftly test
for the avian flu virus at large, remote bird farms
in Asia, Europe and Russia, said Kuchta. The chip
also could be easily reconfigured to use for the
global surveillance of any RNA virus, including SARS,
measles, HIV and hepatitis C, the researchers said.
Other members of the Flu Chip team include CU-Boulder
postdoctoral researchers Erica Dawson, Daniela Dankbar,
Martin Mehlman and Chad Moore, graduate students
James Smagala and Michael Townsend and undergraduate
Amy Reppert. The group has been working on the project
with CDC Influenza Branch Chief Dr. Nancy Cox and
CDC researcher Catherine Smith.