Biochip puts it all together
Technology Research News
Scientists are working to make minuscule
chemistry labs for many uses. Labs-on-a-chip promise to detect and analyze
microorganisms and chemicals in the field, are potentially much faster
and cheaper than today's testing methods, and could enable new types of
It isn't easy cramming all the hallmarks of labs -- the chambers
and channels that hold and guide fluids, the pumps and valves that shunt
fluids around, and the heaters, mixers and sensors that carry out experiments
-- onto a self-contained chip that works automatically.
Researchers from Arizona State University have taken a large step
in that direction, however, by fabricating a biochip that contains all
these elements and is very cheap to produce. The plastic chip is 12 centimeters
long, 6 centimeters wide and 2 millimeters thick, and uses very little
The chip could eventually be used in portable devices that do
genetic analysis, environmental testing and biological warfare agent detection
in the field, said Robin Liu, manager of microfluidic technology at the
Arizona State University Applied NanoBioscience Center.
The researchers demonstrated the prototype by having it prepare
and analyze a raw sample of whole blood from a rabbit. It took the device
3.5 hours to identify a disease-causing E. coli bacteria in the rabbit
blood, according to Liu.
What sets the chip apart from other prototype biochips is that
it carries out all the work needed to prepare a sample like whole blood,
said Liu. "On-chip sample preparation [is] integrated with back-end DNA
detection," he said.
The microfluidic devices that make up the chip perform all of
the front-end sample preparation steps, including target cell capture
using immunomagnetic beads, cell preconcentration and purification, cell
lysis, DNA multiplication and electrochemical detection of low levels
of DNA, said Liu. Cell lysis is the process of breaking down cell membranes,
which is necessary to get at a cell's DNA. "The device is completely self-contained,"
he said. "No external pressure sources, fluid storage, mechanical pumps
or valves are necessary."
Key to the device is its simplicity. Many microfluidic devices
are made in multiple layers. In contrast, the researchers' single-layer,
plastic microfluidic components are simple and inexpensive to manufacture.
"Fabrication and integration [is easy] compared with multi-layer and three-dimensional
structure fabrication," said Liu. These technologies are often too expensive
or too complicated for mass production, he said.
Each of the biochip's components is simple, said Liu. "One example
is our paraffin-based microvalves that simply use a plug of wax as an
actuator." As a result, it costs less than one-tenth of a cent to add
a valve to the chip, he said.
The chip contains a pair of pumps that have no moving parts. One
is an air pocket attached to a heater, which expands the air to pump small
volumes of liquid, and the other is a pair of electrodes that generate
a current between them to carry out electrolysis, which extracts hydrogen
and oxygen gas from water. This type of pump can to move larger volumes
The chip mixes liquids by using sound waves to vibrate air bubbles
trapped in small pockets in the cover of the mixing chamber. The vibrations
move the air bubbles through the liquids, and friction causes the liquids
to mix. Completely mixing two fluids in a 50-microliter chamber takes
six seconds using this cavitation microstreaming process, according to
Liu. Because such small amounts of fluids are extremely viscous, it would
take several hours for the fluids to completely mix by natural diffusion.
The chip's sensor is a DNA microarray developed by Motorola Inc.
that contains DNA strands attached to gold electrodes. When DNA from the
target pathogen combines with the DNA on the chip, it produces an electrical
signal, which indicates that a pathogen is present.
The chip also contains temperature sensors, heaters and a fluidic
circuit, and has a total manufacturing cost of seven dollars, according
to Liu. The cost will drop when the chip is mass-produced, he added.
The researchers are working on increasing the efficiency of the
cell capture step and increasing detection sensitivity, said Liu. The
technology will be ready for commercialization in two to three years,
Liu's research colleague was Piotr Grodzinski. The work appeared
in the October, 2003 issue of the Journal of Microlithography, Microfabrication
and Microsystems. The research was funded by the Defense Advanced
Research Projects Agency (DARPA) and the National Institute of Standards
and Technology (NIST).
Timeline: 2-3 years
TRN Categories: Microfluidics and BioMEMS; Biotechnology;
Integrated Circuits; Materials Science and Engineering
Story Type: News
Related Elements: Technical paper, "Development of Integrated
Microfluidic System for Genetic Analysis," Journal of Microlithography,
Microfabrication and Microsystems, October, 2003
December 3/10, 2003
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