Biochip makes droplet test tubes
Technology Research News
Researchers who are developing biochips
are taking two distinct approaches in devising ways to shunt tiny amounts
of liquids around. One focuses on finding ways to form microscopic channels
and tiny mechanical pumps. The other is aimed at using electricity to
maneuver tiny droplets on surfaces.
Researchers from the University of Texas M.D. Anderson Cancer
Center have advanced the second approach with a programmable biochip that
uses an array of electrodes to place water droplets on a surface, insert
substances into the droplets, and move and merge the droplets. The device
contains no moving parts.
The droplets, which range from 20 to 500 microns in diameter and
0.5 to 65 nanoliters in volume, serve as carriers for samples, contaminants,
chemical reagents, viral and genetic material, and cells. A nanoliter
is one millionth of a milliliter, and there are about 5 milliliters to
The device makes it possible to automate biochemical analysis
and detection to, for instance, identify pathogens in the field.
The biochip and its computer controller could eventually be miniaturized
and incorporated into portable medical, biological and chemical diagnostic
devices, said Jon Schwartz, a research scientist at the University of
Texas. "A long-term goal of this research is to provide a fluidic processor
technology that can form the core of versatile, automated, microscale
devices [for performing] chemical and biological assays at or near the
point of care," he said. This will "increase the availability of modern
medicine to people who do not have ready access to modern medical institutions."
The biochip contains a 32-by-32 array of electrodes. When energized,
electrodes attract water droplets that are suspended in a thin film of
The principle behind the droplet biochip is dielectrophoresis.
Small electrically polarized particles or droplets that are suspended
in a less polarized medium are attracted to nearby electric fields like
those produced by electrodes. Water droplets are naturally polarized because
water molecules are not electrically symmetrical; the arrangement of atoms
leaves one end of the molecule positive and the other negative.
Droplets can be moved and merged simply by sending electrical
current to the right sequence of electrodes. By programming electrodes
in various sequences, multiple droplets can be moved around the chip and
merged to mix their contents.
Droplets are placed on the biochip from liquid-filled pipettes
positioned just above the chip's surface. The fluid pressure is kept just
below the level needed to flow onto the surface. Turning on an electrode
positioned beneath a pipette produces enough force to draw fluid out.
The size of a droplet depends on how long the electrode remains on.
Biochips that manipulate droplets on surfaces have several advantages
over those that control fluids in channels, according to Schwartz. Droplet
biochips can be easily programmed, whereas channel-based biochips are
hardwired for a more specific range of tasks. Mechanical pumps and valves
are also difficult to make at the microscale and are prone to wear.
Other researchers have produced biochips that sandwich droplets
between two surfaces. The University of Texas researchers' single-surface
approach prevents samples and reagents from coming into contact with the
surface and so limits the risk of contamination, said Schwartz. Droplets
can also be made in a wider range of volumes, and using water droplets
as containers shields samples and reagents from the heat and electric
fields produced by the electrodes, he said.
The programmable droplet biochip opens the possibility of producing
specific DNA and RNA sequences and proteins on the spot. "The ability
to mix droplets containing individual nucleic acid bases... would enable
oligonucleotides to be synthesized on-the-fly in situ and used immediately
in a diagnostic or pathogen-detection mode," said Schwartz. Producing
a new oligonucleotide or protein could be as simple as downloading the
right sequence of bases from the Internet, he added.
The ability to mix droplets also makes it easier to create chemical
reagents as they are needed, which could make biological testing safer
and cheaper. "Detection and analysis problems frequently involve the use
of toxic reagents or unstable precursors [that] are undesirable or impractical
to transport and store," said Schwartz. The ability to carry out a set
of programmable reactions autonomously makes it possible to synthesize
substances on-the-fly from a set of less toxic or reactive reagents, he
The researchers tested the device by inserting droplets containing
varying amounts of bovine serum albumin into droplets of o-phthalaldehyde
on the biochip. They measured the fluorescence of the droplets to determine
the relative concentrations of the protein.
The researchers are working on a prototype that is scheduled to
be finished in the first half of 2004, according to Schwartz. They are
aiming to have a miniaturized, fully-automated device available for field
testing within two years, he said.
Schwartz's research colleagues were Jody V. Vykoukal and Peter
R. C. Gascoyne. The system's hardware and software components were developed
by Lawrence Livermore National Laboratories, the University of California
at Davis, LynnTech, Inc. and AppliedMEMS, Inc. The work appeared in the
first quarter 2004 issue of Lab on a Chip. The research was funded
by the Defense Advanced Research Projects Agency (DARPA).
Timeline: 2 years
TRN Categories: Microfluidics and BioMEMS; Biotechnology;
Story Type: News
Related Elements: Technical paper, "Droplet-Based Chemistry
on a Programmable Micro-Chip," Lab on a Chip, first quarter 2004.
February 25/March 3, 2004
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