Article: Thousand-chamber biochip debuts
- Microfluidics storage.
This could lower costs (eventually - more expensive now) and
environmental concerns. 50 picoliters is cheaper and less hazardous
then milliliters. Also this allows diagnostics on a very high
throughput level. The bottleneck though, is not in the rest of the
equipment for sample preparation and analysis. The machines
interacting with this can take up a room. When they get smaller &
cheaper, the technology will become more useful. There are lots of
groups working in this area now, so advances may happen soon. The
genomics Microarray people are working on similar things as well.
Thousand-chamber biochip debuts
By Eric Smalley, Technology Research News
When the computer chip was invented forty-four years ago, it set
the stage for computers to shrink from room-size behemoths filled
with light-bulb-size vacuum tubes to handheld devices powered by
Researchers from the California Institute of Technology are
mirroring that effort with a chip that stores tiny drops of fluid
rather than magnetic or electronic bits of information.
The researchers are aiming to replace roomfuls of chemistry
equipment with devices based on a fluidic storage chip that can
store 1,000 different substances in an area slightly larger than a
The technology could eventually allow experiments that involve
hundreds or thousands of liquid samples to run on desktop or even
handheld devices, potentially reducing the cost and complexity of
medical testing, genetics research and drug development, said
Stephen Quake, an associate professor of physics and applied physics
at Caltech. "Small volumes mean lower cost for expensive reagents,
and mean that samples can be tested for a broader range" of
diseases, he said.
The fluidic storage chip has 1,000 chambers arranged in a 25 by 40
grid with 3,574 microvalves. "It's small plumbing -- pipes, valves,
pumps, et cetera -- all integrated on a small rubber chip," said
Each chamber holds 250 picoliters, or about one 80th of a drop of
water. The connecting channels are 100 microns wide and nine microns
high, which is about twice as high as red blood cells are wide.
Like the bits that store 1s and 0s in computer memory, the chambers
that store fluids at the intersections of the rows and columns of
the researchers' chip can be accessed individually. The key is a
pair of multiplexors that address each chamber by row and column.
Computer memory chips use similar electronic multiplexors to access
individual bits of digital information.
In the fluidic storage chip, the row multiplexor pushes fluids along
one or more rows to fill or purge the chambers in those rows, and
the column multiplexor applies pressure to close the input and
output valves of the chambers along one or more of the columns.
The fluidics multiplexors allow the researchers to control the 1,000
chambers using only 22 connections to the chip, said Quake. "We can
control exponentially many fluid lines," as outside connections, he
said. Thirty connections could theoretically control 32,000 fluid
lines and 40 connections could theoretically control one million
fluid lines. "This greatly simplifies the input/output and
connections required from the real world to the chip," he said.
To make the fluidic chip, the researchers etched patterns into
plastic molds using the same photolithography process used to make
computer chips, then used the molds to shape thin layers of rubber.
The top layer contains fluid channels and chambers, and the bottom
layer holds multiplexors and control lines. In between is a thin
sheet of rubber. The intersection of a fluid channel and a control
line forms a valve; hydraulic pressure in the control line deflects
the thin membrane between the top and bottom layers and pinches off
the fluid channel. The multiplexors determine where the pressure is
applied in order to control the flow.
The chip is made completely of flexible silicone rubber, rather than
the hard silicon used in computer chips. Fluids enter the chip
through steel pins connected through holes punched into the rubber,
which forms a tight seal around the pins.
The researchers also made a chip-size comparator, which measures
samples against a scale or standard to determine properties like the
pH concentration of a fluid.
The researchers' comparator has an array of 256 chambers arranged in
four columns of 64, and is about twice the size of the storage chip.
It contains 2,056 microvalves and performs more complicated
manipulations than the storage chip, according to Quake. Two fluids
can be mixed in any number of the chambers and the results from any
chamber in each column can be removed for further examination, he
The researchers took the comparator through its paces by loading
individual bacteria into some of the chambers and adding a fluid
that becomes fluorescent in the presence of a particular enzyme.
This allowed the researchers to determine which bacteria produced
There are limitations to the rubber chips, according to Quake. Some
liquids, like certain organic solvents, can break down the chip's
rubber material, and there is a danger of contamination from
molecules diffusing through the walls of the chambers and channels.
There is also a possibility that some molecules will stick to the
walls after the chip's contents have been emptied.
In addition, the chip designs are limited by the need to avoid cross-
contamination as samples are shunted about. For example, the
contents of only one of the 64 chambers in each column of the
comparator can be removed without being contaminated because any
residue from the first sample would contaminate subsequent samples
passing through the channel, according to Quake.
The researchers' work is an impressive and significant advance, said
Kenny Breuer, an associate professor of engineering at Brown
University. "There have been many attempts at building such
microfluidic elements, but this is by far the most complex that I
have seen, and the approach... offers the most flexibility for
building a wide variety of microfluidic systems," he said.
The system does have limitations, Breuer added. "There is...
significant hidden machinery that is required to operate the device -
- supplies of compressed air, banks of solenoidal valves and, most
importantly, very large volumes of fluid that need to be flushed
through the system as each cell is loaded and purged," he said. The
volume of this supporting infrastructure could limit the size and
complexity of fluidic systems made with this technology, he said.
It is also true, however, that the first electronic computer chips
used large amounts of power and were not able to do much, but "still
enabled a revolution in electronics and engineering," said Breuer.
The ability to create large-scale integrated microfluidics systems
with such complexity is very exciting, even if this particular
design may eventually be supplanted by other approaches, he said.
The researchers next plan to use the devices in biological research,
said Quake. "One area will be in environmental microbiology."
The technology could be used in practical applications in one to two
years, said Quake. There are some manufacturing issues that need to
be addressed, but "it is already working in some practical
applications," he said. Quake is a director of Fluidigm Corporation,
which is commercializing technology.
Quake's research colleagues were Todd Thorsen and Sebastian Maerkl.
They published the research in the September 26, 2002 online issue
of the journal Science. The research was funded by the Defense
Advanced Research Projects Agency (DARPA) and the Army Research
Timeline: 1-2 years
TRN Categories: Microfluidics and BioMEMS; Biotechnology;
Story Type: News
Related Elements: Technical paper, "Microfluidic Large-Scale
Integration," Sciencexpress, September 26, 2002