news
there will be no problems with toxicity. Another encouraging result was that EgadMe signals were detected in the heads of the embryos, a region that is not accessible to optical microscopes. The biggest problem for the researchers was the delivery of EgadMe. In this study, it was injected into the embryo with a microfine needle at the two-cell stage, an approach that worked well but isn’t practical in all cases. Meade says the researchers are looking into two other possibilities: delivery via modified viruses—an approach similar to the one used in gene therapy— and delivery via a particular peptide that HIV uses to infect cells. The researchers are also working on other enzyme assays. “β-Galactosidase is interesting,” Meade explains, “but it’s not the only game in town.” The assay can be adapted to any reporter
gene and enzyme, he says, provided that the researchers can synthesize the necessary linker sequences and caps. This kind of synthesis is no small feat, because some caps are “leakier” than others, but Meade says the researchers are already well on the way to getting systems that can monitor apoptosis—programmed cell death. In addition, they have begun to explore the use of similar contrast agents to monitor the exchange of intracellular messengers, such as calcium (J. Am. Chem. Soc. 1999, 121, 1413–1414). Together, these approaches promise to give researchers a much more comprehensive view of the biochemical activity of cells in the form of a three-dimensional MR image. And they promise to boost the status of MRI recognition as a bona fide tool for basic research. Elizabeth Zubritsky
Imprinting plastic microchips Although the field of microfluidics has taken off in recent years, there are still several issues related to the microfabrication of silicon- and glass-based chips that have kept some researchers from joining in. At the top of the list are time and cost. In an effort to decrease both, several groups have turned to plastic-based microfluidic devices. Among them are Cheng S. Lee and his graduate student Jingdong (Jay) Xu of the University of Maryland–College Park, who have been collaborating with Laurie Locascio and Michael Gaitan of the National Institute of Standards and Technology to develop new ways of inexpensively mass producing plastic microfluidic devices. In the April 15 issue of Analytical Chemistry (pp 1930–1933), they describe a new room-temperature method for imprinting microchannels onto plastic substrates. Previously, the researchers used a fabrication method that relied on heating two aluminum blocks, which sandwich the plastic substrate and silicon template. “Not only does it take time to heat the silicon templates and cool them down, but when using heat, the templates tend to
CHEMICAL & ENGINEERING NEWS
break after only 5–10 uses,” says Xu. So rather
The EgadMe molecule begins with a galactopyranose cap (upper right). When β-galactosidase is expressed, it cleaves the sugar (green arrow), making EgadMe accessible to water and, thus, generating a signal (lower left) in the frog embryo. 320 A
A N A LY T I C A L C H E M I S T R Y / M A Y 1 , 2 0 0 0
than using heat, the researchers turned to an alternative imprinting method that involves the application of high pressure (450–2700 psi). The high-pressure, room-temperature method is capable of imprinting >100 plastic substrates from 1 silicon template. And it requires much less time
news
Vivak, polycarbonate, and
Once imprinted, the open channels
polystyrene. “One advantage
on the plastic substrate were sealed
of working with plastic is that
with a layer of poly(dimethylsiloxane)
you have a choice,” says Xu.
(PDMS), which was chosen for its low
“Preliminary results show
background fluorescence. PDMS has
that different plastics do offer
other advantages as well. It is chemical-
different surfaces. Some are
ly and physically inert, electrically insu-
better suited for particular
lating, and inexpensive.
applications than others.”
However, using PDMS for the cover
From a mechanical point of
and a different plastic for the substrate
view, some plastics are hard-
has one obvious problem. “The photo
er than others and therefore
properties of PDMS and other plastics
require higher pressures to
are different,” explains Xu. “For some
than previous methods, emphasizes Xu.
achieve the same channel depth. “But
applications, we want a uniform plas-
“From one template, we can make one
from a chemical point of view, some
tic device.” Thus, the researchers are
channel on the plastic in about 5 s,” he
plastics are more transparent than oth-
now investigating alternative plastics,
says. “So we can mass produce hun-
ers,” adds Xu. “If you are going to use
which can be used for both the cover
dreds of devices quickly.” The overall
optical detection, certainly you want to
and substrate.
fabrication time per chip decreases from
pick a transparent one.”
Britt Erickson
Microscopic image of the top view of an imprinted PMMA device.
about 30 min (heating method) to 5 min (room-temperature method). The amount of pressure applied is
NEWS FROM HPCE 2000
controlled with a hydraulic press. The
Britt Erickson reports from Saarbrücken, Germany.
more pressure that is applied, the deep-
HPCE changes course
er the channels. The technique can imprint channels with dimensions ranging from a few to 100 µm. The researchers have investigated the roomtemperature method on a variety of substrate materials, including poly(methyl methacrylate) (PMMA), the co-polyester
The 13th International Symposium on High-Performance Capillary Electrophoresis and Related Microscale Techniques (HPCE 2000), will be the last meeting in the series to have High-Performance Capillary Electrophoresis in its name. Although the meeting will still be referred to as the HPCE symposium, beginning with the 2001 meeting in Boston (Jan. 13–18, 2001), it will be called the 14th International Symposium on Microscale Separations and Analysis. By the 2002 meeting in Stockholm, Sweden (April 13–18, 2002), the organizers plan to completely drop “Separations” from the title and call it the 15th International Symposium on Microscale Techniques. What used to be predominantly a separations meeting will evolve into a microscale meeting, focused on pharmaceuticals and the life sciences.
M A Y 1 , 2 0 0 0 / A N A LY T I C A L C H E M I S T R Y
321 A
