Biomedical Engineering Reference
In-Depth Information
using capillary electrophoresis) powered the creation of most of the irst microluidics-
based companies in the mid-1990s. In 1992, a group from Ciba-Geigy in Switzerland, led
by Michael Widmer, wrote an inluential article in the
Journal of Chromatography
, bearing
a long, forgettable title and a much more memorable subtitle: “Capillary electrophoresis on
a chip.” he three junior authors of this article, Andreas Manz, Jed Harrison, and Elisabeth
Verpoorte, are now widely considered microluidics pioneers. In fact, Andreas Manz and
Michael Widmer had already coauthored an article in 1990, in which they had outlined
the theoretical advantages of miniaturizing “total chemical analysis systems” (without
demonstrating a prototype)—this 1990 article, published in
Sensors and Actuators B
, is
universally regarded as the foundational article of microTAS as a ield.
As it happens, they were not the irst to have conceived the idea that biochemical sep-
arations would be improved by miniaturizing luid manipulation—most of the electro-
phoresis ield had noticed by then: Philpot had invented free-low electrophoresis using
parallel-plate devices in 1940 and Hannig had invented a continuous-low paper electro-
phoresis device in 1950 (see Section 4.4.2). Seeking no publicity, a team of engineers at
McDonnell Douglas worked with Hannig through the mid-1970s to design a continuous-
low device for performing electrophoretic separations in space. he device was even suc-
cessfully tested in various shuttle lights (the irst of them in June 1982). One of the irst
microTAS experiments was performed…away from our planet! (he subtle diference is
that, in these pioneering experiments, the solutions are conined in luid sheets whereas
in microTAS systems, as sketched by Manz and Widmer, the luids would be conined in
microchannels—which would require a new set of fabrication technologies and would
impose a new set of engineering and scientiic constraints on the investigator.)
he other great driver was the Human Genome Project and its seemingly insatiable
demand for enhanced DNA sequencing capacity. Fortunately, DNA can be very eiciently
separated by CE on a chip, and relatively intense labeling allows easy detection using laser-
induced luorescence. Great efort was put into making fused silica, glass, and plastic chips
that could carry out sensitive and highly parallel laser-induced luorescence detection-
based CE chips.
In 2005, Richard Mathies' group (University of California, Berkeley) reported in
PNAS
the development of the Mars Organic Analyzer, a CE chip for amino acid analysis to be
deployed on the rover in the ExoMars Mission in 2016 to 2018. Consider the pace of prog-
ress, starting from Manz and Widmer's 1990 vision: it will have taken the ield slightly
more than 25 years (the measure of a human generation) to take a microluidic chip to
another planet!
Hundreds of complete CE channels can now routinely be fabricated on a single glass wafer.
Richard Mathies' group at the University of California (Berkeley) has been the main power-
horse in this ield, continuously pushing the technology. In 1999, they had already developed
a 96-channel system (110 μm wide, 50 μm deep channels) on a 10-cm-diameter glass wafer
(
Figure 4.3a
) that could be loaded via 96 capillaries (
Figure 4.3b
) and scanned with a radial
laser scanner (
Figure 4.3c
), achieving a separation resolution of one base pair in just 10 minutes
(
Figure 4.3d
). he improved version of this device, which will go into the Mars rover (see previ-
ous text box), now contains on-chip microvalves and micropumps activated by a pneumatically
delectable PDMS membrane. Another group actually manufactured a glass chip nearly a meter
long to maximize the number of channels that could be run in parallel.
Two technical challenges cropped up in the development of highly parallel CE-on-a-chip
systems. To load a sample bolus small enough to take advantage of the small column volumes,
