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Chemical
Engineering
Cornelius (Neil)
F. Ivory
Integrated Proteomics
One
of the key challenges facing bioseparations today is
the large dynamic range of solutes in complex biological
systems. In proteomics, for instance, the dynamic range
of proteins in various cell lines spans 3-6 orders of
magnitude. Furthermore, these proteins range in size
from small oligopeptides to large hetero-complexes with
subsets of variants which are difficult to separate.
To fully analyze these biosystems in a reasonable amount
of time, a multidimensional separations cascade is needed
in which the first step can handle relatively large amounts
of crude sample, e.g., 10-100 mgs, and the last step
before the mass spectrometer(s) is a multiplexed array
of microchips which can process 1-10 nanograms, or less,
of low-abundance proteins. Intermediate steps must help
the low-abundance biosolutes make the transition from
a dilute, highly contaminated mixture to a concentrated,
highly purified substance suitable for analysis.
Dr.
Ivory and his collaborators specialize in designing,
building, and integrating separations devices which
challenge the limits of conventional instrumentation.
Examples include an electrofocusing chamber that
can process 100 milligrams of complex protein mixture
at 15 kV or more. A second apparatus uses an electric
field gradient rather than a pH gradient to focus
10-100 micrograms of protein. Still a third MEMs
device can use isotachophoresis to fractionate
and concentrate nanogram quantities of protein
or metabolites.
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This
variation in scale allows the preparative chamber to
feed smaller fractions into the microgram chamber which,
in turn, feeds fractions into the nanoscale chamber thus
forming the separations cascade. As the process scale
decreases, cycle time decreases exponentially so only
a handful of devices are needed in each stage of the
cascade and, at the smaller scales, parallel devices
can be integrated into “chips” which can
be multiplexed with, for instance, mass spectrometry.
Contact
Information
Cornelius F. Ivory, Ph.D.
Professor of Chemical Engineering
Washington
State University
PO Box 642710
Pullman, WA 99164-2710
Telephone:
509-335-7716
Fax: 509-335-4806
E-mail: cfivory@wsu.edu
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