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My
research involves development of mass spectrometric
instrumentation for the analysis of large biopolymers.
Mass spectrometry is the current state
of the art for high throughput analysis of proteins
such as that required in the field of proteomics,
but current commercial mass spectrometers are
severely limited in their ability to analyze
large molecules such as intact proteins. For
this reason, proteomics researchers have resorted
to techniques such as enzymatic digestion to
break down the proteins of interest into smaller
peptides which are more readily analyzed by
their mass spectrometers. However, enzymatic
digestion has the unfortunate side effect of
complicating an already complex mixture of compounds
leading to mass spectra which are cluttered
and difficult to interpret. This has forced
proteomics researchers to use costly and time
consuming separation steps prior to mass spectrometric
analysis in order to yield usable data. This
problem can be largely attributed to increased
ion beam divergence, detector saturation as
well as decreased detector efficiency at high
m/z. To combat this problem, the Smith group
is developing detectors that will mitigate or
eliminate these effects such as inductive charge
detectors, Faraday cup detectors and nanoelectro-mechanical
devices.
A second focus of my research
involves improving the sensitivity of mass spectrometry.
Our estimates indicate that, for the ESI-ToF
instrument in our laboratory, only about 1 in
1012 analyte molecules that emerge from the
spray tip are actually detected. This is an
alarmingly low number! The Smith group is exploring
several methods of improving this in addition
to the development of more sensitive detectors.
We are developing single droplet ion sources
as a method of overcoming spray losses. We are
also looking to employ aerodynamic lenses for
the collection and focusing of electrospray
generated ions. We are also attempting to recharge
single droplets after electrospray as a method
of overcoming the problem of signal suppression
by preferential charging of certain analytes.
With these advances we feel that it may be possible
to perform single molecule mass spectrometry.
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