We are interested in utilizing micro- and nanofabrication
strategies to create devices that facilitate our abilities to gather
chemical and biochemical information. Our motivations for fabricating
devices include high-throughput biochemical experimentation, development
of new types of chemical sensors, and understanding of transport
mechanisms in nanoscale-confined spaces. The devices that we develop
have application to drug discovery, health care, environmental monitoring,
and basic research.
Many of our projects involve the microfabrication of fluidic networks
that are used to perform biochemical assays. This area of research
is often referred to as microfluidics, microchips, or Lab-on-a-Chip
technology. We are presently interested in developing microfluidic
devices for addressing proteomics problems and automated single cell
assays. Proteomics is a term used to describe the understanding of
the full complement of proteins expressed by an organism. A given
type of cell will contain several thousand proteins and the task
of identifying all proteins is a significant challenge. Traditional
approaches to solving this problem involve the use of milligram quantities
of protein and chemical separations that unfold over a period of
days. We are pursuing microfabricated fluidics approaches to implementing
multidimensional liquid phase separations that utilize nanogram to
picogram quantities of materials with separations unfolding over
a period of tens of minutes. The ability to perform electrospray
ionization from microchips is also being developed to allow structural
analysis via mass spectrometry of the isolated proteins.
Microfluidics devices are also being developed to autonomously manipulate
single non-adherent cells, characterize them using flow cytometry
techniques, lyse the cells and chemical analyze the cell contents
utilizing chemical separations techniques. This automated approach
allows high-throughput characterization at the single cell level
so that statistics can be rapidly generated on cell heterogeneity.
Through collaboration with Prof. Nancy Allbritton (U.C., Irvine)
multiple kinase assays are being implemented on these devices to
study cell signal transduction mechanisms. Moreover, through collaborations
with Prof. Andrew Green (Medical College of Wisconsin) and Prof.
Lloyd Smith (University of Wisconsin) technology is being developed
to perform proteome studies of single cells.
More fundamental in nature is the study of molecular transport through
conduits with nanometer scale dimensions, what we refer to as nanofluidics.
We are studying both fluid and polymer transport through individual
nanoscale conduits or pores that are top-down fabricated in hard
materials such as glass, quartz or silicon. We are attempting to
further reduce lateral dimensions of channels and pores utilizing
bottom-up strategies and interfacing molecular assemblies to features
formed in hard materials. While this work is fundamental, understanding
could lead to new methods for the separation and analysis of polymeric
materials, new types of chemical sensors, or possibly technology
that allows the structure of single polymer molecules to be determined,
e.g., single molecule DNA sequencing.
We are also investigating the prospects of shrinking the size of
conventional mass spectrometry by several orders of magnitude. Specifically
we have been experimentally exploring the reduction in size of Paul-type
ion trap mass analyzers and assessing their performance. Reduction
in length scale of this type of mass spectrometer is particularly
interesting because the mass resolution of the device does not fundamentally
depend on its size. Microscale ion trap MS devices that are a factor
of 40 smaller than conventional scale have been operated with no
loss in mass resolving power. Smaller mass analyzers may also allow
operation at lower ion mean-free path (high pressures). Miniature
mass spectrometers have application to problems such as environmental
monitoring, chemical process control, and high-throughput laboratory
analysis.
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