The research interests of our group are focused on developing novel separation
and sample handling components for microfluidic (Lab-on-a-Chip; μTAS)
devices and then using these devices to solve interesting bioanalytical problems
with special emphasis in the areas of protein separations (proteomics) and
single cell analysis. This research is multidisciplinary in nature drawing
upon knowledge in the fields of chemistry, physics, engineering, cell biology,
Microfluidic devices were first reported
in the early 1990s, and research in the area is expanding rapidly.
These devices consist of a series of channels etched in glass
or molded in various types of plastics. The channels are generally
less than 50 μm wide
and 10 μm deep - smaller than a human hair. Because complex
channel structures can be realized and because the fluids in these
structures can be precisely controlled, analytes and cells can
be manipulated, processed, separated, and detected all on a single
device. The driving forces behind the various sample manipulation,
processing, and control steps are electroosmosis, electrophoresis,
and pressure differentials.
The unique ability of these devices to integrate sample manipulation
and processing operations with separations and analyte detection
allows for the efficient automation of chemical analyses and, as
such, is driving a paradigm shift in the chemical analysis community.
In addition to the automation of chemical analysis, microchips
have several other inherent advantages over conventional chemical
analysis instrumentation. These advantages include: 1) the ability
to perform faster separations with no losses in separation efficiency,
2) lower reagent and sample consumption, 3) less waste production,
and 4) the ability to fabricate many parallel systems on the same
|We are especially interested in developing advanced sample handling, separation, and detection methodologies on microfluidic devices to study protein expression and metabolic pathways in single cells. Following and detecting the changes in protein expression over time in single cells is critical to understanding processes such as cell differentiation, embryology and the evolution of disease states. The ability to identify and quantitate such changes should help 1) in the early diagnosis and successful treatment of diseases like cancer, and 2) in better understanding how complex organisms develop from single cells.
The analysis of such minute, yet complex, samples, however, is
extremely challenging. For example, a typical mammalian cell,
roughly a cube 15 μm on a side, has a volume
of only ~3.5 pL, yet more than 10,000 different proteins are expressed
in that cell at any one time. In addition to the sheer complexity
of the sample, the concentrations of regulatory proteins - the
proteins of most interest - in such a cell are typically in the
sub-nM range. To study changes in the expression of these proteins,
therefore, highly sensitive detection and powerful separation techniques
must be developed for use on these microfluidic devices. To address
these challenges we are 1) exploring the use of novel fluorogenic
and fluorescent compounds for the derivatization of proteins at
low concentrations, and 2) developing multi-dimensional separation
techniques to handle the large number of components that need to
be separated. Other complicating factors, however, must also be
dealt with, such as the propensity of both cells and proteins to
adsorb onto the walls of these devices. To minimize such adsorption
problems, another area of research that we are pursuing is the
development and characterization of new materials both for the
fabrication of microfluidic devices and for coating the walls of
Roman, G.T. Chen, Y. L., Viberg, P., Culbertson, A.H. and Culbertson*, C.T. “Single Cell Manipulaton and Analysis Using Microfluidic Devices.”accepted Analytical Biochemistry (invited)
Meyer, A. R., Clark, A. M., Culbertson*, C.T. “The Effect of Photomask Resolution on Separation Efficiency in Microfabricated Devices.” accepted Lab-on-a-Chip.
Xie, A., Roman, G.T., Culbertson, C.T., Higgins, D.A. “Optical Microscopy Studies of Polymer/Liquid-Crystal Diffractive Optics.” Proc SPIE 2006 vol. 6135, 613505 (invited)
Roman, G. T., Culbertson*, C.T. “Surface Engineering of Poly(dimethylsiloxane) Microfluidic Devices Using Sol-Gel Chemistry.” Langmuir 2006 22(9) 4445-4451.
Roman, G. T., Carroll, S., McDaniel, K. Culbertson*, C.T. “Micellar Electrokinetic Chromatography of Fluorescently Labeled Proteins on Poly(dimethylsiloxane)-based Microchips.” Electrophoresis 2006, 27 2933-2939.
Roman, G. T., McDaniel, K. Culbertson*, C.T. “High Efficiency Micellar Electrokinetic Chromatography of Hydrophobic Analytes on Poly(dimethylsiloxane) Microchips.” The Analyst 2006 131(2), 194-201. HOT ARTICLE
Culbertson*, C. T., Roman, G.T., Tugnawat, Y., Meyer, A., Ramsey, J. M. and Gonda, S. R. “Microchip Separations in Reduced- and Hypergravity Environments.” Anal. Chem.2005, 77(24), 7933-7940. Highlighted in RESEARCH FOCUS of A-PAGE MAGAZINE
Roman, G. T., Hlaus, T., Bass, K., Seelhammer, T., and Culbertson*, C. T. “Sol-gel Modified Poly(dimethylsiloxane) Microfluidic Devices with High Electroosmotic Mobilities and Hydrophilic Channel Wall Characteristics.” Anal. Chem. 2005, 77, 1414-1422
Poulsen, C. R., Culbertson, C. T., Jacobson, S. J., and Ramsey, J. M. Static and Dynamic Acute Cytotoxicity Assays on Microfluidic Devices.” Anal. Chem. 2005, 77, 667-672
McClain, M. A., Culbertson, C. T., Jacobson, S. C., and Ramsey, J. M. “Microfluidic Devices for the High Throughput Chemical Analysis of Cells.” Analytical Chemistry 2003, 75, 5646-5655.