Research Overview

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, and biochemistry.

Culbertson Research Laboratory

Single Cell Analysis

Single cell research in the Culbertson’s lab is focused on developing high throughput microfluidic devices for single cell analysis. On these devices cells are rapidly lysed using a high electric field strength. Cell lysis is followed by lysate injection and the electrophoretic separation of the lysate components. The fluorescently labeled components are then detected using laser induced fluorescent detection (LIF). The fluorescently labeled components are generally small molecules or peptide substrates that are used as probes for reactive nitrogen species or kinase activity. We are also interested in further advancing LIF techniques to create multiple excitation and detections spots via out-of-plane integration of multimode optical fiber bridges. These bridges can be used to monitor both intact cells and the injected and separated lysate from these cells.

Off-chip integration of multimode optical fiber bridge to establish two excitation/detections spots using single excitation source and single detector.

Sequential video rate frames of cell lysis. Jurkat cells loaded with carboxyfluorescein.

Two fundamental light propagation modes to monitor physical characteristics and biological properties of single cells

References

Sadeghi, J.; Patabadige, D.E.W.; Culbertson, A.H.; Latifi, H. and Culbertson, C.T. Out-of-plane integration of a multimode optical fiber for single particle/cell detection at multiple points on a microfluidic device with applications to particle/cell counting, velocimetry, size discrimination and the analysis of single cell lysate injections. 2016 Lab Chip. Just Accepted DOI: 10.1039/c6lc01161f

Patabadige, D.E.W.; Sadeghi, J.; Latifi, H.; Culbertson, A.; and Culbertson, C.T. Integration of Optical Fibers with Multilayer Microfluidic Devices for Single Cell Analysis, 2016, Analytical Chemistry, 88 (20) pp. 9920-9925. DOI: 10.1021/acs.analchem.6b03133.

Patabadige, D.E.W.; Mickleburgh, T.; Ferris, L.; Brummer, G.; Culbertson, A. and Culbertson, C.T. High Throughput Microfluidic Device for Single Cell Analysis using Multiple Integrated Soft Lithographic Pumps, 2016, Electrophoresis, 37(10) pp. 1337-1344 DOI: 10.1002/elps.201500557

Metto, EC; Evans, K; Barney, P; Culbertson, AH; Gunasekara, DB; Caruso, G; Hulvey, MK; Fracassi da Silva, JA; Lunte, SM; Culbertson, CT. An Integrated Microfluidic Device for Monitoring Changes in Nitric Oxide Production in Single T-Lymphocyte (Jurkat) Cells, Analytical Chemistry, 2013, 85(21), 10188-10195. DOI: 10.1021/ac401665u

Mainz, ER; Gunasekara, DB; Caruso, G; Jensen, DT; Hulvey, MK; Fracassi da Silva, JA; Metto, EC; Culbertson, AH.; Culbertson, CT.; Lunte, SM. Monitoring intracellular nitric oxide production using microchip electrophoresis and laser-induced fluorescence detection. Analytical Methods 2012, 4(2), 414-420.

Price AK and Culbertson, CT. “Chemical Analysis of Single Mammalian Cells using Microfluidic Devices.” Analytical Chemistry2007, 79(7), 2614-2621. (PMID 17476726)

Roman, GT Chen, YL, Viberg, P, Culbertson, AH and Culbertson, CT. “Single Cell Manipulation and Analysis Using Microfluidic Devices.” Analytical and Bioanalytical Chemistry 2007 387(1), 9-12 (PMID 16955261)

Culbertson, C. T. “Single Cell Analysis on Microfluidic Devices” in Methods in Molecular Biology, vol. 339: Microchip Capillary Electrophoresis: Methods and Protocols. ed. Charles Henry. The Humana Press, Totowa, NJ 2006 pp. 203-216. ISSN:1064-3745

Poulsen, CR, Culbertson, CT, Jacobson, SJ, and Ramsey, JM. Static and Dynamic Acute Cytotoxicity Assays on Microfluidic Devices.” Anal. Chem. 2005, 77, 667-672. (PMID 15649069)

McClain, MA, Culbertson, CT, Jacobson, SC, and Ramsey, JM. “Microfluidic Devices for the High Throughput Chemical Analysis of Cells.” Analytical Chemistry 2003, 75, 5646-5655. (PMID 14588001)

McClain, MA, Culbertson, CT Jacobson, SC, and Ramsey, JM. “Flow Cytometry of E. coli on Microfluidic Devices.” Analytical Chemistry 2001, 73, 5334-5338.

Schrum, D. S., Culbertson, C. T., Jacobson, S. C. and Ramsey, J. M. “Microchip Flow Cytometry Using Electrokinetic Focusing.” Analytical Chemistry 1999, 71, 4173-4177

IDEAs (Integrated Dielectric Elastomeric Actuators)

References

Price AK, and Culbertson, CT. “Generation of Nonbiased Hydrodynamic Injections on Microfluidic Devices Using Integrated Dielectric Elastomer Actuators.” Anal. Chem. 2009 81(21), 8942-8948 (DOI: 10.1021/ac9015837). (PMID 19817486)

Price, AK., Anderson, KM. and Culbertson, CT. “Demonstration of an Integrated Dielectric Elastomer Actuator on a Microfluidic Electrophoresis Device.” Lab on a Chip 2009, 6, 2076-2084.(DOI: 10.1039/b823465e). (PMID 19568678)

Microfluidic Device Fabrication - Novel Polymers

References

Klasner, SA, Metto, EC, Roman GT and Culbertson*, CT. “Synthesis and Characterization of a Poly(dimethylsiloxane)-Poly(ethylene oxide) Block Copolymer for Fabrication of Amphiphilic Surfaces on Microfluidic Devices.” Langmuir, 2009, 25(17) 10390-10396 (DOI: 10.1021/la900920q). (PMID 19572528)

Microfluidic Device Fabrication - Novel Channel Coatings

References

Roman, GT, Culbertson, CT. “Surface Engineering of Poly(dimethylsiloxane) Microfluidic Devices Using Sol-Gel Chemistry.” Langmuir 2006 22(9) 4445-4451. (PMID 16618201)

Roman, GT, Hlaus, T, Bass, K, Seelhammer, T, and Culbertson, CT. “Sol-gel Modified Poly(dimethylsiloxane) Microfluidic Devices with High Electroosmotic Mobilities and Hydrophilic Channel Wall Characteristics.” Anal. Chem. 2005, 77, 1414-1422

Paper Microfluidics

References

Klasner SA, Price AK, Hoeman KW, Wilson, RS, Bell, KJ, and Culbertson, CT. “Paper-based microfluidic devices for analysis of clinically relevant analytes present in urine and saliva.” Analytical and Bioanalytical Chemistry 2010 397(5), 1821-1829. (PMID 20425107)

Chemical Education

Climate Change and Ocean Acidification

Effects of Ocean Acidification on Oysters

Topical Reviews

Patabadige, D.E.W.; Jia, S.; Sibbitts, J.; Sadeghi, J.; Sellens, K.; and Culbertson, C.T. Micrototal Analysis Systems: Fundamental Advances and applications. 2016, Analytical Chemistry 88(1), pp. 320-338. DOI: 10.1021/acs.analchem.5b04310

Culbertson, CT; Mickleburgh, TG; Stewart-James, SA; Sellens, KA; Pressnall, M. Micro Total Analysis Systems: Fundamental Advances and Biological Applications. Analytical Chemistry, 2014, 86(1), pp 95–118. DOI: 10.1021/ac403688g