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Miniaturized Protein Refolding Devices
Funding: NYSTAR
We are developing microfluidic devices to allow for both (a) combinatorial exploration of protein refolding protocols and (b) continuous-flow protein refolding. In both cases, labor-intensive or robot-automated processes are extensively simplified through microfluidic innovations.

For many years, Escherichia coli has served as a useful host for the production of heterologous proteins. E. coli has long been the model system for bacterial study, and its well-understood host-vector systems, experimental methods, and genetics has made it the most commonly used system for producing recombinant proteins (a classic example of this is production of insulin via expression of proinsulin in E. coli). Promoters are typically used to induce the bacterial system to over-express the recombinant protein and thereby maximize the output of the system. Unfortunately, over-expression of recombinant proteins usually leads to the formation of (insoluble) inclusion bodies, since the bacterial host system often cannot properly fold the protein or induce post-translational modifications such as methylation and glycosylation. Thus the protein is left in a non-functional agglomerated state.

The process of developing refolding protocols to convert the protein from non-functional to functional form is often the costliest and most time-consuming portion of the protein production process. Unfortunately, to date, no technique has been shown universally successful, nor are there techniques for reliably predicting the solution conditions required to refold the protein properly; thus protein refolding has historically been empirical. We are developing microscale devices to allow for rapid exploration of protein refolding protocols, both at low and high pressure.

Archival Publications

PDF version of Refolding of beta-galactosidase: microfluidic device for reagent metering and mixing and quantification of refolding yield 
Sowmya Kondapalli and Brian J. Kirby

Kondapalli S, Kirby BJ
"Refolding of beta-galactosidase: Microfluidic device for reagent metering and mixing and quantification of refolding yield," Microfluidics and Nanofluidics 7(2) 275-281, 2009. doi pdf

PDF version of George, Rana, Hawkins, Kirby: 
Microfluidic devices for terahertz spectroscopy of biomolecules

George PA, Hui W, Rana F, Hawkins BG, Smith AE, Kirby BJ
"Integrated microfluidic devices for terahertz spectroscopy of biomolecules", Optics Express, 16(3) 1577-1582 (2008). doi pdf text

Presentations and Other Publications

16 Nov 2008

Kondapalli S, Kirby BJ
"Refolding of beta-galactosidase: Microfluidic device for reagent metering and mixing and quantification of refolding yield," AIChE 2008.

12 Oct 2008

Kondapalli S Kirby BJ
"Microfluidic Device for Combinatorial Protein Refolding", 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences (uTAS), San Diego, CA.

4-9 Nov 2007

Kondapalli S, Putnam DA, Kirby BJ
"Protein refolding in microchips", AIChE 2007, Salt Lake City, UT, November 2007.

15-20 Jul 2007

Kondapalli S, Putnam DA, Kirby BJ
Gordon Research Conference on Microfluidics, Waterville Valley, NH.

15 Jun 2007

Kondapalli S, Putnam DA, Kirby BJ
New York Complex Matter Workshop, Cornell University, Ithaca, NY.

26 Feb 2007

Kirby BJ
"Design and control of micro/nanoscale fluid systems via polymer synthesis and geometric patterning", Biological and Environmental Engineering Seminar Series, Cornell University, Ithaca, NY.

25 Jan 2007

Kirby BJ
"Design and control of micro/nanoscale fluid systems via polymer synthesis and geometric patterning", Textiles and Apparel Seminar Series, Cornell University, Ithaca, NY.

7-11 Jan 2008

Kondapalli S, Kirby BJ
"Microfluidic devices for protein refolding," CHI PepTalk 2008, San Diego, CA.

6 Oct 2006

Kirby BJ
"Fabrication for design and control of micro/nanofluidic systems", University of Michigan Mechanical Engineering Seminar Series, Ann Arbor, MI.

21 Jun 2006

Kirby BJ
"Electrokinetics in fluid systems: Control of fields with multiscale geometric patterning", 2nd New York Complex Matter Workshop, Ithaca, NY.

Jul 2006

George PA, Rana F, Erickson D, Kirby BJ
"Terahertz microfluidics for on-chip detection and identification of bio-molecular compositions and conformations," IEEE-LEOS Summer Topicals: Optofluidics Quebec City, Canada.

12 Jan 2006

Kirby BJ
"Miniaturized devices for combinatorial chemistry and nanofluidic study", Sandia National Laboratories, Livermore, CA.

9 Dec 2005

Kirby BJ
Kodak Research Laboratories, Rochester, NY.

Structure of native lysozyme, perhaps the most-studied protein in refolding and aggregation studies. We are developing microdevices to study protein refolding for pharmaceutical applications.
A protein refolding microchip with associated external controls (see publication here). We are developing microdevices with the goal of accelerating pharmaceutical development.