A microfluidic platform is proposed that will aid in investigating processes involved in lipid channel formation and dissolution, leading to a deeper understanding of molecular transport across cell membranes, and ultimately contribute to our knowledge of biological channels and their relationships to disease processes. The project will leverage recent results from our team, including the first demonstration of single-molecule detection within a microfluidic ion channel chip using a single membrane-bound biological ion channel as a conductometric sensing element, with real-time control of analyte concentration and buffer conditions on either side of the channel. In this proposal, the proof-of-concept microfluidic platform will be extended to demonstrate in situ phospholipid membrane formation, integrated supporting gels and microporous films for enhanced membrane stability, automated multiplexed lipid channel measurements, and thin film thermal control at the membranes to enable the observation of the relationships between enthalpy and membrane formation, channel formation and dynamics, and analyte/channel interactions. A range of experiments that are not feasible or extremely time-consuming with existing technology will be conducted, with a focus on investigating channels formed by ceramide, a sphingolipid implicated in apoptosis. The structure and function of ceramide channels will be probed using the microfluidic system, with controlling factors manipulated to investigate their impacts on the regulation of channel size and stability. This effort will result in a novel and unique electrophysiology platform which may be applied to a wide range of fundamental and applied investigations of biological channels, together with experimental results that will expand our understanding of an important lipid channel system involved in programmed cell death.

Public Health Relevance

A unique experimental platform is proposed that will elucidate the processes involved inbiological membrane channel formation and dissolution, leading to a deeper understanding of molecular transport across cell membranes, and ultimately contribute to our knowledge of biological channels and their relationships to disease processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB009485-01
Application #
7641919
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Korte, Brenda
Project Start
2009-04-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
1
Fiscal Year
2009
Total Cost
$213,250
Indirect Cost
Name
University of Maryland College Park
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
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Rahmanian, Omid; DeVoe, Don L (2013) Pen microfluidics: rapid desktop manufacturing of sealed thermoplastic microchannels. Lab Chip 13:1102-8
Hood, Renee R; Shao, Chenren; Omiatek, Donna M et al. (2013) Microfluidic synthesis of PEG- and folate-conjugated liposomes for one-step formation of targeted stealth nanocarriers. Pharm Res 30:1597-607
Shao, Chenren; Kendall, Eric L; DeVoe, Don L (2012) Electro-optical BLM chips enabling dynamic imaging of ordered lipid domains. Lab Chip 12:3142-9
Shao, Chenren; Sun, Bing; DeVoe, Don L et al. (2012) Dynamics of ceramide channels detected using a microfluidic system. PLoS One 7:e43513
Rahmanian, Omid; Chen, Chien-Fu; DeVoe, Don L (2012) Microscale patterning of thermoplastic polymer surfaces by selective solvent swelling. Langmuir 28:12923-9
Kendall, Eric L; Shao, Chenren; DeVoe, Don L (2012) Visualizing the growth and dynamics of liquid-ordered domains during lipid bilayer folding in a microfluidic chip. Small 8:3613-9
Shao, Chenren; Sun, Bing; Colombini, Marco et al. (2011) Rapid microfluidic perfusion enabling kinetic studies of lipid ion channels in a bilayer lipid membrane chip. Ann Biomed Eng 39:2242-51
Liu, Jikun; White, Ian; DeVoe, Don L (2011) Nanoparticle-functionalized porous polymer monolith detection elements for surface-enhanced Raman scattering. Anal Chem 83:2119-24