Researchers have demonstrated the potential utility of microfluidics for cell biology and its ability to define the environment. However, the use of microfluidics by biologists is still the exception. With the potential benefits of microfluidics clear, why have microfluidic systems not found more widespread use in cancer research and drug screening applications? Cancer is a complex disease and research into the basic mechanisms of the disease could benefit greatly from the ability to explore more factors more quickly and to utilize functionality (e.g., defined co-culture, precise temporal/spatial environmental control) that is not possible in traditional well culture. We believe there exist several barriers preventing microfluidic culture systems from having a major impact on cancer biology (accessibility, relevance, biological model, efficiency/throughput). Our broad aim is to bridge the gap between the worlds of engineering and cancer biology by understanding the needs/limitations of current cell-based cancer biology research and then providing a technology platform well matched to those needs and capable of addressing emerging needs (e.g., co-culture, 3D culture). Our innovative platform merges simple microfluidic technology (e.g., passive pumping) with existing pipetting methods to provide a range of cell manipulation functionality capable of highly parallel operation. We propose to demonstrate the accessibilty/ease of use of the platform, achieve measureable outcomes in throughput, efficiency, accuracy and robustness, and utilize the system to study growth regulation of mammary epithelial cells. Specific experiments include operational robustness, cell seeding consistency and assay execution. The biological focus of this project will be an extensive 2016 datapoint study exploring the response of the NMuMG cell line and primary mouse mammary epithelial cells (normal or lacking Sdc-1) to a variety of growth factors (EGF, IGF, FGF, insulin, FGF+TGF(3, serum, WntSA) at different concentrations. In addition, we will demonstrate a novel liquid valve to control soluble factor interactions between two cell types to study EMT thresholds. As part of these studies, we will demonstrate a 25X reduction in the number of animals required for typical 24 well plate cell-based studies. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA122672-02
Application #
7422394
Study Section
Special Emphasis Panel (ZCA1-SRRB-Y (J1))
Program Officer
Knowlton, John R
Project Start
2007-05-11
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2010-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$158,607
Indirect Cost
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Moussavi-Harami, S Farshid; Annis, Douglas S; Ma, Wenjiang et al. (2013) Characterization of molecules binding to the 70K N-terminal region of fibronectin by IFAST purification coupled with mass spectrometry. J Proteome Res 12:3393-404
Su, Xiaojing; Young, Edmond W K; Underkofler, Heather A S et al. (2011) Microfluidic cell culture and its application in high-throughput drug screening: cardiotoxicity assay for hERG channels. J Biomol Screen 16:101-11
Puccinelli, John P; Su, Xiaojing; Beebe, David J (2010) Automated high-throughput microchannel assays for cell biology: Operational optimization and characterization. JALA Charlottesv Va 15:25-32
Paguirigan, Amy L; Puccinelli, John P; Su, Xiaojing et al. (2010) Expanding the available assays: adapting and validating In-Cell Westerns in microfluidic devices for cell-based assays. Assay Drug Dev Technol 8:591-601
Kim, Dongshin; Lokuta, Mary A; Huttenlocher, Anna et al. (2009) Selective and tunable gradient device for cell culture and chemotaxis study. Lab Chip 9:1797-800
Mohanty, Swomitra K; Warrick, Jay; Gorski, Jack et al. (2009) An accessible micro-capillary electrophoresis device using surface-tension-driven flow. Electrophoresis 30:1470-81
Frisk, Megan L; Tepp, William H; Johnson, Eric A et al. (2009) Self-assembled peptide monolayers as a toxin sensing mechanism within arrayed microchannels. Anal Chem 81:2760-7
Paguirigan, Amy L; Beebe, David J (2009) From the cellular perspective: exploring differences in the cellular baseline in macroscale and microfluidic cultures. Integr Biol (Camb) 1:182-95
Regehr, Keil J; Domenech, Maribella; Koepsel, Justin T et al. (2009) Biological implications of polydimethylsiloxane-based microfluidic cell culture. Lab Chip 9:2132-9
Paguirigan, Amy L; Beebe, David J (2008) Microfluidics meet cell biology: bridging the gap by validation and application of microscale techniques for cell biological assays. Bioessays 30:811-21

Showing the most recent 10 out of 13 publications