This Program Project is the continuation of collaboration between three research groups that have been working together since 1993. The successful interdisciplinary team represents knowledge in chemical collaborative group has focused on the development of microfabricated DNA analysis devices with complete process integration. The continuation proposal will develop a fully integrated DNA sample handling and analysis technology for genotyping and sequencing. All the steps for extracting genetic information will occur within a single self-contained system having minimal operator interaction. The microfluidic, optical, and electronic components of the system are fabricated on silicon, silicon/glass, or silicon/polymer substrates, yielding a micromechanical integrated DNA analysis technology. To ensure inexpensive design, testing, and production, the devices will be made using photolithographic construction techniques. A genomic sequencing device capable of generating raw DNA sequence at less than $0.01 total costs per base is targeted for completion in five years. The proposal has four Program Goals: 1) Design, construct, and evaluate integrated DNA analysis systems. A system-level approach will be used to evaluate all components and fabrication technologies developed by the Program Project. Success will be measured at the level of complete genotyping and sequencing system. (Project 1) 2) Design, construct, and evaluate improved microfluidics, microreactions, and microseparations. Multistep handling and reactions will be tested on microfabricated devices. Advanced gel electrophoresis systems for sequencing t read-length >500 bp will be designed and tested. (Project 2) 3) Develop improved fabrication methods and optical sensors for integrated microsystems. Thin film deposited polymer and micromolded polymer will be examined for use as substrates and water-tight channels. Optical sensors will be designed and tested for improved sensitivity and stability. (Project 3) 4) Provide facilities and support for construction and testing of complex, integrated microfluidic devices. A central assembly and testing facility will be maintained that can rapidly build and test prototypes and incremental improvements for each of the projects (Core Unit).

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Program Projects (P01)
Project #
5P01HG001984-02
Application #
6182570
Study Section
Special Emphasis Panel (ZHG1-HGR-P (J1))
Program Officer
Schloss, Jeffery
Project Start
1999-04-23
Project End
2002-03-31
Budget Start
2000-06-05
Budget End
2001-03-31
Support Year
2
Fiscal Year
2000
Total Cost
$1,298,854
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Genetics
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Wang, Fang; Burns, Mark A (2009) Performance of nanoliter-sized droplet-based microfluidic PCR. Biomed Microdevices 11:1071-80
Rhee, Minsoung; Burns, Mark A (2009) Microfluidic pneumatic logic circuits and digital pneumatic microprocessors for integrated microfluidic systems. Lab Chip 9:3131-43
Kim, Sung-Jin; Wang, Fang; Burns, Mark A et al. (2009) Temperature-programmed natural convection for micromixing and biochemical reaction in a single microfluidic chamber. Anal Chem 81:4510-6
Wang, Fang; Yang, Ming; Burns, Mark A (2008) Microfabricated valveless devices for thermal bioreactions based on diffusion-limited evaporation. Lab Chip 8:88-97
Zeitoun, Ramsey I; Chen, Zheng; Burns, Mark A (2008) Transverse imaging and simulation of dsDNA electrophoresis in microfabricated glass channels. Electrophoresis 29:4768-74
Rhee, Minsoung; Burns, Mark A (2008) Microfluidic assembly blocks. Lab Chip 8:1365-73
Rhee, Minsoung; Burns, Mark A (2008) Drop mixing in a microchannel for lab-on-a-chip platforms. Langmuir 24:590-601
Srivastava, Nimisha; Burns, Mark A (2007) Microfluidic pressure sensing using trapped air compression. Lab Chip 7:633-7
Chang, Dustin S; Langelier, Sean M; Burns, Mark A (2007) An electronic Venturi-based pressure microregulator. Lab Chip 7:1791-9
Chisa, Jennifer L; Burke, David T (2007) Mammalian mRNA splice-isoform selection is tightly controlled. Genetics 175:1079-87

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