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dc.contributor.advisorIan W. Hunter.en_US
dc.contributor.authorForest, Craig Richard, 1978-en_US
dc.contributor.otherMassachusetts Institute of Technology. Dept. of Mechanical Engineering.en_US
dc.date.accessioned2008-01-10T15:54:06Z
dc.date.available2008-01-10T15:54:06Z
dc.date.copyright2007en_US
dc.date.issued2007en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/39899
dc.descriptionThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.en_US
dc.descriptionIncludes bibliographical references (p. 221-243).en_US
dc.description.abstractDiscovering the genetic causes of common diseases may require scanning for mutations in all of the genes in a million people, a significant undertaking. Such discoveries would revolutionize biotechnology, potentially enabling simple genetic tests for risk and targeted preventative or therapeutic strategies. An increase in throughput of genetic analysis instrumentation by several orders of magnitude is essential to undertake such an ambitious task. In this thesis, progress will be presented towards the creation of such a "mutational spectrometer" instrument containing up to 10,000 capillary channels and enabled with subsystems for loading, separating, and detecting fluorescently-labeled DNA. Challenges include DNA manipulation, optical signal detection, macro/micro design integration, precision alignment and assembly, and thermal control. To manipulate DNA, we have utilized a bioMEMS design platform for interfacing to an array of separation channels that enables electrokinetic biomolecule loading, detection, and fraction collection in independent wells.en_US
dc.description.abstract(cont.) Signal detection is accomplished by a sensitive (107 molecule limit-of-detection), scalable (to 10,000 independent channels), end-of-column fluorescence detection technology that accommodates tightly packed capillary arrays as required for ultra-high throughput electrophoretic separation. Capillary array assembly and constraint technologies have been developed for 2-D arrays containing as many as 10,000 replaceable capillaries. Thermal control requirements of 0.3 °C over the entire 10,000 channel array are met with a cross-flow water heat exchanger. Additional subsystems for forcing a viscous polymer matrix into the capillaries, and interfacing the capillary array to a fluid reservoir for electrophoresis have also been developed, as required. This work lays the foundation for the realization of a mutational spectrometer instrument that will enable population-wide pangenomic analyses to uncover the genetic causes of common diseases.en_US
dc.description.statementofresponsibilityby Craig Richard Forest.en_US
dc.format.extent243 p.en_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582
dc.subjectMechanical Engineering.en_US
dc.titleAn ultra-high throughput mutational spectrometer for human genetic diagnosticsen_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineering
dc.identifier.oclc182546139en_US


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