Distributed REMD Simulation for Probing Alzheimer Molecular Mechanisms
DESCRIPTION: Mass spectrometry is a multiplex technology for high-throughput analysis of biomolecules in newborn screening and clinical laboratories. Complexity in sample preparation has been recognized as the main bottleneck in well-established MS methods. Digital microfluidics is a rapidly advancing field which utilizes microdroplet-based liquid handling. Since high levels of automation and reduced volumes of liquid are intrinsic to the technology, digital microfluidics is uniquely suitable for high-throughput MS sample preparation. The objective of this proposal is the development of a new digital microfluidic platform for manipulating dried blood spot samples prior to introduction into the mass spectrometer. All steps required for sample preparation will be implemented on cartridge, including analyte extraction, addition of appropriate internal standards, and sample derivatization. Novel on-cartridge capabilities such as solvent evaporation and liquid-liquid extraction will be developed for the first time. The specific aims include (i) implementation of novel electrowetting capabilities necessary for extraction and derivatization protocols, (ii) demonstration of scale up capabilities using an existing 8-sample cartridge and development of an application-specific digital microfluidic cartridge and instrument, and (iii) demonstration of sample preparation for newborn screening of amino acids, acylcarnitines and succinylacetone from dried blood spots. This work will be performed in collaboration with Duke University investigators. The proposed platform will reduce complexity, human error, costs and time of current mass spectrometry workflows, thereby providing more effective and precise bioanalysis tests. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Advances in the analytical performance and sensitivity of mass spectrometers have allowed increasingly clinical analysis of biomolecules. Sample preparation has been recognized as the main bottleneck of well-established mass spectrometry methods. The proposed research will develop a novel digital microfluidic platform for automating newborn screening sample preparation protocols prior to introduction into the mass spectrometer. The proposed platform will reduce complexity and time of current mass spectrometry workflows, thereby providing more cost-effective and precise high-throughput tests.
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