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Abstract
Grant Number: 1R43HD057713-01 Project Title: Lab-on-a-chip for multiplexed newborn screening of lysosomal storage disorders
PI Information: Name Title PAMULA, VAMSEE K. vkp@liquid-logic.com Abstract: DESCRIPTION (provided by applicant): Newborn screening is currently performed by collecting dried bloodspots from infants and then sending them to a lab for analysis. There is an increasing necessity to screen for a number of disease conditions for which therapies are becoming available. Lysosomal storage diseases alone number greater than 40. There is a need to minimize the blood collected for screening purposes while maximizing the number of conditions screened. Also, conventional laboratory analysis of blood samples in a birthing center is impractical. An automated, inexpensive, multi-analyte and multiplexed newborn screening analyzer will help reduce the blood analysis volume, reduce the time-to-result, and make the analyzer available at the point-of- delivery (birthing centers). Based on Advanced Liquid Logic's previous demonstrations of digital microfluidic manipulation of nanoliter-sized droplets of enzymatic reagents and sample for dispensing from on-chip reservoirs, high speed transport, mixing, splitting and dilution, and absorbance, fluorescence, and luminescence detection of the assays, a disposable lab-on-a-chip will be developed. Ultimately, a disposable lab-on-a-chip for newborn screening will be developed where one punch from the dried blood spot or fresh blood will be the input to the system and it outputs the screening results in a completely automated fashion. Phase I work will focus on fabricating a microfluidic platform upon which microliters of dried blood spot extracts, reference standards, and reagent droplets will be dispensed, transported, mixed, assayed, and disposed. Fluorescence assays for determining activities of enzymes involved in Pompe, Fabry, and Hurler diseases will be transitioned to droplet-based format. Demonstration of these enzymatic assays establishes the feasibility of a digital microfluidic chip for newborn screening.Advanced Liquid Logic, Inc. is developing a lab-on-a-chip that integrates clinical chemistry, immunoassays, DNA amplification, and DNA sequencing on its proprietary digital (droplet-based) microfluidic platform for clinical diagnostics. The proposed project aims at demonstrating the feasibility of performing newborn screening for lysosomal storage disorders including Pompe, Fabry, and Hurler diseases from a single dried blood spot obtained from the heelstick of a newborn using a microfluidic lab-on-a-chip.
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Institution: ADVANCED LIQUID LOGIC 615 Davis Dr., Suite 800 RESEARCH TRIANGLE PARK, NC 277094025 Fiscal Year: 2007 Department: Project Start: 30-SEP-2007 Project End: 31-MAR-2008 ICD: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT IRG: ZRG1