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dc.contributor.advisor McDevitt, John T.
dc.creatorShadfan, Basil
dc.date.accessioned 2016-01-27T17:19:23Z
dc.date.available 2016-01-27T17:19:23Z
dc.date.created 2015-05
dc.date.issued 2014-12-11
dc.date.submitted May 2015
dc.identifier.citation Shadfan, Basil. "Development of a Diagnostic Assay for the Multiplexed Detection of Ovarian Cancer Biomarkers at the Point-of-Care." (2014) Diss., Rice University. https://hdl.handle.net/1911/88157.
dc.identifier.urihttps://hdl.handle.net/1911/88157
dc.description.abstract Point-of-care (POC) diagnostic platforms have the potential to enable low-cost, large- scale screening. As no single biomarker is shed by all ovarian cancers, multiplexed biomarker panels promise improved sensitivity and specificity to address the unmet need for early detection of ovarian cancer. We have configured the programmable bio-nano-chip (p- BNC) - a multiplexable, microfluidic, modular platform - to quantify a novel multimarker panel comprised of CA125, HE4, MMP-7 and CA72-4. The p-BNC is a bead-based immunoanalyzer system with a credit-card-sized footprint that integrates automated sample metering, bubble and debris removal, reagent storage and waste disposal, permitting POC analysis. Multiplexed p-BNC immunoassays demonstrated high specificity, low cross- reactivity, low limits of detection suitable for early detection, and a short analysis time of 43 minutes. Day-to-day variability, a critical factor for longitudinally monitoring biomarkers, ranged between 5.4-10.5% – well below the biological variation for all four markers. Biomarker concentrations for 31 late-stage sera correlated well (R2 = 0.71 to 0.93 for various biomarkers) with values obtained on the Luminex® platform. In a 31-patient cohort encompassing early- and late-stage ovarian cancers along with benign and healthy controls, the multiplexed p-BNC panel was able to distinguish cases from controls with 68.7% sensitivity at 80% specificity. Utility for longitudinal biomarker monitoring was demonstrated with pre-diagnostic sera from 2 cases and 4 controls. An updated card capable of being manufactured on a large-scale was developed that enabled the transition to true point-of-care measurement. A custom backpack-sized analyzer capable of precise actuation of blister packs (attached to each card) was used to control fluid rates of the various stages and contains all hardware necessary for imaging and analysis. Without sacrificing analytical performance, the multiplexed assay was reduced to 17 minutes in order to return results during an average patient visit. In a 22-patient study, blood was shown to correlate well to plasma and serum in the p-BNC, demonstrating promise for whole blood fingerstick measurements. Taken together, the p-BNC shows strong promise as a diagnostic tool for large-scale screening and takes advantage of faster results and lower costs while leveraging possible improvement in sensitivity and specificity from biomarker panels.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectPoint-of-care
multiplex
biomarker
clinical
diagnostic
diagnosis
ovarian cancer
ovarian
cancer
ca125
he4
mmp-7
ca72-4
lab-on-a-chip
microfluidics
antibody
antigen
protein
immunoassay
detection
fluorescence
screening
screen
blood
serum
fingerstick
dc.title Development of a Diagnostic Assay for the Multiplexed Detection of Ovarian Cancer Biomarkers at the Point-of-Care
dc.contributor.committeeMember Wilson, Lon J
dc.contributor.committeeMember Richards-Kortum, Rebecca
dc.date.updated 2016-01-27T17:19:23Z
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Chemistry
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy


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