Development of a Diagnostic Assay for the Multiplexed Detection of Ovarian Cancer Biomarkers at the Point-of-Care

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dc.contributor.advisorMcDevitt, John T.en_US
dc.contributor.committeeMemberWilson, Lon Jen_US
dc.contributor.committeeMemberRichards-Kortum, Rebeccaen_US
dc.creatorShadfan, Basilen_US
dc.date.accessioned2016-01-27T17:19:23Zen_US
dc.date.available2016-01-27T17:19:23Zen_US
dc.date.created2015-05en_US
dc.date.issued2014-12-11en_US
dc.date.submittedMay 2015en_US
dc.date.updated2016-01-27T17:19:23Zen_US
dc.description.abstractPoint-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.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationShadfan, Basil. "Development of a Diagnostic Assay for the Multiplexed Detection of Ovarian Cancer Biomarkers at the Point-of-Care." (2014) Diss., Rice University. <a href="https://hdl.handle.net/1911/88157">https://hdl.handle.net/1911/88157</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/88157en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectPoint-of-careen_US
dc.subjectmultiplexen_US
dc.subjectbiomarkeren_US
dc.subjectclinicalen_US
dc.subjectdiagnosticen_US
dc.subjectdiagnosisen_US
dc.subjectovarian canceren_US
dc.subjectovarianen_US
dc.subjectcanceren_US
dc.subjectca125en_US
dc.subjecthe4en_US
dc.subjectmmp-7en_US
dc.subjectca72-4en_US
dc.subjectlab-on-a-chipen_US
dc.subjectmicrofluidicsen_US
dc.subjectantibodyen_US
dc.subjectantigenen_US
dc.subjectproteinen_US
dc.subjectimmunoassayen_US
dc.subjectdetectionen_US
dc.subjectfluorescenceen_US
dc.subjectscreeningen_US
dc.subjectscreenen_US
dc.subjectblooden_US
dc.subjectserumen_US
dc.subjectfingersticken_US
dc.titleDevelopment of a Diagnostic Assay for the Multiplexed Detection of Ovarian Cancer Biomarkers at the Point-of-Careen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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