Enhancement of performance in porous bead-based microchip sensors: Effects of chip geometry on bio-agent capture

Eliona Kulla, Jie Chou, Glennon W. Simmons, Jorge Wong, Michael P. McRae, Rushi Patel, Pierre N. Floriano, Nicolaos Christodoulides, Robin J. Leach, Ian M. Thompson, John T. McDevitt

Research output: Contribution to journalArticle

Abstract

Measuring low concentrations of clinically-important biomarkers using porous bead-based lab-on-a-chip (LOC) platforms is critical for the successful implementation of point-of-care (POC) devices. One way to meet this objective is to optimize the geometry of the bead holder, referred to here as a micro-container. In this work, two geometric micro-containers were explored, the inverted pyramid frustum (PF) and the inverted clipped pyramid frustum (CPF). Finite element models of this bead array assay system were developed to optimize the micro-container and bead geometries for increased pressure, to increase analyte capture in porous bead-based fluorescence immunoassays. Custom micro-milled micro-container structures containing an inverted CPF geometry resulted in a 28% reduction in flow-through regions from traditional anisotropically-etched pyramidal geometry derived from Si-111 termination layers. This novel "reduced flow-through" design resulted in a 33% increase in analyte penetration into the bead and twofold increase in fluorescence signal intensity as demonstrated with C-reactive protein (CRP) antigen, an important biomarker of inflammation. A consequent twofold decrease in the limit of detection (LOD) and the limit of quantification (LOQ) of a proof-of-concept assay for the free isoform of prostate-specific antigen (free PSA), an important biomarker for prostate cancer detection, is also presented. Furthermore, a 53% decrease in the bead diameter is shown to result in a 160% increase in pressure and 2.5-fold increase in signal, as estimated by COMSOL models and confirmed experimentally by epi-fluorescence microscopy. Such optimizations of the bead micro-container and bead geometries have the potential to significantly reduce the LODs and reagent costs for spatially programmed bead-based assay systems of this type.

Original languageEnglish (US)
Pages (from-to)48194-48206
Number of pages13
JournalRSC Advances
Volume5
Issue number60
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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    Kulla, E., Chou, J., Simmons, G. W., Wong, J., McRae, M. P., Patel, R., Floriano, P. N., Christodoulides, N., Leach, R. J., Thompson, I. M., & McDevitt, J. T. (2015). Enhancement of performance in porous bead-based microchip sensors: Effects of chip geometry on bio-agent capture. RSC Advances, 5(60), 48194-48206. https://doi.org/10.1039/c5ra07910a