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

1 Citation (Scopus)

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
Externally publishedYes

Fingerprint

Containers
Biomarkers
Geometry
Sensors
Assays
Antigens
Fluorescence
Lab-on-a-chip
Fluorescence microscopy
Prostate-Specific Antigen
C-Reactive Protein
Protein Isoforms
Proteins
Costs

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

Cite this

Kulla, E., Chou, J., Simmons, G. W., Wong, J., McRae, M. P., Patel, R., ... 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

Enhancement of performance in porous bead-based microchip sensors : Effects of chip geometry on bio-agent capture. / Kulla, Eliona; Chou, Jie; Simmons, Glennon W.; Wong, Jorge; McRae, Michael P.; Patel, Rushi; Floriano, Pierre N.; Christodoulides, Nicolaos; Leach, Robin J; Thompson, Ian M.; McDevitt, John T.

In: RSC Advances, Vol. 5, No. 60, 2015, p. 48194-48206.

Research output: Contribution to journalArticle

Kulla, E, Chou, J, Simmons, GW, Wong, J, McRae, MP, Patel, R, Floriano, PN, Christodoulides, N, Leach, RJ, Thompson, IM & McDevitt, JT 2015, 'Enhancement of performance in porous bead-based microchip sensors: Effects of chip geometry on bio-agent capture', RSC Advances, vol. 5, no. 60, pp. 48194-48206. https://doi.org/10.1039/c5ra07910a
Kulla, Eliona ; Chou, Jie ; Simmons, Glennon W. ; Wong, Jorge ; McRae, Michael P. ; Patel, Rushi ; Floriano, Pierre N. ; Christodoulides, Nicolaos ; Leach, Robin J ; Thompson, Ian M. ; McDevitt, John T. / Enhancement of performance in porous bead-based microchip sensors : Effects of chip geometry on bio-agent capture. In: RSC Advances. 2015 ; Vol. 5, No. 60. pp. 48194-48206.
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