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
Department of Cell Systems & Anatomy
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.
RSC Advances
https://doi.org/10.1039/c5ra07910a
10.1039/c5ra07910a
Profundice en los temas de investigación de 'Enhancement of performance in porous bead-based microchip sensors: Effects of chip geometry on bio-agent capture'. En conjunto forman una huella única.
Container Chemistry 100%
Biological Marker Chemistry 60%
Porosity Chemistry 60%
Pyramidal Crystal Chemistry 60%
Assay Chemistry 60%
Microchip Biochemistry, Genetics and Molecular Biology 60%
Antigen Chemistry 40%
Fluorescence Chemistry 40%
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
Enhancement of performance in porous bead-based microchip sensors : Effects of chip geometry on bio-agent capture. / Kulla, Eliona; Chou, Jie; Simmons, Glennon W. et al.
En: RSC Advances, Vol. 5, N.º 60, 2015, p. 48194-48206.
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, n.º 60, pp. 48194-48206. https://doi.org/10.1039/c5ra07910a
Kulla E, Chou J, Simmons GW, Wong J, McRae MP, Patel R et al. Enhancement of performance in porous bead-based microchip sensors: Effects of chip geometry on bio-agent capture. RSC Advances. 2015;5(60):48194-48206. doi: 10.1039/c5ra07910a
Kulla, Eliona ; Chou, Jie ; Simmons, Glennon W. et al. / Enhancement of performance in porous bead-based microchip sensors : Effects of chip geometry on bio-agent capture. En: RSC Advances. 2015 ; Vol. 5, N.º 60. pp. 48194-48206.
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title = "Enhancement of performance in porous bead-based microchip sensors: Effects of chip geometry on bio-agent capture",
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.",
author = "Eliona Kulla and Jie Chou and Simmons, {Glennon W.} and Jorge Wong and McRae, {Michael P.} and Rushi Patel and Floriano, {Pierre N.} and Nicolaos Christodoulides and Leach, {Robin J.} and Thompson, {Ian M.} and McDevitt, {John T.}",
note = "Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2015.",
doi = "10.1039/c5ra07910a",
journal = "RSC Advances",
T1 - Enhancement of performance in porous bead-based microchip sensors
T2 - Effects of chip geometry on bio-agent capture
AU - Kulla, Eliona
AU - Chou, Jie
AU - Simmons, Glennon W.
AU - Wong, Jorge
AU - McRae, Michael P.
AU - Patel, Rushi
AU - Floriano, Pierre N.
AU - Christodoulides, Nicolaos
AU - Leach, Robin J.
AU - Thompson, Ian M.
AU - McDevitt, John T.
N1 - Publisher Copyright: © The Royal Society of Chemistry 2015.
N2 - 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.
AB - 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.
U2 - 10.1039/c5ra07910a
DO - 10.1039/c5ra07910a
JO - RSC Advances
JF - RSC Advances