Browsing by Author "Chou, Jie"

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    Enhancement of performance in porous bead-based microchip sensors: effects of chip geometry on bio-agent capture
    (Royal Society of Chemistry, 2015) Kulla, Eliona; Chou, Jie; Simmons, Glennon; Wong, Jorge; McRae, Michael P.; Patel, Rushi; Floriano, Pierre N.; Christodoulides, Nicolaos; Leach, Robin J.; Thompson, Ian M.; McDevitt, John T.
    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.
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    Hot embossed polyethylene through-hole chips for bead-based microfluidicdevices
    (Elsevier, 2013) Chou, Jie; Du, Nan; Ou, Tina; Floriano, Pierre N.; Christodoulides, Nicolaos; McDevitt, John T.; Rice Quantum Institute
    Over the past decade, there has been a growth of interest in the translation of microfluidic systems into real-world clinical practice, especially for use in point-of-care or near patient settings. While initial fabrication advances in microfluidics involved mainly the etching of silicon and glass, the economics of scaling of these materials is not amendable for point-of-care usage where single-test applications forces cost considerations to be kept low and throughput high. As such, a materials base more consistent with point-of-care needs is required. In this manuscript, the fabrication of a hot embossed, through-hole low-density polyethylene ensembles derived from an anisotropically etched silicon wafer is discussed. This semi-opaque polymer that can be easily sterilized and recycled provides low background noise for fluorescence measurements and yields more affordable cost than other thermoplastics commonly used for microfluidic applications such as cyclic olefin copolymer (COC). To fabrication through-hole microchips from this alternative material for microfluidics, a fabrication technique that uses a high-temperature, high-pressure resistant mold is described. This aluminum-based epoxy mold, serving as the positive master mold for embossing, is casted over etched arrays of pyramidal pits in a silicon wafer. Methods of surface treatment of the wafer prior to casting and PDMS casting of the epoxy are discussed to preserve the silicon wafer for future use. Changes in the thickness of polyethylene are observed for varying embossing temperatures. The methodology described herein can quickly fabricate 20 disposable, single use chips in less than 30 minutes with the ability to scale up 4x by using multiple molds simultaneously. When coupled as a platform supporting porous bead sensors, as in the recently developed Programmable Bio-Nano-Chip, this bead chip system can achieve limits of detection, for the cardiac biomarker C-reactive protein, of 0.3 ng/mL, thereby demonstrating the approach is compatible with high performance, real-world clinical measurements in the context of point-of-care testing.
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    Optimization of Microfluidic, Point of Care, Flow-Through, Bead-Based Microarrays: Towards Affordable Healthcare
    (2012-10-12) Chou, Jie; McDevitt, John T.; Richards-Kortum, Rebecca Rae; Biswal, Sibani Lisa
    Recently, there has been much interest on the development of affordable, portable diagnostic devices for the detection of a wide range of analytes. Advancements in microfluidics and miniaturization bring promise for their use at the point of care over traditional, and for the most part laboratory-confined approaches. The integration of porous beads with microfluidics has demonstrated potential as highly sensitive sensing elements with the capability to detect multiple biological and chemical agents simultaneously. When used in a flow through microarray platform known as the Programmable Bio-Nano-Chip (p-BNC), these beads have demonstrated opportunities for detection of low volumes of sample under short analysis times. However, limitations in traditional microfluidic materials such as silicon and inefficient fractional capture of analytes by porous beads hinder the translation of the p-BNC into broad global and clinical adoption where tests are single use with short analysis times to detect low concentrations of sample. This dissertation aims to optimize the p-BNC through engineering design choices to enhance the performance and reduce the costs associated with the p-BNC. The development of a computational tool to model the porous bead-based system is described herein and used to lead in the design optimization of the system. This tool provides insights into the transport and capture of analytes within the bead array with capture performance as a function of flow rate, porosity, capture distances, molecular affinities, and binding densities. To transition away from a single use and expensive silicon-based microarray, a thermoplastics-based microarray, fabricated through the hot embossing of polyethylene from replicated molds from silicon, is developed and described. Further, to transition towards point of care conditions where sample volume is low and analysis times are short, the geometry of the bead microwell design is optimized to improve the fractional capture efficiency of analytes by the beads in flow through microcontainers. Finally, to improve the imprecision performance in bead-to-bead signal variation within the microarray, exploration of a split design and use of smaller beads reveal a decrease in imprecision.
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    Porous Bead-Based Diagnostic Platforms: Bridging the Gaps in Healthcare
    (MPDI, 2012) Chou, Jie; Wong, Jorge; Christodoulides, Nicolaos; Floriano, Pierre N.; Sanchez, Ximena; McDevitt, John
    Advances in lab-on-a-chip systems have strong potential for multiplexed detection of a wide range of analytes with reduced sample and reagent volume; lower costs and shorter analysis times. The completion of high-fidelity multiplexed and multiclass assays remains a challenge for the medical microdevice field; as it struggles to achieve and expand upon at the point-of-care the quality of results that are achieved now routinely in remote laboratory settings. This review article serves to explore for the first time the key intersection of multiplexed bead-based detection systems with integrated microfluidic structures alongside porous capture elements together with biomarker validation studies. These strategically important elements are evaluated here in the context of platform generation as suitable for near-patient testing. Essential issues related to the scalability of these modular sensor ensembles are explored as are attempts to move such multiplexed and multiclass platforms into large-scale clinical trials. Recent efforts in these bead sensors have shown advantages over planar microarrays in terms of their capacity to generate multiplexed test results with shorter analysis times. Through high surface-to-volume ratios and encoding capabilities; porous bead-based ensembles; when combined with microfluidic elements; allow for high-throughput testing for enzymatic assays; general chemistries; protein; antibody and oligonucleotide applications.