R-3 Repository :: Browsing by Author "McDevitt, John T."

Browsing by Author "McDevitt, John T."

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A disposable bio-nano-chip usuing agarose beads for protein analysis
(2012) Du, Nan; McDevitt, John T.
This thesis reports on the fabrication of a disposable bio-nano-chip (BNC), a microfluidic device composed of polydimethylsiloxane (PDMS) and thiolene-based optical epoxy which is both cost-effective and suitable for high performance immunoassays. A novel room temperature (RT) bonding technique was utilized so as to achieve irreversible covalent bonding between PDMS and thiolene-based epoxy layers, while at the same time being compatible with the insertion of agarose bead sensors, selectively arranged in an array of pyramidal microcavities replicated in the thiolene thin film layer. In the sealed device, the bead-supporting epoxy film is sandwiched between two PDMS layers comprising of fluidic injection and drain channels. The agarose bead sensors used in the device are sensitized with anti-C-reactive protein (CRP) antibody, and a fluorescent sandwich-type immunoassay was run to characterize the performance of this device. Computational fluid dynamics (CFD) was used based on the device specifications to model the bead penetration. Experimental data revealed analyte penetration of the immunocomplex to 100μm into the 280μm diameter agarose beads, which correlated well with the simulation. A dose response curve was obtained and the linear dynamic range of the assay was established over 1ng/mL to 50ng/mL with a limit of detection less than 1ng/mL.
Application of programmable bio-nano-chip system for the quantitative detection of drugs of abuse in oral fluids
(Elsevier, 2015) Christodoulides, Nicolaos; De La Garza, Richard II; Simmons, Glennon W.; McRae, Michael P.; Wong, Jorge; Newton, Thomas F.; Smith, Regina; Mahoney, James J. III; Hohenstein, Justin; Gomez, Sobeyda; Floriano, Pierre N.; Talavera, Humberto; Sloan, Daniel J.; Moody, David E.; Andrenyak, David M.; Kosten, Thomas R.; Haque, Ahmed; McDevitt, John T.; Bioengineering
Objective: There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable bio-nano-chip (p-BNC) platform for the detection of drugs of abuse. Method: The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. Results: Rapid (∼10 min), sensitive detection (∼ng/mL) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. Conclusions: This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace.
Bio-nano-chips for on-site drug screening
(2017-07-18) McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Simmons, Glennon; Rice University; United States Patent and Trademark Office
A bio-nano-chip (BNC) technology that works in connection with non-invasive samples, such as saliva, cheek swab or urine samples that can be easily performed by non-specialists, such as security personnel and police officers is disclosed. The microfluidic system for drug testing includes an analyzer or reader having a housing containing a slot for receiving a cartridge, a drug testing cartridge, a processor having a user interface, an optical or energy sensing means, and a means for moving fluid.
Biomedical Nanocrystal Agents: Design, Synthesis, and Applications
(2013-09-16) Cho, Minjung; Colvin, Vicki L.; McDevitt, John T.; Wong, Michael S.
In these days, nanomaterials are applied in a variety of biomedical applications including magnetic resonance imaging (MRI), cell imaging, drug delivery, and cell separation. Most MRI contrast agents affect the longitudinal relaxation time (T1) and transverse relaxation time (T2) of water protons in the tissue and result in increased positive or negative contrast. Here, we report the optimization of r1 (1/T1) or r2 (1/T2) relaxivity dynamics with diameter controlled gadolinium oxide nanocrystals (2~22 nm) and iron based magnetic nanocrystals (4 ~33 nm). The r1 and r2 MR relaxivity values of hydrated nanocrystals were optimized and examined depending on their core diameter, surface coating, and compositions; the high r1 value of gadolinium oxide was 40-60 S-1mM-1, which is 10-15 fold higher than that of commercial Gd (III) chelates (4.3~4.6 S-1mM-1). Moreover, in vitro toxicological studies revealed that polymer coated nanocrystals suspensions had no significant effect on human dermal fibroblast (HDF) cells even at high concentration. Towards multimodal imaging or multifunctional ability, we developed the iron oxide/QDs complexes, which consist of cores of iron oxide that act as nucleation sites for fluorescent QDs. The choice of variable QDs helped to visualize and remove large iron oxide materials in a magnetic separation. Additionally, diluted materials concentrated on the magnet could be fluorescently detected even at very low concentration. The designed MRI or multifunctional nanomaterials will give great and powerful uses in biomedical applications.
Characterization & Application of Immobilized Biomacromolecules using Microcantilever and QCM Sensors
(2014-04-15) Wang, Jinghui; Biswal, Sibani Lisa; Segatori, Laura; Wong, Michael S.; McDevitt, John T.; Suh, Junghae
The structure and function of immobilized biomacromolecules are likely to be altered because of the solid surface. The long-term objective of this thesis is to develop surface-based biosensors for the characterization and application of biomacromolecules at the liquid-solid interface. In this study, two analytical surface-sensitive sensors are utilized: microcantilevers and quartz crystal microbalance with dissipation (QCM-D). Each offers unique information regarding the molecules of interest. In particular, the systems that are covered in this thesis include the detection of target analytes using specific recognition elements and the characterization of supported lipid membranes. This research has led to a better understanding of the effect of solid surfaces on protein structure and function, as well as the ability to engineer biomolecular surfaces with great control. There are two detection systems that were studied: a phage-derived peptide system for the detection of pathogenic bacteria Salmonella and an antibody displacement assay for the detection of an explosive, 2,4,6-trinitrotoluene (TNT). The microcantilever responds to changes in the surface free energy on the sensor surface by monitoring changes in its deflection. The physisorption or chemisorption of molecules to the cantilever surface induces a mismatch in the surface stress, causing the cantilever to bend. The multiplexed measurement is able to quickly determine the binding affinities of various phage-derived peptides, improving the screening efficiency of the peptides derived from phage display libraries for Salmonella detection. The microcantilever-based technique provides a novel biosensor to rapidly and accurately detect pathogens and holds potential to be further developed as a screening method to identify pathogen-specific recognition elements. QCM measures mass changes on the sensor surface by monitoring the frequency change of the crystal. The combination of a competition assay with QCM using an anti-TNT antibody is able to distinguish a TNT molecule among molecules of similar structure at low concentrations, leading a sensitive and selective assay. The reliability of this method was further investigated in more real environments simulated by fertilizer solution and seawater. Furthermore, this method could be also applied in gas phase detection of TNT, as well as the detection of other chemicals, such as environmental pollutants and illegal drugs. In both of these detection assays, a mathematical model was developed to quantify the binding of the target molecules with the molecules of interest. In the second half of the thesis, the microcantilever sensor is applied to characterize supported lipid bilayers (SLBs), an interesting biomacromolecular assembly that holds great importance as a model system for membranes. Through monitoring the cantilever deflection, the formation of the SLB, its temperature induced phase transitions, and its interactions with membrane-active molecules are investigated. With increasing temperature, the lipid acyl chains transition from an ordered state to a disordered state, accompanied by a changes in the surface stress that can be readily detected using microcantilever. The phase transition temperature of SLBs is different from that of a lipid monolayer, indicating that the existence of the solid support aﬀects the monolayer structure. Two amphipathic membrane-active molecules, peptide (PEP1) and a triblock copolymer (Pluoronic), are studied for their associations with SLBs. PEP1’s association with SLBs highly depends on the ratio of peptide over lipid, while the Pluoronic interacts with SLBs as a function of temperature and the length of lipophilic block in the copolymer. Therefore, the microcantilever sensor is capable of measuring the conformational change of surface-bound molecules, as well as characterizing the kinetics of membrane-peptide interactions with great sensitivity.
Chemical and Physical Graphene Modifications
(2013-07-11) Pembroke, Elvira; Tour, James M.; Ajayan, Pulickel M.; McDevitt, John T.
This dissertation is inspired by recent progress in the chemistry, physics, and nanotechnology of graphene, a single layer of carbon atoms. Studying and controllably modifying the electrical properties of graphene while minimizing damage to the lattice continues to be a challenge to the scientific community. Chapter 1 focuses on the covalent attachment of molecules with different functional groups to graphene and how functionalization modifies the electrical transport properties of graphene field effect transistors (FET) devices. Functionalization is shown to predominantly induce p-type doping, undiminished mobility, and increased conductivity at the neutrality point. Physisorbed molecules desorb easily and do not have a significant effect. Statistical analysis enables us to extract trends even though identically fabricated graphene devices can exhibit a wide range of electrical behaviors, emphasizing that conclusions should not be drawn based on singular extremes. In Chapter 2 we present the fabrication and characterization of graphene antidot lattices produced by placing graphene on pre-patterned substrates. While the graphene remains intact atop a periodic well pattern we observe a surface potential differential inside vs. outside the wells. Chapter 3 investigates graphene FETs with multiple neutrality points. We used Raman mapping to determine if multiple local gating fields can be spatially resolved. While we were able to show doping inhomogeneity in graphene devices, there was no obvious difference between devices with one vs. multiple neutrality points. In Chapter 4 we demonstrate a method to grow graphene from solid carbon sources. I confirmed the single layer nature of the produced graphene using atomic force microscopy (AFM) and fabricated and characterized intrinsic FETs based on solid-derived graphene. In Chapter 5 we propose that graphene layers nucleate along and underneath the edges of existing graphene layers with a continuous layer remaining on top. My AFM characterization of hexagonal graphene onions provided evidence for our proposed nucleation mechanism. Chapter 6 is a report on graphene resistor devices that were contributed to an experiment aboard the International Space Station which seeks to investigate the effects of radiation exposure. Overall, the work accomplished in this dissertation constitutes a step forward toward controllable device behavior in graphene based electronics.
Development of a Diagnostic Assay for the Multiplexed Detection of Ovarian Cancer Biomarkers at the Point-of-Care
(2014-12-11) Shadfan, Basil; McDevitt, John T.; Wilson, Lon J; Richards-Kortum, Rebecca
Point-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.
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.; Bioengineering; Chemistry
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.
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.; Chemistry; Bioengineering; 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.
Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trialsﾠ
(Elsevier, 2015) Speight, Paul M.; Abram, Timothy J.; Floriano, Pierre N.; James, Robert; Vick, Julie; Thornhill, Martin H.; Murdoch, Craig; Freeman, Christine; Hegarty, Anne M.; D’Apice, Katy; Kerr, A. Ross; Phelan, Joan; Corby, Patricia; Khouly, Ismael; Vigneswaran, Nadarajah; Bouquot, Jerry; Demian, Nagi M.; Weinstock, Y. Etan; Redding, Spencer W.; Rowan, Stephanie; Yeh, Chih-Ko; McGuff, H. Stan; Miller, Frank R.; McDevitt, John T.; Bioengineering; Chemistry
Objective: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. Study Design: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. Results: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. Conclusions: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis.
Ionization of Rydberg Atoms at Patterned Electrode Arrays
(2013-07-26) Pu, Yu; Dunning, F. B.; Killian, Thomas C.; McDevitt, John T.
The present work explores the effect of controlled surface fields on the ionization of Rydberg atoms near surfaces. Lithographically-patterned micrometer scale electrode arrays are used to generate controlled surface electric fields. The data show that application of even small electrode biases (~±1V) can lead to a transition from ionization of the incident atoms by short-range tunneling to field ionization well above the target surface. The resulting ions are efficiently detected using ion collection fields whose strengths are substantially smaller than those required for direct field ionization implying the application of surface ionization in the detection of low-n Rydberg atoms. The data are analyzed with the aid of a Monte Carlo model and further demonstrate the critical role that local surface fields can play in governing the nature of atom-surface interactions.
Microfluidic bio-nano-chip platforms for optimized immunoassay using 3D agarose bead-based biosensors
(2013-11-07) Du, Nan; McDevitt, John T.; Biswal, Sibani Lisa; Dunning, F. Barry
This dissertation is devoted to the development of novel bio-nano chip microfluidic platforms suitable for agarose bead-based sensors. Previously, our lab had developed a novel immunoassay sensor based on three-dimensional agarose beads whose surface is marked by micro-size pores. Porous agarose beads have a greater capacity of immobilizing antibodies as compared to other surface based sensors, and thus are expected to yield better assay performance. The first generation of bio-nano-chip platform had been designed to contain an array of three-dimensional wells to host the agarose beads. In the bio-nano-chip platform, a silicon-based bead holder had been designed to generate strong convectional flows around beads and greatly enhance the detection sensitivity. As the silicon microchip was fabricated based on the traditional MEMS techniques, however, the cost of the device remains relatively high. Moreover, the accuracy of the assays and the assay time also need to be improved to meet the standard of point-of-care diagnostics. In efforts to overcome these issues, this dissertation reports works of replacing the material of key components with cheaper materials in the bio-nano-chip platform. Further, this dissertation presents a new mechanism of recirculating assays in a membrane-based chip, and also a new bead design to further enhance the assay performance. In summary, the bio-nano-chip platform had been improved to be more efficient and cost-effective than previous designs, allowing wider applications in resource limited areas such as in developing countries.
A Multiplexable, Microfluidic Platform for the Rapid Quantitation of a Biomarker Panel for Early Ovarian Cancer Detection at the Point-of-Care
(American Association for Cancer Research, 2015) Shadfan, Basil H.; Simmons, Archana R.; Simmons, Glennon W.; Ho, Andy; Wong, Jorge; Lu, Karen H.; Bast, Robert C. Jr.; McDevitt, John T.; Bioengineering; Chemistry
Point-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 multi-marker panel comprising 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% and 10.5%, well below the biologic variation for all four markers. Biomarker concentrations for 31 late-stage sera correlated well (R(2) = 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 prediagnostic plasma from 2 cases and 4 controls. Taken together, the p-BNC shows strong promise as a diagnostic tool for large-scale screening that takes advantage of faster results and lower costs while leveraging possible improvement in sensitivity and specificity from biomarker panels.
Nanosystems: From their design to characterization as advanced MRI contrast agents
(2013-07-29) Sethi, Richa; Wilson, Lon J.; McDevitt, John T.; Richards-Kortum, Rebecca Rae; Decuzzi, Paolo
Ultra-short single-walled carbon nanotubes (US-tubes) have been previously shown to be efficient carriers of imaging agents. In particular, gadonanotubes (GNTs) synthesized by loading and nanoscale confinement of Gd3+ ions within US-tubes have been established as high-performance MRI contrast agents (CAs) with efficiencies 40 to 90 times greater than the current clinical CAs. Using nuclear magnetic resonance dispersion (NMRD) and electron spin resonance (ESR) techniques, this work discusses the origin of the magnetic and proton relaxation behavior in MRI of the GNTs and related structures at low magnetic fields. The likely causes for the observed paramagnetism for these materials are explored and their effect on water proton relaxation is discussed. In addition, Gd3+ chelates, which are currently approved for clinical MRI use, provide relaxivities (or contrast enhancement) well below their theoretical limit, and they also lack tissue speciﬁcity. In this dissertation, using vascularly injectable mesoporous silicon nanoparticles (SiMPs), general methods for increasing the efficiency of Gd3+-based MRI CAs are described. Two different strategies have been successfully tested where Gd3+ chelates are either geometrically confined within the pores of SiMPs or covalently attached to the surface of SiMPs. For both the approaches, SiMPs with different pore sizes have been used to generate a dominant role in the resulting relaxivity. The nanoconstructs designed using these approaches have been shown to produce relaxivities that are many-fold greater than the free CAs in solution. This enhancement is attributed to the optimization of the molecular parameters that govern relaxivity. Co-loading the pores with a Gd3+-based CA and a fluorescently-labeled antibody has shown the potential of SiMP nanoconstructs as multimodal agents. The strategies outlined in this dissertation are general and can be successfully applied to any imaging agent and porous nanosystem. In summary, this work highlights two key outcomes. First, it provides a better understanding of the magnetic and MRI behavior of the GNTs. Second, it demonstrates that geometrical confinement of CAs and covalent functionalization of nanoparticles are universal strategies for enhancing the performance of Gd3+-based CAs.
Optical Imaging Techniques for the Detection of Esophageal Neoplasia in Barrett’s Esophagus
(2013-09-16) Thekkek, Nadhi; Richards-Kortum, Rebecca Rae; Baraniuk, Richard G.; Anandasabapathy, Sharmila; McDevitt, John T.
The main objective of this research was to develop a two-stage optical imaging platform to improve detection of cancer in Barrett’s esophagus (BE). BE caused by chronic reflux and patients with BE are at a higher risk for developing esophageal adenocarcinoma (EAC). However, neoplasia in BE is often unidentifiable under standard endoscopy, and studies have shown nearly half of early cancers can go unidentified by this method. Widefield imaging (resolves ~100 microns) allows efficient surveillance of large BE segments. Two widefield imaging techniques were identified to improve contrast between benign and abnormal lesions during an ex vivo 15 patient feasibility study. Cross-polarized imaging (CPI) reduced specular reflection and improved vascular contrast. Vital-dye fluorescence imaging (VFI) using topically-applied proflavine improved visualization of glandular pattern. Moreover, relevant pathologic features visible during VFI were seen in corresponding histology slides as well as high resolution images of the same sites. Based on these results, a cap-based Multispectral Digital Endoscope (MDE) was designed and built. The MDE can image in three different imaging modes: white light imaging, CPI, and VFI. Modifications to a Pentax EPK-i video processor and a Pentax endoscope were made to incorporate these imaging modes into one system. A 21 patient in vivo pilot study with 65 pathologically correlated sites demonstrated the feasibility of using this system in vivo; image criteria were developed to classify neoplasia with a sensitivity and specificity of 100% and 76% respectively. High resolution imaging (resolves ~2-5 micron) may verify the disease presence in suspicious areas identified using widefield techniques. 2-NBDG, a fluorescent metabolic marker, was used as to identify neoplastic biopsies. In a study with 21 patients yielding 38 pathologically correlated biopsies and 158 image sites, 2-NBDG imaging allowed classification of cancerous biopsies with a sensitivity of 96% and specificity of 90%. The unique contributions of these results is the development of a multimodal cap-based endoscopic system to identify suspicious areas in BE, and using a metabolic marker to verify the presence of disease. This application extends beyond esophageal cancer detection and may be explored for cancer detection in other organ sites characterized by columnar epithelium.
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.
Oral cancer point of care diagnostics
(2017-01-03) McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Thornhill, Martin; Redding, Spencer; Vigneswaran, Nadarajah; Murdoch, Craig; Speight, Paul; Rice University; United States Patent and Trademark Office
A point of care diagnostic test, device and disposables for determining a patient risk for oral cancer in the same visit that a sample is collected.
Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research
(Elsevier, 2016) King, Kevin R.; Grazette, Luanda P.; Paltoo, Dina N.; McDevitt, John T.; Sia, Samuel K.; Barrett, Paddy M.; Apple, Fred S.; Gurbel, Paul A.; Weissleder, Ralph; Leeds, Hilary; Iturriaga, Erin J.; Rao, Anupama K.; Adhikari, Bishow; Desvigne-Nickens, Patrice; Galis, Zorina S.; Libby, Peter; Bioengineering; Chemistry
Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care.
Programmable bio-nano-chip system: a flexible point-of-care platform for bioscience and clinical measurements
(Royal Society of Chemistry, 2015) McRae, Michael P.; Simmons, Glennon W.; Wong, Jorge; Shadfan, Basil; Gopalkrishnan, Sanjiv; Christodoulides, Nicolaos; McDevitt, John T.; Bioengineering; Chemistry; Mechanical Engineering
The development of integrated instrumentation for universal bioassay systems serves as a key goal for the lab-on-a-chip community. The programmable bio-nano-chip (p-BNC) system is a versatile multiplexed and multiclass chemical- and bio-sensing system for bioscience and clinical measurements. The system is comprised of two main components, a disposable cartridge and a portable analyzer. The customizable single-use plastic cartridges, which now can be manufactured in high volumes using injection molding, are designed for analytical performance, ease of use, reproducibility, and low cost. These labcard devices implement high surface area nano-structured biomarker capture elements that enable high performance signaling and are index-matched to real-world biological specimens. This detection modality, along with the convenience of on-chip fluid storage in blisters and self-contained waste, represents a standard process to digitize biological signatures at the point-of-care. A companion portable analyzer prototype has been developed to integrate fluid motivation, optical detection, and automated data analysis, and it serves as the human interface for complete assay automation. In this report, we provide a systems-level perspective of the p-BNC universal biosensing platform with an emphasis on flow control, device integration, and automation. To demonstrate the flexibility of the p-BNC, we distinguish diseased and non-case patients across three significant disease applications: prostate cancer, ovarian cancer, and acute myocardial infarction. Progress towards developing a rapid 7 minute myoglobin assay is presented using the fully automated p-BNC system.
Prostate cancer point of care diagnostics
(2017-06-06) McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Thompson, Ian; Rice University; United States Patent and Trademark Office
The invention relates to point of care diagnostic disposables, devices, methods, and systems for diagnosing or predicting prostate cancer. The present invention employs biomarker specific reagents in disposable cassettes or lab cards for use as analyzers, as well as software to evaluate and report test results. The system promises to improve point of care in vitro diagnostics.

Browsing by Author "McDevitt, John T."

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