Development of an enzymatic glucose biosensor for applications in wearable sweat-based sensing

The recent development and commercial availability of wearable devices like the FITBITî and Apple Watchî reflect an increasing consumer interest in actively monitoring health parameters. Though wearable devices are beginning to emerge in a variety of fields and applications, there is particular interest in the development of wearable monitors for continuously sensing blood glucose levels. Diabetes currently affects nearly 10% of the American population, a number that is expected to rise in the near future, prompting increased interest in noninvasive methods of monitoring glucose levels. This interest in noninvasive monitoring and the recent advent of continuous monitoring products like the FITBITî are coupled together in the concept of wearable glucose sensors that utilize sweat glucose concentration levels as a means to monitor blood glucose concentration. This work centers on sweat-based glucose biosensors with applications in continuous monitoring for diabetes patients. It includes an overview of glucose biosensors and an introduction to electrochemistry (Chapter 1) and an investigation into the effectiveness of electrodeposited platinum nanoparticles as a transduction element in electrochemical glucose biosensor (Chapter 2). A large part of this thesis (Chapter 3) is devoted to the development of an entirely inkjet printable working electrode for applications in wearable sensing. The developed electrode was fabricated entirely through inkjet printing using a commercially available Fujifilm Dimatix Materials Printer and characterization tests show that the sensor performs similarly to sensors fabricated using more costly and time-intensive clean room methods. The sensor consists of a conductive graphene underlayer, an insulative lacquer coating which serves to maintain constant electrode surface area, a transduction layer of platinum-decorated carbon nanotubes, a detection layer of glucose oxidase and stabilizing protein bovine serum albumin, and finally, a cross-linking layer of glutaraldehyde. When operating in phosphate buffer solution the sensor demonstrates a linear sensing range of 10 õM to 2.51 mM glucose, which is within the range of sweat glucose concentrations, a response time of 18 seconds, average sensitivity of 18.09 õA mM-1 cm-2, and a theoretical detection limit of 3.79 õM glucose

Enabling Inkjet Printed Graphene for Ion Selective Electrodes with Postprint Thermal Annealing

Inkjet printed graphene (IPG) has recently shown tremendous promise in reducing the cost and complexity of graphene circuit fabrication. Herein we demonstrate, for the first time, the fabrication of an ion selective electrode (ISE) with IPG. A thermal annealing process in a nitrogen ambient environment converts the IPG into a highly conductive electrode (sheet resistance changes from 52.8 ± 7.4 MΩ/□ for unannealed graphene to 172.7 ± 33.3 Ω/□ for graphene annealed at 950 °C). Raman spectroscopy and field emission scanning electron microscopy (FESEM) analysis reveals that the printed graphene flakes begin to smooth at an annealing temperature of 500 °C and then become more porous and more electrically conductive when annealed at temperatures of 650 °C and above. The resultant thermally annealed, IPG electrodes are converted into potassium ISEs via functionalization with a poly(vinyl chloride) (PVC) membrane and valinomycin ionophore. The developed potassium ISE displays a wide linear sensing range (0.01–100 mM), a low detection limit (7 μM), minimal drift (8.6 × 10–6 V/s), and a negligible interference during electrochemical potassium sensing against the backdrop of interfering ions [i.e., sodium (Na), magnesium (Mg), and calcium (Ca)] and artificial eccrine perspiration. Thus, the IPG ISE shows potential for potassium detection in a wide variety of human fluids including plasma, serum, and sweat

Electrical Differentiation of Mesenchymal Stem Cells into Schwann‐Cell‐Like Phenotypes Using Inkjet‐Printed Graphene Circuits

Graphene-based materials (GBMs) have displayed tremendous promise for use as neuro-interfacial substrates as they enable favorable adhesion, growth, proliferation, spreading and migration of immobilized cells. Herein we report the first case of the differentiation of Mesenchymal Stem Cells (MSCs) into Schwann Cell (SC) like phenotypes through the application of electrical stimuli from a graphene-based electrode. Electrical differentiation of MSCs into SC like phenotypes is carried out on a flexible, inkjet-printed graphene interdigitated electrode (IDE) circuit that is made highly conductive (sheet resistance \u3c 1 kΩ/☐) via a post-print pulse-laser annealing process. MSCs immobilized on the graphene printed IDEs and electrically stimulated/treated (etMSCs) displayed significant enhanced cellular differentiation and paracrine activity above conventional chemical treatment strategies [~85% of the etMSCs differentiated into SCs like phenotypes with ~80 ng/mL of nerve growth factor (NGF) secretion vs. 75% and ~55 ng/mL for chemically treated MSCs (ctMSCs)]. These results help pave the way for in vivo peripheral nerve regeneration where the flexible This article is protected by copyright. All rights reserved. 3 graphene electrodes could conform to the injury site and provide intimate electrical simulation for nerve cell regrowth

Rapid and Label-Free Detection of Interferon Gamma via an Electrochemical Aptasensor Comprising a Ternary Surface Monolayer on a Gold Interdigitated Electrode Array

A label-free electrochemical impedance spectroscopy (EIS) aptasensor for rapid detection (\u3c35 \u3emin) of interferon-gamma (IFN-γ) was fabricated by immobilizing a RNA aptamer capture probe (ACP), selective to IFN-γ, on a gold interdigitated electrode array (Au IDE). The ACP was modified with a thiol group at the 5′ terminal end and subsequently co-immobilized with 1,6-hexanedithiol (HDT) and 6-mercapto-1-hexanolphosphate (MCH) to the gold surface through thiol–gold interactions. This ACP/HDT-MCH ternary surface monolayer facilitates efficient hybridization with IFN-γ and displays high resistance to nonspecific adsorption of nontarget proteins [i.e., fetal bovine serum (FBS) and bovine serum albumin (BSA)]. The Au IDE functionalized with ACP/HDT-MCH was able to measure IFN-γ in actual FBS solution with a linear sensing range from 22.22 pM to 0.11 nM (1–5 ng/mL) and a detection limit of 11.56 pM. The ability to rapidly sense IFN-γ within this sensing range makes the developed electrochemical platform conducive toward in-field disease detection of a variety of diseases including paratuberculosis (i.e., Johne’s Disease). Furthermore, experimental results were numerically validated with an equivalent circuit model that elucidated the effects of the sensing process and the influence of the immobilized ternary monolayer on signal output. This is the first time that ternary surface monolayers have been used to selectively capture/detect IFN-γ on Au IDEs

Platinum Nanoparticle Decorated SiO2 Microfibers as Catalysts for Micro Unmanned Underwater Vehicle Propulsion

Micro unmanned underwater vehicles (UUVs) need to house propulsion mechanisms that are small in size but sufficiently powerful to deliver on-demand acceleration for tight radius turns, burst-driven docking maneuvers, and low-speed course corrections. Recently, small-scale hydrogen peroxide (H2O2) propulsion mechanisms have shown great promise in delivering pulsatile thrust for such acceleration needs. However, the need for robust, high surface area nanocatalysts that can be manufactured on a large scale for integration into micro UUV reaction chambers is still needed. In this report, a thermal/electrical insulator, silicon oxide (SiO2) microfibers, is used as a support for platinum nanoparticle (PtNP) catalysts. The mercapto-silanization of the SiO2 microfibers enables strong covalent attachment with PtNPs, and the resultant PtNP–SiO2 fibers act as a robust, high surface area catalyst for H2O2 decomposition. The PtNP–SiO2 catalysts are fitted inside a micro UUV reaction chamber for vehicular propulsion; the catalysts can propel a micro UUV for 5.9 m at a velocity of 1.18 m/s with 50 mL of 50% (w/w) H2O2. The concomitance of facile fabrication, economic and scalable processing, and high performance—including a reduction in H2O2 decomposition activation energy of 40–50% over conventional material catalysts—paves the way for using these nanostructured microfibers in modern, small-scale underwater vehicle propulsion systems

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Platinum Nanoparticle Decorated SiO 2 Microfibers as Catalysts for Micro Unmanned Underwater Vehicle Propulsion

Micro unmanned underwater vehicles (UUVs) need to house propulsion mechanisms that are small in size but sufficiently powerful to deliver on-demand acceleration for tight radius turns, burst-driven docking maneuvers, and low-speed course corrections. Recently, small-scale hydrogen peroxide (H2O2) propulsion mechanisms have shown great promise in delivering pulsatile thrust for such acceleration needs. However, the need for robust, high surface area nanocatalysts that can be manufactured on a large scale for integration into micro UUV reaction chambers is still needed. In this report a thermal/electrical insulator, silicon oxide (SiO2) microfibers, are used as a support for platinum nanoparticle (PtNP) catalysts. The mercapto-silanization of the SiO2 microfibers enables strong covalent attachment with PtNPs and the resultant PtNP-SiO2 fibers act as a robust, high surface area catalyst for H2O2 decomposition. The PtNP-SiO2 catalysts are fitted inside a micro UUV reaction chamber for vehicular propulsion; the catalysts can propel a micro UUV for 5.9 meters at a velocity of 1.18 m/s with 50 mL of 50% (w/w) H2O2.The concomitance of facile fabrication, economic and scalable processing, and high performance —including a reduction in H2O2 decomposition activation energy of 40-50% over conventional material catalysts—paves the way for using these nanostructured microfibers in modern, small-scale underwater vehicle propulsion systems

Increasing the activity of immobilized enzymes with nanoparticle conjugation

The efficiency and selectivity of enzymatic catalysis is useful to a plethora of industrial and manufacturing processes. Many of these processes require the immobilization of enzymes onto surfaces, which has traditionally reduced enzyme activity. However, recent research has shown that the integration of nanoparticles into enzyme carrier schemes has maintained or even enhanced immobilized enzyme performance. The nanoparticle size and surface chemistry as well as the orientation and density of immobilized enzymes all contribute to the enhanced performance of enzyme–nanoparticle conjugates. These improvements are noted in specific nanoparticles including those comprising carbon (e.g., graphene and carbon nanotubes), metal/metal oxides and polymeric nanomaterials, as well as semiconductor nanocrystals or quantum dots.This is a manuscript of an article from Current Opinion in Biotechnology 34 (2015): 242, doi:10.1016/j.copbio.2015.04.005. </p

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial