Indiana University-Purdue University Indianapolis (IUPUI) / For the past decade, many microfluidic paper-based analytical devices have been developed and used in different research fields. These devices are low-cost, portable, flexible, sterilizable, disposable, and easy to manufacture. The microfluidic paper-based analytical devices offer good alternatives to measurements and assays commonly performed in laboratories for analytical and clinical purposes, especially in diagnostics. In this work, we developed an electrochemical paper-based pH sensor. The determination of pH is essential in applications in areas as diverse as in the food industry, agriculture, health care or water treatment. The method presented in this work is an electroanalytical method that involves quantification of pH using stencil-painted graphite electrodes. Preliminary tests showed that pH can be determined on paper-based devices, thus indicating the presence of electroactive elements sensitive to pH on the surface of our electrodes (Chapter 4). Chemical modification of the electrode by adsorption with sodium carbonate and modification of the surface of the electrode was accomplished via: oxygen (ambient air) plasma treatment and pure oxygen plasma treatment. These treatments were to attempt to improve the definition of redox peaks on the CVs (Chapter 5). The changes made to the design of the paper-based device and the addition of a conditioning step improved the definition of the redox peaks on the CVs and increased the pH-sensing ability of our method (Chapter 6). The pH-sensing ability of our method was evaluated by testing solutions over a wide pH range. Adding sodium chloride to samples adjust the solution for accurate pH determination. The pH was successfully measured for solutions with values ranging from 1 to 13 and for artificial saliva samples prepared with pH values in the cavity-prone range (Chapter 7). This work offers a method that uses electroactive elements sensitive to pH on the surface of the PBD electrodes for pH-sensing.

<p>Paper-based flexible devices represent a new frontier in electronics technology. The research has focused on the fabrication of the lightweight, and flexible paper-based lithium ion batteries. A lithium ion battery relies on the interplay of multiple components. These components themselves, as well as the processes used to create them, need to be adjusted and modified in order to achieve a fully flexible lithium ion battery. These components include the electrode current collector, active material, and electrolyte. By modifying these components to be fully flexible and resistant to damages caused by deformation, a fully flexible battery can be achieved.</p> <p> </p> <p>Herein, the paper-based platform utilized is key to provide flexibility for the battery components. The goal of this work not only focused on the creation of a paper-based flexible battery to be used as an integrable energy storage system for flexible devices, but also on developing methodologies and processes that can advance the emerging area of paper-based electronics, where different functional units must be fabricated within a single paper substrate. The key to make effective paper-based batteries, is to achieve a highly conductive paper structure as the base. In this work, conductive nanomaterials including carbon nanotubes (CNT) and graphene were used to fabricate conductive paper, where wood microfibers were coated with layers of these nanomaterials via layer-by-layer nanoassembly. These fibers were then combined into paper sheets. The resulting paper offers a conductive and porous base for electronic devices that utilized only small quantities of CNT or reduced graphene oxide (rGO) to provide length resistances of 468 Ω/cm and 74.6 Ω/cm, respectively for each fabricated conductive paper. </p> <p> </p> <p>Flexible lithium ion batteries were then made by using CNT paper-based electrodes and a solid polymer gel electrolyte. The electrodes were made by deposition of lithium active materials over the conductive paper and where shown to be flexible, durable, and light weight. With respect to the electrolyte, a new type of gel electrolyte based on PVDF-HFP was fabricated to overcome problems related to the use of liquid electrolytes in flexible batteries. This gel, which provides a high electrolyte uptake (450% by weight), was made by infusing both liquid and ceramic electrolytes inside a polymer gel structure and demonstrated conductivity up to 10^-4 S/cm. The paper-based battery developed with these new materials has a comparable capacity to commercial batteries and represents a flexible and light weight alternative. The use of ultra-high capacity lithium compounds as cathode materials, such as vanadium pentoxide (with theoretical capacities of 440 mAh/g) in conjunction with rGO-paper as a stand-alone electrode (with a reversible capacity 546 mAh/g) were also explored and results will be discussed. </p> <p> </p> <p>This research has led to the development of a novel method of making a fully flexible lithium ion batteries, using paper-based current collectors, leak proof polymer gel electrolytes and ultra-high capacity lithium ion active materials. Thus, flexible high conductive paper-based current collectors, polymer-gel electrolytes, vanadium based ultra-high capacity cathode electrodes, and graphene-based stand-alone paper-based anodes have been developed and tested.</p> <p> </p>

The disproportionate burden of infectious disease and lack of appropriate diagnostic tools in the developing world suggest that future health technology development efforts need to more effectively target these resource-limited settings. Microfluidic systems, like lab-on-a-chip technologies, offer the potential to miniaturize the large, complex processes performed in first-world laboratories onto a portable chip for use in remote settings. The problem with these systems is that they require equipment for fluidic handling and many other aspects of diagnostic assays such as sample preparation and analyte detection. The notion of “paperfluidics” has garnered much attention due to paper’s natural ability to wick fluids through capillary action without the need for pumps or other equipment. This and many other qualities of paper make it well suited for point-of-care diagnostics. Paper diagnostics have successfully been employed to detect the presence of antigens or small molecules in clinical samples; however, the detection of many disease targets relies on the much higher sensitivity and specificity of molecular diagnostics achieved via nucleic acid amplification tests (NAAT). The work presented in this dissertation describes the design and development of a paperfluidic sample-to-answer NAAT platform. Preliminary work focused on the development of separate NAAT modules for the extraction, amplification, and detection of nucleic acids from clinical samples directly within a paper matrix. A paper-based assay was developed, using Influenza A (H1N1) as a model system, for the extraction and purification of RNA directly from patient nasopharyngeal specimens, in situ isothermal amplification, and immediate lateral flow detection of amplified products. We then integrate these paper-based NAAT modules onto a single paperfluidic chip in a modular, foldable system that allows for fully-integrated fluidic handling from sample to answer. We showcase the full functionality of the chip by extracting, amplifying and detecting human papillomavirus (HPV) 16 DNA directly from crude cervical specimens in less than 1 hour, for early point-of-care detection of cervical cancer. The chip is made entirely of paper and adhesive sheets, making it low-cost, portable, and disposable, offering the potential for use in very remote settings and increasing access to screening to those most in need.

The purpose of this study was to examine the usefulness of electronic-based questionnaires as a tool to gather data from field supervisors in the medical profession at various military bases. The study compared the response effects of an electronic evaluation questionnaire with the traditional method of paper-based questionnaires in gathering Level 3 data. The number of returns affects the amount of information available to the course personnel in creating a viable program that ensures the success of service members entering the occupational field and, ultimately, affecting the number of service members who remain beyond their first enlistment. The return rate and amount of missing data were tracked. Supervisors of graduates of a medical program who had observed service members for a minimum of 4-months were participants in the study. The z-test for comparing two proportions was used to determine significance of the study at the .05 level. Findings indicate that there was a significant difference in return rates and the amount of missing data when using the electronic format. Based on this study, the electronic-based questionnaire as a data-gathering tool provided a higher number of returns in a quicker time frame with fewer missing data in the technical training environment. Copyright is held by the author, unless otherwise note

Physically compliant (flexible) electronics are scientifically intriguing, mechanically complex, technologically challenging with huge socio-economical potential. The flexible electronics market is expected to grow from USD 23.92 Billion in 2018 to USD 40.37 Billion by 2023. Until now the target applications for flexible electronics have been limited to displays, solar cells, and printed batteries. A fully flexible electronic system can open up a whole new era of novel applications. On the other hand, there has been a significant growth of IoT devices worldwide. In this Ph.D. research, expanding upon the horizon of applications for flexible electronics, I explore the integration of existing “things” into the IoT ecosystem. The overarching objective is to present low-cost solutions through the use of sustainable materials as active electronic materials and employ DIY integration strategies to build “Add on” standalone sensory systems, which can be attached to any existing things like a “decal”. The add-ons can be tagged on objects or living beings including humans. The objective of using DIY methods is benefited from the low cost readily available recyclable materials which allow anyone, with a little expertise, to create customized versions of add-on modules suited to their needs. The core of the system will have flexible silicon CMOS ICs for data management, instead of conventional rigid ICs. Today, when we think of improving the performance of anything, it has to be replaced by a much more costly and sophisticated new version. By using modular add-on modules, the functionality of most things can be enhanced further without the need of replacing it entirely. On one hand, I show a low-cost add-on module that adds “smart” capabilities to a normal prescription bottle while on the other hand a smart add-on module attached to a personal belonging helps protect it from theft. Finally, a paper-based acoustic sensor housed in Styrofoam packaging will be explored to perform chronic monitoring of respiratory disease while being attached non-invasively to the chest of a human. These modules can be potential lifesavers, while costing less than a few dollars, consequently becoming a critical utility for everyone.

Indiana University-Purdue University Indianapolis (IUPUI) / Improvised explosive devices (IEDs) are a global threat due to their destructive potential, the easy access to raw materials, and online instructions to manufacture them. These circumstances have led to an increase in the number of IEDs using potassium chlorate as an oxidizer. The standard methods to detect chlorate are mainly designed for laboratory-only testing. Thus, field instrumentation capable of detecting oxidizers from explosives fuel-oxidizers is critical for crime scene investigation and counterterrorism efforts (described in Chapter 1). We developed a paper-based sensor for the in-field detection of chlorate (described in Chapter 2). The sensor is low-cost, disposable, portable, and inexpensive to fabricate, and its flexibility features allow for surface sampling without sample destruction. The sensor has an electrodeposited molybdate sensing layer, as chlorate was reported to have a catalytic effect on the molybdate reduction. The chlorate detection relies on monitoring the change in redox activity of the molybdate sensing layer using different electroanalytical techniques. We effectively demonstrated the analytical performance of the sensor (Chapter 3), obtaining a limit of detection of 1.2 mM and a limit of quantification of 4.10 mM. We evaluated the selectivity of the sensor by testing other oxidizers, such as perchlorate and nitrate, which did not present any electrochemical activity with the molybdate sensing layer. Additionally, we performed an interferent study with sugar, commonly used as fuel in IEDs, and other common white household powders such as baking soda, flour, and corn starch and neither a false positive nor a false negative result was observed (Chapter 3). As bromate has been reported to have a stronger catalytic effect than chlorate on the redox activity of molybdate, the quantification of bromate was also explored, and a bromate sensor was developed using the findings of the chlorate sensor (Chapter 4). The reaction mechanism involved in the molybdate reduction was explored and discussed in Chapter 5. The capability of the sensor in detecting chlorate from combusted samples and post-blast samples was successfully demonstrated in Chapter 6, as well as the design of encased prototypes to allow for an in-field presumptive test, storage, and transport for in-laboratory confirmatory tests and compared the performance of the sensor to the available commercial tests.

No description available.

<p>Research in paper-based analytical devices has been increasing in recent years. Before technology transfer and market acceptance, these paper-based sensors have to be validated with field samples. In this study, we have made an attempt to evaluate the effectiveness of paper-based sensors to detect pesticides in real world samples. Generation 1 biosensor has been modified to be user friendly. There is no difference in the performance of generation 2 sensors; they detect pesticides based on colorimetric assay. The assay protocol involves first introducing the sample to the sensing zone by pipetting the water sample. Following an incubation period of 15min, the substrate end of the sensor is dipped into the sample to move paper bound indoxyl acetate (IDA) to the sensing region to initiate the enzyme-catalyzed hydrolysis of the substrate, resulting in the development of blue color. The presence of pesticide is indicated by either a decrease in color intensity or with no color development at all.</p> <p>To evaluate the effectiveness of biosensor in detecting pesticides in real world samples, a field study was conducted in four villages of southern India. Water samples from different aquatic environment including both surface water and ground water, were tested using generation 2 paper-based sensors. The paper-based sensors were capable of detecting organophosphorus pesticides in real world samples. The results were confirmed using GC-MS.</p> <p>The presence of higher concentration of dibutyl phthalate (in the range of 100uM to 10mM) in water can be a potential interference for the paper-based assay for the detection of pesticides in water. The paper-based biosensor assay platform can detect pesticides in the environmental samples and results have been validated by GC-MS. But for transfer of technology to the industry, further optimization is required to improve the stability of substrate to withstand atmospheric temperature fluctuations thus allowing the storage and shipment of the biosensor strips. Additionally to conduct reliable assays and obtain consistent results, the fabrication of biosensor strips needs to be improved to maintain the consistent volumes of bioinks impregnated on paper support.</p> / Master of Applied Science (MASc)

Functional nucleic acids (FNAs), which include both DNA/RNA aptamers and DNA enzymes, have emerged as promising biological recognition elements for biosensors. These species typically require immobilization on or within a solid support, which is usually interfaced to some kind of signal transducer and readout system when use in biosensor. Our group has successfully immobilized several functional nucleic acids in the past, including fluorescence-signalling DNA enzymes, DNA aptamers and RNA aptamers by entrapping them into porous silica or organosilica materials prepared by the sol-gel method using percursors such as sodium silicate (SS), diglyceryl silane (DGS), tetrametylorthosilicate (TMOS) and trimethoxymethysilane (MTMS). While the earlier work established the ability of entrapped FNAs to retain binding and catalytic activity, only limited information was obtained on how different factors affect the performance of immobilized FNAs, and no information was obtained on the effects of aging and storage conditions on FNA performance. The initial objective of this thesis was to employ advanced fluorescence methods to better understand the nature of immobilized DNA and RNA aptamers, and in particular how entrapment in different sol-gel based materials affected FNA performance for detection of small molecule analytes. It was found that the ability of the entrapped aptamer reporters to remain fully hybridized was the most important factor in terms of signalling capability for both DNA and RNA aptamer reporters. It was also observed that more polar materials derived from SS were optimal for both types of aptamer reporters, since these allowed the entrapped aptamers to remain hydridized to their complementary strands and still retain the dynamic motion needed to undergo structure switching, while providing a minimum degree of leaching. The second objective of my research was to develop a paper-based biosensing device incorporating immobilized DNA and RNA aptamers that could be used in the fields of point-of-care diagnostics to further expand the utility of structure-switching aptamer reporters to real world application. A dual response (fluorescence / colorimetric) paper-based sensor utilized printed graphene oxide to immobilize both a RNA and a DNA aptamer in a recognition zone. Upon target addition, the aptamer desorbed and eluted to an amplification zone where rolling circle amplification was used to generate a colorimetric output. This sensor could function with clinical samples such as serum and stool, and allowed detection of key bacterial markers (ATP and glutamate dehydrogenase) at clinically relevant levels. / Thesis / Doctor of Philosophy (PhD)

<p>Swift recognition of disease-causing pathogens at the point-of-care enables life-saving treatment and infection control. However, current rapid diagnostic devices often fail to detect the low concentrations of pathogens present in the early stages of infection, causing delayed and even incorrect treatments. Rapid diagnostics that require multiple steps and/or elevated temperatures to perform have a number of barriers to use at the point-of-care and in the field, and despite efforts to simplify these platforms for ease of use, many still require diagnostic-specific training for the healthcare professionals who use them. Most nucleic acid amplification assays require hours to perform in a sterile laboratory setting that may be still more hours from a patient’s bedside or not at all feasible for transport in remote or low-resourced areas. The cold-chain storage of reagents, multistep sample preparation, and costly instrumentation required to analyze samples has prohibited many nucleic acid detection and antibody-based assays from reaching the point-of-care. There remains a critical need to bring rapid and accessible pathogen identification technologies that determine disease status and ensure effective treatment out of the laboratory.</p> <p>Paper-based diagnostics have emerged as a portable platform for antigen and nucleic acid detection of pathogens but are often limited by their imperfect control of reagent incubation, multiple complex steps, and inconsistent false positive results. Here, I have developed mechanisms to economically improve thermal incubations, automate dried reagent flow for multistep assays, and specifically detect pathogenic antigens while improving final output sensitivity on paper-based devices. First, I characterize miniaturized inkjet printed joule-heaters (microheaters) that enable thermal control for pathogen lysis and nucleic acid amplification incubation on a low-cost paper-based device. Next, I explore 2-Dimensional Paper Networks as a means to automate multistep visual enhancement reactions with dried reagents to increase the sensitivity and readability of nucleic acid detection with paper-based devices. Lastly, I aim to create a novel Reverse-Transcription Recombinase Polymerase Reaction mechanism to amplify and detect a specific region of the Spike protein domain of SARS-CoV-2. This will allow the rapid detection of SARS-CoV-2 infections to aid in managing the current COVID-19 pandemic. In the future, these tools could be integrated into a rapid diagnostic test for SARS-CoV-2 and other pathogens, ultimately improving the accessibility and sensitivity of rapid diagnostics on multiple fronts.</p>