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This book offers a comprehensive overview of the development and application of microfluidics and biosensors in cancer research, in particular, their applications in cancer modeling and theranostics. Over the last decades, considerable effort has been made to develop new technologies to improve the diagnosis and treatment of cancer. Microfluidics has proven to be a powerful tool for manipulating biological fluids with high precision and efficiency and has already been adopted by the pharmaceutical and biotechnology industries. With recent technological advances, particularly biosensors, microfluidic devices have increased their usefulness and importance in oncology and cancer research. The aim of this book is to bring together in a single volume all the knowledge and expertise required for the development and application of microfluidic systems and biosensors in cancer modeling and theranostics. It begins with a detailed introduction to the fundamental aspects of tumor biology, cancer biomarkers, biosensors and microfluidics. With this knowledge in mind, the following sections highlight important advances in developing and applying biosensors and microfluidic devices in cancer research at universities and in the industry. Strategies for identifying and evaluating potent disease biomarkers and developing biosensors and microfluidic devices for their detection are discussed in detail. Finally, the transfer of these technologies into the clinical environment for the diagnosis and treatment of cancer patients will be highlighted. By combining the recent advances made in the development and application of microfluidics and biosensors in cancer research in academia and clinics, this book will be useful literature for readers from a variety of backgrounds. It offers new visions of how this technology can influence daily life in hospitals and companies, improving research methodologies and the prognosis of cancer patients.
Since four decades, rapid detection and monitoring in clinical and food diagnostics and in environmental and biodefense have paved the way for the elaboration of electrochemical biosensors. Thanks to their adaptability, ease of use in relatively complex samples, and their portability, electrochemical biosensors now are one of the mainstays of analy
Nanobioelectrochemistry covers the modern aspects of bioelectrochemistry, nanoscience and materials science. The combination of nanostructured materials and biological molecules enables the development of biodevices capable to detect specific substances. Furthermore, by using the bioelectrochemistry approach, the interaction between bio-systems and nanostructured materials can be studied at the molecular level, where several mechanisms of molecular behavior are elucidate from redox reactions. The combination of biological molecules and novel nanomaterials components is of great importance in the process of developing new nanoscale devices for future biological, medical and electronic applications. This book describes some of the different electrochemical techniques that can be used to study new strategies for patterning electrode surfaces with enzymes, organelles, cells and biomimetic systems. Also, it focuses on how enzymes and microorganisms can be used as biological catalysts in fuel cells for green power generation. By bringing together these different aspects of nanobioelectrochemistry, this book provides a valuable source of information for many students and scientists.
The occurrence of cancer involves altered protein expression, known as biomarkers of disease. The serum levels of biomarker proteins are used as indicators to differentiate between diseased and healthy states, and to monitor disease progression. Sensitive measurement of proteins over-expressed in individuals with cancer holds excellent promise for early disease detection and personalized therapies. However, the required point-of-care measurement has yet to be broadly realized. Thus, there is an urgent need for simpler, faster and inexpensive detection of serum biomarkers with high sensitivity and accuracy. In this dissertation, new methodologies for ultrasensitive multiplexed detection of serum biomarker proteins for oral cancer, as well as other malignancies, utilizing different aspects of nanotechnology in conjunction with electrochemical detection have been developed and characterized. The first part of the approach addresses the study of interleukin-6 (IL-6) using single-walled carbon nanotube forests based electrochemical immunosensor on pyrolytic graphite (PG) electrodes. With two levels of multi-enzyme labeling in a sandwich immunoassay format, 25 fM human IL-6 in serum, and experimental samples, was reproducibly measured. The second part features 8-sensor microfluidic array equipped with four specific capture antibodies to detect ultralow levels of interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor C (VEGF-C) proteins, and these proteins when captured off-line using magnetic beads derivatized with 120,000 antibodies and 400,000 enzyme labels, greatly decreased non-specific binding and enhanced sensitivity. This approach provided unprecedented detection limits in low fg mL−1 range for all four biomarkers in calf serum, essentially used as a human serum surrogate. This oral cancer biomarker panel was validated by detecting proteins in sera of oral cancer patients and cancer-free controls. Receiver operating characteristic (ROC) analysis showed that a normalized combination of the levels of all 4 biomarkers enhanced the clinical discrimination of oral cancer from non-cancer conditions compared to single biomarkers, with 89% sensitivity and 98% specificity. The use of microfluidic immunoarrays for multiplexed detection of biomarker proteins offers distinct advantages. The capability and versatility of these methodologies for simultaneous, sensitive, accurate, low cost real-time monitoring of protein biomarkers with high clinical selectivity and sensitivity holds excellent promise for diagnosis and prognosis of cancer with potential for rationalizing treatment options. Also described in this dissertation is the development of electrochemical sensors for peanut allergen Ara h2 in serum, along with various analytical techniques to characterize the sensors to establish the primary reasons for high sensitivity and selectivity.
Cancer is one of leading cause of deaths, and responsible for 8.2 million deaths worldwide. Especially, 70% of deaths from cancer occur in low or mid income countries. In order to deliver affordable and accessible cancer care to low income developing countries, it is critical to develop rapid, low cost, and highly accurate tools for cancer detection and treatment. Recently, liquid biopsy and circulating cancer biomarkers such as circulating tumor cells (CTC), extracellular vesicles (EV), and cell free DNA (cfDNA) have gained great attentions for early diagnosis, prognosis, and treatment monitoring of cancer patients because they can be accessed in less invasive approaches through body fluids while providing quantitative information about original tumors at low cost. To facilitate detection of circulating cancer biomarkers, we developed electromagnetic biosensing systems for rapid and quantitative molecular analysis. First, we report portable nuclear magnetic resonance (NMR) system that detects cancer cells or proteins labelled with magnetic nanoparticles (MNPs). The developed NMR system could detect as low as 20 cancer cells in 5 uL samples. Second, we describe micro-Hall magnetometer that molecularly profiles single cancer cell with magnetic multiplexing. The micro-Hall magnetometer, which consisted of an array of 7 um x 7 um Hall sensors, showed its capability to differentiate magnetic particles with distinct magnetic moments. We applied this technology to molecular profiling of single ovarian cancer cell. Last, we introduce wirelessly powered electrochemical system that detect cancer specific EV and DNA. Using immuno-magnetic sandwich assay, we could enrich almost 100% of EVs from clinical specimens without ultracentrifugation and profile cancer specific transmembrane proteins from as low as 105 EVs. Also, we demonstrated PCR-free detection of single stranded DNA with in-vitro protein synthesis assay. These electromagnetic biosensors will be powerful tools to deliver more accessible and affordable cancer care to resource limited areas in developing countries.
This thesis is focused on development of Surface Plasmon Resonance imaging (SPRi) and electrochemical immunoarrays for sensitive and accurate detection of biomarker proteins using offline capture of analytes onto the antibody coated magnetic beads. First, it elucidates kinetic characterization of super-paramagnetic particles decorated with over 100,000 antibodies binding to protein antigens attached to flat surfaces. Surface plasmon resonance (SPR) was used to show that these antibody-derivatized MPs (MP-Ab2) provide essentially irreversible binding and 100-fold increased association rates compared to free antibodies. These findings were consistent with highly efficient capture of protein antigens in solution by the MP-Ab2, and explain in part the utility of these beads for ultrasensitive protein detection into the fM and aM range. SPR imaging microarrays were developed for detection of epitope specific immunoglobuling E (IgE) antibodies relevant to the diagnosis of severe nut allergies. Microarrays feature 16-25 gold sensor spots equipped with peptide and carbohydrate epitopes from major peanut allergen glycoprotein Arachis hypogaea 2 (Ara-h2). A monoclonal anti-IgE antibody was included as positive control. IgEs were pre-captured onto magnetic beads loaded with polyclonal anti- IgE antibodies to enhance sensitivity and minimize non-specific binding for serum proteins. As low as 0.1 attomole of IgE antibodies were detected from serum samples in 45 min assay time. Enzyme linked electrochemical immunoassays were developed on 8 screen-printed carbon electrode arrays for detection of prostate cancer biomarker proteins. These proteins are Insulin growth factor-1 (IGF-1), pigment epithelium derived factor (PEDF), vascular endothelium growth factor-D (VEGF-D), and prostate specific antigen (PSA). Serum levels of all these proteins are elevated during different stages of prostate cancer malignancy. Massively enzyme labeled magnetic beads carrying secondary antibodies were used to capture analyte proteins from serum samples. The beads were then magnetically separated, washed and transferred to an electrochemical device housing an 8 nano- structured electrode array modified with capture antibodies. Amperometric signal generated after injection of reagent solution containing 0.1 mM hydrogen peroxide and 1 mM hydroquinone mediator was directly proportional to the amount of captured antigen. Using this strategy, specific and ultrasensitive immunoassays are developed with detection limits in lower femtomolar ranges.
Encyclopedia of Interfacial Chemistry: Surface Science and Electrochemistry, Seven Volume Set summarizes current, fundamental knowledge of interfacial chemistry, bringing readers the latest developments in the field. As the chemical and physical properties and processes at solid and liquid interfaces are the scientific basis of so many technologies which enhance our lives and create new opportunities, its important to highlight how these technologies enable the design and optimization of functional materials for heterogeneous and electro-catalysts in food production, pollution control, energy conversion and storage, medical applications requiring biocompatibility, drug delivery, and more. This book provides an interdisciplinary view that lies at the intersection of these fields. Presents fundamental knowledge of interfacial chemistry, surface science and electrochemistry and provides cutting-edge research from academics and practitioners across various fields and global regions
Medical Biosensors for Point of Care (POC) Applications discusses advances in this important and emerging field which has the potential to transform patient diagnosis and care. Part 1 covers the fundamentals of medical biosensors for point-of-care applications. Chapters in part 2 go on to look at materials and fabrication of medical biosensors while the next part looks at different technologies and operational techniques. The final set of chapters provide an overview of the current applications of this technology. Traditionally medical diagnostics have been dependent on sophisticated technologies which only trained professionals were able to operate. Recent research has focused on creating point-of-care diagnostic tools. These biosensors are miniaturised, portable, and are designed to be used at the point-of-care by untrained individuals, providing real-time and remote health monitoring. Provides essential knowledge for designers and manufacturers of biosensors for point-of-care applications Provides comprehensive coverage of the fundamentals, materials, technologies, and applications of medical biosensors for point-of-care applications Includes contributions from leading international researchers with extensive experience in developing medical biosensors Discusses advances in this important and emerging field which has the potential to transform patient diagnosis and care