Clinical Detection of Diagnostic Biomarker Panels Using Microfluidic Electrochemical Immunoarrays

Cancer is a worldwide infliction. Cancer does not discriminate. Cancer does not care if you are young or old, rich or poor, disabled or in the prime of your life. It can be caused by genetics, environmental factors and/or lifestyle. The challenge, how do we diagnose and treat such a dynamic disease? Cancer detection is expensive, invasive, inaccurate and lacks sensitivity. New methods that rely on measurements of analytes in solution for detection and quantification are promising alternatives. Panels of protein biomarkers may aid in personalized diagnosis as protein levels in patients are often upregulated or down regulated in relation to a specified disease. For the medical field this provides opportunities to bring cancer detection to clinical practice as it will enable physicians’ access to blood, saliva, or urine bioassays for screening, as well as monitoring progression and response to therapy. The objectives of this thesis are to utilize new technology in microfluidic fabrication, 3D printing and nanomaterial synthesis for ELISA alternatives. The sensors are developed to be sensitive, rapid, inexpensive and multiplexed for point of care diagnostics. These technically facile immunoassays in human patient serum comprise a multivariable approach for statistically improving the probability of diagnosing and differentiating forms of cancer

Digital watermarking and novel security devices

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Advances in Polymeric Materials for Biomedical Applications

Significant research efforts are currently being undertaken in the field of natural and synthetic polymers for a range of biomedical applications. (Co)polymer molecular structure, topology, self-assemblies, biodegradation, and hydrophobicity are of biomaterial importance for intrinsically biocompatible polymer systems. This book is comprised of nine chapters, published previously as original research contributions of the Special Issue focused on advances in polymeric materials for biomedical applications. The authors of these contributions are predominantly from central European countries, Italy and the United Kingdom. The content of this book will be of interest to scientists, scholars and students working in this area of knowledge, reflecting the progress in the development of advanced natural and synthetic polymer biomaterials

Design of Materials for Bone Tissue Scaffolds

The book proposes extensive and varied design strategies for bone tissue engineering. The design process of materials for bone tissue scaffolds presently represents an issue of crucial importance and is being studied by many researchers throughout the world. A number of studies have been conducted, aimed at identifying the optimal material, geometry, and surface that the scaffold must possess to stimulate the formation of the largest amounts of bone in the shortest time possible

Soft and flexible bioelectronic micro-systems for electronically controlled drug delivery

The concept of targeted and controlled drug delivery, which directs treatment to precise anatomical sites, offers benefits such as fewer side effects, reduced toxicity, optimized dosages, and quicker responses. However, challenges remain to engineer dependable systems and materials that can modulate host tissue interactions and overcome biological barriers. To stay aligned with advancements in healthcare and precision medicine, novel approaches and materials are imperative to improve effectiveness, biocompatibility, and tissue compliance. Electronically controlled drug delivery (ECDD) has recently emerged as a promising approach to calibrated drug delivery with spatial and temporal precision. This article covers recent breakthroughs in soft, flexible, and adaptable bioelectronic micro-systems designed for ECDD. It overviews the most widely reported operational modes, materials engineering strategies, electronic interfaces, and characterization techniques associated with ECDD systems. Further, it delves into the pivotal applications of ECDD in wearable, ingestible, and implantable medical devices. Finally, the discourse extends to future prospects and challenges for ECDD

2019 IMSAloquium: Student Inquiry and Research Program and IMSA Internship Program

Welcome to IMSAloquium 2019! This is IMSA’s 32nd year of leading in educational innovation, the 31st year of the IMSA Student Inquiry and Research (SIR) Program, and the first year of the newly imagined IMSA Internship Program.https://digitalcommons.imsa.edu/archives_sir/1029/thumbnail.jp

Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering

Cardiovascular disease (CVD) currently represents one of the leading causes of death worldwide. Each year, more than 17.9 million people die due to CVD manifestations. To reverse these manifestations, the transplantation of secondary vessels or the use of synthetic vascular grafts represents the gold standard procedure. However, significant adverse reactions have been described in the literature regarding the use of these type of grafts. In this regard, modern therapeutic strategies focused on CVD therapeutics must be proposed and evaluated. As alternative therapies, advanced tissue engineering approaches, including decellularization procedures and the 3D additive bio-printing methods, are currently being investigated. In this Special Issue of Bioengineering, we aimed to highlight modern approaches regarding CVD. This Special Issue, entitled “Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering”, includes 5 articles. These articles are related to the efficient production of small-diameter vascular grafts, vascular graft development with 3D printing approaches, and in vitro models for the improved assessment of atherosclerosis mechanisms. The Guest Editors of this Special Issue wish to express their gratitude to all contributors for their unique and outstanding articles. Additionally, special credit is given to all reviewers for their comprehensive analysis and overall effort in improving the quality of the published articles

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance

Development of microfluidic devices for cancer cell isolation

[eng] The emergence of liquid biopsies has been useful for the diagnosis of physiological conditions, inflammatory processes, and especially represents a good alternative tool for non-invasive analysis of tumor-derived materials. Currently, tissue biopsies are still the gold standard for tumor profiling. Nevertheless, this technique presents many limitations that include invasiveness, risk and depending on some anatomical locations is not easy (or even impossible) to obtain. Moreover, it provides a limited picture of the tumor profile, considering that tumors are heterogeneous entities composed of different subpopulations of cells, which display a variability of genetic and epigenetic changes. In this context, liquid biopsies are a cheaper, faster, non-invasive alternative to conventional biopsies, that can be used for personalized cancer therapy. In a broad sense, liquid biopsy is based on the isolation of biomarkers from the blood that can be used for cancer diagnosis and monitoring. This definition englobes Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA) and nanovesicles. CTCs are cancer cells, which leave the primary tumor and enter the bloodstream initiating a process called metastasis. Nevertheless, one of the most relevant challenges in this field involves the processing and analysis of CTCs, due to their low amount in peripheral blood (1 to 100 CTCs per 109 blood cells) and high heterogeneity. Furthermore, the approaches for isolating CTCs from blood samples are limited due to high cell contamination rates or substantial loss of cancer cells, and high-cost methods. To overcome these limitations, microfluidic devices have been designed for isolating CTCs based on their intrinsic properties like density, size, deformability, and difference in membrane protein expression. This project was undertaken to develop microfluidic devices for isolating CTCs based on inertial focusing and affinity binding principle methods. We first developed a spiral microfluidic device that can efficiently separate the CTCs from most of the blood cells by their differences in size by applying a hydrodynamic sorting principle. The CTC output sample is contaminated by the largest leukocytes (~12 to 21 μm) which are in the same size range as the CTCs (~9 μm to 30 μm). The research has also explored the development of microfluidic spiral devices using a 3D printer, in which the geometry dimensions were adapted to remove Leukocytes binding to polystyrene particles functionalized with CD45 antibody, allowing a more CTCs sample purity. Alternatively, second type of microfluidic device known as a Herringbone chip was designed to capture the remaining leukocytes (negative enrichment of CTCs) from the spiral CTC output sample. This device uses an affinity-binding principle based on a mixed Self Assembled Monolayer (SAM) composed of a Silane-PEG-Biotin, Silane-PEG-OH and CD45- antibody (common antigen for leukocytes).Moreover, the microfluidic platform was optimized for highthroughput blood sample processing including a lysis pre-treatment, guaranteeing a high recovery of CTC and its viability for further analysis. On the other hand, an electronic circuit was successfully developed using piezoelectric micropumps MP6 controlled by Raspberry PI zero, which allowed to overcome some limitations of traditional syringe pumps, as well as facilitate the use of this platform in a clinical environment. Finally, the clinical proof of concept was initiated with samples from colon cancer patients in collaboration with the Vall d'Hebron hospital.[spa] Las biopsias líquidas representan una buena herramienta alternativa para el análisis no invasivo de materiales derivados de tumores. Esta definición engloba las células tumorales circulantes (CTC), el ADN tumoral circulante (ctDNA) y las nanovesículas. Las CTC son células cancerosas que abandonan el tumor primario e ingresan al torrente sanguíneo iniciando un proceso llamado metástasis. Sin embargo, uno de los desafíos más relevantes implica el procesamiento y análisis de las CTC, debido a su baja cantidad en sangre periférica (1 a 100 CTC por 109 células sanguíneas) y su alta heterogeneidad. Además, los enfoques para aislar CTC de muestras de sangre son limitados debido a las altas tasas de contaminación celular, la pérdida sustancial de células cancerosas y los elevados costos. Para superar estas limitaciones, se han diseñado dispositivos microfluídicos para aislar CTC en función de sus propiedades intrínsecas como densidad, tamaño, deformabilidad y diferencia en la expresión de proteínas de membrana. Durante esta tesis se desarrollaron dispositivos microfluídicos para aislar CTC basados en métodos de principio de unión por afinidad y enfoque inercial. Primero, desarrollamos un dispositivo microfluídicos en espiral que puede separar eficientemente las CTC de la mayoría de las células sanguíneas por sus diferencias de tamaño mediante la aplicación de un principio de clasificación hidrodinámica. La muestra de salida de CTC está contaminada por los leucocitos más grandes (~12 a 21 µm) que están en el mismo rango de tamaño que las CTC (~9 µm a 30 µm). La investigación también ha explorado el desarrollo de dispositivos en espiral utilizando una impresora 3D, en los que las dimensiones geométricas se adaptaron para eliminar la unión de leucocitos a partículas de poliestireno fucionalizadas con anticuerpo CD45, permitiendo una mayor pureza de la muestra de CTC. Alternativamente, se diseñó un segundo tipo de dispositivo conocido como chip en espiga para capturar los leucocitos restantes (enriquecimiento negativo de CTC) de la muestra de salida de CTC en espiral. Este dispositivo utiliza un principio de unión por afinidad basado en una monocapa autoensamblada (SAM) mixta compuesta de silano-PEG-biotina, silano-PEG-OH y anticuerpo CD45 (antígeno leucocitario común). Por otro lado, se desarrolló con éxito un circuito electrónico utilizando microbombas piezoeléctricas MP6 controladas por Raspberry PI zero, lo que permitió superar algunas limitaciones de las bombas de jeringa tradicionales, así como facilitar el uso de esta plataforma en un entorno clínico. Finalmente, se inició la prueba clínica de concepto con muestras de pacientes con cáncer de colon en colaboración con el hospital Vall d'Hebron