Lab-on-a-Chip Fabrication and Application

The necessity of on-site, fast, sensitive, and cheap complex laboratory analysis, associated with the advances in the microfabrication technologies and the microfluidics, made it possible for the creation of the innovative device lab-on-a-chip (LOC), by which we would be able to scale a single or multiple laboratory processes down to a chip format. The present book is dedicated to the LOC devices from two points of view: LOC fabrication and LOC application

MRI-Based Tumour Targeting Enhancement with Magnetotactic Bacterial Carriers

RÉSUMÉ Le cancer constitue la première cause de mortalité au Québec, avec 20,000 décès estimés par année. Parmi tous les patients atteints du cancer, une grande proportion pourrait profiter de l’avancement technologique en ce qui concerne le transport de médicaments. En effet, l’un des meilleurs moyens d’augmenter l’efficacité d’un médicament contre le cancer, tout en réduisant sa toxicité sur les cellules saines, est de le diriger vers la tumeur et de le maintenir à cet endroit jusqu’à ce qu’un effet thérapeutique se produise. Le transport ciblé de médicaments vers la tumeur peut considérablement améliorer l’efficacité thérapeutique, surtout si le transporteur est capable d’atteindre les zones nécrotiques et se répartir uniformément dans la zone à traiter. Les bactéries, de par leur motilité, sont d’excellents candidats pour une telle application, surtout qu’elles peuvent aussi être facilement fonctionnalisées. Ainsi, la recherche sur le traitement du cancer utilisant des bactéries s’est imposée comme une approche prometteuse surtout qu’elle pallie à une limitation majeure de la chimiothérapie et de la radiothérapie en permettant le traitement des zones anaérobies. Alors que des laboratoires à travers le monde tentent de fabriquer des systèmes miniatures en se basant sur le modèle bactérien, nous avons opté pour l’utilisation des bactéries qui existent dans la nature. Notre stratégie a été de trouver un système biologique ayant les caractéristiques essentielles (e.x. diamètre total de moins de deux micromètres, force de poussée de plus de 4 pN, etc.) et de concentrer nos efforts à identifier une interface et une méthode permettant son contrôle pour des fins de ciblages thérapeutiques dans les lésions tumorales. Nous avons identifié les bactéries magnétotactiques de type MC-1 comme le meilleur transporteur potentiel de médicaments pour le ciblage du cancer. Les MC-1 sont à la fois dirigeables par champs magnétiques et anaérobies, ce qui leur donne un grand avantage par rapport aux bactéries traditionnellement utilisées pour le ciblage du cancer. Le ciblage du cancer avec des bactéries exploite le plus souvent l’affinité des bactéries anaérobies à la région nécrotique faible en oxygène de la tumeur. Certes, ce ciblage manque de spécificité et un des problèmes le plus reconnu est la nécessité d’injecter une forte dose de bactéries pour assurer une croissance de celles-ci à l’intérieur de la tumeur. Ceci n’est pas le cas avec les MC-1 car elles sont à la fois anaérobies et magnétotactiques grâce à une chaîne de nanoparticules d’environ 70 nanomètres de diamètre, formant une sorte de « nano-boussole » magnétique à----------ABSTRACT Magnetotactic Bacteria (MTB) are being explored as potential drug transporters to solid tumours. The MTB’s active motility combined with magnetotaxism (their ability to swim following the direction of a magnetic field) offer new and potentially more accurate solutions in delivering drugs to tumours. In fact, the flagella bundles of the MC-1 bacteria (with an overall ideal cell diameter of approximately 50% the diameter of the tiniest human blood vessels) provide 4.0 to 4.7pN of thrust force for propulsion (roughly 10 times the value of many other well-known flagellated bacteria). Since there are no existing methods or technologies capable of inducing an equivalent force on a carrier of appropriate size for traveling inside a tumour’s microvasculature, live microorganisms are considered as a viable option. Many of the parameters in a tumour microenvironment, such as malformed angiogenesis capillaries, heterogeneous blood flow, and high interstitial pressure, hinder the delivery of blood-borne drugs to the affected area. Active motility might prove to be helpful in bypassing these limitations and may facilitate the uniform distribution of the drug in the targeted area. An MTB navigation technique that allows targeting without prior knowledge of the exact architecture of the vessels network has been developed. This navigation technique exploits both the ability of the MTB to swim following an imposed magnetic field and their random, continuous motion at low magnetic fields. Firstly, a focused magnetic field on the target sets the overall direction of the bacteria. Then, as the bacteria approach the targeted zone, the intensity of the magnetic field is decreased, which allows better bacteria repartition by exploiting their free motion. An additional approach that enhances MTB targeting relies on modulating the magnetic field direction in time, while keeping the magnetic field lines pointed toward the target. Navigation experiments in complex micro-channel networks highlight this process, where the successful targeting of bacteria is demonstrated when an appropriate magnetic field algorithm is applied, especially when it takes into account the nature of the channel network. Tridimensional control and navigation of MTB is also possible with the same technique through proper powering of the magnetic coils. In fact, by controlling their magnetic environment, it is possible to form a swarm of MTB, control its size and position within a given volume using a computer program

Extending Cognitive Work Analysis and Engaging Nanotechnology: Embodied, Embedded and Socially Situated Processes

With current advances in material science and the growth of novel technologies, the nature of human technology interaction is changing. Specifically, the growth and convergence of Nano-, Bio-, Info- and Cognitive Science (NBIC) related technologies has resulted in the emergence of new systems, which requires considerations of the embodied, embedded and socially situated aspects of the human behavior for advanced interaction with intelligent and responsive environments. Currently, Cognitive Work Analysis (CWA) and the associated Ecological Interface Design (EID) are well positioned to draw requirements from these future smart environments; however, the role of the body in human knowing and acting as currently conceptualized in CWA requires further development. This thesis extends CWA by addressing the role of the body in human knowing and acting. Further, it also extends CWA by making the link between interpretive social approaches to human knowing and acting (specifically, symbolic interactionism) and CWA. Thus, this thesis supports the conception of the human in advanced technological environments as an embodied, embedded and socially situated construct. In this thesis, CWA was extended at a fundamental level. This strategy required returning to the basic assumptions of CWA derived from Rasmussen’s approach. A considerable portion of this thesis scrutinizes the fundamental assumptions of CWA by revisiting Rasmussen’s papers and highlighting the engineering dimension of his approach. CWA is then extended via consideration of Rasmussen’s approach along with other theoretical approaches from ecological psychology, action theory and symbolic interactionism, in order to produce a framework for gathering requirements for interface design. In this extended CWA, the first step allows for an interpretative understanding of the user’s traditional ways of knowing and acting. Whereas the second step consists of an analysis amenable for eliciting the design requirements. To show the applicability of the new extended framework, the work domain of nanotechnology is chosen. A field study was conducted in the area of nanotechnology that comprised of three subdomains pertaining to devices, robotics and materials. The requirements derived from these three areas were compared between the standard CWA and the extended CWA. In all the three cases the extended CWA supported the traditional CWA, as well as provided a greater number of requirements pertaining to the role of the body and the social dimension of activity in human knowing and acting. Therefore, this shows that the theoretical extensions have a practical feasibility in terms of using the extended CWA

Ultrasonic locating and tracking of small particles for biomedical applications

This dissertation focuses on the development of two novel ultrasound technologies with the idea of tracking and locating small particles: 1) Ultrasound tracking of the acoustically actuated microswimmers, 2) Super-resolution ultrasound (SRU) imaging by locating the microbubbles. Artificial microswimmers that navigate in hard-to-reach spaces and microfluidic environments inside human bodies hold a great potential for various biomedical applications. For eventual translation of the microswimmer technology, a capability of tracking the microswimmers in 3-D through tissues is particularly required for reliable navigation. In this work, after first proposing and demonstrating the proof-of-concept of ultrasound tracking of the microswimmer in a 2-D setup in vitro, we built a 3-D ultrasound tracking system using two clinical ultrasound probes. A reliable performance for tracking the arbitrary 3-D motions of the newly designed 3-D microswimmers in real-time was demonstrated in vitro. The developed 3-D ultrasound tracking strategy could be a strong motivation and foundation for the future clinical translation of the novel microswimmer technology. SRU that can identify microvessels with unprecedented spatial resolution is promising for diagnosing the diseases associated with abnormal microvascular changes. One of the potential applications is to assess the changes in renal microvasculature during the progressive kidney disease. In this work, we applied the developed deconvolution-based SRU imaging on the mouse acute kidney injury (AKI) model to show the capability of SRU for noninvasive assessment of renal microvasculature changes during the progression from AKI to chronic kidney disease (CKD). SRU that can identify microvessels with unprecedented spatial resolution is promising for diagnosing the diseases associated with abnormal microvascular changes. One of the potential applications is to assess the changes in renal microvasculature during the progressive kidney disease. In this work, we applied the developed deconvolution-based SRU imaging on the mouse acute kidney injury (AKI) model to show the capability of SRU for noninvasive assessment of renal microvasculature changes during the progression from AKI to chronic kidney disease (CKD). Future endeavors for integrating SRU locating technology with a reliable tracking capability of microparticles will provide a unique tool for various biomedical applications of the novel microdrones for diagnosis and drug delivery

Grand challenges in bioengineered nanorobotics for cancer therapy

One of the grand challenges currently facing engineering, life sciences, and medicine is the development of fully functional nanorobots capable of sensing, decision making, and actuation. These nanorobots may aid in cancer therapy, site-specific drug delivery, circulating diagnostics, advanced surgery, and tissue repair. In this paper, we will discuss, from a bioinspired perspective, the challenges currently facing nanorobotics, including core design, propulsion and power generation, sensing, actuation, control, decision making, and system integration. Using strategies inspired from microorganisms, we will discuss a potential bioengineered nanorobot for cancer therapy. © 2013 IEEE.Link_to_subscribed_fulltex