Soft Robot-Assisted Minimally Invasive Surgery and Interventions: Advances and Outlook

Since the emergence of soft robotics around two decades ago, research interest in the field has escalated at a pace. It is fuelled by the industry's appreciation of the wide range of soft materials available that can be used to create highly dexterous robots with adaptability characteristics far beyond that which can be achieved with rigid component devices. The ability, inherent in soft robots, to compliantly adapt to the environment, has significantly sparked interest from the surgical robotics community. This article provides an in-depth overview of recent progress and outlines the remaining challenges in the development of soft robotics for minimally invasive surgery

Recent advances in micro-electro-mechanical devices for controlled drug release applications

In recent years, controlled release of drugs has posed numerous challenges with the aim of optimizing parameters such as the release of the suitable quantity of drugs in the right site at the right time with the least invasiveness and the greatest possible automation. Some of the factors that challenge conventional drug release include long-term treatments, narrow therapeutic windows, complex dosing schedules, combined therapies, individual dosing regimens, and labile active substance administration. In this sense, the emergence of micro-devices that combine mechanical and electrical components, so called micro-electro-mechanical systems (MEMS) can offer solutions to these drawbacks. These devices can be fabricated using biocompatible materials, with great uniformity and reproducibility, similar to integrated circuits. They can be aseptically manufactured and hermetically sealed, while having mobile components that enable physical or analytical functions together with electrical components. In this review we present recent advances in the generation of MEMS drug delivery devices, in which various micro and nanometric structures such as contacts, connections, channels, reservoirs, pumps, valves, needles, and/or membranes can be included in their design and manufacture. Implantable single and multiple reservoir-based and transdermal-based MEMS devices are discussed in terms of fundamental mechanisms, fabrication, performance, and drug release applications.Fil: Villarruel Mendoza, Luis A.. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Scilletta, Natalia Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; ArgentinaFil: Bellino, Martin Gonzalo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; ArgentinaFil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Catalano, Paolo Nicolás. Comisión Nacional de Energía Atómica. Gerencia de Área de Investigación y Aplicaciones no Nucleares. Gerencia de Desarrollo Tecnológico y Proyectos Especiales. Departamento de Micro y Nanotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Cable-driven parallel mechanisms for minimally invasive robotic surgery

Minimally invasive surgery (MIS) has revolutionised surgery by providing faster recovery times, less post-operative complications, improved cosmesis and reduced pain for the patient. Surgical robotics are used to further decrease the invasiveness of procedures, by using yet smaller and fewer incisions or using natural orifices as entry point. However, many robotic systems still suffer from technical challenges such as sufficient instrument dexterity and payloads, leading to limited adoption in clinical practice. Cable-driven parallel mechanisms (CDPMs) have unique properties, which can be used to overcome existing challenges in surgical robotics. These beneficial properties include high end-effector payloads, efficient force transmission and a large configurable instrument workspace. However, the use of CDPMs in MIS is largely unexplored. This research presents the first structured exploration of CDPMs for MIS and demonstrates the potential of this type of mechanism through the development of multiple prototypes: the ESD CYCLOPS, CDAQS, SIMPLE, neuroCYCLOPS and microCYCLOPS. One key challenge for MIS is the access method used to introduce CDPMs into the body. Three different access methods are presented by the prototypes. By focusing on the minimally invasive access method in which CDPMs are introduced into the body, the thesis provides a framework, which can be used by researchers, engineers and clinicians to identify future opportunities of CDPMs in MIS. Additionally, through user studies and pre-clinical studies, these prototypes demonstrate that this type of mechanism has several key advantages for surgical applications in which haptic feedback, safe automation or a high payload are required. These advantages, combined with the different access methods, demonstrate that CDPMs can have a key role in the advancement of MIS technology.Open Acces

Size-Controlled Microencapsulation of Mesenchymal Stem Cells and Imaging Agents for Site-Specific Delivery and Tracking

Tissue engineering seeks to develop biological substitutes and/or to foster the remodeling of tissue by manipulating cells and their extracellular environment. One of the many exciting subjects under tissue engineering involve the use of mesenchymal stem cells as paracrine factories to stimulate vascular repair via multiple chemical pathways. There has been extensive in vitro research on the efficacy of stem cell-assisted therapies. However, hypothesized outcomes become more nebulous when translating into the clinical setting due to the many factors associated with the much more complicated in vivo system. Among them are the difficulty in delivering the stem cells to the desired locations, the lack of visual information regarding the transplanted cells, and the inability to ensure that the transplanted cells are viable and can undertake the intended therapeutic mechanisms effectively. In this thesis, we explore several strategies of microencapsulating stem cells while allowing the transplanted cells to be effectively visualized with conventional clinical scanners noninvasively. First, we developed a platform based on droplet microfluidics to produce small, highly uniform, imaging-visible microcapsules without cells. We studied the capsules’ physical, chemical, and imaging properties as well as tissue compatibility in a chronic study involving gastric embolization in pigs. We then modified the platform to accommodate for the co-encapsulation of stem cells and imaging agents. Lastly, we explored a 3-dimensional bioprinting platform using a piezoelectrically actuated inkjet printer head. The resulting microcapsules were able to achieve more rapid throughput compared to the microfluidic platform and was more amenable to the use of different carrying solutions, including biopolymers intended to enhance the efficacy of the encapsulated stem cells. The smaller microcapsules produced by our platforms also allow for more controlled delivery using conventional catheters when compared to the larger conventional cell encapsulation techniques

BioPacer: Electrospun Polyurethane Scaffold Containing hMSCs for Autonomous Cardiac Pacing

The purpose of this project was to design a scaffold to contain modified human mesenchymal stem cells, which would couple with cardiac myocytes, forming a biological pacemaking unit. The objectives of the scaffold were to prevent hMSC migration out of the scaffold, allow gap junction formation with neighboring myocytes, and protect the hMSCs from damage during and after implantation. The final design components included a stent-like structure made of Nitinol to provide structure yet remain flexible in the heart and an electrospun polyurethane sheath to encapsulate the hMSCs but still allow gap junction formation. To characterize the thickness of the polyurethane we completed a migration assay, showing an ideal thickness achieved by 45-minute spin times

UTILIZING DIELECTROPHORESIS TO DETERMINE THE PHYSIOLOGICAL DIFFERENCES OF EUKARYOTIC CELLS

Type 1 diabetes affects over 108,000 children, and this number is steadily increasing. Current insulin therapies help manage the disease but are not a cure. Over a child’s lifetime they can develop kidney disease, blindness, cardiovascular disease and many other issues due to the complications of type 1 diabetes. This autoimmune disease destroys beta cells located in the pancreas, which are used to regulate glucose levels in the body. Because there is no cure and many children are affected by the disease there is a need for alternative therapeutic options that can lead to a cure. Human mesenchymal stem cells (hMSCs) are an important cell source for stem cell therapeutics due to their differentiation capacity, self-renewal, and trophic activity. hMSCs are readily available in the bone marrow, and act as an internal repair system within the body, and they have been shown to differentiate into insulin producing cells. However, after isolation hMSCs are a heterogeneous cell population, which requires secondary processing. To resolve the heterogeneity issue hMSCs are separated using fluorescent- and magnetic-activate cell sorting with antigen labeling. These techniques are efficient but reduce cell viability after separation due to the cell labeling. Therefore, to make hMSCs more readily available for type 1 diabetes therapeutics, they should be separated without diminishing there functional capabilities. Dielectrophoresis is an alternative separation technique that has the capability to separated hMSCs. This dissertation uses dielectrophoresis to characterize the dielectric properties of hMSCs. The goal is to use hMSCs dielectric signature as a separation criteria rather than the antigen labeling implemented with FACS and MACS. DEP has been used to characterize other cell systems, and is a viable separation technique for hMSCs

Smart knives: controlled cutting schemes to enable advanced endoscopic surgery

With the backdrop of the rapidly developing research in Natural Orifice Transluminal Endoscopic Surgery (NOTES), analysis of the literature supported the view that inventing new, controlled tissue dissection methods for flexible endoscopic surgery may be necessary. The literature also confirmed that white space exists for research into and the development of new cutting tools. The strategy of “deconstructing dissection” proposed in this thesis may provide dissection control benefits, which may help address the unique manoeuvring challenges for tissue dissection at flexible endoscopy. This assertion was supported by investigating six embodiments of the strategy which provided varying degrees of enhanced tissue dissection control. Seven additional concepts employing the strategy which were not prototyped also were offered as potential solutions that eventually might contribute evidence in defence of the strategy. One concept for selective ablation — dye-mediated laser ablation — was explored in-depth by theoretical analysis, experimentation and computation. The ablation process was found to behave relatively similar to unmediated laser ablation, but also to depend on cyclic carbonisation for sustained ablation once the dye had disappeared. An Arrhenius model of carbonisation based on the pyrolysis and combustion of wood cellulose was used in a tissue ablation model, which produced reasonable results. Qualitative results from four methods for dye application and speculation on three methods for dye removal complete the framework by which dye-mediated laser ablation might deliver on the promise offered by “deconstructing dissection”. Overall, this work provided the “deconstructing dissection” strategic framework for controlled cutting schemes and offered plausible evidence that the strategy could work by investigating embodiments of the scheme. In particular, dye-mediated laser ablation can provide selective ablation of tissue, and a theoretical model for the method of operation was offered. However, some practical hurdles need to be overcome before it can be useful in a clinical setting

Urology

УЧЕБНО-МЕТОДИЧЕСКИЕ ПОСОБИЯУРОЛОГИЯУРОЛОГИЧЕСКИЕ БОЛЕЗН

SU-8 microprobes for biomedical applications

152 p. : il.[ES]La presente tesis doctoral aborda el diseño, fabricación, encapsulado, y caracterización de microagujas de SU-8 para aplicaciones médicas. En la actualidad existe una amplia variedad de agujas para el registro, estimulación y dispensado de drogas, pero se han observado algunas limitaciones en relación a su diseño y material estructural utilizados. En este trabajo se han desarrollado microagujas basadas en la tecnología de SU-8 como alternativa a las agujas actuales. Primeramente se diseñan las agujas para cada tipo de aplicación, después se determinan los procedimientos de fabricación y finalmente se desarrollan los encapsulados para conectar la aguja miniaturizada con el exterior macroscópico. La aplicación de las agujas se ha centrado en dos campos biomédicos: 1) la monitorización de órganos tal como el riñón, y 2) el registro de la actividad neuronal, añadiendo la posibilidad de realizar dispensado de drogas de forma simultánea. El primer objetivo es crear microagujas que causen el menor daño posible en el tejido biológico. Las mediciones eléctricas que se llevan a cabo para conocer el estado real del tejido pueden resultar modificadas, debilitadas o destruidas si las células que constituyen el tejido han sido previamente dañadas. En este trabajo, se desarrollan microagujas basadas en la tecnología MEMS (micro electromechanical systems) para evitar daños profundos en el tejido y poder así realizar mediciones fidedignas. La tecnología MEMS integra elementos y dispositivos eléctricos, mecánicos y electrónicos miniaturizados, los cuales están basados en la industria consolidada de los Circuitos Integrados (IC). Generalmente, las dimensiones de los elementos basados en MEMS son de entre 1 y 100 micras y los dispositivos pueden variar entre 20 micras y 1 milímetro. Las técnicas base de esta tecnología son la deposición de materiales en láminas, la fotolitografía y el grabado. El silicio es el material más utilizado para crear los múltiples dispositivos MEMS, sin embargo, su rigidez y fragilidad ha motivado el estudio de otros materiales tales como los polímeros. En esta tesis se ha utilizado el polímero SU-8 como material estructural debido a sus propiedades favorables para la fabricación de microagujas. Además, la fabricación de microagujas con este polímero permite el uso de procesos de bajo coste. Esta fotoresina presenta una baja absorción a la luz UV, posibilitando exposiciones uniformes en función del espesor del polímero. Así, se obtienen perfiles verticales y un buen control dimensional para toda la estructura. Además, estudios recientes muestran una adecuada biocompatibilidad del polímero SU-8. El segundo objetivo es obtener la más alta relación señal-ruido posible en las mediciones eléctricas. Para ello se han integrado microelectrodos en las agujas y se ha estudiado la constitución física, la configuración espacial y los tratamientos superficiales de los mismos. Un determinado diseño para cada aplicación y la modificación de las técnicas de fabricación han dado como resultado una óptima capacidad sensora de los electrodos. Así, se ha demostrado su uso a través de la monitorización de episodios de isquemia y reperfusión en riñón de rata. En cuanto a las aplicaciones neuronales, se han registrado potenciales de acción con una amplitud de hasta 400-500 ¿V en hipocampo de rata. Además, se ha demostrado que los microelectrodos son capaces de discriminar diferentes fuentes neuronales. Todos estos resultados han demostrado la versatilidad del polímero para crear dispositivos sensores con aplicación en diversas áreas biomédicas. El último objetivo de esta tesis ha sido integrar canales microfluídicos en la aguja para poder dispensar drogas en aplicaciones neuronales y como resultado, detectar cambios en la actividad neuronal. Finalmente, se han llevado a cabo los primeros experimentos fluídicos in vivo en hipocampo de rata como prueba de concepto. Se dispensan 0.5 ¿l de una disolución de kainato y a continuación se registra un incremento en la actividad neuronal. Los resultados preliminares han demostrado la funcionalidad de la aguja para dispensar y monitorizar de forma simultánea aunque se tienen que realizar más experimentos y optimizar el protocolo experimental para verificar el buen funcionamiento de la aguja. En estos momentos, se están realizando más experimentos neuronales para llegar a establecer la tecnología desarrollada en esta tesis