Protective coatings for intraocular wirelessly controlled microrobots for implantation : corrosion, cell culture, and in vivo animal tests

Grup: Gnm3 FundingDiseases in the ocular posterior segment are a leading cause of blindness. The surgical skills required to treat them are at the limits of human manipulation ability, and involve the risk of permanent retinal damage. Instrument tethering and design limit accessibility within the eye. Wireless microrobots suturelessly injected into the posterior segment, steered using magnetic manipulation, are proposed for procedures involving implantation. Biocompatibility is a prerequisite for these procedures. This paper investigates the use of cobalt-nickel microrobots coated with polypyrrole, and gold, which has been used as an ocular implant material. Polypyrrole has well-established biocompatibility properties, but no reports concerning its ocular implantation is available. Coated and uncoated microrobots were investigated for their corrosion properties, and solutions that had contained coated and uncoated microrobots for one week were tested for cytotoxicity by monitoring NIH3T3 cell viability. None of the microrobots showed significant corrosion currents and corrosion potentials were as expected in relation to the intrinsic nobility of the materials. NIH3T3 cell viability was not affected by the release medium, in which coated/uncoated microrobots were stored. In vivo tests inside rabbit eyes were performed using coated microrobots. There were no significant inflammatory responses during the first week after injection. An inflammatory response detected after two weeks was likely due to a lack of longer-duration biocompatibility. The results provide valuable information for those who work on implant technology and biocompatibility. Coated microrobots have the potential to facilitate a new generation of surgical treatments, diagnostics and drug-delivery techniques, when implantation in the ocular posterior segment will be possible

Porous polysulfone coatings for enhanced drug delivery

The synthesis of a porous polysulfone (PSU) coating for use in drug delivery applications is presented. PSU can serve as a functional surface coating for drug delivery vehicles, such as intraocular biomicrorobots. The coatings can be applied using spin coating or dip coating. The porosity is introduced by selectively dissolving calcium carbonate nanoparticles embedded in the bulk polymer. The network of pores thus formed increases by a factor of thirty the amount of Rhodamine B (model drug) that can be loaded and by a factor of fifteen the amount that can be released. The films do not affect cell viability and exhibit poor cell adhesion. The straightforward synthesis and predictability of porosity enables the tuning of the amount of drug that can be loade

Medical Imaging of Microrobots: Toward In Vivo Applications

Medical microrobots (MRs) have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery, and assisted fertilization, among others. However, most of these demonstrations have been carried out in in vitro settings and under optical microscopy, being significantly different from the clinical practice. Thus, medical imaging techniques are required for localizing and tracking such tiny therapeutic machines when used in medical-relevant applications. This review aims at analyzing the state of the art of microrobots imaging by critically discussing the potentialities and limitations of the techniques employed in this field. Moreover, the physics and the working principle behind each analyzed imaging strategy, the spatiotemporal resolution, and the penetration depth are thoroughly discussed. The paper deals with the suitability of each imaging technique for tracking single or swarms of MRs and discusses the scenarios where contrast or imaging agent's inclusion is required, either to absorb, emit, or reflect a determined physical signal detected by an external system. Finally, the review highlights the existing challenges and perspective solutions which could be promising for future in vivo applications

Medical imaging for the tracking of micromotors

Micro/nanomotors are useful tools for several biomedical applications, including targeted drug delivery and minimally invasive microsurgeries. However, major challenges such as in vivo imaging need to be addressed before they can be safely applied on a living body. Here, we show that positron emission tomography (PET), a molecular imaging technique widely used in medical imaging, can also be used to track a large population of tubular Au/PEDOT/Pt micromotors. Chemisorption of an iodine isotope onto the micromotor’s Au surface rendered them detectable by PET, and we could track their movements in a tubular phantom over time frames of up to 15 min. In a second set of experiments, micromotors and the bubbles released during self-propulsion were optically tracked by video imaging and bright-field microscopy. The results from direct optical tracking agreed with those from PET tracking, demonstrating that PET is a suitable technique for the imaging of large populations of active micromotors in opaque environments, thus opening opportunities for the use of this mature imaging technology for the in vivo localization of artificial swimmers

Engineering Intelligent Nanosystems for Enhanced Medical Imaging

Medical imaging serves to obtain anatomical and physiological data, supporting medical diagnostics as well as providing therapeutic evaluation and guidance. A variety of contrast agents have been developed to enhance the recorded signals and to provide molecular imaging. However, fast clearance from the body or nonspecific biodistribution often limit their efficiency, constituting challenges that need to be overcome. Nanoparticle-based systems are currently emerging as versatile and highly integrated platforms providing improved circulating times, tissue specificity, high loading capacity for signaling moieties, and multimodal imaging features. Furthermore, nanoengineered devices can be tuned for specific applications and the development of responsive behaviors. Responses include in situ modulation of nanoparticle size, increased intratissue mobility through active propulsion of motorized particles, and active modulation of the particle surroundings such as the extracellular matrix for an improved penetration and retention at the desired locations. Once accumulated in the targeted tissue, smart nanoparticle-based contrast agents can provide molecular sensing of biomarkers or characteristics of the tissue microenvironment. In this case, the signal or contrast provided by the nanosystem is responsive to the presence or concentration of an analyte. Herein, recent developments of intelligent nanosystems to improve medical imaging are presented

Microfluidics and Bio-MEMS for Next Generation Healthcare.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2018

Modeling and design of an electromagnetic actuation system for the manipulation of microrobots in blood vessels

Tese de mestrado integrado em Física, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015A navegação de nano/microdispositivos apresenta um grande potencial para aplicações biomédicas, oferecendo meios de diagnóstico e procedimentos terapêuticos no interior do corpo humano. Dada a sua capacidade de penetrar quase todos os materiais, os campos magnéticos são naturalmente adequados para controlar nano/microdispositivos magnéticos em espaços inacessíveis. Uma abordagem recente é o uso de um aparelho personalizado, capaz de controlar campos magnéticos. Esta é uma área de pesquisa prometedora, mas mais simulações e experiências são necessárias para avaliar a viabilidade destes sistemas em aplicações clínicas. O objectivo deste projecto foi a simulação e desenho de um sistema de atuação eletromagnética para estudar a locomoção bidimensional de microdispositivos. O primeiro passo foi identificar, através da análise de elementos finitos, usando o software COMSOL, diferentes configurações de bobines que permitiriam o controlo de dispositivos magnéticos em diferentes escalas. Baseado nos resultados das simulações, um protótipo de um sistema de atuação magnética para controlar dispositivos com mais de 100 m foi desenhado e construído de raiz, tendo em conta restrições de custos. O sistema consistiu num par de bobines de Helmholtz e rotacionais e um par de bobines de Maxwell dispostas no mesmo eixo. Além disso, componentes adicionais tiveram de ser desenhados ou selecionados para preencher os requisitos do sistema. Para a avaliação do sistema fabricado, testes preliminares foram realizados. A locomoção do microrobot foi testada em diferentes direções no plano x-y. As simulações e experiências confirmaram que é possível controlar a força magnética e o momento da força que atuam num microdispositivo através do campos produzidos pelas bobines de Maxwell e Helmholtz, respectivamente. Assim, este tipo de atuação magnética parece ser uma forma adequada de transferência de energia para futuros microdispositivos biomédicos.Navigation of nano/microdevices has great potential for biomedical applications, offering a means for diagnosis and therapeutic procedures inside the human body. Due to their ability to penetrate most materials, magnetic fields are naturally suited to control magnetic nano/microdevices in inaccessible spaces. One recent approach is the use of custom-built apparatus capable of controlling magnetic devices. This is a promising area of research, but further simulation studies and experiments are needed to estimate the feasibility of these systems in clinical applications. The goal of this project was the simulation and design of an electromagnetic actuation system to study the two dimensional locomotion of microdevices. The first step was to identify, through finite element analysis using software COMSOL, different coil configurations that would allow the control of magnetic devices at different scales. Based on the simulation results, a prototype of a magnetic actuation system to control devices with more than 100 m was designed and built from the ground up, taking into account cost constraints. The system comprised one pair of rotational Helmholtz coils and one pair of rotational Maxwell coils placed along the same axis. Furthermore, additional components had to be designed or selected to fulfil the requirements of the system. For the evaluation of the fabricated system, preliminary tests were carried out. The locomotion of a microdevice was tested along different directions in the x-y plane. The simulations and experiments confirmed that it is possible to control the magnetic force and torque acting on a microdevice through the fields produced by Maxwell and Helmholtz coils, respectively. Thus, this type of magnetic actuation seems to provide a suitable means of energy transfer for future biomedical microdevices

MRI-Based Communication with Untethered Intelligent Medical Microrobots

RESUME Les champs magnétiques présent dans un système clinique d’Imagerie par Résonance Magnétique (IRM) peuvent être exploités non seulement, afin d’induire une force de déplacement sur des microrobots magnétiques tout en permettant l’asservissement de leur position - une technique connue sous le nom de Navigation par Résonance Magnétique (NRM), mais aussi pour mettre en œuvre un procédé de communication. Pour des microrobots autonomes équipés de senseurs ayant un certain niveau d'intelligence et opérant à l'intérieur du corps humain, la puissance de transmission nécessaire pour communiquer des informations à un ordinateur externe par des méthodes présentement connues est insuffisante. Dans ce travail, une technique est décrite où une telle perte de puissance d'émission en raison de la mise à l'échelle de ces microrobots peut être compensée par le scanner IRM agissant aussi comme un récepteur très sensible. La technique de communication prend la forme d'une modification de la fréquence du courant électrique circulant le long d'une bobine miniature incorporé dans un microrobot. La fréquence du courant électrique peut être réglée à partir d'une entrée de seuil prédéterminée du senseur mis en place sur le microrobot. La fréquence devient alors corrélée à l’information de l’état du senseur recueilli par le microrobot et elle est déterminée en utilisant l'IRM. La méthode proposée est indépendante de la position et l'orientation du microrobot et peut être étendue à un grand nombre de microrobots pour surveiller et cartographier les conditions physiologiques spécifiques dans une région plus vaste à n’importe quelle profondeur à l'intérieur du corps.----------ABSTRACT The magnetic environment provided by a clinical Magnetic Resonance Imaging (MRI) scanner can be exploited to not only induce a displacement force on magnetic microrobots while allowing MR-tracking for serving control purpose or positional assessment - a technique known as Magnetic Resonance Navigation (MRN), but also for implementing a method of communication with intelligent microrobots. For untethered sensory microrobots having some level of intelligence and operating inside the body, the transmission power necessary to communicate information to an external computer via known methods is insufficient. In this work, a technique is described where such loss of transmission power due to the scaling of these microrobots can be compensated by the same MRI scanner acting as a more sensitive receiver. A communication scheme is implemented in the form of a frequency alteration in the electrical current circulating along a miniature coil embedded in a microrobot. The frequency of the electrical current could be regulated from a predetermined sensory threshold input implemented on the microrobot. Such a frequency provides information on the level of sensory information gathered by the microrobot, and it is determined using MR imaging. The proposed method is independent of the microrobot's position and orientation and can be extended to a larger number of microrobots for monitoring and mapping specific physiological conditions inside a larger region at any depths within the body