Franziska Ullrich

Mobility experiments with microrobots for minimally invasive intraocular surgery.

PURPOSE To investigate microrobots as an assistive tool for minimally invasive intraocular surgery and to demonstrate mobility and controllability inside the living rabbit eye. METHODS A system for wireless magnetic control of untethered microrobots was developed. Mobility and controllability of a microrobot are examined in different media, specifically vitreous, balanced salt solution (BSS), and silicone oil. This is demonstrated through ex vivo and in vivo animal experiments. RESULTS The developed electromagnetic system enables precise control of magnetic microrobots over a workspace that covers the posterior eye segment. The system allows for rotation and translation of the microrobot in different media (vitreous, BSS, silicone oil) inside the eye. CONCLUSIONS Intravitreal introduction of untethered mobile microrobots can enable sutureless and precise ophthalmic procedures. Ex vivo and in vivo experiments demonstrate that microrobots can be manipulated inside the eye. Potential applications are targeted drug delivery for maculopathies such as AMD, intravenous deployment of anticoagulation agents for retinal vein occlusion (RVO), and mechanical applications, such as manipulation of epiretinal membrane peeling (ERM). The technology has the potential to reduce the invasiveness of ophthalmic surgery and assist in the treatment of a variety of ophthalmic diseases.

Electroforming of Implantable Tubular Magnetic Microrobots for Wireless Ophthalmologic Applications

Magnetic tubular implantable micro-robots are batch fabricated by electroforming. These microdevices can be used in targeted drug delivery and minimally invasive surgery for ophthalmologic applications. These tubular shapes are fitted into a 23-gauge needle enabling sutureless injections. Using a 5-degree-of-freedom magnetic manipulation system, the microimplants are conveniently maneuvered in biological environments. To increase their functionality, the tubes are coated with biocompatible films and can be successfully filled with drugs.

Microrobots: a new era in ocular drug delivery

Introduction: Ocular microrobots have the potential to change the way in which we treat a variety of diseases at the anterior and the posterior segments of the eye. Wireless manipulation and positioning of drug delivery magnetic millimeter and submillimeter platforms into the eye constitute a potential route for minimally invasive targeted therapy. However, the field is still in its infancy and faces challenges related to the fabrication, control an interaction with complex biological environments. Areas covered: This review briefly introduces the complex anatomy and physiology of the eye, which renders limitations to the current treatments of ocular diseases. The topical administration of eye drops, intravitreal injections and drug delivery implants is briefly mentioned together with their drawbacks. The authors also analyze the minimally invasive microrobotic approach as an alternative method and report the recent advancements in the fabrication, control, manipulation and drug delivery. Expert opinion: Although microrobotics is a young field, a significant amount of work has been developed to face different challenges related to the minimally invasive manipulation of microdevices in the eye. Current research is already at the state of in vivo testing for systems and their biocompatibility. It is expected that the general concepts acquired will soon be applied for specific interventions, especially for posterior eye pathologies.

Automated capsulorhexis based on a hybrid magnetic-mechanical actuation system

This paper presents a hybrid magnetic-mechanical manipulation system for automated capsulorhexis utilizing a flexible catheter with a sharp edge magnetic tip. Vision based closed loop control is implemented to guide the tip on a circular path in the anterior eye segment. A continuous motion with high repeatability is achieved. The system shows the first catheter-based application of the electromagnetic manipulation system, OctoMag, for fast and safe ophthalmic surgery that potentially reduces the risk of complications and improves precision.

Magnetically actuated and guided milli-gripper for medical applications

This paper presents the design, kinematics, fabrication, and magnetic manipulation of a milli-gripper for medical applications. The design employs a permanent magnet for two purposes. It actuates the compliant gripper and allows for maneuverability of the milli-gripper in an externally applied magnetic field generated by an electromagnetic manipulation system. The modular milli-gripper can be manipulated directly or attached to the distal tip of a magnetically steered catheter. Experiments show successful actuation of the gripper and guidance of the device with the integrated gripper in both the tethered and untethered configuration.

Swimming characteristics of helical microrobots in fibrous environments

Wireless magnetic microrobots show great potential for targeted drug delivery or as minimally invasive surgical tools in the human body. In order to swim through bodily fluids, such as the vitreous humor in the eye, they must be equipped to successfully move through viscoelastic fluids, where they are obstructed by fibrous networks or microparticles. Prior researchers have shown an increased propulsion efficiency with increasing viscoelastic properties for artificial helical swimmers and bacteria with helical flagella. This work investigates the effect of solutions with increasing collagen concentrations on the propulsion velocity of a magnetically actuated helical microswimmer. Results are in agreement with prior experiments and theory and show a performance peak for a helical microrobot of length 280 μm swimming in a fibrous solution with collagen concentration of 1578 μg/ml.

Non-contact, 3D magnetic biomanipulation for in vivo and in vitro applications

Micro/nano robots have the potential to revolutionize many aspects of medicine. These untethered, wirelessly controlled and powered devices will make existing therapeutic and diagnostic procedures less invasive and will enable new procedures never before possible. Here we present five degree of freedom (5-DOF) wireless control of fully untethered magnetic micro/nano agents (3-DOF position, 2-DOF orientation). We accomplish this level of wireless control with electromagnetic manipulation systems that we call OctoMag and MiniMag. We demonstrate different magnetic control strategies and combination thereof for potential in vivo and in vitro applications. We show that these systems have the potential to be employed for targeted drug delivery and for procedures such as retinal-vein cannulation that require a high degree of dexterity.

Assistive Device for Efficient Intravitreal Injections

Intravitreal therapy is the most common treatment for many chronic ophthalmic diseases, such as age-related macular degeneration. Due to the increasing worldwide demand for intravitreal injections, there exists a need to render this medical procedure more time- and cost-efficient while increasing patient safety. The authors propose a medical assistive device that injects medication intravitreally. Compared to the manual intravitreal injection procedure, an automated device has the potential to increase safety for patients, decrease procedure times, allow for integrated data storage and documentation, and reduce costs for medical staff and expensive operating rooms. This work demonstrates the development of an assistive injection system that is coarsely positioned over the patients head by the human operator, followed by automatic fine positioning and intravitreal injection through the pars plana. Several safety features, such as continuous eye tracking and iris recognition, have been implemented. The functioning system is demonstrated through ex vivo experiments with porcine eyes. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:752-762.].

Recent Progress in Magnetically Actuated Microrobotics for Ophthalmic Therapies

Age-related visual loss and ageing demographics account for a large impact on societal health costs on a global scale. Efficient ocular surgery must be precise, safe and cost effective. Current research focuses on robotic systems to assist in ophthalmic surgery. Furthermore, several platforms for drug delivery in the posterior segment of the eye have been introduced. Moreover, magnetic manipulation of tethered and untethered structures has been suggested to assist in teleoperated ophthalmic surgery and targeted drug delivery in the posterior eye due to its many advantages. Magnetic manipulation systems generate magnetic fields and gradients to guide magnetic objects with high precision and force feedback. A hybrid actuation system for guiding a flexible catheter with a sharp edge magnetic tip has been introduced for capsulorhexis – a major step in cataract surgery. Research has demonstrated the potential of wireless magnetic microrobots for targeted drug delivery and simple mechanical operations in the posterior eye segment in ex vivo and in vivo experiments.

Self-folding hydrogel bilayer for enhanced drug loading, encapsulation, and transport

Hydrogel-based robotic microdevices are currently investigated for minimally invasive medical procedures. Hydrogels are especially suited to targeted drug delivery applications as they are able to carry several times more drug solution than its dry weight. A major drawback of these system is that drug release takes place before reaching the targeted area in the body. We introduce a strategy based on a self-folding bilayer to prevent release during transportation without hindering the drug loading efficiency of the hydrogel. The drug is loaded into the hydrogel matrix at room temperature. When the temperature is increased to body temperature, the hydrogel-matrix collapses and the self-folded bilayer refolds into another tube. In this configuration, we observed a significant reduction in drug leakage with less than 5% drug loss during encapsulation. Finally, we demonstrate that the tube can be manipulated magnetically, which shows its potential use in targeted drug delivery applications.