Juho Pokki

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.

Undulatory Locomotion of Magnetic Multilink Nanoswimmers

Micro- and nanorobots operating in low Reynolds number fluid environments require specialized swimming strategies for efficient locomotion. Prior research has focused on designs mimicking the rotary corkscrew motion of bacterial flagella or the planar beating motion of eukaryotic flagella. These biologically inspired designs are typically of uniform construction along their flagellar axis. This work demonstrates for the first time planar undulations of composite multilink nanowire-based chains (diameter 200 nm) induced by a planar-oscillating magnetic field. Those chains comprise an elastic eukaryote-like polypyrrole tail and rigid magnetic nickel links connected by flexible polymer bilayer hinges. The multilink design exhibits a high swimming efficiency. Furthermore, the manufacturing process enables tuning the geometrical and material properties to specific applications.

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.

In Vitro Oxygen Sensing Using Intraocular Microrobots

We present a luminescence oxygen sensor integrated with a wireless intraocular microrobot for minimally-invasive diagnosis. This microrobot can be accurately controlled in the intraocular cavity by applying magnetic fields. The microrobot consists of a magnetic body susceptible to magnetic fields and a sensor coating. This coating embodies Pt(II) octaethylporphine (PtOEP) dyes as the luminescence material and polystyrene as a supporting matrix, and it can be wirelessly excited and read out by optical means. The sensor works based on quenching of luminescence in the presence of oxygen. The excitation and emission spectrum, response time, and oxygen sensitivity of the sensor were characterized using a spectrometer. A custom device was designed and built to use this sensor for intraocular measurements with the microrobot. Due to the intrinsic nature of luminescence lifetimes, a frequency-domain lifetime measurement approach was used. An alternative sensor design with increased performance was demonstrated by using poly(styrene-co-maleic anhydride) (PS-MA) and PtOEP nanospheres.

Electroplated porous polypyrrole nanostructures patterned by colloidal lithography for drug-delivery applications

Porous nanostructures of polypyrrole (Ppy) were fabricated using colloidal lithography and electrochemical techniques for potential applications in drug delivery. A sequential fabrication method was developed and optimized to maximize the coverage of the Ppy nanostructures and to obtain a homogeneous layer over the substrate. This was realized by masking with electrophoretically-assembled polystyrene (PS) nanospheres and then electroplating. Drug/biomolecule adsorption and the release characteristics for the porous nanostructures of Ppy were investigated using rhodamine B (Rh-B). Rh-B is an easily detectable small hydrophobic molecule that is used as a model for many drugs or biological substances. The porous Ppy nanostructures with an enhanced surface area exhibited higher Rh-B loading capacity than bulk planar films of Ppy. Moreover, tunability of surface morphology for further applications (e.g., sensing, cell adhesion) was demonstrated.

Cooperative manipulation and transport of microobjects using multiple helical microcarriers

Manipulation and transport of microscale objects in 3D with high spatiotemporal resolution require precise control over the applied forces. We report a strategy that uses specially engineered microbars having engagement points and multiple helical microcarriers that can apply reversible loads onto these holders. The helical microcarriers are actuated by externally generated, low strength magnetic fields. By optimizing the design of helical structures for precise manipulation, we fabricated microcarriers that swim with little wobbling even at low rotating frequencies. The cooperation of microcarriers generates higher propulsive forces while application of forces at multiple locations results in motion control with multiple degrees of freedom (DOF). The microbar loaded with multiple microcarriers can be employed as a single mobile device for the realization of higher order manipulation tasks.

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.

Characterization of Puncture Forces for Retinal Vein Cannulation

For this study, we have collected puncture force data from the vasculature of the chorioallantoic membranes (CAM) of developing chicken embryos to examine forces required for retinal vein cannulation. The CAM vessels of a developing chicken embryo have been shown to be an appropriate model for human retinal veins. The effect of microneedle geometry and vessel size on puncture forces was investigated. The results of this work are important for researchers working on robotic vitreoretinal surgical systems. [DOI: 10.1115/1.4005318]

Colloidal polycrystalline monolayers under oscillatory shear

In this paper we probe the structural response to oscillatory shear deformations of polycrystalline monolayers of soft repulsive colloids with varying area fraction over a broad range of frequencies and amplitudes. The particles are confined at a fluid interface, sheared using a magnetic microdisk, and imaged through optical microscopy. The structural and mechanical response of soft materials is highly dependent on their microstructure. If crystals are well understood and deform through the creation and mobilization of specific defects, the situation is much more complex for disordered jammed materials, where identifying structural motifs defining plastically rearranging regions remains an elusive task. Our materials fall between these two classes and allow the identification of clear pathways for structural evolution. In particular, we demonstrate that large enough strains are able to fluidize the system, identifying critical strains that fulfill a local Lindemann criterion. Conversely, smaller strains lead to localized and erratic irreversible particle rearrangements due to the motion of structural defects. In this regime, oscillatory shear promotes defect annealing and leads to the growth of large crystalline domains. Numerical simulations help identify the population of rearranging particles with those exhibiting the largest deviatoric stresses and indicate that structural evolution proceeds towards the minimization of the stress stored in the system. The particles showing high deviatoric stresses are localized around grain boundaries and defects, providing a simple criterion to spot regions likely to rearrange plastically under oscillatory shear.

Measuring localized viscoelasticity of the vitreous body using intraocular microprobes

Vitrectomy is a standard ophthalmic procedure to remove the vitreous body from the eye. The biomechanics of the vitreous affects its duration (by changing the removal rate) and the mechanical forces transmitted via the vitreous on the surrounding tissues during the procedure. Biomechanical characterization of the vitreous is essential for optimizing the design and control of instruments that operate within the vitreous for improved precision, safety, and efficacy. The measurements are carried out using a magnetic microprobe inserted into the vitreous, a method known as magnetic microrheology. The location of the probe is tracked by a microscope/camera while magnetic forces are exerted wirelessly by applied magnetic fields. In this work, in vitro artificial vitreous, ex vivo human vitreous and ex vivo porcine vitreous were characterized. In addition, in vivo rabbit measurements were performed using a suturelessly injected probe. Measurements indicate that viscoelasticity parameters of the ex vivo human vitreous are an order of magnitude different from those of the ex vivo porcine vitreous. The in vivo intra-operative measurements show typical viscoelastic behavior of the vitreous with a lower compliance than the ex vivo measurements. The results of the magnetic microrheology measurements were validated with those obtained by a standard atomic force microscopy (AFM) method and in vitro artificial vitreous. This method allows minimally-invasive characterization of localized mechanical properties of the vitreous in vitro, ex vivo, and in vivo. A better understanding of the characteristics of the vitreous can lead to improvements in treatments concerning vitreal manipulation such as vitrectomy.