George Chatzipirpiridis

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.

Chitosan Electrodeposition for Microrobotic Drug Delivery

A method to functionalize steerable magnetic microdevices through the co-electrodeposition of drug loaded chitosan hydrogels is presented. The characteristics of the polymer matrix have been investigated in terms of fabrication, morphology, drug release and response to different environmental conditions. Modifications of the matrix behavior could be achieved by simple chemical post processing. The system is able to load and deliver 40-80 μg cm(-2) of a model drug (Brilliant Green) in a sustained manner with different profiles. Chitosan allows a pH responsive behavior with faster and more efficient release under slightly acidic conditions as can be present in tumor or inflamed tissue. A prototype of a microrobot functionalized with the hydrogel is presented and proposed for the treatment of posterior eye 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.

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.

Multisegmented FeCo/Cu nanowires: electrosynthesis, characterization and magnetic control of biomolecule desorption

In this paper, we report on the synthesis of FeCo/Cu multisegmented nanowires by means of pulse electrodeposition in nanoporous anodic aluminum oxide arrays supported on silicon chips. By adjustment of the electrodeposition conditions, such as the pulse scheme and the electrolyte, alternating segments of Cu and ferromagnetic FeCo alloy can be fabricated. The segments can be built with a wide range of lengths (15-150 nm) and exhibit a close-to-pure composition (Cu or FeCo alloy) as suggested by energy-dispersive X-ray mapping results. The morphology and the crystallographic structure of different nanowire configurations have been assessed thoroughly, concluding that Fe, Co, and Cu form solid solution. Magnetic characterization using vibrating sample magnetometry and magnetic force microscopy reveals that by introduction of nonmagnetic Cu segments within the nanowire architecture, the magnetic easy axis can be modified and the reduced remanence can be tuned to the desired values. The experimental results are in agreement with the provided simulations. Furthermore, the influence of nanowire magnetic architecture on the magnetically triggered protein desorption is evaluated for three types of nanowires: Cu, FeCo, and multisegmented FeCo15nm/Cu15nm. The application of an external magnetic field can be used to enhance the release of proteins on demand. For fully magnetic FeCo nanowires the applied oscillating field increased protein release by 83%, whereas this was found to be 45% for multisegmented FeCo15nm/Cu15nm nanowires. Our work suggests that a combination of arrays of nanowires with different magnetic configurations could be used to generate complex substance concentration gradients or control delivery of multiple drugs and macromolecules.

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.

Electroforming of Magnetic Microtubes for Microrobotic Applications

Hard- and soft-magnetic microtubes are proposed for minimal invasive drug delivery and assistance in surgical operations. Cobalt-based alloys are electroformed on sacrificial wires and subsequently released. Cobalt-platinum (CoPt) is used as hard-magnetic material and cobalt-nickel (CoNi) as soft-magnetic. CoPt microtubes show coercivities of 160 kA/m (2 kOe) and remanence of 0.2 T. CoNi microtubes show coercivities below 1.6 kA/m (20 Oe) with a saturation magnetization above 1.3 T. The CoPt microtubes were magnetized perpendicular to their cylindrical axes, (i.e., short axis) using a 5 T magnetizer. The microtubes were tested with a custom magnetic manipulation setup and their behavior under applied fields was analyzed.

Cobalt-nickel microcantilevers for biosensing

We present microcantilevers that utilize magnetic actuation for use as mass sensors for bioapplications. The microcantilevers are made of electroplated cobalt–nickel that has low coercivity and high saturation magnetization. The microcantilevers are actuated by applying magnetic fields, and the deflection is measured using a laser Doppler vibrometer. The microfabrication of the microcantilevers is based on two lithography steps, an electroplating step and a sacrificial layer etching step. The magnetic actuation and optical readout using the fabricated cobalt–nickel microcantilever were successfully demonstrated in air under atmospheric pressure and in deionized water. A feedback circuit is used to enhance the quality factor of the microcantilever. The quality factor increased from approximately 550 to 1600 in air and from 7.3 to 10.6 in deionized water. The microcantilevers can be readily functionalized with selective binding molecules and used as a biomass sensor.

Characterization and actuation of a magnetic photosensitive polymer cantilever

Magnetic polymer microactuators made of SU-8 and superparamagnetic nanoparticles are reported. Homogenous distribution of nanoparticles in the composite was obtained using superparamagnetic nanoparticles and a surfactant. The magnetic polymer composite (MPC) was micromachined into cantilevers using photolithography. The magnetic characterization of the MPC was performed by a superconducting quantum interference device (SQUID). An electromagnet applied magnetic forces to this composite. The force per volume of composite was determined experimentally by measuring the force on a film of MPC using a micro-force sensor. The cantilevers were excited with an AC electromagnet at different frequencies, and their resonance modes were captured by a laser-Doppler vibrometer. Deflections were increased about 10 times by the addition of a DC field. The tip deflection amplitude of a cantilever (160 µm x 1.65 µm) in resonance was found to be 63 nm at 15.78kHz.

Oxygen sensing using microrobots

We present a luminescence oxygen sensor incorporated in 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 employed. An alternative sensor implementation using poly(styrene-co-maleic anhydride) (PS-MA) and PtOEP was successfully demonstrated with nanospheres to increase sensor performance.