Bio-implantable microdevices and structures for functional electrical stimulation applications

This dissertation describes the development of microstructures and devices for applications in functional electrical stimulation. A nerve cuff electrode design has been developed for applications in neural electrical stimulation and recording, which addresses limitations with existing cuff electrodes. The developed clip-on micro-cuff electrode design consists of a naturally closed cuff with inner diameter in the micro-scale or above. A novel pinch-hinge feature allows a user to easily open the cuff and place it on target nerve tissue for stimulation or recording purposes. Upon release of the pinch-hinge, the cuff assumes its normally closed nature. The device conducts and reads electrical signals in the amplitude and frequency range of typical neural signals. A typical clip-on cuff device with 800 µm inner diameter is opened to its maximum extent by a relatively low force of less than 0.8 N, offering an alternative to other designs requiring application of a force for cuff closure. For applications involving gastric muscle stimulation, a novel gastric pacing electrode is fabricated in biocompatible silicone elastomer. In response to physiological temperature of about 37 ˚C, polyethylene glycol embedded inside the device body melts due to which the structure changes from a more rigid state initially to a more flexible state. This is expected to reduce tissue penetration during and after electrode implantation. A comprehensive piece-wise discrete element equivalent circuit model has been developed to represent an electrode-neural tissue interface. This model addresses internal aspects of both the tissue and the electrode surface and is an improvement over previous models. The equivalent circuit is employed in conjunction with electronic circuit simulation software to study the electrical response of an axon to external stimulus. Simulation results broadly correlate with practical observations reported by others. Lastly, a new percutaneous access device functioning as an interface between implants and the external world is reported here. The device made of silicone elastomer incorporates stress concentration features and shows promise for improved robustness and reliability. The device also incorporates micro-scale porous structures to allow for tissue in-growth to facilitate anchoring of the device

Design, development and testing of miniature instruments for flexible endoscopy

This thesis describes the design and development of single-stitch and chain-stitch endoscopic sewing machines for flexible endoscopy as well as devices and methods for tying knots and cutting thread at flexible endoscopy. The work also includes a comparative study of clipping methods for endoscopic haemostasis and a feasibility study of a wireless endoscope that might allow images to be transmitted from sites in the gastrointestinal tract without wires, cables or fibre optic bundles. The development and testing of simple prototypes of such an endoscope are reported. Chapter 1 reviews the surgical instruments and methods used for tissue approximation in general surgery, laparoscopic surgery and flexible endoscopic surgery. The design of existing, conventional sewing machines and the ways in which they form stitches are also considered. In Chapter 2, a comparative study of clipping methods for endoscopic haemostasis is reported. In Chapter 3, the design and development of new single-stitch endoscopic sewing machines are described, together with data on the clinical use of one of these machines. In Chapter 4, studies of ways of improving endoscopic vision during endoscopic sewing and the effects of needle size and the size and shape of the suction cavity are reported. In Chapter 5, the design and development of novel chain-stitch endoscopic sewing machines are reported. These make use of two new catch mechanisms. In Chapter 6, knot tying at flexible endoscopy is considered, and a number of new devices and methods are described and clinical results reported. In Chapter 7, cutting thread at flexible endoscopy is described. Several new endoscopic thread cutting devices and methods together with results are presented. In Chapter 8, a feasibility study of wireless endoscopy is reported. The study includes tests of the concept of wireless endoscopes made using prototypes constructed from miniature CCD cameras and microwave transmitters. Finally, some concluding remarks relating to the work described in this thesis are given

A Novel Bio-Inspired Insertion Method for Application to Next Generation Percutaneous Surgical Tools

The use of minimally invasive techniques can dramatically improve patient outcome from neurosurgery, with less risk, faster recovery, and better cost effectiveness when compared to conventional surgical intervention. To achieve this, innovative surgical techniques and new surgical instruments have been developed. Nevertheless, the simplest and most common interventional technique for brain surgery is needle insertion for either diagnostic or therapeutic purposes. The work presented in this thesis shows a new approach to needle insertion into soft tissue, focussing on soft tissue-needle interaction by exploiting microtextured topography and the unique mechanism of a reciprocating motion inspired by the ovipositor of certain parasitic wasps. This thesis starts by developing a brain-like phantom which I was shown to have mechanical properties similar to those of neurological tissue during needle insertion. Secondly, a proof-of-concept of the bio-inspired insertion method was undertaken. Based on this finding, the novel method of a multi-part probe able to penetrate a soft substrate by reciprocal motion of each segment is derived. The advantages of the new insertion method were investigated and compared with a conventional needle insertion in terms of needle-tissue interaction. The soft tissue deformation and damage were also measured by exploiting the method of particle image velocimetry. Finally, the thesis proposes the possible clinical application of a biologically-inspired surface topography for deep brain electrode implantation. As an adjunct to this work, the reciprocal insertion method described here fuelled the research into a novel flexible soft tissue probe for percutaneous intervention, which is able to steer along curvilinear trajectories within a compliant medium. Aspects of this multi-disciplinary research effort on steerable robotic surgery are presented, followed by a discussion of the implications of these findings within the context of future work

Parylene Based Flexible Multifunctional Biomedical Probes And Their Applications

MEMS (Micro Electro Mechanical System) based flexible devices have been studied for decades, and they are rapidly being incorporated into modern society in various forms such as flexible electronics and wearable devices. Especially in neuroscience, flexible interfaces provide tremendous possibilities and opportunities to produce reliable, scalable and biocompatible instruments for better exploring neurotransmission and neurological disorders. Of all the types of biomedical instruments such as electroencephalography (EEG) and electrocorticography (ECoG), MEMS-based needle-shape probes have been actively studied in recent years due to their better spatial resolution, selectivity, and sensitivity in chronical invasive physiology monitoring. In order to address the inherent issue of invasiveness that causes tissue damage, research has been made on biocompatible materials, implanting methods and probe structural design. In this dissertation, different types of microfabricated probes for various applications are reviewed. General methods for some key fabrication steps include photolithography patterning, chemical vapor deposition, metal deposition and dry etching are covered in detail. Likewise, three major achievements, which aim to the tagets of flexibility, functionality and mechanical property are introduced and described in detail from chapter 3 to 5. The essential fabrication processes based on XeF2 isotropic silicon etching and parylene conformal deposition are covered in detail, and a set of characterization is summarized

Parylene Based Flexible Multifunctional Biomedical Probes And Their Applications

MEMS (Micro Electro Mechanical System) based flexible devices have been studied for decades, and they are rapidly being incorporated into modern society in various forms such as flexible electronics and wearable devices. Especially in neuroscience, flexible interfaces provide tremendous possibilities and opportunities to produce reliable, scalable and biocompatible instruments for better exploring neurotransmission and neurological disorders. Of all the types of biomedical instruments such as electroencephalography (EEG) and electrocorticography (ECoG), MEMS-based needle-shape probes have been actively studied in recent years due to their better spatial resolution, selectivity, and sensitivity in chronical invasive physiology monitoring. In order to address the inherent issue of invasiveness that causes tissue damage, research has been made on biocompatible materials, implanting methods and probe structural design. In this dissertation, different types of microfabricated probes for various applications are reviewed. General methods for some key fabrication steps include photolithography patterning, chemical vapor deposition, metal deposition and dry etching are covered in detail. Likewise, three major achievements, which aim to the tagets of flexibility, functionality and mechanical property are introduced and described in detail from chapter 3 to 5. The essential fabrication processes based on XeF2 isotropic silicon etching and parylene conformal deposition are covered in detail, and a set of characterization is summarized

Exploring novel, minimally invasive, multi-modal bronchoscopic biopsy tools and techniques using radial endobronchial ultrasound and the guide sheath to improve the diagnostic yield of peripheral pulmonary lesions suspected of lung cancer

Peripheral pulmonary lesions (PPL) suspected of lung cancer require a safe, high-yield diagnostic biopsy with concurrent mediastinal staging to reduce treatment delays. Emerging lung cancer screening programmes amplify this need. Radial EBUS is a safe bronchoscopy biopsy method for PPL, but the diagnostic yield is low. This thesis hypothesised that it was possible to improve the yield with novel biopsy tools and techniques. Four multi-centre interventional studies were performed. The novel biopsy tools (cryobiopsy and GenCut tool) were examined, and existing biopsy tools (guide sheath and aspiration needle) were optimised and combined as a multi-modal biopsy. This thesis consists of the first published head-to-head comparison of multi-modal Cryo-Radial biopsy against percutaneous CT-guided biopsy (CT-TTB) for PPL: a study compromised by slow recruitment that resulted in its early termination. Available data showed a modestly lower diagnostic yield than CT-TTB, but significantly fewer critical adverse events, pneumothorax, or haemorrhage. Bronchoscopic cryobiopsy was introduced to tertiary hospitals in New Zealand, for the first time, through this study in 2015 with relevant safety precautions. To cater for centres where cryobiopsy was not widely available but a core tissue sample was required, a novel GenCut tool was explored as an alternative suitable for sedation bronchoscopy. A multi-modal biopsy approach, rather than reliance on forceps alone, improved the diagnostic yield with adequate tissue obtained for critical molecular testing. This concept of multi-modal biopsy was not reported in Radial EBUS literature at the time of these studies in 2015. The addition of these safe diagnostic techniques will allow rapid, personalised diagnostic pathways for patients with suspected lung cancer

Biomechanics of a parasitic wasp ovipositor : Probing for answers

Insects such as mosquitoes, true bugs, and parasitic wasps, probe for resources hidden in various substrates. The resources are often, located deep within the substrate and can only be reached with long and thin (slender) probes. Such probes can, however, easily bend or break (buckle) when pushed inside the substrate, which makes probing a challenging task. Nevertheless, the mentioned insects use their probes repeatedly throughout their lifetime without apparent damage. Furthermore, the probes are also used for sensing the targets, can be steered during insertion, and can transport both fluids (e.g. blood, phloem sap) and eggs. Insect probes seem highly versatile structures that satisfy many functional requirements, including buckling avoidance, steering, sensing, and transport. Similar requirements also hold for minimally invasive medical procedures, where slender tools are used to minimize damage to the patient. Understanding the probing process in insects can bring insights in the insect ecology and evolution and it may also help in the development of novel surgical tools. In this thesis, I focus on the mechanical and motor adaptations of insect probing, while other aspects are only briefly discussed. In chapter 2, we review the literature on the probing structures and their operating principles across mosquitoes, parasitic wasps, and hemipterans. Probes are either modified mouthparts (mosquitoes, true bugs) or special tubular outgrowths of the abdomen (parasitic wasps). Despite having different developmental origins, the probes share three major morphological characteristics, which may reflect the shared functional requirements of buckling avoidance and steering: (i) the probes consist of multiple, interconnected elements that can slide along each other, (ii) the probe diameters are very small, which leaves no space for internal musculature, and (iii) the distal ends (tips) of the probe elements are asymmetric and often bear various serrations, hooks, bulges, or notches. How such slender multi-element probes avoid buckling during insertion has been hypothesized in the so-called push–pull mechanism. According to this mechanism, the probe is inserted into the substrate by reciprocal movements of the elements. The insects therefore simultaneously push on some of the probe elements, while pulling on the others. The tip serrations are directed such, that they primarily increase the friction upon pulling of the elements. This puts the pulled elements under tension and makes them effectively stiffer in bending (like when pulling a rope). The elements under tension can serve as guides along which the other elements are pushed inside the substrate without the risk of buckling. The insect alternates the pushing and pulling between the elements to incrementally insert the probe in the substrate. This mechanism has, however, never been quantified in insects and it was hitherto unknown whether the animals rely on it during probing. The probe tip asymmetry presumably facilitates steering. The asymmetric tip geometry leads to asymmetric reaction forces from the substrate on the tip during insertion, which push the probe tip sideways into a curved path. Controlling the tip geometry therefore allows for control of probing direction. Although offsetting the elements by sliding already changes the shape of the probe tip, these changes might be too small to induce the necessary change of probing direction. A number of mechanisms that enhance the tip asymmetry during the sliding of the elements have been suggested. However, few mechanisms have been observed or studied in vivo, so it is not completely clear how insects steer with their probes. Additionally, the effect of the substrate on both the steering and insertion mechanisms is unknown. To understand the biomechanics of insect probing, we investigated the probing behaviour of the braconid parasitic wasp Diachasmimorpha longicaudata. This is an ideal species for studying the buckling avoidance and steering, because it: (i) possess a slender ovipositor several millimetres in length, (ii) probes into solid material (e.g. citrus fruits), and (iii) attack fruit-fly larvae that are freely moving within the substrate (i.e. steering can be expected). The ovipositor of D. longicaudata is similar to other hymenopterans and consists of three interconnected elements (valves), one dorsal and two ventral ones. The interconnection is a tongue-and-groove mechanism, which allows for sliding of the valves, but prevents their separation. The ovipositor has an asymmetric tip—the distal end of the dorsal valve is enlarged (bulge), while the ventral valve tips have harpoon-like serrations. Additionally, just proximal to the bulge of the dorsal valve, the ovipositor is characteristically bent in an S-shape. This seems to be a feature present only in D. longicaudata and closely related species. The wasps also possess a pair of sheaths that envelop the ovipositor at rest and throughout most of the probing process, but do not penetrate into the substrate. In chapter 3, we studied the kinematics of ovipositor insertion into translucent, artificial substrates of various stiffnesses. Ovipositor insertion was filmed in a three camera setup, which allowed us to reconstruct the ovipositor insertion in 3D, while also monitoring the orientation of the insect’s body. We discovered that the wasps can explore a wide range of the substrate by probing in any direction with respect to their body orientation from a single puncture point. Probing range and speed decreased with increasing substrate stiffness. Wasps used two strategies of ovipositor insertion. In soft substrates, all ovipositor valves were pushed inside the substrate at the same time. In stiff substrates, wasps always moved the valves alternatively, presumably employing the hypothesized push–pull mechanism. We observed that ovipositors can follow curved trajectories inside the substrate. Detailed kinematic analysis revealed that the ovipositors followed a curved path during probing with protracted ventral valve(s). In contrast, probing with protracted dorsal valve resulted in straight trajectories. We linked the changes in the probing direction to the shape changes in the ovipositor tip. When the ventral valves were protracted, they curved towards the dorsal valve, resulting in an enhanced bevel which presumably caused a change in insertion direction. In chapter 4, we investigated the above described steering mechanism by quantifying the bending stiffness (three point bend test) and the geometry (high-resolution computer tomography) of the ovipositor in D. longicaudata. Additionally, we qualitatively assessed the material composition of the valves using fluorescence imaging. The thick dorsal valve bulge might be stiff and could straighten the S-shaped region of the ovipositor during the valve offset, causing bending of the tip. We discovered that the S-shaped region of the ovipositor is significantly softer than its neighbouring regions, which is mostly due to the presence of resilin in the S-shaped region of the ventral valve. Resilin is a rubber-like protein and reduces the stiffness of the otherwise heavily sclerotized valves. Additionally, we showed that the ventral valves have a higher bending stiffness than the dorsal valve along most of their length. The exception is presumably the bulge on the dorsal valve—although we could not directly measure its bending stiffness, its geometrical properties show that it is the thickest (and therefore stiffest) region in the distal end of the ovipositor. Outside the substrate, offsetting of the valves in any direction (i.e. pro- or retraction of the ventral valves) caused a straightening of the S-shaped region of the ovipositor and a curving towards the dorsal side. However, during probing in a substrate, such curving was only observed upon protraction of the ventral valves. We hypothesize this is due to the interaction of the ovipositor with the substrate. Namely, the bevelled ventral valve tips generate substrate reaction forces that promote dorsal curving, while the bevelled tip of the dorsal valve generates substrate forces that promote ventral bending. The interaction between the ventral and dorsal valves straightens the S-shaped region of the ovipositor and enhances dorsal curving. This therefore facilitates strong shape changes of the tip only upon protraction of the ventral valves, while counteracting the ventral curving of the dorsal valve. These opposing mechanisms presumably result in an approximately straight protraction of the dorsal valve. In chapters 2 and 3 we describe how the wasps use the reciprocal valve movements when probing in stiff substrates. As such substrates presumably require strong forces during insertion, the reciprocal valve movements may indeed serve to avoid buckling. However, how the valves are actuated or the forces generated during probing have never been quantified. In chapter 5, we therefore investigated the ovipositor base and the muscles driving the movements of the valves. At the base, the valves attach to plate-like structures that are interconnected with a series of linkages. The muscles attach to these plates and can move them with respect to each other. Such movements also result in the movements of the valves. To analyse the mechanics of this linked system, we performed high-resolution computer tomography scans of wasps in different stages of the probing cycle. This allowed us to compare the configurational changes of the basal plates to the valve offset, and measure the muscle cross-sections and attachment sites. We also calculated the muscle moment arms and estimated the forces and moments of the most relevant musculature actuating the ovipositor movements, by assuming a tensile muscle stress previously reported for insect muscles. For the ventral valves only, we also calculated the forces the valves can exert onto the substrate. The dorsal valve can only be moved by moving the base that is linked inside the abdomen, and therefore force estimation could not be made. The displacement magnitude of the basal plates corresponded to the valve offset, indicating that the valves are indeed moved due to the changes in the arrangement of the basal plates. We also showed that the ventral valve plates move most during the probing cycle, while the magnitude of the dorsal valve plate movements is much smaller. This suggests that the ventral valves move along the dorsal valve, while the dorsal valve moves together with the abdomen during probing. Additionally, in the situation where the animal keeps its abdomen stationary, we estimated the maximal forces actuating the ventral valves. The estimated maximal pushing forces can be higher than the estimated buckling load of the unsupported ovipositor outside the substrate. Assuming the maximal pushing forces are required during probing, antibuckling mechanisms are needed to avoid damaging the ovipositor. Buckling can be limited (prevented) by either supporting the ovipositor outside the substrate with additional sheaths, employing the push–pull mechanism, or both. Subtracting the maximal estimated pushing and pulling forces on the ventral valves, results in a net pushing force that is very close to the buckling threshold of the ovipositor, albeit still slightly higher. The sheaths, although being flexible, might provide the additional support if needed. In this thesis, I show that multi-element probes are inserted into the substrate using reciprocal movements of the individual elements. These movements appear to be necessary in stiff substrates, which presumably require high pushing forces on a single element during probing. This is in accordance with the hypothesis that reciprocal valve movements serve as an anti-buckling mechanism. Additionally, such valve movements are also important for steering of the probe during insertion. The valve offset controls the shape of the probe tip and therefore the net substrate reaction forces that result in bending of the probe. Wasps evolved special structures that enhance the shape changes of their ovipositor tips and facilitate steering. Our findings may be interesting for a broad range of audiences. Entomologists, evolutionary biologists, and ecologists may find them useful when studying the diversification of probing insects, their evolutionary success, or their ecological interactions (e.g. insect–plant, parasite–host). The anti-buckling and steering mechanisms may be helpful when developing novel, man-made probes. These mechanisms allow for minimization of the probe thickness and accurate steering control, which minimizes substrate damage during probing. Our findings may be particularly useful in the development of slender, steerable needles for minimally invasive surgery.</p

Stents for transcatheter aortic valve replacement

Rheumatic heart disease (RHD) is the leading cause of aortic valve disease in the world. Surgery to repair or replace the diseased valves is the only means to save a patient's life once the disease becomes symptomatic. Transcatheter aortic valve replacement (TAVR) has revolutionised the treatment of age-related degenerative aortic valve disease, but is currently not suitable for the majority of RHD sufferers due to the rapid degeneration of flexible leaflet valves in younger patients, contraindications of commercial devices to regurgitant or non-calcific aortic valve disease, and also due to resource or funding limitations. The current research project aimed to develop and test novel compressible balloon-expandable stents suitable for patients with symptomatic rheumatic aortic valve disease, and which would allow for a percutaneous polymeric valve to be manufactured, be crimped onto balloon-based devices, and be expanded into a compliant or non-calcific native aortic valve. Several stent concepts were developed and evaluated using Finite Element Analysis (FEA) and two favoured concepts were selected for more complex FEA, in which the balloon was simulated using an Ogden material model, and rigorous testing. The stent material, a nickel-cobalt-chromium alloy, was modelled as an isotropic elasto-plastic material with isotropic hardening. The novel stent designs incorporated a native leaflet-mimicking crown shape for continuous leaflet attachment and mechanisms to anchor the stented valve within compliant aortic roots. The first of the favoured designs provided tactile location during delivery and anchored using self-expanding arms on a balloon-expandable frame of the same material ("self-locating stents"). The second design anchored using arms that protruded during deployment as a consequence of plastic deformation incurred during crimping ("expanding arm stents"). Prototypes were successfully manufactured through laser cutting and electropolishing and showed good surface quality. In vitro testing included determination of crimping and expansion behaviour and measurement of mechanical properties such as resistance to migration in the anatomy. Valve performance was evaluated through in vitro haemodynamics in a pulse duplicator and durability was tested in a high-cycle fatigue tester. Simulated use testing was performed using cadaveric animal hearts. Finally, valves were also implanted into the aortic valve position of pigs (in acute termination experiments) through a transapical approach in order to verify valve deployment behaviour and function in vivo, and determine the stent's ability to anchor in the native anatomy. Stents could be crimped to diameters below 6mm and deployed using commercial balloons and proprietary non-occlusive deployment devices. FEA simulations of stent crimping and deployment matched experimental behaviour well and provide a tool to optimise stent performance. Peak Von Mises stresses during deployment (1437 MPa and 1633 MPa for self-locating and expanding arm stents, respectively) were comparable to a "zig-zag" stent simulated for control purposes (1650 MPa). Radial strength, evaluated for expanding arm stents, was lower than the Control stent (116 N vs. 347 N). This design, although predicted to be safe under fatigue loading, had a lower fatigue safety factor than the Control stent. Stents resisted migration to forces of at least 22 N, which is four times greater than physiological loading on the valves. Polymeric valves incorporating the stents were constructed and demonstrated good in vitro haemodynamic performance (Effective Orifice Areas ≥2.0cm², ΔP<9 mmHg, regurgitation <6%) and durability of over 400 million cycles. Designs functioned as intended in simulated use tests. Valves constructed using self-locating stents could be successfully deployed without rapid pacing in eight of nine pigs, and valve position was correct in seven of these. Valves of expanding arm stents remained anchored in six of eight attempted implants in pigs. This study has demonstrated proof of concept for a novel balloon-expandable stent for a polymeric transcatheter heart valve that is capable of anchoring in a compliant native aortic valve

Endoscopy

Endoscopy is a fast moving field, and new techniques are continuously emerging. In recent decades, endoscopy has evolved and branched out from a diagnostic modality to enhanced video and computer assisting imaging with impressive interventional capabilities. The modern endoscopy has seen advances not only in types of endoscopes available, but also in types of interventions amenable to the endoscopic approach. To date, there are a lot more developments that are being trialed. Modern endoscopic equipment provides physicians with the benefit of many technical advances. Endoscopy is an effective and safe procedure even in special populations including pediatric patients and renal transplant patients. It serves as the tool for diagnosis and therapeutic interventions of many organs including gastrointestinal tract, head and neck, urinary tract and others

Force-Sensing-Based Multi-Platform Robotic Assistance for Vitreoretinal Surgery

Vitreoretinal surgery aims to treat disorders of the retina, vitreous body, and macula, such as retinal detachment, diabetic retinopathy, macular hole, epiretinal membrane and retinal vein occlusion. Challenged by several technical and human limitations, vitreoretinal practice currently ranks amongst the most demanding fields in ophthalmic surgery. Of vitreoretinal procedures, membrane peeling is the most common to be performed, over 0.5 million times annually, and among the most prone to complications. It requires an extremely delicate tissue manipulation by various micron scale maneuvers near the retina despite the physiological hand tremor of the operator. In addition, to avoid injuries, the applied forces on the retina need to be kept at a very fine level, which is often well below the tactile sensory threshold of the surgeon. Retinal vein cannulation is another demanding procedure where therapeutic agents are injected into occluded retinal veins. The feasibility of this treatment is limited due to challenges in identifying the moment of venous puncture, achieving cannulation and maintaining it throughout the drug delivery period. Recent advancements in medical robotics have significant potential to address most of the challenges in vitreoretinal practice, and therefore to prevent traumas, lessen complications, minimize intra-operative surgeon effort, maximize surgeon comfort, and promote patient safety. This dissertation presents the development of novel force-sensing tools that can easily be used on various robotic platforms, and robot control methods to produce integrated assistive surgical systems that work in partnership with surgeons against the current limitations in vitreoretinal surgery, specifically focusing on membrane peeling and vein cannulation procedures. Integrating high sensitivity force sensing into the ophthalmic instruments enables precise quantitative monitoring of applied forces. Auditory feedback based upon the measured forces can inform (and warn) the surgeon quickly during the surgery and help prevent injury due to excessive forces. Using these tools on a robotic platform can attenuate hand tremor of the surgeon, which effectively promotes tool manipulation accuracy. In addition, based upon certain force signatures, the robotic system can precisely identify critical instants, such as the venous puncture in retinal vein cannulation, and actively guide the tool towards clinical targets, compensate any involuntary motion of the surgeon, or generate additional motion that will make the surgical task easier. The experimental results using two distinct robotic platforms, the Steady-Hand Eye Robot and Micron, in combination with the force-sensing ophthalmic instruments, show significant performance improvement in artificial dry phantoms and ex vivo biological tissues