Modeling and simulation of an active robotic device for flexible needle insertion

Master'sMASTER OF ENGINEERIN

Prediction Control for Brachytherapy Robotic System

In contemporary brachytherapy procedure, needle placement at desired location is challenging due to a variety of reasons. We have designed and fabricated an image-guided robot-assisted brachytherapy system to improve the needle placement and seed delivery. In this article we have used two different predictive control strategies in order to investigate the needle insertion efficacy and system dynamics during prostate brachytherapy. First, we used neural network predictive control (NNPC) to predict an insertion force. The NNPC uses the linearized state-space model of the robotic system to predict future system performances. Second, we used feedforward model predictive control (MPC) which allows the controller to compensate the influence of a measured disturbance's impact immediately rather than waiting until the effect appears in the system. Feedback control problem for the contact force regulation is considered. The simulation results and experiments for both cases are presented and compared

Research on real-time physics-based deformation for haptic-enabled medical simulation

This study developed a multiple effective visuo-haptic surgical engine to handle a variety of surgical manipulations in real-time. Soft tissue models are based on biomechanical experiment and continuum mechanics for greater accuracy. Such models will increase the realism of future training systems and the VR/AR/MR implementations for the operating room

<i>Plasmodium </i>Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle

Characterization of soft tissue cutting for haptic display: experiments and computational models

Real-time medical simulation for robotic surgery planning and surgery training requires realistic yet computationally fast models of the mechanical behavior of soft tissue. This work presents a study to develop such a model to enable fast haptics display in simulation of softtissue cutting. An apparatus was developed and experiments were conducted to generate force-displacement data for cutting of soft tissue such as pig liver. The force-displacement curve of cutting pig liver revealed a characteristic pattern: the overall curve is formed by repeating units consisting of a local deformation segment followed by a local crack-growth segment. The modeling effort reported here focused on characterizing the tissue in the local deformation segment for fast haptic display. The deformation resistance of the tissue was quantified in terms of the local effective modulus (LEM) consistent with experimental forcedisplacement data. An algorithm was developed to determine LEM by solving an inverse problem with iterative finite element models. To enable faster simulation of cutting of a threedimensional (3D) liver specimen of naturally varying thickness, three levels of model order reduction were studied. Additionally, the variation of the LEM with cutting speed was determined. The values of LEM decreased as the cutting speed increased. This thesis also includes the characteristic response of soft tissue to the growth of a cut (cracking) with a scalpel blade. The experimentally measured cut-force versus cut-length data was used to determine the soft tissue’s resistance to fracture (resistance to crack extension) in scalpel cutting. The resistance to fracture of the soft tissue is defined as the amount of mechanical work needed to cause a cut (crack) to extend for a unit length in a soft-tissue sample of unit thickness. The equipment, method, and model are applicable for all soft tissue.Finally, the method of determining the property of the pig liver tissue during cutting was verified. Dual C-arm fluoroscopes were used to obtain the motion of the beads embedded inside the specimen during cutting. The experimentally measured displacement field was compared to the displacement field obtained through finite element model based on the LEM values at each localized area.Ph.D., Mechanical Engineering and Mechanics -- Drexel University, 200

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

Investigating the Regulation of Indole-3-Acetic Acid Production By the Plant Associated Microbe \u3ci\u3ePantoea\u3c/i\u3e sp. YR343

The auxin indole-3-acetic acid (IAA) plays a central role in plant growth and development and many plant-associated microbes produce IAA. Several IAA biosynthetic pathways have been identified in microbes which use the precursor tryptophan. Pantoea sp. YR343, which was isolated from the Populus deltoides rhizosphere, is a robust plant root colonizer that produces IAA. Using genomic and metabolomics analyses, we predicted that the indole-3-pyruvate (IPA) pathway is the major pathway in Pantoea sp. YR343 for IAA production. To better understand IAA biosynthesis and the effects of IAA exposure on cell physiology, we performed proteomics on Pantoea sp. YR343 grown in the presence of tryptophan or IAA. These data indicate that indole-3-pyruvate decarboxylase, a major enzyme in the IPA pathway, is upregulated in the presence of both tryptophan and IAA. Moreover, exposure to IAA induced changes in the proteome, including upregulation of proteins predicted to function in carbohydrate and amino acid transport and EPS biosynthesis. Finally, we constructed a mutant in which the ipdC gene was disrupted. The ΔipdC mutant showed a significant decrease in IAA production, but was still able to efficiently colonize poplar, suggesting that microbial IAA production is not required for initiation of plant association