Mechanical Manipulation and Characterization of Biological Cells

Mechanical manipulation and characterization of an individual biological cell is currently one of the most exciting research areas in the field of medical robotics. Single cell manipulation is an important process in intracytoplasmic sperm injection (ICSI), pro-nuclei DNA injection, gene therapy, and other biomedical areas. However, conventional cell manipulation requires long training and the success rate depends on the experience of the operator. The goal of this research is to address the drawbacks of conventional cell manipulation by using force and vision feedback for cell manipulation tasks. We hypothesize that force feedback plays an important role in cell manipulation and possibly helps in cell characterization. This dissertation will summarize our research on: 1) the development of force and vision feedback interface for cell manipulation, 2) human subject studies to evaluate the addition of force feedback for cell injection tasks, 3) the development of haptics-enabled atomic force microscope system for cell indentation tasks, 4) appropriate analytical model for characterizing the mechanical property of mouse embryonic stem cells (mESC) and 5) several indentation studies on mESC to determine the mechanical property of undifferentiated and early differentiating (6 days under differentiation conditions) mESC. Our experimental results on zebrafish egg cells show that a system with force feedback capability when combined with vision feedback can lead to potentially higher success rates in cell injection tasks. Using this information, we performed experiments on mESC using the AFM to understand their characteristics in the undifferentiated pluripotent state as well as early differentiating state. These experiments were done on both live as well as fixed cells to understand the correlation between the two during cell indentation studies. Our results show that the mechanical property of undifferentiated mESC differs from early differentiating (6th day) mESC in both live and fixed cells. Thus, we hypothesize that mechanical characterization studies will potentially pave the way for developing a high throughput system with force feedback capability, to understand and predict the differentiation path a particular pluripotent cell will follow. This finding could also be used to develop improved methods of targeted cellular differentiation of stem cells for therapeutic and regenerative medicine

The Shape of Damping: Optimizing Damping Coefficients to Improve Transparency on Bilateral Telemanipulation

This thesis presents a novel optimization-based passivity control algorithm for hapticenabled bilateral teleoperation systems involving multiple degrees of freedom. In particular, in the context of energy-bounding control, the contribution focuses on the implementation of a passivity layer for an existing time-domain scheme, ensuring optimal transparency of the interaction along subsets of the environment space which are preponderant for the given task, while preserving the energy bounds required for passivity. The involved optimization problem is convex and amenable to real-time implementation. The effectiveness of the proposed design is validated via an experiment performed on a virtual teleoperated environment. The interplay between transparency and stability is a critical aspect in haptic-enabled bilateral teleoperation control. While it is important to present the user with the true impedance of the environment, destabilizing factors such as time delays, stiff environments, and a relaxed grasp on the master device may compromise the stability and safety of the system. Passivity has been exploited as one of the the main tools for providing sufficient conditions for stable teleoperation in several controller design approaches, such as the scattering algorithm, timedomain passivity control, energy bounding algorithm, and passive set position modulation. In this work it is presented an innovative energy-based approach, which builds upon existing time-domain passivity controllers, improving and extending their effectiveness and functionality. The set of damping coefficients are prioritized in each degree of freedom, the resulting transparency presents a realistic force feedback in comparison to the other directions. Thus, the prioritization takes effect using a quadratic programming algorithm to find the optimal values for the damping. Finally, the energy tanks approach on passivity control is a solution used to ensure stability in a system for robotics bilateral manipulation. The bilateral telemanipulation must maintain the principle of passivity in all moments to preserve the system\u2019s stability. This work presents a brief introduction to haptic devices as a master component on the telemanipulation chain; the end effector in the slave side is a representation of an interactive object within an environment having a force sensor as feedback signal. The whole interface is designed into a cross-platform framework named ROS, where the user interacts with the system. Experimental results are presented

Development of novel high-performance six-axis magnetically levitated instruments for nanoscale applications

This dissertation presents two novel 6-axis magnetic-levitation (maglev) stages that are capable of nanoscale positioning. These stages have very simple and compact structure that is advantageous to meet requirements in the next-generation nanomanufacturing. The 6-axis motion generation is accomplished by the minimum number of actuators and sensors. The first-generation maglev stage is capable of generating translation of 300 ??m in x, y and z, and rotation of 3 mrad about the three orthogonal axes. The stage demonstrates position resolution better than 5 nm rms and position noise less than 2 nm rms. It has a light moving-part mass of 0.2126 kg. The total power consumption by all the actuators is only around a watt. Experimental results show that the stage can carry, orient, and precisely position an additional payload as heavy as 0.3 kg. The second-generation maglev stage is capable of positioning at the resolution of a few nanometers over a planar travel range of several millimeters. A novel actuation scheme was developed for the compact design of this stage that enables 6-axis force generation with just 3permanent-magnet pieces. Electromagnetic forces were calculated and experimentally verified. The complete design and construction of the second-generation maglev stage was performed. All the mechanical part and assembly fixtures were designed and fabricated at the mechanical engineering machine shop. The single moving part is modeled as a pure mass due to the negligible effect of the magnetic spring and damping. Classical as well as advanced controllers were designed and implemented for closed-loop feedback control. A nonlinear model of the force was developed and applied to cancel the nonlinearity of the actuators over the large travel range. Various experiments were conducted to test positioning, loading, and vibration-isolation capabilities. This maglev stage has a moving-part mass of 0.267 kg. Its position resolution is 4 nm over a travel range of 5 ?? 5 mm in the x-y plane. Its actuators are designed to carry and precisely position an additional payload of 2 kg. Its potential applications include semiconductor manufacturing, micro-fabrication and assembly, nanoscale profiling, and nano-indentation

Contribution au micro-actionnement multi-stable piloté par radiations optiques

In this work, a bistable mechanism based on antagonistic pre-shaped double beams was proposed. Employing the proposed bistable mechanism, a quadristable micro-actuator was designed. ln order to validate the quadristability of the device, a meso-scaled prototype was fabricated from MDF by laser cutting. After the quadristability was experimentally confirmed, a quadristable micro-actuator was realized on SOl wafer using DRIE technique. Strokes for inner row and outer row were reduced to 300 µm and 200 µm respectively. For the actuation of the quadristable micro-actuator,laser heated SMA elements with deposited Si02 layer were used to realize the optical wireless actuation. With the help of a laser beam steering micro-mirror, both inner row and outer row were successfully actuated. ln order to further reduce the stroke, a bistable actuator with stroke reducing structure was designed and a prototype eut from MDF was tested. Bistability was validated and a stroke of 1µm was experimentally achieved. Based on this bistable module, a multistable nano-actuator, which contains four parallel coupled bistable modules,was designed and simulated. The simulated result have indicated that it was capable of outputs 16 discrete stable positions available from 0 nm to 150 nm with a step of 10 nm between two stable positions.Cette thèse traite le sujet du micro-actionnement multistable employant des radiations optiques pour atteindre les différentes positions offertes par le micro-actionneur. Dans le cadre des travaux réalisés, un mécanisme bistable reposant sur un principe de doubles poutres préformées situées en position antagoniste est proposé, et, sur cette brique élémentaire, un micro-actionneur quadristable a été conçu. Afin de valider le principe de fonctionnement de micro-actionneur, des procédés de fabrication Laser (sur le matériau « médium - MDF») puis DRIE (sur un wafer SOI de silicium) ont été utilisés. Sur le prototype en silicium, permettant une réduction des courses du rang interne et du rang externe du micro-actionneur, celles-ci ont été fixées à 300 µm et 200 µm respectivement. L’actionnement à distance de ce micro-actionneur a été prouvé en utilisant le chauffage laser d’un élément actif en Nitinol structuré par un dépôt de SiO2, ceci générant un effet « deux sens » de l’élément actif permettant d’annuler la charge sur les poutres du micro-actionneur une fois celui-ci déclenché puis en position stable. L’utilisation d’un banc expérimental incluant une membrane MEMS de balayage laser a permis de démontrer la quadristabilité du micro-actionneur sur 90 000 cycles. Afin de réduire davantage la course de ce micro-actionneur, des concepts de dispositifs de réduction de course ont été développés pour démontrer, à partir de prototypes fabriqué en MDF par usinage laser, la capacité à atteindre une course de 1 µm. Enfin, à la suite de ces travaux de réduction de course, un concept de nano-actionneur multistable a été proposé. Ce nano-actionneur est composé de quatre modules bistables liés et disposés en parallèle pour offrir 16 positions discrètes sur une course rectiligne. Les simulations de cet actionneur montrent la possibilité d’atteindre les 15 positions espacées de 10 nm sur une course de 150 nm