Microdevices and Microsystems for Cell Manipulation

Microfabricated devices and systems capable of micromanipulation are well-suited for the manipulation of cells. These technologies are capable of a variety of functions, including cell trapping, cell sorting, cell culturing, and cell surgery, often at single-cell or sub-cellular resolution. These functionalities are achieved through a variety of mechanisms, including mechanical, electrical, magnetic, optical, and thermal forces. The operations that these microdevices and microsystems enable are relevant to many areas of biomedical research, including tissue engineering, cellular therapeutics, drug discovery, and diagnostics. This Special Issue will highlight recent advances in the field of cellular manipulation. Technologies capable of parallel single-cell manipulation are of special interest

Study of Speed and Force in Biomanipulation

Ph.DDOCTOR OF PHILOSOPH

Cooperative Manipulation using a Magnetically Navigated Microrobot and a Micromanipulator

The cooperative manipulation of a common object using two or more manipulators is a popular research field in both industry and institutions. Different types of manipulators are used in cooperative manipulation for carrying heavy loads and delicate operations. Their applications range from macro to micro. In this thesis, we are interested in the development of a novel cooperative manipulator for manipulation tasks in a small workspace. The resultant cooperative manipulation system consists of a magnetically navigated microrobot (MNM) and a motorized micromanipulator (MM). The MNM is a small cylinder permanent magnet with 10mm diameter and 10mm height. The MM model is MP-285 which is a commercialized product. Here, the MNM is remotely controlled by an external magnetic field. The property of non-contact manipulation makes it a suitable choice for manipulation in a confined space. The cooperative manipulation system in this thesis used a master/slave mechanism as the central control strategy. The MM is the master side. The MNM is the slave side. During the manipulation process, the master manipulator MM is always position controlled, and it leads the object translation according to the kinematic constraints of the cooperative manipulation task. The MNM is position controlled at the beginning of the manipulation. In the translation stage, the MNM is switched to force control to maintain a successful holding of the object, and at the same time to prevent damaging the object by large holding force. Under the force control mode, the motion command to the MNM is calculated from a position-based impedance controller that enforces a relationship between the position of the MNM and the force. In this research, the accurate motion control of both manipulators are firstly studied before the cooperative manipulation is conducted. For the magnetic navigation system, the magnetic field in its workspace is modeled using an experimental measurement data-driven technique. The developed model is then used to develop a motion controller for navigating of a small cylindrical permanent magnet. The accuracy of motion control is reached at 20 µm in three degrees of freedom. For the motorized micromanipulator, a standard PID controller is designed to control its motion stage. The accuracy of the MM navigation is 0.8 µm. Since the MNM is remotely manipulated by an external magnetic field in a small space, it is challenging to install an on-board force sensor to measure the contact force between the MNM and the object. Therefore, a dual-axial o_-board force determination mechanism is proposed. The force is determined according to the linear relation between the minimum magnetic potential energy point and the real position of the MNM in the workspace. For convenience, the minimum magnetic potential energy point is defined as the Bmax in the literature. In this thesis, the dual-axial Bmax position is determined by measuring the magnetic ux density passing through the workspace using four Hall-effect sensors installed at the bottom of an iron pole-piece. The force model is experimentally validated in a horizontal plane with an accuracy of 2 µN in the x- and y- direction of horizontal planes. The proposed cooperative manipulator is then used to translate a hard-shell small object in two directions of a vertical plane, while one direction is constrained with a desired holding force. During the manipulation process, a digital camera is used to capture the real-time position of the MNM, the MM end-effector, and the manipulated object. To improve the performance of force control on the MNM, the proposed dual-axial force model is used to examine the compliant force control of the MNM while it is navigated to contact with uncertain environments. Here, uncertain refers to unknown environmental stiffness. An adaptive position-based impedance controller is implemented to estimate the stiffness of the environment and the contact force. The controller is examined by navigating the MNM to push a thin aluminum beam whose stiffness is unknown. The studied cooperative manipulation system has potential applications in biomedical microsurgery and microinjection. It should be clarified that the current system setup with 10mm ×10 mm MNM is not proper for this micromanipulation. In order to conduct research on microinjection, the size of the MNM and the end-effector of the MNM should be down-scaled to micrometers. In addition, the navigation accuracy of the MNM should also be improved to adopt the micromanipulation tasks

Image-Guided Robot-Assisted Techniques with Applications in Minimally Invasive Therapy and Cell Biology

There are several situations where tasks can be performed better robotically rather than manually. Among these are situations (a) where high accuracy and robustness are required, (b) where difficult or hazardous working conditions exist, and (c) where very large or very small motions or forces are involved. Recent advances in technology have resulted in smaller size robots with higher accuracy and reliability. As a result, robotics is fi nding more and more applications in Biomedical Engineering. Medical Robotics and Cell Micro-Manipulation are two of these applications involving interaction with delicate living organs at very di fferent scales.Availability of a wide range of imaging modalities from ultrasound and X-ray fluoroscopy to high magni cation optical microscopes, makes it possible to use imaging as a powerful means to guide and control robot manipulators. This thesis includes three parts focusing on three applications of Image-Guided Robotics in biomedical engineering, including: Vascular Catheterization: a robotic system was developed to insert a catheter through the vasculature and guide it to a desired point via visual servoing. The system provides shared control with the operator to perform a task semi-automatically or through master-slave control. The system provides control of a catheter tip with high accuracy while reducing X-ray exposure to the clinicians and providing a more ergonomic situation for the cardiologists. Cardiac Catheterization: a master-slave robotic system was developed to perform accurate control of a steerable catheter to touch and ablate faulty regions on the inner walls of a beating heart in order to treat arrhythmia. The system facilitates touching and making contact with a target point in a beating heart chamber through master-slave control with coordinated visual feedback. Live Neuron Micro-Manipulation: a microscope image-guided robotic system was developed to provide shared control over multiple micro-manipulators to touch cell membranes in order to perform patch clamp electrophysiology. Image-guided robot-assisted techniques with master-slave control were implemented for each case to provide shared control between a human operator and a robot. The results show increased accuracy and reduced operation time in all three cases

The classification and new trends of shared control strategies in telerobotic systems: A survey

Shared control, which permits a human operator and an autonomous controller to share the control of a telerobotic system, can reduce the operator's workload and/or improve performances during the execution of tasks. Due to the great benefits of combining the human intelligence with the higher power/precision abilities of robots, the shared control architecture occupies a wide spectrum among telerobotic systems. Although various shared control strategies have been proposed, a systematic overview to tease out the relation among different strategies is still absent. This survey, therefore, aims to provide a big picture for existing shared control strategies. To achieve this, we propose a categorization method and classify the shared control strategies into 3 categories: Semi-Autonomous control (SAC), State-Guidance Shared Control (SGSC), and State-Fusion Shared Control (SFSC), according to the different sharing ways between human operators and autonomous controllers. The typical scenarios in using each category are listed and the advantages/disadvantages and open issues of each category are discussed. Then, based on the overview of the existing strategies, new trends in shared control strategies, including the “autonomy from learning” and the “autonomy-levels adaptation,” are summarized and discussed

Cognitive Reasoning for Compliant Robot Manipulation

Physically compliant contact is a major element for many tasks in everyday environments. A universal service robot that is utilized to collect leaves in a park, polish a workpiece, or clean solar panels requires the cognition and manipulation capabilities to facilitate such compliant interaction. Evolution equipped humans with advanced mental abilities to envision physical contact situations and their resulting outcome, dexterous motor skills to perform the actions accordingly, as well as a sense of quality to rate the outcome of the task. In order to achieve human-like performance, a robot must provide the necessary methods to represent, plan, execute, and interpret compliant manipulation tasks. This dissertation covers those four steps of reasoning in the concept of intelligent physical compliance. The contributions advance the capabilities of service robots by combining artificial intelligence reasoning methods and control strategies for compliant manipulation. A classification of manipulation tasks is conducted to identify the central research questions of the addressed topic. Novel representations are derived to describe the properties of physical interaction. Special attention is given to wiping tasks which are predominant in everyday environments. It is investigated how symbolic task descriptions can be translated into meaningful robot commands. A particle distribution model is used to plan goal-oriented wiping actions and predict the quality according to the anticipated result. The planned tool motions are converted into the joint space of the humanoid robot Rollin' Justin to perform the tasks in the real world. In order to execute the motions in a physically compliant fashion, a hierarchical whole-body impedance controller is integrated into the framework. The controller is automatically parameterized with respect to the requirements of the particular task. Haptic feedback is utilized to infer contact and interpret the performance semantically. Finally, the robot is able to compensate for possible disturbances as it plans additional recovery motions while effectively closing the cognitive control loop. Among others, the developed concept is applied in an actual space robotics mission, in which an astronaut aboard the International Space Station (ISS) commands Rollin' Justin to maintain a Martian solar panel farm in a mock-up environment. This application demonstrates the far-reaching impact of the proposed approach and the associated opportunities that emerge with the availability of cognition-enabled service robots

Force-controlled Biomanipulation for Biological Cell Mechanics Studies

Ph.DDOCTOR OF PHILOSOPH

Ultrasound-Guided Mechatronic System for Targeted Delivery of Cell-Based Cancer Vaccine Immunotherapy in Preclinical Models

Injection of dendritic cell (DC) vaccines into lymph nodes (LN) is a promising strategy for eliciting immune responses against cancer, but these injections in mouse cancer models are challenging due to the small target scale (~ 1 mm × 2 mm). Direct manual intranodal injection is difficult and can cause architectural damage to the LN, potentially disrupting crucial interactions between DC and T cells. Therefore, a second-generation ultrasound-guided mechatronic device has been developed to perform this intervention. A targeting accuracy of \u3c 500 μm will enable targeted delivery of the DCs specifically to a LN subcapsular space. The device was redesigned from its original CT-guided edition, which used a remote centre of motion architecture, to be easily integrated onto a commercially available VisualSonics imaging rail system. Subtle modifications were made to ensure simple workflow that allows for live-animal interventions that fall within the knockout periods stated in study protocols. Several calibration and registration techniques were developed in order to achieve an overall targeting accuracy appropriate for the intended application. A variety of methods to quantify the positioning accuracy of the device were investigated. The method chosen involved validating a guided injection into a tissue-mimicking phantom using ultrasound imaging post-operatively to localize the end-point position of the needle tip in the track left behind by the needle. Ultrasound-guided injections into a tissue-mimicking phantom revealed a targeting accuracy of 285 ± 94 μm for the developed robot compared to 508 ± 166 μm for a commercial-available manually-actuated injection device from VisuailSonics. The utility of the robot was also demonstrated by performing in vivo injections into the lymph nodes of mice

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 403)

This bibliography lists 217 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during July 1995. Subject coverage includes: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance