Hybrid optical and magnetic manipulation of microrobots

Microrobotic systems have the potential to provide precise manipulation on cellular level for diagnostics, drug delivery and surgical interventions. These systems vary from tethered to untethered microrobots with sizes below a micrometer to a few microns. However, their main disadvantage is that they do not have the same capabilities in terms of degrees-of-freedom, sensing and control as macroscale robotic systems. In particular, their lack of on-board sensing for pose or force feedback, their control methods and interface for automated or manual user control are limited as well as their geometry has few degrees-of-freedom making three-dimensional manipulation more challenging. This PhD project is on the development of a micromanipulation framework that can be used for single cell analysis using the Optical Tweezers as well as a combination of optical trapping and magnetic actuation for recon gurable microassembly. The focus is on untethered microrobots with sizes up to a few tens of microns that can be used in enclosed environments for ex vivo and in vitro medical applications. The work presented investigates the following aspects of microrobots for single cell analysis: i) The microfabrication procedure and design considerations that are taken into account in order to fabricate components for three-dimensional micromanipulation and microassembly, ii) vision-based methods to provide 6-degree-offreedom position and orientation feedback which is essential for closed-loop control, iii) manual and shared control manipulation methodologies that take into account the user input for multiple microrobot or three-dimensional microstructure manipulation and iv) a methodology for recon gurable microassembly combining the Optical Tweezers with magnetic actuation into a hybrid method of actuation for microassembly.Open Acces

Design and Implementation of Electromagnetic Actuation System to Actuate Micro/NanoRobots in Viscous Environment

The navigation of Micro/Nanorobots (MNRs) with the ability to track a selected trajectory accurately holds significant promise for different applications in biomedicine, providing methods for diagnoses and treatments inside the human body. The critical challenge is ensuring that the required power can be generated within the MNR. Furthermore, ensuring that it is feasible for the robot to travel inside the human body with the necessary power availability. Currently, MNRs are widely driven either by exogenous power sources (light energy, magnetic fields, electric fields, acoustics fields, etc.) or by endogenous energy sources, such as chemical interaction energy. Various driving techniques have been established, including piezoelectric as a driving source, thermal driving, electro-osmotic force driven by biological bacteria, and micro-motors powered by chemical fuel. These driving techniques have some restrictions, mainly when used in biomedicine. External magnetic fields are another potential power source of MNRs. Magnetic fields can permeate deep tissues and be safe for human organisms. As a result, magnetic fields’ magnetic forces and moments can be applied to MNRs without affecting biological fluids and tissues. Due to their features and characteristics of magnetic fields in generating high power, they are naturally suited to control the electromagnetically actuated MNRs in inaccessible locations due to their ability to go through tiny spaces. From the literature, it can be inferred from the available range of actuation technologies that magnetic actuation performs better than other technologies in terms of controllability, speed, flexibility of the working environment, and far less harm may cause to people. Also, electromagnetic actuation systems may come in various configurations that offer many degrees of freedom, different working mediums, and controllability schemes. Although this is a promising field of research, further simulation studies, and analysis, new smart materials, and the development and building of new real systems physically, and testing the concepts under development from different aspects and application requirements are required to determine whether these systems could be implemented in natural clinical settings on the human body. Also, to understand the latest development in MNRs and the actuation techniques with the associated technologies. Also, there is a need to conduct studies and comparisons to conclude the main research achievements in the field, highlight the critical challenges waiting for answers, and develop new research directions to solve and improve the performance. Therefore, this thesis aims to model and analyze, simulate, design, develop, and implement (with complete hardware and software integration) an electromagnetic actuation (EMA) system to actuate MNRs in the sixdimensional (6D) motion space inside a relatively large region of interest (ROI). The second stage is a simulation; simulation and finite element analysis were conducted. COMSOL multi-physics software is used to analyze the performance of different coils and coil pairs for Helmholtz and Maxwell coil configurations and electromagnetic actuation systems. This leads to the following.: • Finite element analysis (FEA) demonstrates that the Helmholtz coils generate a uniform and consistent magnetic field within a targeted ROI, and the Maxwell coils generate a uniform magnetic gradient. • The possibility to combine Helmholtz and Maxwell coils in different space dimensions. With the ability to actuate an MNR in a 6D space: 3D as a position and 3D as orientation. • Different electromagnetic system configurations are proposed, and their effectiveness in guiding an MNR inside a mimicked blood vessel environment was assessed. • Three pairs of Helmholtz coils and three pairs of coils of Maxwell coils are combined to actuate different size MNRs inside a mimicked blood vessel environment and in 6D. Based on the modeling results, a magnetic actuation system prototype that can control different sizes MNRs was conceived. A closed-loop control algorithm was proposed, and motion analysis of the MNR was conducted and discussed for both position and orientation. Improved EMA location tracking along a chosen trajectory was achieved using a PID-based closed-loop control approach with the best possible parameters. Through the model and analysis stage, the developed system was simulated and tested using open- and closed-loop circumstances. Finally, the closedloop controlled system was concluded and simulated to verify the ability of the proposed EMA to actuate an MN under different trajectory tracking examples with different dimensionality and for different sizes of MNRs. The last stage is developing the experimental setup by manufacturing the coils and their base in-house. Drivers and power supplies are selected according to the specifications that actuate the coils to generate the required magnetic field. Three digital microscopes were integrated with the electromagnetic actuation system to deliver visual feedback aiming to track in real-time the location of the MNR in the 6D high viscous fluidic environment, which leads to enabling closed-loop control. The closed-loop control algorithm is developed to facilitate MNR trajectory tracking and minimize the error accordingly. Accordingly, different tests were carried out to check the uniformity of the magnetic field generated from the coils. Also, a test was done for the digital microscope to check that it was calibrated and it works correctly. Experimental tests were conducted in 1D, 2D plane, and 3D trajectories with two different MNR sizes. The results show the ability of the proposed EMA system to actuate the two different sizes with a tracking error of 20-45 µm depending on the axis and the size of the MNR. The experiments show the ability of the developed EMA system to hold the MNR at any point within the 3D fluidic environment while overcoming the gravity effects. A comparison was made between the results achieved (in simulation and physical experiments) and the results deduced from the literature. The comparison shows that the thesis’s outcomes regarding the error and MNR size used are significant, with better performance relative to the MNR size and value of the error

The advancement of blood cell research by optical tweezers

Demonstration of the light radiation pressure on a microscopic level by A. Ashkin led to the invention of optical tweezers (OT). Applied in the studies of living systems, OT have become a preferable instrument for the noninvasive study of microobjects, allowing manipulation and measurement of the mechanical properties of molecules, organelles, and cells. In the present paper, we overview OT applications in hemorheological research, placing emphasis on red blood cells but also discussing OT applications for the investigation of the biomechanics of leukocytes and platelets. Blood properties have always served as a primary parameter in medical diagnostics due to the interconnection with the physiological state of an organism. Despite blood testing being a well-established procedure of conventional medicine, there are still many complex processes that must be unraveled to improve our understanding and contribute to future medicine. OT are advancing single-cell research, promising new insights into individual cell characteristics compared to the traditional approaches. We review the fundamental and practical findings revealed in blood research through the optical manipulation, stretching, guiding, immobilization, and inter-/intracellular force measurements of single blood cells

Light‐Powered Microrobots: Challenges and Opportunities for Hard and Soft Responsive Microswimmers

Worldwide research in microrobotics has exploded in the past two decades, leading to the development of microrobots propelled in various manners. Despite significant advances in the field and successful demonstration of a wide range of applications, microrobots have yet to become the preferred choice outside a laboratory environment. After introducing available microrobotic propulsion and control mechanisms, microrobots that are manufactured and powered by light are focused herein. Referring to pioneering works and recent interesting examples, light is presented not only as a fabrication tool, by means of twophoton polymerization direct laser writing, but also as an actuator for microrobots in both hard and soft stimuli–responsive polymers. In this scenario, a number of challenges that yet prevent polymeric light-powered microrobots from reaching their full potential are identified, whereas potential solutions to overcome said challenges are suggested. As an outlook, a number of real-world applications that light-powered microrobots should be particularly suited for are mentioned, together with the advances needed for them to achieve such purposes. An interdisciplinary approach combining materials science, microfabrication, photonics, and data science should be conducive to the next generation of microrobots and will ultimately foster the translation of microrobotic applications into the real world

Medical Robotics

The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently “medical roboticists” or not

The Role of MEMS in In-Vitro-Fertilization

The assisted reproduction has been considered a viable solution for the infertility of humankind for more than four decades. In-Vitro-Fertilization (IVF) is one of the most successful assisted reproduction techniques, where the reproductive cell of the female partner is fertilized outside of her body. Initially, the IVF process has been conducted manually by an experienced embryologist. However, even with a highly experienced individual, the operation had extremely lower success rates due to the limited control in environmental conditions and the requirement of precise movements. Therefore, to address this technological deficit, the feasibility of the mechatronics devices for IVF procedures has been investigated. Among the different mechatronics concepts, micro-electromechanical system (MEMS) technologies have been gradually attracted to the IVF process and improved its capabilities. The purpose of this paper is to present a brief overview of the role of MEMS technologies in IVF. The article classifies the MEMS technologies in IVF based on their application in order to emphasize its contribution. In addition, the article extensively discusses the state-of-the-art mechatronic techniques utilized in Intracytoplasmic Sperm Injection (ICSI), one of the most popular techniques used in IVF. This review article expects to become extremely beneficial for the engineering researchers new to this field who seek critical information on IVF in simple terms with highlights on the possible advancements and challenges that may emerge in the future

Quantitative characterization of mechano-biological interrelationships of single cells

Abstract(#br)This paper presented a quantitative investigation on the alteration of cell biological functions in relation to the change of mechanical properties of single cells. Leukemia NB4 cells were used as cell line. The dielectrophoresis (DEP) method was utilized to verify the mechanical properties variation of NB4 cells under the electric field treatment. A quantitative study of cell mechanical properties was then carried out using optical tweezers (OT), and cell biological properties using gene expression measurement. The result shows cell stiffness decreased after electric treatment. Biological properties related to cell motility, structure, apoptosis, migration, invasion, and metastases changed with cell mechanical properties variation

Cell patterning via optimized dielectrophoretic force within hexagonal electrodes in vitro for skin tissue engineering

Abstract(#br)Tissue reconstruction through in vitro cell seeding is a popular method for tissue engineering. In this paper, we proposed a thin-layer structure consisting of multiple hexagons for the regeneration of skin tissue. Cells could be seeded and cultured within the structure via dielectrophoresis (DEP) actively. A thin layer of the structure was fabricated with biocompatible medical-grade stainless steel via precise laser cutting. The fabricated layers were stacked together to form a 3D electrode pair, which could be used to generate a 3D electric field. Thus, the suspended cells within the structure could be patterned via DEP manipulation. The input voltage was examined and optimized to ensure cell viability and patterning efficiency during the DEP manipulation process. As soon..

The development of optical nanomachines for studying molecules : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Mechatronics Engineering at Massey University, Palmerston North, New Zealand

Chapter 3 is ©2020 IEEE. Accepted manuscript is reprinted, with permission, from 2020 IEEE/ASME International Conference on Advanced Intelligent Mechatronics (AIM). Chapter 5 is ©2022 IEEE. Accepted manuscript is reprinted, with permission, from 2022 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS).Optical tweezers have been used for a number of applications since their invention by Arthur Ashkin in 1986, and are particularly useful for biological and biophysical studies due to their exceptionally high spatial and force-based resolution. The same intense laser focus that allows light to be used as a tool for micro-nanoscale manipulation also has the potential to damage the objects being studied, and the extremely high force resolution is coupled with the limitation of very low forces. There is potential to overcome these drawbacks of optical manipulation through making use of another laser based technique: two-photon absorption polymerisation (TPAP). This thesis has brought these together to demonstrate the uses of optical nanomachines as helpful tools for optical tweezer studies. The project was highly interdisciplinary, concerning the intersection of optical trapping, 3D micromachine design and development, and DNA stretching. The thesis was based around the strategy of first developing microrobots and demonstrating their manipulation using optical tweezers, then adjusting the design for specific applications. Microlevers were developed for lever-assisted DNA stretching and amplification of optical forces. The influence of design features and TPAP parameters on microlever functionality was investigated; particularly the influence of overlapping area and presence of supports, and the effects of differently shaped "trapping handles". These features were important as lever functionality was tested in solutions of different ionic strength, and stable trapping of the levers was required for force amplification. DNA stretching was chosen as a target application for distanced-application of optical forces due to its status as a well-known and characterised example of single-molecule studies with optical tweezers. Amplification of optical forces was also seen as an application that could demonstrate the utility of optical micromachines, and microlevers with a 2:1 lever arm ratio were developed to produce consistent, two-fold amplification of optical forces, in a first for unsupported, pin-jointed optical microrobotics. It is hoped that in the future fully-remote, micromachine-assisted studies will extend optical tweezer studies of laser-sensitive subjects, as well as increasing the forces that can be applied, and the results obtained in this thesis are encouraging. All in all, the thesis confirms the potential of optical micromachines for aiding studies using optical tweezers, and demonstrates concrete progress in both design and application