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

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

Micro/nano devices for blood analysis

[Excerpt] The development of microdevices for blood analysis is an interdisciplinary subject that demandsan integration of several research fields such as biotechnology, medicine, chemistry, informatics, optics,electronics, mechanics, and micro/nanotechnologies.Over the last few decades, there has been a notably fast development in the miniaturization ofmechanical microdevices, later known as microelectromechanical systems (MEMS), which combineelectrical and mechanical components at a microscale level. The integration of microflow and opticalcomponents in MEMS microdevices, as well as the development of micropumps and microvalves,have promoted the interest of several research fields dealing with fluid flow and transport phenomenahappening at microscale devices. [...

Force Sensing and Control in Micromanipulation

Ph.DDOCTOR OF PHILOSOPH

Roadmap for optofluidics

Optofluidics, nominally the research area where optics and fluidics merge, is a relatively new research field and it is only in the last decade that there has been a large increase in the number of optofluidic. applications, as well as in the number of research groups, devoted to the topic. Nowadays optofluidics applications include, without being limited to, lab-on-a-chip devices, fluid-based and controlled lenses, optical sensors for fluids and for suspended particles, biosensors, imaging tools, etc. The long list of potential optofluidics applications, which have been recently demonstrated, suggests that optofluidic technologies will become more and more common in everyday life in the future, causing a significant impact on many aspects of our society. A characteristic of this research field, deriving from both its interdisciplinary origin and applications, is that in order to develop suitable solutions a. combination of a deep knowledge in different fields, ranging from materials science to photonics, from microfluidics to molecular biology and biophysics,. is often required. As a direct consequence, also being able to understand the long-term evolution of optofluidics research is not. easy. In this article, we report several expert contributions on different topics. so as to provide guidance for young scientists. At the same time, we hope that this document will also prove useful for funding institutions and stakeholders. to better understand the perspectives and opportunities offered by this research field

Ultrasound Harmonic Classification of Microemboli

The ultrasound community has experienced dramatic technical advances over the last decades, such as blood °ow measurements with elabo rate Doppler techniques or real time three-dimensional imaging with 2-D phased array transducers. This was partly ascribed to the advantages of ultrasound over other diagnostic modalities, including its low cost, real time character and safety. One of these recent ultrasound technologies is Transcranial Doppler (TCD). TCD is a non-invasive ultrasound method used to assess blood °ow velocity in the major basal intracranial arteries on a real time basis. Since the early 60's, experimental studies have been carried out to evaluate the ability of TCD to detect, quantify and classify intracranial emboli. Many research centers have investigated the appearance of high intensity tran sient signals in the TCD waveform as indicators of circulating microemboli, in a wide variety of clinical areas: cardiac and carotid surgery1;2, following prosthetic heart valve insertion3, cerebral angiography4, atrial ¯brillation5 and decompression sickness6 . Many reports have emphasized the ability of TCD, combined to sophisticated signal processing techniques, to iden tify microemboli in the brain circulation. Unfortunately, this technology presents some limitations to distinguish between emboli and artefacts7¡11 and more importantly to determine the embolus composition12¡14 . There fore, the accuracy and clinical signi¯cance of the TCD technique for emboli classi¯cation has not yet been scienti¯cally established. Further research is currently undergoing to implement an on-line automated embolus de tection and classi¯cation method in clinical routine15¡17

Nano handling and measurement of biological cells in culture

A thesis submitted to the University of Bedfordshire in partial fulfillment of the requirements for the degree of Doctor of PhilosophyThis thesis systematically investigates the nano handling and measurement techniques for biological cells in culture and studies the techniques to realize innovative and multi-functional applications in biomedicine. Among them, the technique based on AFM is able to visualize and quantify the dynamics of organic cells in culture on the nano scale. Especially, the cellular shear adhesion force on the various locations of biological cells was firstly accurately measured in the research of the cell-substrate interaction in terms of biophysical perspective. The innovative findings are conductive to study the cell-cell adhesion, the cell-matrix adhesion which is related to the cell morphology structure, function, deformation ability and adhesion of cells and better understand the cellular dynamic behaviors. Herein, a new liquid-AFM probe unit and an increment PID control algorithm were implemented suitable for scanning the cell samples under the air conditions and the liquid environments. The influence between the surface of sample and the probe, and the damage of probe during the sample scanning were reduced. The proposed system is useful for the nano handling and measurement of living cells. Besides, Besides, to overcome the limitations of liquid-AFMs, the multiple optical tweezers were developed to integrate with the liquid-AFM. The technique based on laser interference is able to characterize the optical trap stiffness and the escape velocity, especially to realize the capture and sorting of multiple cells by a polarization-controlled periodic laser interference. It can trap and move hundreds of cells without physical contact, and has broad application prospects in cytology. Herein, a new experimental method integrated with the positioning analysis in the Z direction was used to improve the fluid force method for the calibration and characterize the mechanical forces exerted on optical traps and living cells. Moreover, a sensitive and highly efficient polarization-controlled three-beam interference set-up was developed for the capture and sorting of multiple cells. By controlling the polarization angles of the beams, various intensity distributions and different sizes of dots were obtained. Subsequently, we have experimentally observed multiple optical tweezers and the sorting of cells with different polarization angles, which are in accordance with the theoretical analysis