Study of Speed and Force in Biomanipulation

Ph.DDOCTOR OF PHILOSOPH

Modelling of a planar magnetic micropusher for biological cell manipulations.

International audienceThe improving of the efficiency and the automation of biological cell technologies is currently of great importance. One way is to build biological micro-factories which are able to perform complete biotechnological processes automatically. This technology requires the development of new automatic cell transport system to feed work stations in microfactories. An original magnetic cell micropusher is described in this paper. The ferromagnetic pusher which is submerged in the biological medium follows the movement of a permanent magnet located in the air. This paper focuses on the modelling of the dynamic behaviour of the micropusher according to the magnet trajectory. The generic model proposed is able to determine pusher trajectory according to the micropusher magnetic properties and the permanent magnet shape and properties. This simulation tool will permit to optimize and to study cell trajectory control in further works

Microforce sensor for microbiological applications based on a floating-magnetic principle.

International audienceIn this paper, we present the design of a new magentic nano and microforce sensor for microbiological applications. The sensing part of the sensor presents a naturally stable six degrees of freedom equilibrium state using the combination of upthrust buoyancy and magnetic force. The sensor allows force measurement without deformation of the sensing element using a feedback control loop and is able to measure the components, in the horizontal plan, of the external force applied. The measurement range varies between around ± 100 µN with a resolution of 20 nN and a linear output. The mechanical stiffness of the passive system is about 0.018 N.m−1(same order of magnitude than an AFM micro-cantilever). A complete static study and experimental validation of the used principle are presented in this paper

Sensorized Tools for Haptic Force Feedback in Computer Assisted Surgery

Structural engineerin

A microgripper for single cell manipulation

This thesis presents the development of an electrothermally actuated microgripper for the manipulation of cells and other biological particles. The microgripper has been fabricated using a combination of surface and bulk micromachining techniques in a three mask process. All of the fabrication details have been chosen to enable a tri-layer, polymer (SU8) - metal (Au) - polymer (SU8), membrane to be released from the substrate stress free and without the need for sacrificial layers. An actuator design, which completely eliminates the parasitic resistance of the cold arm, is presented. When compared to standard U-shaped actuators, it improves the thermal efficiency threefold. This enables larger displacements at lower voltages and temperatures. The microgripper is demonstrated in three different configurations: normally open mode, normally closed mode, and normally open/closed mode. It has-been modelled using two coupled analytical models - electrothermal and thermomechanical - which have been custom developed for this application. Unlike previously reported models, the electrothermal model presented here includes the heat exchange between hot and cold arms of the actuators that are separated by a small air gap. A detailed electrothermomechanical characterisation of selected devices has permitted the validation of the models (also performed using finite element analysis) and the assessment of device performance. The device testing includes electrical, deflection, and temperature measurements using infrared (IR) thermography, its use in polymeric actuators reported here for the first time. Successful manipulation experiments have been conducted in both air and liquid environments. Manipulation of live cells (mice oocytes) in a standard biomanipulation station has validated the microgripper as a complementary and unique tool for the single cell experiments that are to be conducted by future generations of biologists in the areas of human reproduction and stem cell research

Control of a particular Micro-Macro positioning system applied to cell Micromanipulation.

International audienceBiological research requires new tools for cell micromanipulations. Currently, biological cell sizes range from a few to hundreds of micrometers, their manipulation therefore belonging to the field of microrobotics. This paper presents a new wireless micromanipulation system which allows cells placed in a droplet of liquid to be pushed on a glass slide. The cell micropusher is a ferromagnetic object which follows the movement of a permanent magnet located under the glass slide. It has been proved in previous works that two kinds of micropusher movements can induce a movement of the pushed object: turning the micropusher around the contact point (rotation), or moving the micropusher in translation. Rotation allows an object to be placed with a precision below 1 μm ,but acts within a narrow range. Translation allows placement of an object with lower accuracy, but within a wide range. We propose a specific coarse-fine control strategy to push an object, with good precision, within a wide range. Furthermore, experimentation on polystyrene balls of 50 μm in diameter, and immature human oocytes of 150 μm in diameter are presented

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