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

Design, control, and application of piezoelectric actuator: External-sensing and self-sensing actuator

Ph.DDOCTOR OF PHILOSOPH

Recent microfluidic innovations for sperm sorting

Sperm selection is a clinical need for guided fertilization in men with low-quality semen. In this regard, microfluidics can provide an enabling platform for the precise manipulation and separation of high-quality sperm cells through applying various stimuli, including chemical agents, mechanical forces, and thermal gradients. In addition, microfluidic platforms can help to guide sperms and oocytes for controlled in vitro fertilization or sperm sorting using both passive and active methods. Herein, we present a detailed review of the use of various microfluidic methods for sorting and categorizing sperms for different applications. The advantages and disadvantages of each method are further discussed and future perspectives in the field are given

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

DEVELOPMENT OF A NOVEL Z-AXIS PRECISION POSITIONING STAGE WITH MILLIMETER TRAVEL RANGE BASED ON A LINEAR PIEZOELECTRIC MOTOR

Piezoelectric-based positioners are incorporated into stereotaxic devices for microsurgery, scanning tunneling microscopes for the manipulation of atomic and molecular-scale structures, nanomanipulator systems for cell microinjection and machine tools for semiconductor-based manufacturing. Although several precision positioning systems have been developed for planar motion, most are not suitable to provide long travel range with large load capacity in vertical axis because of their weights, size, design and embedded actuators. This thesis develops a novel positioner which is being developed specifically for vertical axis motion based on a piezoworm arrangement in flexure frames. An improved estimation of the stiffness for Normally Clamped (NC) clamp is presented. Analytical calculations and finite element analysis are used to optimize the design of the lifting platform as well as the piezoworm actuator to provide maximum thrust force while maintaining a compact size. To make a stage frame more compact, the actuator is integrated into the stage body. The complementary clamps and the amplified piezoelectric actuators based extenders are designed such that no power is needed to maintain a fixed vertical position, holding the payload against the force of gravity. The design is extended to a piezoworm stage prototype and validated through several tests. Experiments on the prototype stage show that it is capable of a speed of 5.4 mm/s, a force capacity of 8 N and can travel over 16 mm

Force Sensing and Control in Micromanipulation

Ph.DDOCTOR OF PHILOSOPH

Design & control of precision surgical device for otitis media with effusion

Ph.DDOCTOR OF PHILOSOPH

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

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

Development of image processing and vision systems with industrial applications

Ph.DDOCTOR OF PHILOSOPH