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

Cell Biomechanical Modeling Based on Membrane Theory with Considering Speed Effect of Microinjection

As an effective method to deliver external materials into biological cells, microinjection has been widely applied in the biomedical field. However, the cognition of cell mechanical property is still inadequate, which greatly limits the efficiency and success rate of injection. Thus, a new rate-dependent mechanical model based on membrane theory is proposed for the first time. In this model, an analytical equilibrium equation between the injection force and cell deformation is established by considering the speed effect of microinjection. Different from the traditional membrane-theory-based model, the elastic coefficient of the constitutive material in the proposed model is modified as a function of the injection velocity and acceleration, effectively simulating the influence of speeds on the mechanical responses and providing a more generalized and practical model. Using this model, other mechanical responses at different speeds can be also accurately predicted, including the distribution of membrane tension and stress and the deformed shape. To verify the validity of the model, numerical simulations and experiments are carried out. The results show that the proposed model can match the real mechanical responses well at different injection speeds.Comment: 10 pages, 12 figures, submitted to IEEE TMech

Frontiers of Medical Micro/Nanorobotics: in vivo Applications and Commercialization Perspectives Toward Clinical Uses

The field of medical micro/nanorobotics holds considerable promise for advancing medical diagnosis and treatment due to their unique ability to move and perform complex task at small scales. Nevertheless, the grand challenge of the field remains in its successful translation towards widespread patient use. We critically address the frontiers of the current methodologies for in vivo applications and discuss the current and foreseeable perspectives of their commercialization. Although no “killer application” that would catalyze rapid commercialization has yet emerged, recent engineering breakthroughs have led to the successful in vivo operation of medical micro/nanorobots. We also highlight how standardizing report summaries of micro/nanorobotics is essential not only for increasing the quality of research but also for minimizing investment risk in their potential commercialization. We review current patents and commercialization efforts based on emerging proof-of-concept applications. We expect to inspire future research efforts in the field of micro/nanorobotics toward future medical diagnosis and treatment

Vision guided automation for intra-cytoplasmic sperm injection

Biological cell injection is an effective technique in which a foreign material is directly introduced into the target cell. Intracytoplasmic Sperm Injection (ICSI) is a microinjection technique which is used for infertility treatment. In this technique, a single sperm cell is directly injected into an oocyte using micropipettes. The operations in this application are manually controlled by an embryologist and more importantly, this reduces the accuracy, repeatability, and consistency of the operation. Therefore, the full automation is a prerequisite for microinjection operations, particularly in ICSI application. This thesis focuses on enhancing the microinjection procedure by developing vision-guided processes prior to and during the operation. Initially, a vision-controlled technique was proposed to align the injection and holding pipettes in three orthogonal axes which is essential for successful microinjection. To conduct reliable injection, the vibrational displacement of the injection pipette’s tip needs to be evaluated and improved before the operations continue further. A novel vision-based sensor was developed to measure the displacement changes at the tip in three orthogonal axes. By employing the developed vision sensor, the effect of injection speed on vibrational displacement creation was analysed to determine the value of various injection parameters, such as force fluctuation, and penetration force on cell damages. An ultimate automation task is required in microinjection to position the randomly located biological cell within the Petri dish to the system’s field of view. The proposed technique fills a gap in the literature by proposing a real-time cell recognising and positioning system that can be employed with different types of biological cells at various maturation stages, as well as with different microscope types that are being used in microinjection applications

Robotic Manipulation and Selection of Single Sperm for In Vitro Fertilization

In vitro fertilization (IVF) is the standard clinical treatment for infertility, which is a growing global health issue with psychological, social, and economic implications. DNA fragmentation of the sperm used in IVF treatments deterministically lowers the fertilization rate, causes embryo arrest in development, increases the miscarriage rate, and results in genetic disorders in the offspring. Current clinical practice of sperm selection either destroys the sperm for invasive DNA assessment or assumes that sperm motility and morphology are correlated with sperm DNA integrity. However, this correlation has never been proved due to the lack of single-cell manipulation and characterization techniques. Targeting non-invasive selection of high DNA integrity sperm, this thesis focuses on (1) developing enabling robotic manipulation techniques for pick-place of single sperm for subsequent DNA analysis, and (2) establishing, for the first time, the correlation between sperm motility and morphology parameters and the same sperm's DNA integrity. Closed-loop visual servo control algorithms were developed to adjust sperm position and orientation, based on which robotic immobilization of motile sperm were achieved via two approaches: tapping the sperm tail with a micropipette or firing laser pulses to ablate the motor proteins on the sperm tail. Computer vision algorithms were also developed to non-invasively measure sperm motility and morphology parameters in real-time. The same sperm, with its motility and morphology characteristics recorded, was transferred for DNA integrity analysis. These robotic techniques not only free human from tedious labor operation, but also bring state of the art population-based sperm analysis to the single-cell level. Experimental results confirmed the long-hypothesized correlation that sperm with normal motility and normal morphology have low DNA fragmentation. Finally, based on the established correlation, a set of quantitative criteria was formulated for automated, objective, and non-invasive selection of sperm with high DNA integrity.Ph.D