In this paper we present for the first time the results of analysis using FAST. We demonstrate the FAST capability on hundreds of motile human sperm swimming in both diluted semen and high-viscosity media. We hope that this ability to accurately quantify the flagellar waveform in large populations of motile cells will enable an abundant array of diagnostic, toxicological and therapeutic possibilities, as well as creating new opportunities for assessing and treating male subfertility.
In this review paper we explore the past and present of Computer Aided Sperm Analysis (CASA), discuss clinical uses and potential areas for clinical translation of existing research technologies. In particular we look ahead to the future of computer analysis and potential to revolutionise the science of male fertility, laying out the potential for automated flagellar tracking such as that provided by FAST.
In this modelling paper we show how the NEAREST code package enables easy and accurate simulation of flagellar motility. Using the NEAREST package we are able to calculate the disturbance to flow around swimming cells, enabling visualisation of the impact a sperm has on its environment without need for complicated experimental protocols, which can be expensive and, on these scales, significantly affected by noise.
In this paper we developed an experimental system to reveal the response of individual cells to pharmacological motility stimulus. The system consists of adhering sperm to a surface and imaging flagellar motion before and after perfusion with a compound (in this case the potassium channel modulator 4-aminopyridine). Mathematically analysing the flagellar waveform and combining this data with fluid dynamic modelling then enables the estimation of forces and energy dissipation. A surprising finding was that cells may actually dissipate less energy during hyperactivation than prior to induction of hyperactivation.
In this review paper we tackle the question of viscosity, and whether it is essential for successful internal fertilisation. Viscous effects play many roles in the migration of sperm through the female tract, be it allowing entrance into the cervix, preventing entrance through use of the female contraceptive pill, or having a significant impact in controlling the migrating sperm and their flagellar waveforms.
Successfully migrating human sperm are able to push their way through fluids that are over 200 times the viscosity of saline, without significantly slowing down. In this experimental paper we perform high frame rate imaging on the flagellum of human sperm in high viscosity fluidic environments, characterising in detail the development and propagation of the waveform, and its remarkable adaptation to the challenge presented by the surrounding viscous fluid.