A methodology towards the design and control of a microfluidic device for single sperm capture and isolation

Hughes, Arran J. R. (2024). A methodology towards the design and control of a microfluidic device for single sperm capture and isolation. University of Birmingham. Ph.D.

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Abstract

Intracytoplasmic Sperm Injection (ICSI) is an Assisted Reproductive Technology (ART) where a singular sperm is injected directly into an egg for fertilisation to assist couples experience trouble conceiving. Sperm selection is a necessary procedure prior to ICSI for the choosing of the cell to be injected into the egg. In this technique, an embryologist manually selects a sperm based on observation, leading to inconsistencies in the operation between clinicians due to varying experience levels. Therefore, there is a need to assist and automate this procedure to deliver consistent sperm selection prior to injection for more consistent success rates. Microfluidics is a promising technique for the manipulation of cells and other objects of sizes ranging between one to several hundreds of micrometers. This thesis focuses on the develop of a novel microfluidic technique for automated capture, isolation and retrieval of single objects/cells from a larger population with application to ICSI. Initially, a novel manufacturing technique was developed utilising an ablation method with a red femtosecond laser to develop rapid prototypes for the device structure which had replication of 300 µm channels and 200 µm gates gate sizes were 40 µm smaller compared to the original design. Next, a simulation model with particle tracing was developed to determine the key requirements of a countercurrent design in order to facilitate successful capture and release of objects. From this, fundamental pressure requirements were determined to achieve the device function where the pressure difference across the gate dictates flow direction. Geometric restrictions were also determined based on proximity to inlets and outlets where 300 µm from the fluid inlets is required for successful object capture/release. Finally, a theoretical model was developed utilising electrical circuit analogies for fluids to give an analytical solution to the fluid flow in the device as well as to determine controller pressure requirements and the errors determined based on experimental validation. The proposed technique offers a novel method for isolation of objects/cells from a larger population, with the key function of being able to deliver any captured objects/cells individually.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):