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LEAD SUPERVISOR: Professor Sonia Contera, Department of Physics

Co-supervisor: Professor Sarah Waters, Department of Maths

Commercial partner: CytoSwim Ltd, Warwick

Motivation: Around 1 in 6 couples worldwide suffer from infertility, fertility rates decline by ~1.5% per year. 800,000 IVF cycles are carried out annually in Europe at ~£5,000 per cycle. Success rate of IVF remains relatively low (e.g. 25% for women aged 35 to 37 in the UK). This is partly due to (i) damage produced by the semen processing process, and (ii) lack of techniques to assess sperm health/motility. A particularly important case is “sperm cryopreservation”, utilised routinely for over 40 years. Cryopreservation of sperm is crucial e.g. for men undergoing cancer treatment; 15%–30% of patients remain permanently infertile as a consequence of treatments. However, sperm cells (the sperm cell membrane, in particular) are damaged during cryopreservation due to osmotic/oxidative stress, toxicity from cryoprotectants, the physical removal of cryoprotectants upon thawing, and the formation of intra/extra-cellular ice crystals, causing a reduction in the number of normally functional sperm and sperm motility and a reduction of the success rate of IVF treatments.

Currently protocols are developed by trial and error, each clinic has its own “recipe”, and the assessment of successful cryopreservation is not standardised. There are no standards, and therefore there are no effective regulations to control and assess this crucial medical activity, which is expected to grow in importance as fertility continues to decline.

Project: We propose to co-supervise a DPhil student to use experimental biophysics and applied mathematics models to develop fully quantitative cryopreservation protocols by combining Oxford and Cytoswim’s expertise:

  • Contera is an expert in quantitative measurement of mechanical properties of living cells; has established techniques based on atomic force microscopy (AFM) to assess mechanical damage of freeze/thaw cycles in cell membranes (Gabbutt , et al. Sci Rep. 2019, 19;9(1):19473) and effect of cryoprotectants (Pearce and Contera, J Microscopy, 2022 submitted). She also develops polymeric physical-cryoprotectants.
  • Waters models cell cryopreservation with PDE-based methods. She has co-developed a quantitative mathematical method to optimise the cooling rate during cell freezing to minimise damage by ice/cryoprotectants that we will use in our project (Dalwadi et al., SIAM J. Applied Math, 2020, 80(2): 657.
  • Cytoswim uses a unique microstructure-based technology that enables collection of the best sperm cells from a sample with up to 10x less DNA fragmentation than samples processed via traditional techniques. We will use Cytoswim technology to assess quantitatively the success of our protocols. Cytoswim’s platform is key for quantitatively assessing/improving cell survival.

Main Objectives:

  • Assess structural/mechanical damage to cells after freezing/thawing by protocols currently used clinics, using optical microscopy /AFM and correlate with the outcomes of the assays developed by Cytoswim.
  • Optimisation of the cryopreservation protocol using biophysical/math modelling techniques and Cytoswim technology.
  • A mathematical model for optimising cryopreservation that is fully validated by experiments based on the model developed by Waters et al. at the Maths Institute.

Outcomes:

  • Reduction (>80%) of concentration of toxic cryoprotectants.
  • Improved removal of cryoprotectants.
  • Improved survival/collection/yield of sperm after cryopreservation.
  • Improved device for sperm assays.
  • A quantitative validated protocol that can be used in the clinic and by regulators

Apply using course: DPhil in Condensed Matter Physics

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