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(BBSRC DTP CASE) Optical coherence tomography dynamic light scattering for the measurement of protein aggregation and particulate formation in biologic fluids


Project Description

Proteins are susceptible to aggregation during their production which can reduce their bioactivity and prevent their effective formulation in pharmaceutical products. Dynamic light scattering (DLS) is a standard technique to measure the aggregation state of proteins. However, DLS functions at low protein concentrations in which only single light scattering occurs. At higher protein concentrations, measurements lose their accuracy. Typically Fujifilm production lines function at much higher protein concentrations (e.g. for pharmaceutical grade antibodies) than can be explored with DLS. In contrast, newly developed optical coherence tomography (OCT) DLS techniques can function at much higher protein concentrations, since multiple scattering is suppressed by a coherence gate. The OCT apparatus can be reasonably cheaply built using fibre optical based components, which will allow robust characterisation of samples during processing (either in line or ex situ depending on the availability of a transparent window in the production line). Another major advantage of OCT is that it is more robust to imperfections in the optical systems used, making it better suited to industrial applications.
Our group has extensive expertise in developing OCT techniques under flow (6 articles) e.g. [1]. The methodology allows 3 pL volumes to be studied and will allow both the velocity of the flow field and the size of the protein aggregates to be measured as a function of time.
This BBSRC Case PhD studentship will create a working prototype OCT DLS device. New software will also be created to provide robust and straightforward quantification of correlation functions from OCT DLS and in house highly parallelized DLS measurements (already available at Fujifilm). The ideal applicant will have expertise in optical physics and/or biological physics.

https://personalpages.manchester.ac.uk/staff/t.a.waigh/
https://www.research.manchester.ac.uk/portal/jian.lu.html
https://www.research.manchester.ac.uk/portal/mark.dickinson.html

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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