3D measurement of fouling in membrane filtration: towards model based investigation and design

Lead Research Organisation: University College London
Department Name: Biochemical Engineering

Abstract

Bioprocess challenge the project seeks to address
Fouling of membrane filtration systems is an ever-increasing issue due to upstream titre and associated burden increases [1]. These complex feeds contain a large array of unwanted material that can detrimentally affect performance through several fouling mechanisms that can reduce permeation through membrane structure and change sieving coefficients [2]. Here we aim to develop a better understanding of these mechanisms using a measurement and visualisation approach that will inform modelling and simulation efforts core the CoE vision of enabling improved membrane design and operation.

Objectives
- To advance imaging approaches to measure foulant locations within membrane and feed types representative of current bioprocessing challenges
- To combine confocal microscopy and x-ray CT techniques to determine at new levels of resolution the location and species of foulant within membranes.
- Use these methods at multiple length scales, from small samples initially up to pleated sheet cartridges and single pass TFF systems to determine the impact of scale-up approach.
- Interface the three dimensional data acquired with modelling approaches.

Project Description
Fouling during filtration is a commonplace issue for industrial bioprocesses [1, 2], with a variety of target product sizes to consider and impurities that must be removed. At UCL and within the CoE various high-resolution imaging techniques have been applied to visualise and characterise Pall separation media, including x-ray CT, confocal microscopy, electron microscopy and focused ion beam microscopy [3-5]. This has shown that utilising multiple techniques in a complementary manner can overcome the shortcomings of individual methods and maximise the data gathered about a sample. In this project confocal and super-fluorescence microscopy, will enable optical slicing and large field of view imaging respectively on tagged feeds to identify the location and composition of entrapped material within Pall filtration membranes of varying characteristics such as pore size and asymmetry.

The research would build upon a CoE MSc project that investigated the location liposome entrapment within Pall membranes using confocal microscopy applied to dual layer membrane systems. It would further this by using liposome material with differing sizes and compositions in order to mimic products such as lentivirus and potential foulants e.g. extracellular vesicles that could be individually labelled prior to imaging. These mimics will be designed to align with other CoE EngD projects such as in lentivirus manufacture, and the data generated will support the CoE vision.
[1] Gronemeyer et al. (2014), [2], Fallahianbijan et al. (2019) [3], Johnson et al. (2017)
[4] Johnson et al. (2018), [5] Jackson et al. (2014)

Proposed timeline
Year 1: Imaging and analysis training (e.g. confocal), initial membrane experiments with liposomes
Year 2: Expand media (including dual layer) and formulation (move to liposome mimic of lentivirus)
Year 3: Combine results with other imaging data in the CoE, investigate multi-length scale imaging
Year 4: Complete studies, compare lenti mimic to actual, CoE imaging collaboration, submit thesis

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S021868/1 01/10/2019 31/03/2028
2417227 Studentship EP/S021868/1 28/09/2020 27/09/2024 Piotr Kucia