Development of an optical system for on-line tracking of cell growth on microcarriers

Lead Research Organisation: Loughborough University
Department Name: Chemical Engineering

Abstract

In order that people can live longer and lead more active lives there is a need to develop novel affordable and effective treatments for ill health. In some cases, cells that we have within our own bodies can be used to repair damaged tissues or organs. However, in adults, this repair mechanism is very limited and often inefficient so we may need to rely on cells from donors. Unfortunately, since it takes billions of cells to repair, for example the heart muscle of a heart-attack patient, we must isolate cells from donors and expand their numbers before they can be used for treatment. So far we can do this at the laboratory scale, generating for instance, millions of mesenchymal stem cells in a stirred tank over a period of 2 weeks. However, as we consider how this will be achieved on a bigger manufacturing scale, we need to develop tools that will help us monitor and control the process to ensure the cells grown in this way are the same every time - just as we would expect other medicines to be identical from batch to batch. This feasibility project aims to combine the expertise of both biologists and engineers, to create an optical device that can monitor the growth of these cells in this stirred tank environment by giving the operator information about cell number and morphology. If successful, it will help optimise growing conditions so enough cells to treat multiple patients can be manufactured consistently.

Planned Impact

In order to make the manufacture of new cell-based therapy products commercially viable such that society can benefit from them, the development of scalable bioprocessing techniques for producing large numbers of clinically relevant cells is critical. One method being developed relies on adherent cells such as mesenchymal stem cells to be grown on microcarriers in a stirred tank bioreactor. The One impact of this project would be to revolutionise how this process is monitored and potentially controlled in the future such that high quality cells (i.e. product) are consistently manufactured and cell yields maximised.

The innovative study proposed here will generate an optical device based on interferometry to image moving microcarriers within the stirred tank bioreactor. This approach moves away from the need to manually sample from the bioreactor and carry out off-line analysis in order to assess cell growth progression and morphology and when to supplement in additional microcarriers in order to maximise cell yield. Therefore, with potential benefits to not just the cell-based therapy or regenerative medicine community but the bioprocessing community as a whole, the rights to related IP would carry considerable prestige and be worthy of further exploitation.

In addition, this project will have impact in other areas of high value manufacturing. The interferometric and machine vision techniques developed will have potential impact on other areas of high value manufacturing where dynamic interferometric detection of sub-micron scale defects on roll-to-roll processes such as those emerging for vapour barrier coatings for use in OLED display and solar PV technologies. There is potential impact for metrology instrumentation companies through IP exploitation in order to produce marketable cutting edge detection technologies for industry.

Publications

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Description This grant focused on the development of an optical device that would enable online monitoring of cells growing on microcarriers. Growing cells on microcarriers, small plastic particles that provide a surface for adherent cells to grow on in stirred tank environment, is one way of scaling up the process for human mesenchymal stem cell production. However, one of the challenges is that tracking of cell growth in the tank requires sampling and assessing when to add more microcarriers (i.e. surface area) can be difficult. The project collaborators on the grant in Huddersfield focused on developing the device and at Loughborough we developed the Matlab scripts that enabled images to be analysed for cell number and morphology. An MSc student aligned to the project developed a Labview script such that images could be processed automatically and information graphically visualised on the user interface.
Exploitation Route Although the optical device itself requires more refinement it has the potential to become a commercially sold device for use in the cell therapy industry. Aside from this, the image analysis done could be used by the sector more widely to avoid manual steps in cell counting and assessment of differentiation (through morphology), providing alternatives to existing methods.
Sectors Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology