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Background Dielectric spectroscopy (DS) has been used for over two decades to measure the live cell concentration of animal cells in bioreactors online. The technology measures the build up of charge around live cell membranes under the influence of an induced electric field. Dead cells, debris, air bubbles and solid media particles do not have the capability to hold charge around themselves and are hence, invisible to the technology. The capacitance thus measured is proportional to the live bio-volume of the culture. DS has been used extensively to monitor and control live cell concentrations in bioreactors from process development through to large scale production. For DS to be employed as a PAT tool, it is essential that it successfully measures cell concentration over a wide range of culture volumes. Utilising the same cell measurement technique through the entire scale up protocol can also be a distinct advantage. This paper describes the latest developments in dielectric spectroscopy, especially the scaling down of the technology for measurement of lower volume cultures (up to 1 ml) in real time. The paper will also illustrate the application of dielectric spectroscopy to single use bioreactors. |
