Concentrated effort

EKB Technology has developed an electrical system to remove harmful by-products from bioreactors, making the synthesis of therapeutic proteins more effective.

Therapeutic proteins are produced by cell cultures grown in laboratories and are used to treat conditions including some cancers, cardiovascular disease, diabetes, anaemia and haemophilia. The manufacturing process creates lactic acid and ammonium which contaminates the reaction making it less efficient, or in some cases causing death of the cells in culture.

EKB is a spin-out joint venture between Oxford University and C-Tech Innovation of Capenhurst near Cheshire. It was founded to commercialise a patent to use electricity to extract lactic acid from the reaction chamber during the commercial production of the acid.

Dr David Baghurst, EKB’s general manager, said: ‘If you take the lactic acid out of a reaction, you can concentrate it. This makes downstream processing easier, because you end up with your product concentrated in a reaction chamber that doesn’t contain all the cell debris you get in a biocatalysis chamber.’

EKB discovered that during mammalian cell culture reaction, there is contamination by lactase and ammonium, which are by-products of the production of proteins and which inhibit and limit the density of cells that can be used in the reactor.

They can also inhibit the formation of the target enzymes, as the cells that produce them treat them as toxins. The researchers realised that they could use almost exactly the same kind of electrical system to remove by-products as well as the products.

‘They did some experiments and found that when cells sit around in the by-products then the cells die. But if you continuously remove the by-products, you get healthy cells, so the cells become more productive and keep going longer,’ said Baghurst.

A reactor consists of a series of chambers with the biocatalysis reaction taking place in the middle with a membrane either side of it. Plates with an electrical potential are placed outside the membranes. When a field is applied across them, the charged species move across the membrane — in this case, ammonium goes to one electrode and lactate to the other. The non-charged cells remain in the central reaction chamber unharmed by the by-products.

The hardware employs the same technology used in electrodialysis that makes seawater drinkable, but is being used in bioreactors for the first time.

So far the technology has been tested on model systems. EKB is now seeking an industry partner to trial it in a real cell system.

‘This technology could make manufacturer’s current systems more productive,’ said Baghurst. ‘If you can remove the contaminants, the reactions can be carried out at higher cell densities which means the same volume of reactor can make more product.

Also, some systems are so sensitive that the existing equipment doesn’t make a commercially viable process; it’s just too expensive to generate the materials. This technology could make it affordable.’

Berenice Baker