Microfluidics- the perfect meeting-place for viruses and cells
Viruses get a bad press. SARS-CoV-2 did little to improve matters, but those of us working in gene and cell therapy are only too aware of the critical role lentiviruses, adeno- and adeno-associated viruses play in the manufacture of these life-saving medicines.
Viral vectors are super-effective at inducing gene expression in cells and conferring T-cells with therapeutic properties such as tumor detection; but the production of these biomolecular tools is complex and expensive, and yields are often incredibly low. A typical process requires culturing CHO cells to produce plasmids, which are used to transfect HEK293 cells, which in turn produce the viral particles, all under GMP conditions. A few microliters of virus can cost several thousand dollars to manufacture, so when using large volume conventional bioreactors things quickly become prohibitively expensive.
Infecting target cells with the viral vector presents further challenges. The objective is to achieve optimal interaction between cell and virus particle so that as many cells as possible are infected within the bioreactor, whilst minimizing multiple infection of cells (regulators typically specify <5 infections per cell). Conventional bioreactors are not well-designed for homogeneous interaction between virus particle and cell: some cells may get infected multiple times, others not at all.
But there is another way. Both of these problems (non-uniform cell infection and low viral yield) can be overcome by the use of microfluidics. As Césaré Cejas, PhD, MFX’s VP of Microfluidics explains; “Microfluidics require significantly less virus, and co-localizing target cells and virus particles within microfluidic channels enables fine control of the interaction between cells and the virus. The cells are homogeneously distributed across a thin film of fluid ensuring that every cell is in contact with the fluid – not buried under other cells. The viral particles, moving by Brownian motion, do not have to travel far to encounter a cell and all the cells are equally likely to be infected.”
Microfluidics requires around 10x less virus, shortens the viral transduction process by several days, and ensures a homogeneous number of infections per cell. Our proprietary Cyto Engine™ platform is harnessing the power of microfluidics to transform viral transduction processes for cell and gene therapies.