Discussion

Current in vivo animal models do not accurately represent human physiology and 9 out of 10 drugs that pass animal testing fail during clinical testing, costing the industry $ millions per failed drug candidate. Traditional in vitro techniques can provide valuable insights but there are limitations to these systems: they only partially replicate normal biological processes, which impacts on the utility and reliability of the resultant data.

Quasi Vivo® perfusion systems provide nutrient flow which allows for co-culture and development of 3D structures. Cell viability and function are improved, and modelling of the QV500 shows improved oxygen availability in comparison with other milli- and micro-fluidic systems. Analysis of cell signalling (by sampling proteins expressed into media) will give key information about mechanisms of action and coupling Quasi Vivo® with mass spectroscopy can provide information about expressed proteins. We have shown that after 3 days, MS analysis detects five proteins present in the medium when cells are cultured under flow conditions compared with static. This short feasibility study has shown that small changes in cell activity triggered by flow conditions can be detected.

Future work includes improving the sampling procedure, examining more cell types and creating an integrated protocol that combines MS with, for example, aptamers. Combining these technologies will allow researchers to detect specific proteins in the medium quickly using aptamers, while maintaining the ability to analyse the whole protein profile using MS.