A novel bioluminescent bacterial biosensor for measurement of Ara-CTP and cytarabine potentiation by fludarabine in seven leukaemic cell lines

This study evaluates an in vitro biosensor assay capable of detecting the intracellular levels of the tri-phosphorylated form of cytarabine (Ara-CTP) within one working day. The biosensor predicted the response of seven leukaemic cell lines with varying known sensitivities to cytarabine alone and in combination with fludarabine. High-performance liquid chromatography (HPLC), 3-day assessment of cellular viable mass, and flow cytometric assessment of apoptosis were used to validate biosensor performance. A correlation between the biosensor results and Ara-CTP quantitation by HPLC was confirmed (R=0.972). The biosensor was also capable of detecting enhanced accumulation of Ara-CTP following sequential pre-treatment of leukaemic cells with cytarabine±fludarabine.