Percutaneous fiber-optic biosensor for immediate evaluation of chemotherapy efficacy in vivo (Part Ⅱ): In vitro and in vivo characterization

摘要

A fiber-optic sensor with customized sensing probe made of optical fibers and microcapillaries connected to a low price off-the-shelf portable system was characterized for monitoring the chemotherapy agent induced tumor apoptosis both in vitro and in vivo. The extrinsic fiber-optic platform is aimed to provide in vivo monitoring of non-homogeneously distributed apoptotic biomarker induced by the chemotherapy agent to adjust the tunable delivery of the agent as a personalized chemotherapy system. During apoptosis sensing, fluorescent response of phospholipid conjugated marina blue (Fluo_(Mb), cell distribution indicator) was firstly detected for verifying the cell densities (in the vicinity of sensor probe) were larger than 1 × 10~7 cells/ml (sensitivity limit), regardless of apoptosis activity (with or without CPA treatment). Fluorescent response of FM 1-43 (Fluo_(FM 1-43), apoptotic activity indicator) was measured later, and applied to indicate the induction of tumor apoptosis by establishing a threshold value as the ratio of two fluorophore emissions (Fluo_(FM 1-43)/Fluo_(Mb), see Part 1), which was 17 from in vitro cell culture study and 23.5 from in vivo xenografts study. Reproducibility of the sensor detection was found to have a bias lower than 16%.