We propose a sensor event-driven, open-column chromatographic sample preparation system─OpenPrep. This system replaces the problematic flow selector valve with a noncontact built-in sensor, eliminating carryover and clogging issues, which are commonly encountered in pump-driven chromatographic systems. The innovative valveless column-flow design, combined with a compact gantry dispenser and motion stage-based fraction collector, reduces the sample flow path to a disposable component with a postcolumn dead volume of only 0.5 mL. This configuration is superior to conventional dynamic flow systems owing to its ability to minimize sample consumption, eluent loss, and cleaning waste generation. Thus, OpenPrep can be ideal for preventing cross-contamination. Owing to the rapid flow-transfer and stop approach, OpenPrep achieves higher reagent delivery accuracy and precision compared to ISO 8655-2 piston-operated pipettes, by minimizing liquid residue on the dispensing tip. Sensor-driven flow control ensures precise eluent collection and automatic regulation of the mobile-phase flow rate through an online calibration algorithm, meeting all the requirements for accurate and reproducible column flow control. OpenPrep features an open architecture for both hardware and software, offering high flexibility for analyzing samples with considerable variations in radioactivity and matrix compositions, such as radioactive waste. The proof-of-concept implementation of a multistage sequential separation strategy, using five resin columns to separate Re, Sr, Fe, and Ni from a single sample, demonstrates that OpenPrep provides enhanced flexibility and reconfigurability, improved operational efficiency, and cost-effective customization. Excellent chemical yields were obtained for Re, Sr, and Ni in the range of 83-97%, with less than 2.6% relative standard deviation at a flow rate three times faster than the gravity method. Additionally, improved recovery performance of Fe was achieved by applying a slower flow rate compared to gravity flow.