Nanospray is an essential tool in high-sensitivity mass spectrometry; however, limitations with sample throughput present challenges with the routine use of nanospray for quantitative applications. Current trends toward MS-based biomarker quantitation impose strict requirements on nanobore LC-MS performance. A vision-based, self-tuning source was developed to interface with gradient chromatography and automatically control emitter-tip position1. We extend this analytical format with an automated ESI column-switching methodology wherein a digital trigger control switches the emitter between two column positions. Vision-based control maintains the spray at an optimized inlet position from two different packed-tip columns as fi ne tuning of emitter position is optimized by this vision-based control.