With the intention of alleviating multiple problems arising from instrument clogs, a novel though inexpensive plumbing set-up was implemented on our walk-up LCMS systems. The inherent novelty of our approach lies in the simplicity of the modification, not requiring an additional pump and valve, or any changes to the existing LC methods. This solution proved to be both simple and effective. We hypothesized that, by simple installation of a filter in tandem with serial back-flushing of the needle seat after each injection, we can drastically reduce the instances of clogging. To test the robustness of this method, a heterogeneous sample, which had previously been observed to instantly cause a shutdown due to a blockage on our standard instruments, was set to run sequentially on a modified LCMS system. This sample was observed to run for 144 consecutive injections over a period of 24 hours with no system shutdown, pressure errors or observation of pressure spikes providing a reasonable peak area reproducibility of 5.6 % RSD (Figure ) as compared to 1.7% for homogeneous samples (see Supporting Information). The method enables previously inaccessible LCMS data to be generated for heterogeneous samples. There are several other factors that need to be considered when implementing a process change in one's operation. One such factor is evaluating whether the change will have any significant impact on the chromatography. Given the set-up and positioning of the back-flush, we expected it to have a negligible effect on the chromatogram and this hypothesis is evidenced by the data presented in Figure , which shows a chromatogram before and after back-flush installation. The minor change in the peak retention time does not influence data interpretation as a mass spectrometer is attached to these systems for peak identification purposes. The overall modification of the system represents a significant gain in robustness for the walk-up instrument. Prior to deployment of the heterogeneous sample analysis method on all the walk-up LCMS instruments throughout the department, one final challenge remained to be surmounted. On most of our walk-up production LCMS injector systems (Agilent Model G1329B), there is no flush port for the controlled disposal of the solvent resulting from the back-flush process. As such, excess solvent from the back-flush is likely to congregate on the needle seat and shut down the instrument by triggering a leak alarm. To address this, a series of 1mm holes were drilled in the needle seat cover allowing the solvent to drain through a custom-made drip tray into a suitable hazardous waste container for disposal (See SI Fig S ).