Here we introduce a universal metal-based barcoding technique for Laser Ablation Inductively Coupled Plasma Time-of-Flight Mass Spectrometry (LA-ICP-TOFMS) that optimizes experimental procedures and enhances data reliability across diverse cell types. By enabling the analysis of multiple experiments on a single cytospin slide, our method reduces the number of required slides by 90%, minimizing cell suspension time and potential cellular changes due to interventions such as drug treatments. This consolidation leads to significant time savings and decreased variability in cell behavior.

To demonstrate the effectiveness of our barcoding technique in increasing throughput, we applied it to a biological question: examining different metal-based drug uptake and quantification in sensitive and resistant cell lines for various drugs. By utilizing barcoding, we were able to simultaneously assess multiple drugs and cell lines, significantly enhancing throughput and data quality.

During antibody labelling, reagent consumption is reduced by up to 90% since only one barcoded sample requires staining instead of multiple individual samples which dramatically cuts costs. Measurement time is notably decreased as the technique allows for the assessment of a single barcoded sample rather than multiple separate ones. These streamlining saves time as well as resources and reduces system sensitivity variability between different days.

As Data processing is simplified, this not only increases efficiency but also allows for the exclusion of misssegmented cells identified as doubly positive for barcodes thus furthermore increasing data robustness. 

By standardizing cell suspension treatment, staining, and measurement conditions, our method ensures all experiments undergo identical procedures, significantly reducing variability and enhancing data robustness. This technique is particularly beneficial for applications such as drug testing, concentration testing, time-series studies, and the development of marker panels across different cell types. Our application of this method to quantify metal-based drug uptake in sensitive and resistant cell lines underscores its potential to increase throughput and improve data quality in biological research. This advancement represents a substantial improvement in LA-ICP-TOFMS methodologies, demonstrating increased efficiency and data quality across various cell types.