In conclusion, we have demonstrated remarkable performance of two-electrode electrochemical detectors integrated in low-cost clinical analyzers. The two-electrode detectors are ideally suited for paper-based devices, where the fabrication of reference electrodes is cumbersome. The two-electrode sensors also excel at flow injection analysis, to their high detection efficiency and reliable sensing performance. We have confirmed the critical role of the counter electrode design, in order to ensure a sufficient number of redox probes for the reverse reaction. Importantly, the two-electrode system is capable of handling the entire development workflow of a novel assay. As a model system, we successfully developed an FIA assay for urinary creatinine, providing unprecedented insights into the ferricyanide-mediated reaction, and offering clinical performances comparable with commercial laboratory assays, at almost zero material cost. The cost competence is even further strengthened with our $3 smart reader owing to the simplified circuitry for driving two-electrode systems. We believe that our findings will be readily translatable to other ferricyanide-mediated assays such as glucose or lactate, and anticipate that the ultralow cost paper-based cartridges presented here will facilitate the development of quantitative assays at the point of need.