This paper reports on recent research creating a family of electrophoresis-based point of care devices for the determination of a wide range of ionic analytes in various sample matrices. These devices are based on a first version for the point-of-care measurement of Li+, reported in 2010 by Floris etal. (Lab Chip 2010, 10, 1799-1806). With respect to this device, significant improvements in accuracy, precision, detection limit, and reliability have been obtained especially by the use of multiple injections of one sample on a single chip and integrated data analysis. Internal and external validation by clinical laboratories for the determination of analytes in real patients by a self-test is reported. For Li+ in blood better precision than the standard clinical determination for Li+ was achieved. For Na+ in human urine the method was found to be within the clinical acceptability limits. In a veterinary application, Ca2+ and Mg2+ were determined in bovine blood by means of the same chip, but using a different platform. Finally, promising preliminary results are reported with the Medimate platform for the determination of creatinine in whole blood and quantification of both cations and anions through replicate measurements on the same sample with the same chip.