Ultrasensitive Ionophore-Based Liquid Sensors for Colorimetric Ion Measurements in Whole Blood

Self-monitoring of electrolytes using a small volume of capillary blood is needed for the management of many chronic dis-eases. Herein we report an ionophore-based colorimetric sensor for electrolyte measurements in a small drop of blood. The sensor is a pipette microtip preloaded with a segment of oil (plasticizer) containing a pH-sensitive chromoionophore, a cation exchanger, and an ionophore. The analyte is extracted from the sample into the oil via a mixing protocol controlled by a stepper motor. The oil with an optimized ratio of sensing chemicals shows an unprecedentedly large color response for elec-trolytes in the very narrow concentration range of clinical relevance. This ultrahigh sensitivity is based on an exhaustive re-sponse mode with a novel mechanism of defining lower and higher limits of detection. Compared to previous optodes and molecular probes for ions, the proposed platform is especially suitable for at-home blood electrolyte measurements because 1) the oil sensor is interrogated independently from the sample and, therefore, works for whole blood without requiring plasma separation; 2) the liquid sensor does not need individual calibration as the consistency between sensors from the same solution or different batches of solution is high compared to solid sensors such as ion-selective electrodes and optodes; 3) the sensing system consisting of a disposable oil sensor, a programmed stepper motor, and a smartphone is portable, cost-effective, and user-friendly. The accuracy and precision of Ca2+ sensors are validated in 51 blood samples with varying con-centrations of total plasma Ca2+. Oil sensors with an ultrasensitive response can also be obtained for other ions such as K+.