Ion-modulated interfacial fluorescence in droplet microfluidics using an ionophore-doped oil.

Fluorescence at the oil-water interface is used for chemical sensing in droplet microfluidics. Potassium ions in aqueous droplets are extracted into oil segments doped with an ionophore, a cation exchanger, and a cationic dye to expel the dye. When a low concentration of dye with a balanced solubility is used, it actively accumulates at the thin interface between oil and water instead of getting dissolved in the aqueous phase. The interfacial fluorescence is monitored distinct from the fluorescence in the oil sensor and the aqueous sample, allowing for highly sensitive and selective turn-on fluorescence sensing of ions.

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

The self-monitoring of electrolytes using a small volume of capillary blood is needed for the management of many chronic diseases. Herein, we report an ionophore-based colorimetric sensor for electrolyte measurements in a few microliters of blood. The sensor is a pipet 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 electrolytes in a very narrow concentration range that is clinically relevant. This ultrahigh sensitivity is based on an exhaustive response mode with a novel mechanism for defining the 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 independent of the sample and therefore works for whole blood without requiring plasma separation; (2) the sensor does not need individual calibration as the consistency between liquid sensors is high compared to solid sensors, such as ion-selective electrodes and optodes; and (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 concentrations of total plasma Ca2+. Oil sensors with an ultrasensitive response can also be obtained for other ions, such as K+.

Ion-Induced Phase Transfer of Cationic Dyes for Fluorescence-Based Electrolyte Sensing in Droplet Microfluidics.

Fluorescence-based sensing in droplet microfluidics requires small sample volumes, allows for high-throughput assays, and does not suffer from photobleaching as each flowing sensor is only scanned one time. In this paper, we report a selective and sensitive fluorescence-based ion-sensing methodology in droplet microfluidics using a T-junction PDMS chip. The oil stream is doped with sensor ingredients including an ionophore, a cation exchanger, and a permanently cationic fluorophore as the optical reporter. Electrolyte cations from the aqueous sample are extracted into oil segments and displace the cationic dyes into aqueous droplets. Laser-induced fluorescence of the two immiscible phases is collected alternately, which is in clear contrast to most other ion-selective optode configurations such as nanoparticle suspensions that rely on mixed optical signals of two phases. The cation exchanger, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, is found to dramatically enhance the dye emission in the nonpolar sensing oil by preventing ion-pairing interactions and aggregations of the dye molecules, providing new insights into the mechanism of cationic dye-based ion sensors. The high dye brightness allows us to use low concentrations of sensing chemicals (e.g., 10 µM) in the oil and attain high sensitivity for detection of ions in an equal volume of sample. Using valinomycin as the ionophore and methylene blue as the dye, K+ is detected with a response time of ∼11 s, a logarithmic linear range of 10-5 to 10-2 M, a 20-fold total fluorescence response, >1000-fold selectivity against other electrolyte cations, and negligible cross-sensitivity toward the sample pH. The K+ concentration in untreated and undiluted whole blood and sweat samples is successfully determined by this microfluidic sensing method without optical interference from the droplet sample to the sensing oil. Detection of other ionic analytes can be achieved using the corresponding ionophores.