Ultrasensitive Ion-Selective Optodes for Self-Testing of Blood Electrolytes

SUMMARY Electrolyte imbalances are the cause or the consequence of a variety of endocrine, renal, cardiac, and hepatic disorders. It has been envisioned that self-testing of electrolyte levels by patients will revolutionize the management of chronic conditions such as hypoparathyroidism, arginine vasopressin deficiency, congestive heart failure, and kidney failure, akin to the revolution witnessed in diabetes management through self-testing of blood sugars. However, in contrast to the widespread success of minimally invasive self-monitoring devices for glucose, there are currently no products designed for quantitative measurements of blood electrolytes by non- healthcare professionals. Although blood gas/electrolyte analyzers have been prevalent in hospitals for decades, the minimum required blood volume is hundreds of times greater than that of a typical glucose strip, and the analyzer price is hundreds of times higher than that of a glucometer. These limitations prohibit their use in decentralized settings such as patients’ homes for self-monitoring. Using the calcium ion as an example analyte, we have recently developed a novel colorimetric ion sensor (ultrasensitive ion-selective liquid optode) capable of detecting electrolytes in only a few microliters of whole blood. The optode is a non-volatile and viscous oil that contains hydrophobic sensing chemicals including an ionophore to recognize the analyte ion, a dye as the optical reporter, and an ion exchanger to maintain the charge balance. The target electrolyte from blood is selectively extracted into the sensing oil to change the oil color. The oil is uniquely formulated to yield an exceptionally large color response within the very narrow clinical range of the electrolyte, ensuring high-precision and high-confidence measurements. In this project, we aim to 1) develop ultrasensitive ion-selective optodes to measure blood electrolytes, including calcium, sodium, potassium, magnesium, and chloride ions, for the management of corresponding diseases, 2) select the calcium sensor as an example to conduct a clinical validation study using venous and fingerprick blood samples from patients with thyroid and parathyroid disorders; 3) design a multiplexed sensing platform for simultaneous measurements of multiple electrolytes in a drop of blood. The handheld electrolyte monitor will consist of a stepper motor-based liquid control module, a mini camera serving as the optical detector, and a single-use colorimetric sensor. The permanent component will cost a few hundred dollars, while each disposable part will cost no more than a dollar. The required blood (1-3 microliters) can be easily obtained through finger pricks using small-sized lancets without the finger squeezing that often causes hemolysis. If successful, this home-use technology will empower patients to self-monitor their blood electrolytes in a timely and frequent manner, minimizing complications and risks associated with their chronic diseases.