Multiplexed cytokine detection using electrochemical point-of-care sensing device towards rapid sepsis endotyping

Tanak, Ambalika S.; Muthukumar, Sriram; Krishnan, Subramaniam; Schully, Kevin L.; Clark, Danielle V.; Prasad, Shalini

The implementation of endotype-driven effective intervention strategies is now considered as an important component for sepsis management. Rapid screening and frequent monitoring of immune responses are critical for evidence-based informed decisions in the early hours of patient arrival. Current technologies focus on pathogen identification that lacks rapid testing of the patient's immune response, impeding clinicians from providing appropriate sepsis treatment. Herein, we demonstrate a first-of-its-kind novel point-of-care device that uses a unique approach by directly monitoring a panel of five cytokine biomarkers (IL-6, IL-8, IL-10, TRAIL & IP-10), that is attributed as a sign of the body's host immune response to sepsis. The developed point-of-care device encompasses a disposable sensor cartridge attached to an electrochemical reader. High sensitivity is achieved owing to the unique sensor design with an array of nanofilm semiconducting/metal electrode interface that is functionalized with specific capture probes to measure target biomarkers simultaneously using non-faradaic electrochemical impedance spectroscopy. The sensor has a detection limit of ∼1 pg/mL and provides results in less than 5 min from a single drop of an undiluted plasma sample. Furthermore, the sensor demonstrates an excellent correlation (Pearson's r > 0.90) with the reference method for a total n = 40 clinical samples and the sensor's performance is ∼30 times faster compared to the standard reference technique. We have demonstrated the sensor's effectiveness to enhance diagnosis with a mechanistic biomarker-guided approach which can be helpful towards disease endotypying for effective clinical management of sepsis at the patient bedside.