Development and Validation of a Continuous Real-Time Optical Sensor for Indocyanine Green Clearance Measurement During Ex-Vivo Perfusion of Human Livers

Abstract

Liver transplantation remains the only curative treatment for end-stage liver failure, yet its impact is constrained by organ shortages and graft non-utilisation. Machine perfusion (MP) enables ex-vivo assessment of donated livers; however, existing viability criteria rely on intermittent sampling, reducing temporal resolution and accuracy. Indocyanine green (ICG), a clinically validated dye cleared exclusively by hepatocytes, provides a continuous index of hepatic function beyond initial injury. Accordingly, we present a non-invasive, clamp-on optical sensor that enables continuous, real-time quantification of ICG clearance during MP. The sensor consists of a clamp-on module with an 808nm laser and phototransistor connected to a microcontroller-based unit and computer for real-time plotting. The raw phototransistor signal was linearised to a unitless absorbance signal proportional to perfusate ICG; bi-exponential fitting yielded plasma disappearance rate (PDRbi, %/min) and the 15-minute residual fraction (R15). Across 10 whole and 3 split human livers (45 boluses; 13 paired with spectrophotometry), the sensor closely matched spectrophotometric measurements (mean R2 = 0.994; range 0.983-0.999). The sensor resolved expected physiological trends: ICG clearance increased with temperature (PDRbi: 8.2%/min (subnormothermic MP) to 22.6%/min (normothermic MP) (n=4); 9.3%/min (32{degrees}C) to 11.9%/min (36{degrees}C) (n=1)). The sensors continuous signal traces also revealed early mixing dynamics and medication-related effects that are missed by intermittent sampling. This optical sensor enables accurate, real-time monitoring of ICG clearance during ex-vivo perfusion. The ex-vivo setting is uniquely positioned to validate ICG clearance models and enhance clinical interpretation.