Slippery Viscosity-Sensing Platform with Time Readout for the Detection of Hyaluronidase and Its Inhibitor

Hyaluronidase (HAase) is a biomarker for cancer, and its detection is of great significance for early diagnosis. However, the requirement of sophisticated instruments, tedious operation procedures, and labeled molecules of conventional HAase biosensing methods hampers their widespread applications. Herein, we report a portable slippery viscosity-sensing platform with time readout for the first time and demonstrate HAase and tannic acid (TA, HAase inhibitor) detection as a model system. HAase specifically cleaves hyaluronic acid (HA) and decreases HA solution viscosity, thereby shortening the aqueous droplet's sliding time on a slippery surface. Thus, the HA solution viscosity alteration due to enzymatic hydrolysis is used to quantify the HAase concentration through the difference in the sliding time of the aqueous droplets on a slippery surface. The developed HAase sensing platform exhibits high sensitivity with a minimum detection limit of 0.23 U/mL and excellent specificity without the use of specialized instruments and labeled molecules. HAase detection in actual urine samples by a standard addition method is performed as well. Moreover, the quantitative detection of TA with an IC50 value of 37.68 ± 1.38 μg/mL is achieved. As an equipment-free, label-free, and high-portability sensing platform, this method holds promise in developing a user-friendly and inexpensive point-of-care testing (POCT) device for HAase detection, and its use can be extended to analyze other analytes with different stimuli-responsive polymers for great universality and expansibility in biosensing applications.