Joint Entropy-Assisted Graphene Oxide-Based Multiplexing Biosensing Platform for Simultaneous Detection of Multiple Proteases.

Due to the limited clinical utility of individual biomarkers, there is growing recognition of the need for combining multiple biomarkers as a panel to improve the accuracy and efficacy of disease diagnosis and prognosis. The conventional method to detect multiple analyte species is to construct a sensor array, which consists of an array of individual selective probes for different species. In this work, by using cancer biomarker matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs) as model analytes and functionalized nanographene oxide (nGO) as a sensing element, we developed a multiplexing fluorescence sensor in a nonarray format for simultaneous measurement of the activities of multiple proteases. The constructed nGO-based biosensor was rapid, sensitive, and selective and was also utilized for the successful profiling of ADAMs/MMPs in simulated serum samples. Furthermore, we showed that joint entropy and programming could be utilized to guide experiment design, especially in terms of the selection of a subset of proteases from the entire MMPs/ADAMs family as an appropriate biomarker panel. Our developed nGO-based multiplex sensing platform should find useful application in early cancer detection and diagnosis.