Multiresolution Functional Characterization and Correction of Biofouling for Improved Biosensing Efficacy

Multielectrode electrochemical biosensors promise on-the-spot inspection of target compounds in biofluids, reducing costs in personalized healthcare. However, sensor sensitivity may decrease after each use due to biofouling, where chemical attachments on sensor electrodes curtail sensing signals. Current biofouling characterization techniques rely on time-consuming offline tests and analysis, making them impractical for on-the-spot signal correction. Alternatively, we propose to statistically model and correct the biofouling-induced signal changes. However, in addition to biofouling, the signals are influenced by multiple sources of variation, each with different levels of impact. To effectively characterize and separate biofouling effects from the major sources of variability, we establish a multiresolution functional mixed-effect model based on domain knowledge. A biosensing signal is first decomposed into a smooth trend and local peaks. The smooth trend models the effects of population-level biofluid composition, as well as patient and electrode effects to isolate variability sources. Changes in local peak location and amplitude indicate biofouling. These local peaks are modeled using a sparse subset of high-order functional terms. By modeling the changes of those high-order terms, we can characterize and predict the biofouling between consecutive measurements. We propose a sequential parameter estimation procedure that ensures model identifiability. A nonparametric regression model is developed for biofouling prediction. The proposed strategy is validated through simulation and real case studies, effectively correcting biofouling-affected signals from new patients.