Anti-fouling peptide functionalization of ultraflexible neural probes for long-term neural activity recordings in the brain

Implantable neural probes constitute an essential tool for neuronal activity recordings in basic neuroscience and also hold great promise for the development of neuroprosthesis to restore lost motor or sensory functions of the body. However, conventional neural probes are susceptible to biofouling because of their physicochemical mismatch with neural tissues, resulting in signal degradation in chronic studies. Here, we describe an ultraflexible neural probe (uFNP) with anti-fouling zwitterionic peptide modification for long-term stable neural activity recordings. The anti-fouling zwitterionic peptide consists of two parts: negatively charged glutamic acid (E) and positively charged lysine (K) formed EKEKEK (EK) head to create a hydration layer that resists protein adsorption on the microelectrodes, and a fragment of laminin formed IKVAV tail to increase the adhesion of the microelectrodes to neuronal cells. We demonstrate that EK-IKVAV modified uFNPs can allow for stable neuronal activity recordings over 16 weeks. Immunohistological studies confirm that EK-IKVAV functionalized uFNPs could induce greatly reduced neuronal cell loss. Collectively, these results suggest that the anti-fouling zwitterionic peptide functionalization of uFNPs provide a promising route to construct biocompatible and stable neural interfaces.