Towards a Universal Biosensing Platform based on Graphene/Pyrene Surfaces for Neurotransmitters

The development of new therapeutic treatments and diagnosis of neural-related illnesses is linked to research in the electronic devices field. Devices as neural implants allow the recording of electrical signals to better understand the central and peripheral nervous systems^1,2and, therefore, advance in the diagnosis and treatment of these diseases. One of the main issues of current implants, mostly based on silicon technology (and thus, rigid) is that they are invasive. The use of graphene-based transistors may overcome this drawback, taking advantage of graphene’s mechanical and electronic properties, and also opening the possibility to include chemical recording capabilities to the implant. Here, we develop a versatile graphene/pyrenebutyric acid (PyBA) platform for the detection of neurotransmitters, or other analytes of interest, while recording electrical neural activity.<br/><br/>To build this platform, we perform physical evaporation of PyBA, a molecule capable to interact with the p system of graphene thanks to its aromatic nature, and to covalently interact, due to its carboxylic group, with an aptamer of interest through the formation of a peptide bond.<br/>We optimize the PyBA evaporation conditions, which are those leading to the formation of a PyBA monolayer on the surface of graphene. This optimization and further detailed characterization of the pyrenebutyric layer is key for ensuring an understanding of the future sensor functionality.<br/>The viability of the system is studied with electrical characterizations of the transistors fabricated including the PyBA layer on graphene.<br/>Then, the binding of an aptamer that recognizes a specific neurotransmitter – thrombin in our particular case- is explored and used as a prove of the utility of the platform presented. Thrombin is detected by electrical characterization of the functionalized graphene transistors, while morphological characterization of the samples is performed by Atomic force microscopy (AFM) and Raman spectroscopy.<br/>The thrombin biosensing results reveal changes in the electrical properties of graphene corresponding to each concentration tested, and the detection range achieved is correspondent to the one achieved by reported approaches based on in-liquid functionalization³ – more difficult to control-. This demonstrates the ability of the system to recognize the analyte of interest through binding to its specific aptamer. This graphene/PyBA universal biosensing platform is in the pipeline for the development of a new generation of multifunctional graphene-based neural implants.<br/><br/><b>REFERENCES</b><br/><br/>1. Masvidal-Codina, E., Illa, X., Dasilva, M., et al (2019) High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors, <i>Nature Mater</i>.<br/>2. Garcia-Cortadella, R., Schwesig, G., Jeschke, C., et al (2021) Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity, <i>Nat Commun.</i><br/>3. Hinnemo, M., Zhau, J., Ahlberg, P., et al (2017) On Monolayer Formation of Pyrenebutyric Acid on Graphene, <i>Langmuir.</i>