Unpredictable protein adsorption on nanoparticles remains a considerable challenge towards effectively applying nanotechnologies in biological environments.1 However, if well understood and controlled, proteins adsorbed on nanoparticles can be exploited to develop protein-based nanosensors.Herein, we employ our knowledge of spontaneous “protein corona” formation on single-walled carbon nanotubes (SWCNTs) in biofluids towards rational nanosensor design based on protein-SWCNT complexation.2 SWCNTs are implemented as the sensor platform due to their desirable optical and physical characteristics, including photostable fluorescence in the near-infrared tissue transparency window3 and high aspect ratio that confers delivery capabilities.4 We functionalize carbon nanotubes with proteins that, in turn, bind to their natural ligand partners. The adsorbed protein thus acts as the recognition moiety that interacts with the environment and detects the analyte of interest, tethered to the SWCNT that serves as the signal transducer. This nanosensor platform combines the sensitive and selective binding capabilities of proteins for their ligand partners with the near-infrared fluorescence readout of SWCNTs that is modulated upon protein-ligand binding. In this manner, we demonstrate that although formation of the nanoparticle protein corona can impede the intended nanobiotechnology application, it also presents an opportunity to create improved protein-nanoparticle architectures by manipulating selective protein adsorption on the nanoparticle surface. References Pinals, R. L. et al. Protein Corona Composition and Dynamics on Carbon Nanotubes in Blood Plasma and Cerebrospinal Fluid. bioRxiv 2020.01.13.905356 (2020) doi:10.1101/2020.01.13.905356.Pinals, R. L., Yang, D., Lui, A., Cao, W. & Landry, M. P. Corona Exchange Dynamics on Carbon Nanotubes by Multiplexed Fluorescence Monitoring. J. Am. Chem. Soc. 142, 1254–1264 (2020).Boghossian, A. A. et al. Near-Infrared Fluorescent Sensors based on Single-Walled Carbon Nanotubes for Life Sciences Applications. ChemSusChem 4, 848–863 (2011).Demirer, G. S. et al. High aspect ratio nanomaterials enable delivery of functional genetic material without DNA integration in mature plants. Nat. Nanotechnol. 14, 456–464 (2019).