On-Chip Electrical Monitoring of Real-Time Soft and Hard Protein Corona Formation on Carbon Nanoparticles

When nanoparticles encounter a biological fluid, proteins, lipids, and other biomolecules adsorb on the nanoscale surface consequently leading to the evolution of a protein shell or corona. The corona formed is dynamic in nature and depends on the synthetic identity of the NPs, ultimately affecting their biological response. In this paper, an integrated microfluidic platform coupled with an electrical resistance measurement setup is developed to monitor and investigate the real-time formation of a biomolecular corona of carbon nanoparticles. Soft and hard corona formation stages are effectively discriminated based on their nanoscale surface chemistries when combined with a time-frequency tool known as wavelet transform and machine-learning techniques. Additionally, the corona and its composition are studied using different techniques such as dynamic light scattering, nanoparticle tracking analysis, zeta potential, excitation-emission profiles, 1D sodium dodecyl polyacrylamide gel electrophoresis and subsequently, liquid chromatography-mass spectrometry analysis. The dynamic setup can eventually be used as a valuable tool for screening of any nanoparticles formulations with distinct surface chemistries for the purpose of reduced protein adsorption/weaker protein corona formation and consequently enhance the success of targeted drug delivery.