Cell-Interface-Deciphering Lipid Nanotablet for Nanoparticle Logic Gate-Based Real-Time Single-Cell Analysis

Analyzing the cell interface is of paramount importance in understanding how cells interact and communicate with other cells, but an advanced analytical platform that can process complex and networked interactions between cell surface ligands and receptors is lacking. Herein, we developed the cell-interface-deciphering lipid nanotablet (CID-LNT) for multiplexed real-time cell analysis. LNT is a nanoparticle-tethered lipid bilayer chip where freely diffusing plasmonic nanoparticles induce scattering signal changes. The CID-LNT transduces cell surface protein information into DNA data, which operate as nanoparticle logic gates. As a proof of concept, we detected and analyzed programmed death-ligand 1 (PD-L1) and associated immune signals (TNF-α, EGF, and IFN-γ). PD-L1 is an immune checkpoint that suppresses T cell activity with inflammatory biomolecules facilitating its expression. The CID-LNT can serve as a dynamic nanoparticle logic board, enabling the logic gate-based analysis of membrane proteins, and can be expanded to immunological synapse analysis, cell interface engineering, and molecular diagnostics.