(182d) Magneto-Nanosensors for Detecting Novel Protein Interactions and Early Stage Diseases

Substantial efforts have been made to understand the interactions between immune checkpoint receptors and their ligands targeted in immunotherapies against cancer. To carefully characterize the complete network of interactions involved and the binding affinities between their extracellular domains, an improved kinetic assay is needed to overcome limitations with surface plasmon resonance (SPR). Here we present a magneto-nanosensor platform integrated with a microfluidic chip that allows measurement of dissociation constants in the micromolar-range. High-density conjugation of magnetic nanoparticles with prey proteins allows multivalent receptor interactions with sensor-immobilized bait proteins, more closely mimicking natural receptor clustering on cells. The platform has advantages over traditional SPR in terms of insensitivity of signal responses to pH and salinity, less consumption of proteins, and better sensitivities. Using this platform, we characterized the binding affinities of the PD-1 â?? PD-L1/PD-L2 co-inhibitory receptor system, and discovered an unexpected interaction between the two known PD-1 ligands, PD-L1 and PD-L2.

The magneto-nanosensors are also well-suited for medical diagnostics of diseases at early stages because they possess attomolar to femtomolar sensitivities for protein biomarkers. The technology platform has been applied to in vitro diagnostics of lung cancer, prostate cancer, liver cancer, autoimmunity, radiation exposure, hepatitis, and cannabis abuse. The magneto-nanosensors are being adapted for point of care settings, mobile health, and global health, and Qualcomm Tricorder XPRIZE competition.

This work is supported in part by National Cancer Institute (NCI) through the Stanford Center for Cancer Nanotechnology Excellence (U54CA151459) and by National Institute of Allergy and Infectious Diseases (NIAID) through the Autoimmunity Center of Excellence (ACE) at Stanford (U19AI110491).