Nanoarray-based assays offer advantages over standard microarray assays such as minimal sample consumption, high efficiency, and enhanced multiplexing capacity. However, despite their potential, they face challenges such as the complexity and high cost of spotting and fabrication, as well as a lack of effective detection schemes. This impedes many practical applications and more widespread adoption.
Membrane proteins, such as G protein-coupled receptors (GPCRs), ion channels, and transporters, are critical for many cellular functions and represent over 60% of drug targets. Because of this, it is important to measure their binding activities with molecular ligands and drug candidates. However due to difficulties in extraction, purification, and preservation of physiological functions, they are hard to study as well as develop therapeutics that target them. Current approaches to studying membrane proteins lack sufficient throughput to be used on large drug libraries.
Researchers at the Biodesign Institute of Arizona State University have developed a novel spotting-free nanoarray platform utilizing a virion display technique to study membrane proteins in their native states. In this method, barcoded nanoparticle-conjugated virions are anchored to a gold chip via flexible molecular linkers, and act as nano-oscillators in an alternating electric field. These nano-oscillators are self-assembled to form a barcoded, spotting-free nanoarray, which can be detected through plasmonic imaging. Using these nano-oscillators, quantitative characterization of small molecule ligand binding kinetics to membrane proteins, at single molecule resolution, is enabled. Multiplexed decoding and affinity-addressed barcodes enhance efficiency in this innovative nanoarray platform.
This breakthrough technology opens avenues for drug screening and sensing applications in biological and biomedical research, offering a promising tool for advancing the study of membrane proteins and facilitating drug discovery.
Potential Applications
- Nanoarray platform for studying membrane proteins
- Drug discovery/screening
- Validate new therapies for cancer and other diseases
- Sensing applications for biological and biomedical research such as determining disease-related cellular signaling processes
- Membrane protein research
Benefits and Advantages
- Multiplexing capabilities without the need to print the nanoarray
- Enables low zoom imaging with large FOV for higher throughput
- Compatible with commercial SPRi systems
- Self-assembled for spotting-free nanoarray fabrication
- Allows for quantitative characterization of small molecule ligand binding kinetics to membrane proteins at the single nano-oscillator resolution
For more information about the inventor(s) and their research, please see