Nano-Oscillator Arrays for Sensitive Plasmonic Detection of Molecular Interactions and Reactions

ABSTRACT Detecting molecular interactions and reactions are basic tasks to understand biochemical processes in living organismsdiscover biomarkers and develop drugsTodayandapos s mainstream commercial detection technologies are based on measuring mass changeswhich struggle to detect small moleculese gmetaboliteshormonesand neurotransmittersand biochemical reactions involving small mass changese gprotein phosphorylation and other post translational modificationsHoweverthese molecules and reactions are critical to biological functionsand disease initiation and progressionSmall molecules also count for overof FDA approved drugsTo address this unmet needthis project aims to develop a nano oscillator arrayNOAdetection technologyEach nano oscillator consists of a nanoparticle tethered to a surface plasmon resonanceSPRsensor surface with a flexible molecular linkerThe nanoparticle is pre functionalized with target proteinsWhen applying an alternating electric field normal to the sensor surfacethe nanoparticle is forced to oscillateand the oscillation amplitude is measured with a SPR imaging method with sub nm resolutionThis resolution corresponds to a fraction of electron chargemaking NOA particularly sensitive to the binding of molecules to the proteins on the nanoparticleor post translational modification of the proteins via a change in the net charge or charge distribution of the proteinsCollaborative efforts among Biosensing InstrumentIncArizona State Universityand pharmaceutical companies have resulted in substantial preliminary data that demonstrates the powerful potential of NOAIn this fast track projectthe team will work together to prepare NOA for commercialization by Iexpanding on preliminary and feasibility studies of NOA as a new commercial technology for quantifying small molecule binding and biochemical reactionsIIdeveloping a commercial prototype NOA systemincluding optical instrumentationsignal processing algorithmsNOA sensor production methodsworkflow processesand application specific toolsand IIIcarrying out both validation tests and show case studies on NOA enabled applicationsi ekiller applicationsThe success of this project will lead to a new technology to address the unmet need for quantifying small molecule binding kinetics and biochemical reactions kinetics PROJECT NARRATIVE The project will develop a label free technology using an array of nano oscillatorsNOAto detect molecular interactions and biochemistry reactions that involve small mass changesThis new technology will address the unmet need for uncovering cellular signaling mechanismse gphosphorylationand screening small molecule drugs