Detecting molecular interactions and reactions are basic tasks to understand biochemical processes in living organisms, discover biomarkers and develop drugs. Today's mainstream commercial detection technologies are based on measuring mass changes, which struggle to detect small molecules (e.g., metabolites, hormones, and neurotransmitters), and biochemical reactions involving small mass changes (e.g., protein phosphorylation and other post-translational modifications). However, these molecules and reactions are critical to biological functions, and disease initiation and progression. Small molecules also count for over 90% of FDA approved drugs. To address this unmet need, this project aims to develop a nano-oscillator array (NOA) detection technology. Each nano-oscillator consists of a nanoparticle tethered to a surface plasmon resonance (SPR) sensor surface with a flexible molecular linker. The nanoparticle is pre-functionalized with target proteins. When applying an alternating electric field normal to the sensor surface, the nanoparticle is forced to oscillate, and the oscillation amplitude is measured with a SPR imaging method with sub-nm resolution. This resolution corresponds to a fraction of electron charge, making NOA particularly sensitive to the binding of molecules to the proteins on the nanoparticle, or post-translational modification of the proteins via a change in the net charge or charge distribution of the proteins. Collaborative efforts among Biosensing Instrument, Inc., Arizona State University, and pharmaceutical companies have resulted in substantial preliminary data that demonstrates the powerful potential of NOA. In this fast track project, the team will work together to prepare NOA for commercialization by I) expanding on preliminary and feasibility studies of NOA as a new commercial technology for quantifying small molecule binding and biochemical reactions, II) developing a commercial prototype NOA system, including optical instrumentation, signal processing algorithms, NOA sensor production methods, workflow processes, and application specific tools, and III) carrying out both validation tests and show case studies on NOA enabled applications (i.e. killer applications). The 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.
The project will develop a label-free technology using an array of nano-oscillators (NOA) to detect molecular interactions and biochemistry reactions that involve small mass changes. This new technology will address the unmet need for uncovering cellular signaling mechanisms (e.g., phosphorylation), and screening small molecule drugs.
| Ma, Guangzhong; Syu, Guan-Da; Shan, Xiaonan et al. (2018) Measuring Ligand Binding Kinetics to Membrane Proteins Using Virion Nano-oscillators. J Am Chem Soc 140:11495-11501 |
