Prototyping and demonstration of an ultra-sensitive novel micro-resonator for x-band EPR spectroscopy of diluted and volume-limited samples

The National Institute of General Medical Sciences awarded Wichita State University $534,074 on July 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to design, simulate, build, and demonstrate an ultra-sensitive micro-resonator for X-band electron paramagnetic resonance (EPR) spectroscopy.

The project addresses a critical limitation in EPR applications: proteins such as metalloproteins, membrane proteins, and G-proteins—which constitute nearly 30 percent of all drug targets—are often difficult to purify in sufficient quantities to yield measurable signals using standard EPR methods. The proposed micro-resonator is designed to increase X-band EPR spectrometer sensitivity by an order of magnitude, enabling structure-function analysis of low-yield biomacromolecular samples currently poorly understood due to insufficient analytical sensitivity. The resonator design prioritizes manufacturability using standard commercial printed circuit board substrate and seamless integration with existing X-band EPR spectrometers.

Work is performed at Wichita State University in Wichita, Kansas, with a period of performance from July 1, 2026, through June 30, 2029. The funding is classified as a Project Grant under the NIGMS basic research portfolio, which supports investigator-initiated biomedical research to advance understanding of biological processes underlying disease diagnosis, treatment, and prevention.

Abstract

Proteins are often used for drug targets. Understanding the structure, function, and reaction mechanisms of proteins is crucial. Over the last three decades, inductively detected electron paramagnetic resonance (EPR) has been utilized to elucidate the structure, function, and reaction mechanisms of enzymes and membrane proteins, as well as to quantify reactive oxygen and nitrogen species. The EPR is useful because IT is a highly sensitive, powerful, and versatile technique. Proteins such as metalloproteins, membrane proteins, and g-proteins are challenging to purify in sufficient quantities to obtain measurable signals using standard EPR methods. These proteins, metalloproteins, membrane proteins, and g-proteins constitute almost 30% of all drug targets. However, due to the scarcity of sufficient samples, understanding the structure-function relation using EPR is challenging and thus poorly understood. This proposal focuses on developing a novel micro-resonator to increase the sensitivity of the current state-of-the-art x-band EPR spectrometer by an order of magnitude. If successful, the unprecedented sensitivity for EPR spectroscopy would broaden its applicability to low- yield biomacromolecular samples whose structures are currently poorly understood due to a lack of sensitivity. The resonator is at the heart of any EPR spectrometer, which interfaces with the samples and enhances the signal-to-noise ratio. The ultimate goal of the proposed project is to design, simulate, build, and demonstrate the proposed novel micro-resonator. The proposed project also focuses on a resonator design that is easy to manufacture using a standard commercial PCB substrate and integrates seamlessly with the existing x-band EPR spectrometer. The preliminary simulated result indicates that the proposed resonator would exhibit ultra-high sensitivity due to its high quality factor (q ~ 9000), nanoliter fill factor, and highly efficient magnetic field concentration for electron paramagnetic resonance.