Abstract: Electron paramagnetic resonance (EPR) spectroscopy can provide information about the
structure and dynamics of biomacromolecules in physiologically relevant conditions. Its inherently high
sensitivity is still inadequate for some mass-limited samples -- for example, membrane proteins -- which
are notoriously difficult to express, purify, and crystallize. This project aims to decrease the limit of
detection for inductive-detection EPR spectroscopy at room temperature, so that low-yield
biomacromolecular samples can be studied under physiologically relevant conditions. To achieve this
objective, we will use a novel resonator design that bridges the gap between planar microresonators and
conventional cavity resonators. Our novel planar inverse anapole microresonator design provides
nanoliter active volumes combined with high quality factors, providing a projected improvement of two
orders of magnitude in sensitivity at room temperature. Our first aim is to design and fabricate
microresonators for operation at 9 GHz and 34 GHz. First, we will carry out finite element simulations of
the field distributions and reflection coefficients for resonators coupled to waveguides. Based on these
results, we will optimize the device geometry and dimensions to obtain nanoliter magnetic-field hotspots
and high quality-factors. We will fabricate these optimized resonators at the NIST Nanofabrication
facility. Next, we will characterize the microresonators and integrate them into a commercial 9 GHz and
home-built 34 GHz EPR spectrometer. Our second aim is to demonstrate the viability of these resonators
for structural biology EPR spectroscopy experiments. To do this, we will first design and fabricate
microfluidic devices capable of localizing nanoliter sample volumes in the magnetic hotspot volume of
the microresonator. To validate the device performance, we will use a concentration series of spin-labeled
peptides. Finally, to demonstrate applicability to a biomacromolecular sample, we will study the Gprotein
coupled receptor melanopsin. If successfully implemented, this resonator design will achieve an
unprecedented sensitivity for EPR spectroscopy, broadening its applicability to low-yield
biomacromolecular samples whose structures are currently poorly understood.
