# Development of high-throughput, high-sensitivity EPR sample handling capabilities for biomedical research

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $371,864

## Abstract

Project Summary/Abstract
Electron paramagnetic resonance (EPR) spectroscopy is a critically important technique in biomedical research
with a unique ability to detect naturally occurring or engineered unpaired electrons in complex biological
environments. EPR has wide-ranging applicability to structural biology, metalloprotein research, redox biology,
rational drug design, and clinical diagnostics. Groundbreaking advancements in sample volume requirements
for biomedical EPR spectroscopy applications were made nearly four decades ago with the development of the
loop-gap resonator (LGR), which represented breakthrough benefits such as 10-fold lower sample volume
requirements and higher resonator efficiencies to increase signals over the commonly used cavity resonator. To
accommodate the biomedical needs of even further increased signal intensity and to provide the broader
scientific community with accessible technology, we propose to capitalize on our recent development of the
dielectric LGR (dLGR) concept and optimize this resonator technology to increase sensitivity beyond that
achieved upon introduction of the LGR. A dLGR is effectively a small dielectric resonator placed inside the inner
loop of an LGR where the return flux of the dielectric flows through the outer loops of the LGR. Analytic theory
and our high-frequency structure simulations indicate that the dLGR enables an order-of-magnitude
improvement in sensitivity over the LGR. To take full advantage of the extremely low volume requirements for
the dLGR, we propose to develop efficient sample handling technologies that couple the dLGR to high-
throughput sample handling instrumentation. We aim to develop two transformative technologies for biomedical
EPR applications: i) a nano-dLGR with a 10-fold increase in sensitivity for ~0.2 µL sample volumes integrated
with a customized autosampler and ii) a micro-dLGR for a dramatic increase in sensitivity for ~2 µL sample
volumes with an optimized stopped-flow system for millisecond time scale kinetics measurements. These
transformative and innovative prototypes with outstanding sensitivity will be easy to use and ultimately widely
available to the scientific community. Where the LGR was a transformative advance compared with cavity
resonators, the dLGR is expected to be another transformative leap from an LGR.

## Key facts

- **NIH application ID:** 10744232
- **Project number:** 5R01GM140385-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** CANDICE S KLUG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $371,864
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10744232

## Citation

> US National Institutes of Health, RePORTER application 10744232, Development of high-throughput, high-sensitivity EPR sample handling capabilities for biomedical research (5R01GM140385-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10744232. Licensed CC0.

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