Towards single-cell pulsed EPR using VCO-based EPR-on-a-chip detectors

Mohamed Atef Hassan; Michal Kern; Anh Chu; Gatik Kalra; Ekaterina Shabratova; Aleksei Tsarapkin; Neil MacKinnon; Klaus Lips; Christian Teutloff; Robert Bittl; Jan Gerrit Korvink; Jens Anders

doi:10.1515/freq-2022-0096

Article

Towards single-cell pulsed EPR using VCO-based EPR-on-a-chip detectors

Mohamed Atef Hassan , Michal Kern , Anh Chu , Gatik Kalra , Ekaterina Shabratova , Aleksei Tsarapkin , Neil MacKinnon , Klaus Lips , Christian Teutloff , Robert Bittl , Jan Gerrit Korvink and Jens Anders

Published/Copyright: September 16, 2022

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From the journal Frequenz Volume 76 Issue 11-12

Abstract

Electron paramagnetic resonance (EPR) is the gold standard for studying paramagnetic species. As an example, in structural biology, it allows to extract information about distance distributions on the nanometer scale via site-directed spin labeling. Conventional pulsed EPR of biological samples is currently limited to relatively large sample concentrations and cryogenic temperatures, mainly due to low sensitivity and the significant dead time associated with conventional resonator-based EPR setups, essentially precluding in-cell EPR under physiological conditions. This paper presents our latest progress toward single-cell pulsed EPR using VCO-based EPR-on-a-chip (EPRoC) sensors. Together with an analytical model for VCO-based pulsed EPR, we present an experimental scheme to perform dead-time-free pulsed EPR measurements using EPRoC detectors. The proposed scheme is validated using extensive numerical simulations and proof-of-concept experiments on the spin dynamics of an organic radical at room temperature using a custom-designed EPRoC detector operating in the Ka-band around 30.4 GHz. Additionally, we discuss methods to improve the excitation field homogeneity and sample handling through chip post-processing and custom-designed microfluidics. Finally, we present our progress towards compact, portable pulsed EPR spectrometers incorporating EPRoC detectors, microfluidics, and custom-designed permanent magnets. Such portable EPR spectrometers can pave the way toward new EPR applications, including point-of-care diagnostics.

Keywords: dead time free EPR; EPR; EPR-on-a-chip; EPRoC; Rabi oscillations; VCO-based pulsed EPR

Corresponding author: Jens Anders, Institute of Smart Sensors, University of Stuttgart, Pfaffenwaldring 47, 70569 Stuttgart, Germany; and Center for Integrated Quantum Science and Technology, Stuttgart and Ulm, Germany, E-mail: jens.anders@iis.uni-stuttgart.de

Funding source: German Research Foundation (Deutsche Forschungsgemeinschaft)

Award Identifier / Grant number: AN 984/16-1

Award Identifier / Grant number: BI 464/14-1

Award Identifier / Grant number: KO 1883/34-1

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by the DFG within SPP 1857 under contracts no. AN 984/16-1, BI 464/14-1, KO 1883/34-1.
Conflict of interest statement: J.G.K. is a shareholder of Voxalytic GmbH, a company that markets miniaturized NMR equipment. The other authors declare no conflicts of interest.

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Received: 2022-05-01

Accepted: 2022-08-01

Published Online: 2022-09-16

Published in Print: 2022-12-16

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DOI: doi.org/10.1515/freq-2022-0096

Keywords for this article

dead time free EPR; EPR; EPR-on-a-chip; EPRoC; Rabi oscillations; VCO-based pulsed EPR