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| Format: | Preprint |
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2025
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| Online Access: | https://arxiv.org/abs/2508.12499 |
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| _version_ | 1866911725234683904 |
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| author | Huver, Sean D. |
| author_facet | Huver, Sean D. |
| contents | The characterization of ligand--receptor interactions is a cornerstone of modern pharmacology; however, current methods are hampered by limitations such as ensemble averaging and invasive labeling. We propose a theoretical quantum sensing solution, the Quantum Ligand-Binding Interrogator (QLI), designed to overcome these challenges. The QLI is a differential sensor, or gradiometer, that uses a pair of co-trapped atomic ions to perform label-free detection of the electric field gradient produced by a single ligand binding to its receptor in vitrified samples. This gradiometric approach provides robust common-mode rejection of background electric field noise. To bridge the gap between the cryogenic, ultra-high-vacuum environment required for the sensor and the biological sample, we propose an architecture based on a vitrified sample mounted on a scanning probe. This enables the detection of the electrostatic signature of a single molecule in a specific conformational state (e.g., bound vs.\ unbound). This paper details the conceptual framework of the QLI, the experimental architecture, the measurement protocol using entangled two-ion spin states, and an analysis of key engineering risks. Anchoring to state-of-the-art single-ion low-frequency sensitivities (sub-mV\,m$^{-1}$/\,$\sqrt{\mathrm{Hz}}$), we project SNR\,=\,1 in tens of seconds at a 10\,\textmu m ion--sample separation for $Δp \sim 20$\,D, with feasibility dominated by the (as yet unmeasured) electrostatic stability of vitrified samples. If realized, QLI would provide direct single-molecule measurements of binding-induced electric field changes, offering a new path for experimental validation of computational models of drug--receptor interactions. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2508_12499 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | A Ramsey Ion Gradiometer for Single-Molecule State Detection Huver, Sean D. Quantum Physics The characterization of ligand--receptor interactions is a cornerstone of modern pharmacology; however, current methods are hampered by limitations such as ensemble averaging and invasive labeling. We propose a theoretical quantum sensing solution, the Quantum Ligand-Binding Interrogator (QLI), designed to overcome these challenges. The QLI is a differential sensor, or gradiometer, that uses a pair of co-trapped atomic ions to perform label-free detection of the electric field gradient produced by a single ligand binding to its receptor in vitrified samples. This gradiometric approach provides robust common-mode rejection of background electric field noise. To bridge the gap between the cryogenic, ultra-high-vacuum environment required for the sensor and the biological sample, we propose an architecture based on a vitrified sample mounted on a scanning probe. This enables the detection of the electrostatic signature of a single molecule in a specific conformational state (e.g., bound vs.\ unbound). This paper details the conceptual framework of the QLI, the experimental architecture, the measurement protocol using entangled two-ion spin states, and an analysis of key engineering risks. Anchoring to state-of-the-art single-ion low-frequency sensitivities (sub-mV\,m$^{-1}$/\,$\sqrt{\mathrm{Hz}}$), we project SNR\,=\,1 in tens of seconds at a 10\,\textmu m ion--sample separation for $Δp \sim 20$\,D, with feasibility dominated by the (as yet unmeasured) electrostatic stability of vitrified samples. If realized, QLI would provide direct single-molecule measurements of binding-induced electric field changes, offering a new path for experimental validation of computational models of drug--receptor interactions. |
| title | A Ramsey Ion Gradiometer for Single-Molecule State Detection |
| topic | Quantum Physics |
| url | https://arxiv.org/abs/2508.12499 |