Magnetometry of neurons using a superconducting qubit

Iron's crucial physiological and pathological roles in the human body necessitate microscopic analysis, including redox status assessment. However, conventional electron spin resonance (ESR) spectroscopy faces limitations in spatial resolution and sensitivity. This study aims to overcome these limitations by employing a superconducting flux qubit as a highly sensitive, microscale magnetometer to perform ESR spectroscopy on cultured neurons. The goal is to achieve single-cell ESR spectroscopy, providing a spectroscopic fingerprint for individual cells, thereby advancing our understanding of cellular iron metabolism and its implications in various diseases.

Existing techniques for analyzing metallic elements in cells include mass spectrometry (MS) and optical methods like Raman spectroscopy. While MS offers quantitative analysis, it requires cell homogenization, preventing in situ investigation. Optical methods allow in situ observation but lack detailed information about element valence and coordination. Conventional ESR spectroscopy can provide this detailed information, but its spatial resolution and sensitivity are insufficient for single-cell analysis. Microscale magnetometers, such as scanning Hall probe microscopes, magnetic force microscopes, nitrogen-vacancy centers in diamond, and SQUIDs, have been explored, but they often compromise between spatial resolution and sensitivity. Superconducting devices offer a potential solution, allowing for tunable spatial resolution and a balance between these two factors. Recent advancements in superconducting technologies have led to the development of superconducting ESR spectrometers using either superconducting resonators or magnetometers like SQUIDs or superconducting flux qubits, offering high sensitivity at the microscale.

Cultured neurons on a parylene-C film were placed on a superconducting flux qubit chip. The qubit served as a sensitive magnetometer, detecting changes in magnetization by monitoring its resonance frequency shift when an in-plane magnetic field (B||) was applied to polarize electron spins in the neurons. Magnetometry was performed at various temperatures (12.5–200 mK) and magnetic fields (2.5–12.5 mT). To enhance signal intensity, neurons were cultured in an Fe³⁺-rich medium. A conventional X-band ESR spectrometer was used to verify the origin of the magnetization signal from the neurons cultured under the same conditions. The distance between the qubit and neurons was minimized using ethanol to promote adhesion and was estimated to be a few micrometers using an optical interference method. The authors calculated the average distance between neurons to be 14 µm, similar to the qubit size, indicating that the qubit primarily interacts with one neuron. The electron spin Hamiltonian of iron ions within the cells was used to model the field and temperature dependence of the magnetization. The spin temperature was determined by comparing the experimental results to the theoretical prediction considering the low thermal conductivity of parylene-C.

The study successfully detected the magnetization signal from cultured neurons using a superconducting flux qubit. The magnetization signal exhibited temperature and magnetic field dependence consistent with the behavior of electron spins of Fe³⁺ ions. The signal was significantly higher than the background signal from the parylene-C film alone. Conventional ESR spectroscopy confirmed that the magnetization signal originated from iron ions in the neurons, specifically demonstrating characteristic peaks corresponding to the high-spin state iron at g’ = 4.3 and 9.8. The results indicated that the sensing area of the qubit encompasses a single neuron and that the spin density is consistent between the qubit magnetometry and conventional ESR spectroscopy. The effective spin temperature was found to deviate from the cold plate temperature in the low temperature range, suggesting the need for materials with higher thermal conductivity for insulation.

The successful detection of electron spins in single neurons using a superconducting flux qubit opens up new possibilities for single-cell ESR spectroscopy. This technique addresses the limitations of conventional ESR by providing high sensitivity and spatial resolution at the cellular level. The observed temperature and magnetic field dependence of the magnetization signal, confirmed by conventional ESR, directly supports the identification of iron ions as the source of the signal. The study's findings have implications for understanding cellular iron metabolism, transport and distribution and their roles in health and disease. The close correspondence between the spin density estimated from the qubit magnetometry and the conventional ESR further validates the results.

This study successfully demonstrated the detection of electron spins in cultured neurons using a superconducting flux qubit. The technique offers the potential for single-cell ESR spectroscopy, providing spectroscopic fingerprints of individual cells. Future work could focus on improving thermal conductivity to achieve better spin temperature control, using materials compatible with higher magnetic fields to explore the saturation regime and obtain more material parameters, and developing qubit arrays for magnetic imaging of iron ions within tissues. This technology holds promise for understanding cellular iron metabolism and related diseases.

The study's primary limitation is the low thermal conductivity of the parylene-C film used for insulation, which led to a discrepancy between the spin temperature and the cold plate temperature. This affected the accuracy in determining material parameters from the magnetization curve. Additionally, the current qubit design is limited to in-plane magnetic fields below 20 mT, preventing the observation of full magnetization saturation. Furthermore, a precise conversion factor from magnetization to the number of spins is needed for a fully quantitative analysis.