Detection of ferric ions in neurons using a superconducting flux qubit — Towards pathology examinations at the single-cell level —

1．Background

Iron is a most abundant trace element in the human body and plays important physiologic and pathologic roles. One of the most frequently used methods to investigate such metallic elements is electron spin resonance (ESR) 2. The ESR spectrum gives fruitful information about trace elements like redox states. However, a conventional spectrometer requires several milliliters of sample, containing more than 1013 spins. This feature prevents the investigation of trace elements at a single-cell level or imaging of the distribution of metallic ions.

The research group had previously identified impurities in solid-state materials by using a superconducting flux qubit. This method features a high sensitivity of 20 spins/√Hz and high spatial resolution of a few micrometers. It is also possible to apply it to biosensing, in which trace elements in biological tissues are analyzed, at a single-cell level.


2．Achievements

The research group measured the magnetization 3 from neurons by using a highly sensitive magnetometer based on a superconducting flux qubit (Fig. 1). Combining magnetometry and conventional ESR spectral measurements, the origin of the magnetization was identified as ferric ions in the neurons. The magnetometry also gave quantitative information: the dried neurons contained iron with a concentration of 6 μg/g, a value that is consistent with the literature reports.

This result can be extended to a broad range of biomaterials. By imaging trace elements at the single-cell level, more detailed information can be obtained in pathological examinations.

NTT designed the experiment, prepared the neurons, and measured the superconducting qubit. Shizuoka University performed ESR spectroscopy.

3． Technical features

(1) A superconducting flux qubit is used as a magnetometer with high sensitivity and high spatial resolution. The qubit can detect 20 electron spins (ferric ions), and the detection area is typically several to 100 μm2, as determined by the loop area of the flux qubit.

(2) Neurons are cultured on a biocompatible insulation film, parylene 4. The thickness of the film should be minimized to keep high magnetic sensitivity. In this study, the thickness was 2 μm (Fig. 4).


4． Outlook

The reported method enables magnetometry of biological samples at the single-cell level with quantitative information. A conventional ESR spectrometer 5 is currently used to identify the ion species. In future, the method will be improved to perform ESR spectroscopy on chip.

The sensitivity and spatial resolution will be further improved towards single spin detection. The development of the sensing schemes with high sensitivity and high spatial resolution may lead to the realization of advanced pathology examinations that will enable advanced treatments of diseases.


[Technical details]

[1] Magnetometry using a superconducting flux qubit
The superconducting flux qubit used in this study is one of several kinds of superconducting qubit. A flux qubit is suitable for magnetometry since its sensitivity to a magnetic field can be enhanced by changing the design parameters. The sample for magnetometry was prepared by culturing neurons on parylene film and bonding the film to the qubit chip. Parylene was used as an insulation film to electrically isolate the qubit from the neurons.
The magnetization of the sample originates from the alignment of electron spins. By applying a magnetic field to a sample, unpaired electrons 6 align at low temperatures, resulting in a large magnetization. On the other hand, unpaired electrons are randomly oriented at high temperatures, resulting in a small magnetization. This phenomenon was confirmed by magnetometry using a superconducting flux qubit. The circles in Fig. 2 (a) show the temperature dependence of the magnetization under a magnetic field of 10 mT. The magnetic flux detected by the superconducting flux qubit increased as the temperature decreased. Here, the magnetization of the sample was detected as magnetic flux. The magnetization of the sample also depends on the applied magnetic field, as investigated in Fig. 2 (b). The figure clearly shows that the magnetization increased as the applied field increased. These experimental results indicate that the sample contained unpaired electrons.

[2] Identification of the origin of the magnetization
To determine the origin of the magnetization, we performed magnetometry with different experimental configurations. The magnetization may have originated from the neurons, insulation film, or both. The magnetization of the insulation film itself was measured as a control [Fig. 2 (b), triangles]. Compared with the results for the sample with neurons, it can be seen that the contribution to the magnetization from the insulation film is negligible. This proves that the neurons mainly contributed to the magnetization.
Neurons may contain several different trace elements. However, magnetometry cannot distinguish the type. To identify the type of trace element, the ESR spectrum was obtained using a conventional spectrometer. The spectrum in Fig. 3 shows three peaks with g-factors 7 of 9.8, 4.3, and 2.0. The first two peaks are specific to ferric ions. The intensity of the peak with g = 9.8 dominates the spectrum, which indicates that the magnetization originated from the ferric ions in the neurons. The small peak with g = 2.0 may have originated from other ions, like copper.