Ultra-sensitive biosensor based on superconducting flux qubit

The magnetization of electron spins at the single-cell level was detected using superconducting flux qubits. The major hurdle to achieving this was the application of a qubit sensor to biological samples.
Ultra-sensitive biosensor based on superconducting flux qubit

Is it possible to understand biological phenomena using methods that go beyond the limits of classical physics? Quantum biosensing is a growing and challenging research topic that uses quantum science and technology to measure and understand life phenomena. In publishing our paper [Toida et al., Communications Physics, 6, 19 (2023)], we report the successful detection of magnetization in a single cell using an ultra-sensitive sensor based on superconducting flux qubits.

I joined this project as a biosensor researcher while undergoing training in my first year at NTT Corporation. The purpose of the training was to develop a cross-disciplinary perspective by spending three months on a research team engaged in a different field. The team I joined was working on superconducting quantum circuits and had already developed an ultra-sensitive sensor that can detect electron spins of semiconductor materials with a spatial resolution of 10 mm [Budoyo et al., Applied Physics Letters, 116, 194001 (2020)]. It was also investigating the possibility of applying the technology to biological samples. As I had some sense of the limitations of biosensors based on classical physics, I was intrigued by sensors based on quantum science and technology and immediately offered to provide a biological sample.

The first biological sample tested was liver tissue from a rat. Liver tissue is known to contain high iron content and is not difficult to collect. Therefore, electron spins of the ferric irons should have been detected. However, superconducting flux qubits with liver tissue did not work well. Placing the tissue directly on the superconducting circuit affected its operation. To solve this problem, we placed a thin film of a polymer called parylene-C between the circuit and the biological sample. Parylene-C has excellent insulating and biocompatible properties and is widely used as an insulating layer in the biosensor field. In addition, it has high film-forming properties and can maintain its shape even at a thickness of about one micron. In addition to introducing insulating films, we also discussed cell types. I suggested using neurons because they are known to be susceptible to iron deposition, which can cause brain disorders. It is also well known that neurons grow on parylene-C films. The tight adhesion of neurons to parylene-C film is suitable for forming couplings with superconducting circuits. We attached neurons cultured on the parylene film to superconducting flux qubits and confirmed that the qubits worked properly even when a biological sample was placed on them.

As I have been studying living samples in an environment of 37 °C in air, it was an exciting experience for me to take measurements in a vacuum below 0.02 K. In particular, it was interesting to pay attention to minute amounts of heat, such as that generated by the electrically resistive elements in the dilution refrigerator, and I observed many curious phenomena. For example, the first time I injected microwaves into a circuit to obtain an ESR signal, I was under the wrong impression that the change in the qubit spectrum caused by the microwave-induced heat was an electron spin resonance (ESR) signal. To fully analyze the response of the qubit to temperature and magnetic fields described in this paper, we needed some discussion. When we observed the saturation of the change in magnetization with respect to temperature and magnetic field, we initially thought that the plot followed the saturation curve of Brillouin function. However, as we compared the theoretical curve with the plot, we realized that the saturation of the curve was caused by unexpected limitation of cooling. The thermal conductivity of parylene-C is low, and the sample was not sufficiently cooled compared to the temperature of the dilution refrigerator. After this consideration, we were finally able to estimate the concentration of electron spin in neurons from a reliable range of values. As a future strategy, we are looking at the possibility of incorporating insulating films with better thermal conductivity than parylene-C, such as alumina.

In closing, we are opening up new technologies step by step by introducing knowledge and ideas related to biomaterials into quantum physics. In the future, we aim to develop applications for the acquisition of ESR signals from single cells and the evaluation of excessive iron deposition in neurons for a better understanding of biological phenomena based on quantum science and technology.

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