Highly Sensitive Liquid-Phase Detection of Biological Targets With Magnetic Markers and High <inline-formula> <tex-math notation="TeX">$T_{\rm c}$</tex-math></inline-formula> SQUID

Abstract

We developed a highly sensitive HTS SQUID system for liquid-phase detection of biological targets using magnetic markers. The SQUID consists of a ramp-edge Josephson junction made using an RE123-based multilayer process, and it showed a flux noise of 7.5 μΦ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> /Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> in the white noise region. The 1/f noise was 14 μΦ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> /Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> at f = 1 Hz when the SQUID was operated in AC bias mode. Using the SQUID system, we detected a biological target called biotin. In the experiment, biotins were fixed to a large polymer bead 3.3 μm in diameter. Streptavidin-coated magnetic markers were used for the detection. The bound and unbound (free) markers were magnetically distinguished using the difference in their Brownian relaxation time, i.e., without using a washing process to separate them. The minimum detectable number of biotins was as low as 2×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> , corresponding to a sensitivity of 9.5×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-19</sup> mol/ml. This result indicates that the developed method is highly sensitive. We also show the effect of the excitation field on the signals from free and bound markers for quantitative evaluation of the immunoassay.