We developed a highly sensitive HTS SQUID system for liquid-phase detection of biological targets using Brownian relaxation of magnetic markers. The SQUID was made of a ramp-edge Josephson junction using RE123-based multilayer process, and it showed a flux noise of 7.5 micro flux-quantam/Hz1/2 in the white noise region. The 1/f noise was 14 micro flux-quantam/Hz1/2 at f = 1 Hz when the SQUID was operated with 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 with a diameter of 3.3 micron meter. 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 the washing process to separate them. The minimum detectable number of biotins was as low as 10 4, corresponding to a sensitivity of 4.8×10-19 mol/ml. This result indicates a high sensitivity of the developed method.