We developed improved methods of liquid-phase detection of biological targets using HTS SQUID and Brownian relaxation of magnetic markers. In a real sample, the aggregation and precipitation of free markers deteriorate their Brownian relaxation and cause so-called blank signals. In order to solve this problem, we developed two methods. First, we introduced a reaction field Bre during the binding reaction between the markers and targets. Using this method, we could obtain a strong signal from the bound markers without increasing the aggregation of the free markers. Next, we introduced a fieldreversal method in the measurement procedure in order to differentiate the signal from the markers in suspension from that from the precipitated markers. Using this procedure, we could eliminate the signal from the precipitated markers. Then, we detected biotin molecules by using these methods. The biotins were immobilized on the surfaces of large polymer beads with diameters of 3.3 μm and were detected with streptavidinconjugated magnetic markers. The minimum detectable molecular number concentration was 1.8 × 10-19mol/ml, indicating the high sensitivity of the present method.