Methods, compositions, kits and systems for detecting and/or capturing a target entity in a sample are disclosed. In particular, the methods, compositions and kits described herein can be used for pretreatment of target-binding agents with a blocking agent to reduce non-target binding in a complex matrix (e.g., blood). Methods and compositions for detecting and/or capturing a microbe in a test sample, including bodily fluids such as blood and tissues of a subject, food, water, and environmental surfaces are also disclosed.