Disclosed are a method and system for enriching and detecting microorganisms in a biological sample. The method allows the biological sample to be filtered through a polymer-modified substrate. The polymer-modified substrate is highly specific in capturing or separating human-derived nucleated cells, and allows the microorganisms to penetrate through it. During the process, a high level of microorganisms (bacteria, mycoplasmas, fungi, viruses, spores etc.) can be enriched in the sample and thus the interference from nucleated cells such as leukocytes can be reduced.