We are investigating the development of a rapid and highly sensitive detection method for immunoreactive substances combining MEMS (Micro Electro Mechanical Systems) technology and the appropriate immune stimulant or response factors. Cantilevers of micrometer scale can be used for trace detection of mass change. When a layer of an antigenic substance is covalently deposited, the cantilever is capable of capturing antibodies from samples with high affinity and specificity. The antigen/antibody binding causes multiple physical changes in the cantilever device, including a shift of effective mass and a change in surface tension. The change of effective mass consequently induces a shift in the cantilever’s natural resonant frequency. By monitoring these changes with an optical readout mechanism, the presence of immunoreactive targets in the sample can be detected. This detection method can be used for various types of targets with immunoreactivity and therefore is potentially applicable in hazardous substance monitoring and disease diagnosis. In our effort, <i>phoS1</i>, an antigen shed by <i>Mycobacterium tuberculosis</i>, the causative agent of tuberculosis (TB), is utilized for rapid and economic TB detection.