A bio-sensing semiconductor structure is provided. A transistor includes a channel region and a gate underlying the channel region. A first dielectric layer overlies the transistor. A first opening extends through the first dielectric layer to expose the channel region. A bio-sensing layer lines the first opening and covers an upper surface of the channel region. A second dielectric layer lines the first opening over the bio-sensing layer. A second opening within the first opening extends to the bio-sensing layer, through a region of the second dielectric layer overlying the channel region. A method for manufacturing the bio-sensing semiconductor structure is also provided.