A biological sensing structure includes a mesa integrally connected a portion of a substrate, wherein the mesa has a top surface and a sidewall surface adjacent to the top surface. The biological sensing structure includes a first light reflecting layer over the top surface and the sidewall surface of the mesa. The biological sensing structure includes a filling material surrounding the mesa, wherein the mesa protrudes from the filling material. The biological sensing structure includes a stop layer over the filling material and a portion of the first light reflecting layer. The biological sensing structure includes a second light reflecting layer over a portion of the stop layer and a portion of the top surface of the mesa. The biological sensing structure includes an opening in the second light reflecting layer to partially expose the top surface of the mesa.