High sensitivity sensors for detection of molecules are aspired in various fields of application, particularly in medical technology, pharmacy and environmental sciences. In the present research, we have developed a high-performance molecular detection sensor for diagnosis, medication, and medical treatments that utilizes waveguide modes as basic technology. We successfully obtained sensors with high sensitivity and stability by applying nano-perforation technology, optical simulation and experiments, and an originally developed sensing-plate fabrication process. In this report, the scenario of the present research, elemental technologies and their synthesis for achieving the scenario and the properties of the realized sensors are described. In addition, a rapid progress in sensing performance obtained by a breakthrough is reported.