Bio(chemical) sensors play an outsized role in medical care, biological research, drug development, national security, and environmental monitoring, as exemplified by the current need for SARS-CoV-2 virus detection. I will outline the inherent challenges associated with the development and large-scale deployment of reliable sensors for detection of new viral and bacterial pathogens and environmental pollutants. I will also discuss the approaches we are exploring to meet these challenges by combining photonic amplification, biological recognition & nano-mechanical forces on nano-photonic and nano-plasmonic chips. As one of the examples, I will introduce a concept of the High Contrast Probe Cleavage Detection mechanism, which makes use of the dramatic optical signal amplification caused by cleavage of large numbers of high-contrast nanoparticle labels. This method is drastically different from the common photonic biosensing approach based on recognizing and amplifying the signal caused by the adsorption of low-index biological molecules, and holds promise for rapid development of new sensors for detecting SARS-CoV-2 virus and other yet-unknown harmful pathogens. I will also briefly mention our work on new materials development aimed at preventing future environmental pollution and reducing risks of transmission of bacterial and viral infections.