Rapid, quantitative molecular diagnostics in the field, at home, and in resource poor settings is needed for evidence-based disease management, control, and prevention. Conventional molecular diagnostics requires extensive sample preparation, sophisticated instruments, and trained personnel, restricting their use to centralized laboratories. To overcome the limitations of laboratory-based procedures, we designed a simple, inexpensive, hand-held, smartphone-based mobile detection platform “smart-connected cup”, for rapid, connected, and quantitative detection of pathogens’ nucleic acids. More recently, we have been expanding our technology platform to include detection of rare cancer biomarkers in body fluids for cancer screening and individualized therapy. To overcome the challenge of identifying very low concentrations of mutant alleles within a large background of very similar wild type nucleic acids, we are using programmable enzymes to cleave wild type alleles and improve signal to noise ratio. We anticipate that our methods will improve quality of health care in regions lacking sophisticated laboratories and enable patients to assume greater responsibility for their care.