Biocomputing for Portable, Resettable, and Quantitative Point-of-Care Diagnostics: Making the Glucose Meter a Logic-Gate Responsive Device for Measuring Many Clinically Relevant Targets

It is recognized that biocomputing can provide intelligent solutions to complex biosensing projects. However, it remains challenging to transform biomolecular logic gates into convenient, portable, resettable and quantitative sensing systems for point-of-care (POC) diagnostics in a low-resource setting. To overcome these limitations, the first design of biocomputing on personal glucose meters (PGMs) is reported, which utilizes glucose and the reduced form of nicotinamide adenine dinucleotide as signal outputs, DNAzymes and protein enzymes as building blocks, and demonstrates a general platform for installing logic-gate responses (YES, NOT, INHIBIT, NOR, NAND, and OR) to a variety of biological species, such as cations (Na⁺), anions (citrate), organic metabolites (adenosine diphosphate and adenosine triphosphate) and enzymes (pyruvate kinase, alkaline phosphatase, and alcohol dehydrogenases). A concatenated logical gate platform that is resettable is also demonstrated. The system is highly modular and can be generally applied to POC diagnostics of many diseases, such as hyponatremia, hypernatremia, and hemolytic anemia. In addition to broadening the clinical applications of the PGM, the method reported opens a new avenue in biomolecular logic gates for the development of intelligent POC devices for on-site applications.