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.     

Recent Advances on Electrochemical Biosensing Strategies toward Universal Point‐of‐Care Systems

A number of very recently developed electrochemical biosensing strategies are promoting electrochemical biosensing systems into practical point‐of‐care applications. The focus of research endeavors has transferred from detection of a specific analyte to the development of general biosensing strategies that can be applied for a single category of analytes, such as nucleic acids, proteins, and cells. In this Minireview, recent cutting‐edge research on electrochemical biosensing strategies are described. These developments resolved critical challenges regarding the application of electrochemical biosensors to practical point‐of‐care systems, such as rapid readout, simple biosensor fabrication method, ultra‐high detection sensitivity, direct analysis in a complex biological matrix, and multiplexed target analysis. This Minireview provides general guidelines both for scientists in the biosensing research community and for the biosensor industry on development of point‐of‐care system, benefiting global healthcare.     

A SERS Optophysiological Probe for the Real‐Time Mapping and Simultaneous Determination of the Carbonate Concentration and pH Value in a Live Mouse Brain

To have a profound understanding of the physiological and pathological processes in a brain, both chemical and electrical signals need to be recorded, but this is still very challenging. Herein, micrometer‐ to nanometer‐sized SERS optophysiological probes were created to determine both the CO₃^2? concentration and the pH in live brains and neurons because both species play important roles in regulating the acid–base balance in the brain. A ratiometric SERS microarray of eight microprobes with tip sizes of 5 μm was established and used for the first time for real‐time mapping and simultaneous quantification of CO₃^2? and pH in a live brain. We found that both the CO₃^2? concentration and the pH value dramatically decreased under ischemic conditions. The present SERS technique can be combined with electrophysiology without cross‐talk to record both electrical and chemical signals in brains. To deepen our understanding of the mechanism of ischemia on the single‐cell level, a SERS nanoprobe with a tip size of 200 nm was developed for use in a single neuron.