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

Abstract

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.

An in Vitro–Selected DNAzyme Mutant Highly Specific for Na+ under Slightly Acidic Conditions

“…Using NaA43 for detecting Na + in live cells has already been demonstrated . In this work, we studied a different biological sample matrix—serum . In the presence of 1 % fetal bovine serum (FBS), the background signal was low (Figure D), thus indicating that our sensor was stable in the serum.…”

Nanobiohybrid Material‐Based Bioelectronic Devices

“…Recently, a logic gate based on an enzymatic cascade reaction was developed by using pyruvate kinase (PK) and citrate as the input molecules, and lactate dehydrogenase (LDH), citrate lyase (CL), and malate dehydrogenase (MDH) as the logic units to achieve the functions of NOT logic gates [ 104 ] ( Figure 3 A). PK catalyzes the transphosphorylation of phosphoenolpyruvate to ADP, which produces pyruvate and adenosine triphosphate.…”

“…Figure 3A reproduced with permission. [ 104 ] Copyright 2018, Wiley‐VCH. Figure 3B reproduced with permission.…”

Locus-patterned sequence oriented enrichment for multi-dimensional gene analysis

“…Then various loci output signals with distinct patterns which can be encoded as unique codes for gene decoding. 22,23 The principle of our approach is illustrated in Fig. 1.…”