ABSTRACT
Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.
Subject(s)
Copper , Electrochemical Techniques , Sulfides , Thiophenes , Electrochemical Techniques/instrumentation , Copper/chemistry , Sulfides/chemistry , Cadmium Compounds/chemistry , Biosensing Techniques/instrumentation , Bismuth/chemistry , Transistors, Electronic , Photochemical Processes , Polystyrenes/chemistry , MicroRNAs/analysis , Electrodes , Polymers/chemistryABSTRACT
DNA intercalation has increasingly been studied for various scenario implementations due to the diverse functions of DNA/intercalators. Nascent organic photoelectrochemical transistor (OPECT) biosensing taking place in organic electronics and photoelectrochemical bioanalysis represents a promising technological frontier in the arena. In this work, we first devise DNA intercalation-enabled OPECT for miRNA detection with a superior gain up to 17100. Intercalation of [Ru(bpy)2dppz]2+ within the miRNA-initiated hybrid chain reaction (HCR)-derived duplex DNA is realized for producing anodic photocurrent upon light stimulation, causing the corresponding target-dependent alternation in gate voltage (VG) and hence the modulated channel current (IDS) of poly (3,4-ethylenedioxythiophene) doped with poly (styrene sulfonate) (PEDOT:PSS) under specific drain voltage (VDS) for quantitative miRNA-21 analysis, which shows a wide linear relationship and a low detection limit of 5.5 × 10-15 mol L-1. This study features the DNA intercalation-enabled organic electronics with superior gain and is envisaged to attract more attention to explore DNA adducts for innovative bioelectronics and biosensing, given the diverse DNA binders with multiple functions.
Subject(s)
Biosensing Techniques , MicroRNAs , DNA/analysis , Styrene , Intercalating AgentsABSTRACT
Organic photoelectrochemical transistor (OPECT) biosensing represents a new platform interfacing optoelectronics and biological systems with essential amplification, which, nevertheless, are concentrated on depletion-type operation to date. Here, a polymer dot (Pdot)-gated accumulation-type OPECT biosensor is devised and applied for sensitive urea detection. In such a device, the as-designed Pdot/poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) is validated as a superior gating module against the diethylenetriamine (DETA) de-doped poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel, and the urea-dependent status of Pdots has been shown to be sensitively correlated with the device's response. High-performance urea detection is thus realized with a wide linear range of 1 µM-50 mM and a low detection limit of 195 nM. Given the diversity of the Pdot family and its immense interactions with other species, this work represents a generic platform for developing advanced accumulation-type OPECT and beyond.
Subject(s)
Biosensing Techniques , Polymers , Urea , Styrene , GoldABSTRACT
GPR40, also known as free fatty acid receptor 1 (FFAR1), is a member of G protein-coupled receptors (GPCR) family and has emerged as an attractive target for the treatment of type 2 diabetes mellitus. So far, most of the synthetic GPR40 agonists, including several drug candidates discontinued in clinical trials, were derived from the phenylpropionic acid scaffold. For discovering novel GPR40 agonists with diverse chemical structures, a series of phenylpropiolic acid derivatives were designed, synthesized, and evaluated under a battery of bioassays. Compound 9, the most potent compound in this series, exhibited submicromolar agonist activity and similar agonistic efficacy compared to that of TAK-875. In addition, compound 9 was able to dose-dependently amplify glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cell line MIN6, which could be reversed by a selective GPR40 antagonist GW1100. In addition, compound 9 was found to have potent glucose-lowering effects during an oral glucose tolerance test in normal C57BL/6 mice.
Subject(s)
Glucose/metabolism , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Phenylpropionates/chemistry , Phenylpropionates/pharmacology , Receptors, G-Protein-Coupled/agonists , Animals , Cell Line , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Drug Design , Glucose Tolerance Test , HEK293 Cells , Humans , Hypoglycemic Agents/chemical synthesis , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Male , Mice, Inbred C57BL , Phenylpropionates/chemical synthesis , Receptors, G-Protein-Coupled/metabolismABSTRACT
Inhibition of the mycolic acid pathway has proven a viable strategy in antitubercular drug discovery. The AccA3/AccD4/FadD32/Pks13 complex of Mycobacterium tuberculosis constitutes an essential biosynthetic mechanism for mycolic acids. Small molecules targeting the thioesterase domain of Pks13 have been reported, including a benzofuran-based compound whose X-ray cocrystal structure has been very recently solved. Its initial inactivity in a serum inhibition titration (SIT) assay led us to further probe other structurally related benzofurans with the aim to improve their potency and bioavailability. Herein, we report our preliminary structure-activity relationship studies around this scaffold, highlighting a natural product-inspired cyclization strategy to form coumestans that are shown to be active in SIT. Whole genome deep sequencing of the coumestan-resistant mutants confirmed a single nucleotide polymorphism in the pks13 gene responsible for the resistance phenotype, demonstrating the druggability of this target for the development of new antitubercular agents.
