Search Results (1,502)

Synthetic biology is transforming biosensors from passive molecular detectors into programable systems capable of integrating biological sensing with therapeutic decision-making. Conventional biosensors respond to a single molecular input and are inherently limited in interpreting complex biological environments that characterize human disease. Synthetic biology logic gates address this limitation by implementing Boolean computation through modular transcriptional regulators, RNA switches, CRISPR-based regulators, and recombinase systems, enabling autonomous biological decision-making within living cells. These genetic circuits enable biosensors to evaluate multiple disease-relevant inputs simultaneously and generate context-specific diagnostic or therapeutic outputs. This review critically analyzes how logic-gated biosensing systems integrate biological sensing, genetic computation, and therapeutic actuation, while identifying the engineering and translational barriers that currently limit their clinical implementation. Comparison of current platforms shows that increasing circuit complexity generally improves disease specificity and therapeutic precision but often reduces robustness, scalability, and translational feasibility because of circuit leakage, metabolic burden, crosstalk, and biological variability. While AND and SynNotch circuits provide superior target discrimination for cell therapies, CRISPR-based and memory-enabled systems expand programable control but introduce additional engineering challenges. Current clinical translation remains constrained by circuit stability, manufacturing complexity, biosafety, and the lack of standardized regulatory frameworks. Emerging modular circuit design, cell-free biosensing, and artificial intelligence-assisted optimization are beginning to address these limitations and provide more scalable strategies for precision therapeutics. Collectively, this review identifies the engineering principles and design trade-offs that will govern the development of next-generation logic-enabled biosensors from proof-of-concept platforms to clinically deployable therapeutic systems. Full article

A self-driven terahertz metamaterial liquid biosensor composed of channel-structured metamaterials and a quartz microcavity is proposed for glioblastoma sample detection. The device transports liquid samples via capillary force. The permittivity (ε_eff) of liquid suspensions is comprehensively analyzed to provide theoretical support for the detection. For suspensions with the same contents, ε_eff decreases with increasing concentration, while under the same concentration condition, ε_eff decreases as particle size grows. An electric dipole resonance is excited at ~1.54 THz with theoretical sensitivity ≥ 242 GHz/RIU (where RIU denotes refractive index unit). For the same type of cell discrimination, the frequencies of the biosensor’s feature peaks shift from ~1.14, ~1.18, and ~1.20 THz with the rise in cell concentration of glioblastoma stem cell (GSC) suspension from 4 × 10⁵, 6 × 10⁵ to 8 × 10⁵ cells/mL, respectively. In addition, the GSC, U87 and U251—whose average diameters increase in that order—tested at the same concentration of 4 × 10⁵ cells/mL lead to feature peak shifts from ~1.14, ~1.17, and ~1.20 THz. Clear THz differences exist between healthy and patient serum, with peaks at 1.18 and 1.19 THz. The sensor effectively distinguishes cell suspensions but has limited serum discrimination capacity. The sensor retains cell morphology, requires little pretreatment, and is low-cost and fast for rapid glioblastoma clinical screening. Full article

In this research, a high-performance plasmonic refractive index ($RI$) biosensor based on an external metal deposition ($EMD$) technique and photonic crystal fiber ($PCF$) platform for potential cancer detection is presented, investigated, and linked with real-time cancer cells. Variations in the $RI$ of biological fluids are closely associated with pathological conditions, including cancer, due to changes in cellular composition and biomolecular concentration. The proposed tetra-core $PCF–SPR$ biosensor operates within the biologically relevant $RI$ range of $1.33–1.37$, enabling the detection of subtle $RI$ variations corresponding to various cancerous cells. The sensing mechanism of the proposed sensor is based on surface plasmon resonance ($SPR$) and analyzed using coupled mode light theory for both $x\text{-}$ and $y\text{-}$ polarized modes. Key sensing performance parameters, including confinement loss ($CL$), wavelength sensitivity ($WS$), amplitude sensitivity ($AS$), sensor resolution ($SR$), and figure of merit ($FOM$) are systematically evaluated. The biosensor reports a $WS$ of $9769$ and $9069 nm/RIU$ for $x\text{-}pol.$ and $y\text{-}pol.,$ respectively, $AS$ of $623.182$ and $645.087 {RIU}^{-1}$ for $x\text{-}pol.$ and $y\text{-}pol.$ respectively, $SR$ in the order of ${10}^{-5}$ $RIU$, coefficient of determination ($R^2$) of $0.97$ and $0.96$, and $FOM$ of $60.17$ and $53.01 {RIU}^{-1}$ for $x\text{-}pol.$ and $y\text{-}pol.$, respectively. Thus, the proposed $PCF–SPR$ biosensor exhibits a dynamic range of $0.04 RIU$. The sensing results demonstrate high sensitivity and strong resonance characteristics, indicating the capability of the proposed biosensor for label-free and non-invasive detection of cancer-associated $RI$ changes in biological fluids. Thus, the presented biosensor offers a promising approach for the highly sensitive label-free detection of early-stage cancer cells by photonics sensing application. Full article

Organoid and organ-on-chip technologies are rapidly evolving platforms for viral research that integrate stem cell biology, tissue engineering, and microfluidics to recapitulate key structural, mechanical, biochemical, and cellular features of human and animal physiology. By incorporating multicellular organoids into perfused microfluidic systems, these models can provide complex, dynamic, and physiologically relevant micro-environments for investigating virus–host interactions that are difficult to capture in conventional two-dimensional cultures and static organoids. Controlled flow, shear stress, extracellular matrix organization, tissue–tissue interfaces, and multicellular signaling enable mechanistic investigation of viral infectivity, dissemination, tissue injury and immune activation. Integration of real-time imaging and biosensors further permits longitudinal monitoring of viral replication, host responses, and tissue integrity, expanding the potential of these platforms for antiviral drug discovery. Recent organoid-on-chip studies using brain, skin, vaginal, respiratory, and intestinal models have demonstrated how tissue architecture, mechanical forces, glycocalyx dynamics, and immune–stromal interactions influence viral tropism and pathogenesis. In this review, we provide a mechanistic and translational overview of organoid and organ-on-chip technologies for studying viral infections, with particular emphasis on models of herpes simplex virus (HSV)-mediated disease. We further examine advances in immune integration, multi-organ systems, biosensing, and computational approaches that are expanding the complexity and predictive potential of these models. Importantly, patient-derived organoids and organ-on-chip platforms can capture interindividual differences in viral susceptibility, host responses, and therapeutic efficacy, providing pharmaceutical research with more precise, patient-relevant data to support drug prioritization and precision antiviral medicine. Finally, we discuss key barriers to broader adoption, including organoid maturation, biological and technical variability, reproducibility, scalability, biosafety, cost, standardization, and regulatory validation. Collectively, these advances position organoid and organ-on-chip technologies as powerful human-relevant models that bridge reductionist in vitro systems and human disease, while continued optimization, standardization, and validation will be essential to realize their full potential for mechanistically informed antiviral discovery, therapeutic development, and precision medicine. Full article

Carminic acid (CA) is a high-value natural anthraquinone pigment used in foods, cosmetics, textiles, and pharmaceuticals, but its current industrial supply depends largely on extraction from the scale insect Dactylopius coccus, creating constraints in yield, cost, sustainability, and allergen control. This review summarizes recent progress from pathway elucidation to microbial production. We first outline the structure, occurrence, applications, and biosynthetic logic of CA, emphasizing the convergence of type III polyketide assembly with insect-associated tailoring reactions, especially C-glycosylation. We then compare heterologous production strategies in Escherichia coli, Saccharomyces cerevisiae, Yarrowia lipolytica, and Aspergillus nidulans, focusing on chassis-specific advantages, bottlenecks, precursor supply, malonyl-CoA engineering, dynamic regulation, enzyme compatibility, compartmentalization, and downstream processing. Structurally related anthraquinone pigments are further discussed to extract broader design principles for pathway diversification and synthetic biology. Finally, we highlight key challenges for industrial translation, including low titers, incomplete enzyme characterization, host–pathway incompatibility, and scalable purification, and propose integrated strategies combining precursor-pathway rewiring, AI-assisted enzyme engineering, biosensor-based regulation, and process optimization to develop competitive microbial cell factories. Full article

Carbohydrates are among the most highly oxygenated biomolecules in nature, possessing dense arrays of hydroxyl, ether, carbonyl, carboxylate, phosphate, and sulfate functionalities that govern hydration, hydrogen bonding, molecular recognition, and supramolecular organization. Their stereochemically organized oxygen-donor groups provide numerous appropriately oriented diol motifs capable of selective and reversible coordination with boric acid and borate ions. This review examines the structural and physicochemical principles underlying carbohydrate–borate interactions, with particular emphasis on oxygen-rich biological interfaces. Pentoses, hexoses, oligosaccharides, polysaccharides, glycolipids, and membrane-associated glycoconjugates are considered to illustrate how hydroxyl-group orientation, molecular conformation, pH, hydration, and local environment determine borate recognition, complex stability, and dynamic assembly. Evidence from NMR and other spectroscopic methods, crystallography, mass spectrometry, calorimetry, and molecular simulations demonstrates that borate coordination follows common stereochemical and thermodynamic principles despite the remarkable structural diversity of carbohydrates. Biological examples include borate-mediated crosslinking in plant cell walls and interactions involving microbial carbohydrates, marine polysaccharides and glycoconjugates, photosynthetic membrane lipids, and cyanobacterial heterocyst glycolipids. Particular attention is given to distinguishing experimentally established borate complexes from membrane-associated interactions that remain proposed and require further characterization. Reversible borate crosslinking of oxygen-rich carbohydrate networks also provides the chemical basis for emerging applications in responsive hydrogels, biosensors, supramolecular assemblies, drug-delivery systems, and functional biomaterials. Collectively, the available evidence indicates that the spatial organization of oxygen donor atoms within carbohydrates provides the molecular basis for selective borate recognition, whereas boron can convert this functionality into reversible higher-order organization. This oxygen-centered perspective integrates coordination chemistry, glycobiology, membrane biology, and materials science into a unified framework for understanding carbohydrate–borate interactions in natural and engineered systems. Full article

The bacterial Quorum Sensing system refers to the recognition of signaling molecules called autoinducers produced by bacteria when a certain cell density is reached in the environment. Those cell-density-dependent autoinducers regulate and coordinate diverse functional processes, such as bioluminescence, biofilm production, sporulation, and even the expression of some virulence factors, among others. There is a wide variety of autoinducers, and for Gram-negative bacteria, the canonical autoinducers are the N-acyl-homoserine lactones (AI-1). Presently, the production of autoinducers in Leptospira has not been described; therefore, the objective of this study was to detect and identify autoinducers in this bacterial genus. We report here the expression of AI-1 in cultures ≥2.4 × 10⁸ of Leptospira meyeri. Ethyl acetate extracts of Leptospira culture supernatants were capable of activating the β-galactosidase system in the biosensor Agrobacterium tumefaciens strain NTL4. Partial identification of the leptospiral supernatant extracts was done by thin-layer chromatography (TLC), showing a similar retention factor to the synthetic standard N-Octanoyl-DL-homoserine lactone (C8-AHL) in the Leptospira supernatant extracts. In addition, infrared spectroscopy (IR) analysis showed peaks corresponding to the lactone and amide groups in both the C8-AHL standard and the Leptospira meyeri culture extracts. Moreover, High-Performance Liquid Chromatography–Mass Spectrometry (HPLC-MS/MS) confirmed the same retention time (10.7 ± 0.1 min) in both the Leptospira meyeri supernatant extracts and the C8-AHL standard. These results show that Leptospira meyeri synthesizes N-acyl homoserine lactone family autoinducers, particularly the N-Octanoyl-DL-homoserine lactone, and lay the groundwork for future research on Quorum Sensing systems in Leptospira. Full article

Localized surface plasmon resonance biosensors are promising devices for label-free detection of live cells and biomolecules. However, typical plasmonic sensors have limited surface area, planar electromagnetic fields, and poor compatibility with three-dimensional (3D) interactions with cells or biomolecules. In this study, a 3D plasmonic sensor around microposts was developed using reversal nanoimprint lithography for highly sensitive cell and DNA detection. Au nanopillars were conformally integrated onto the bottom, sidewall, and top of microposts, forming additional sensing surface area along the sidewall of microposts for plasmonic sensing. The 3D plasmonic sensors exhibited tunable resonance peaks and refractive index (RI) sensitivities by varying the micropost height. The highest sensitivity of 1306 nm per RI unit was obtained from the sensor with 10 μm-tall microposts at a resonance wavelength of 1315 nm, which was significantly higher than that of typical planar plasmonic sensors. The platform was applied to live MC3T3-E1 cell detection, showing a resonance peak shift of 71 ± 11.6 nm at a cell concentration of 10⁶ cells/mL with a cell concentration ranging from 10² to 10⁶ cells/mL. In addition, DNA hybridization detection was demonstrated over a concentration range of 10⁻¹⁵–10⁻⁷ M complementary target DNA, with a resonance shift of 68 ± 2.5 nm observed at 10⁻⁷ M target DNA concentration. The 3D plasmonic sensor provides a scalable device for additional plasmonic biointerfaces with enhanced analyte accessibility and light–matter interactions. This platform offers high-sensitivity biosensing involving live cells, nucleic acids, and other biological targets. Full article

We report a freeze-dried ready-to-use yeast thyroid screen (YTS), preserving the general dose–response characteristics of the freshly prepared counterpart. This field-deployable method reduces the assay time of the overall procedure from several days to 5 h with no requirement for sterile conditions, thus fulfilling key requirements for on-site implementation in a biosensor array. The effects of cell density and concentration of the cryoprotectant trehalose on median effective concentrations (EC₅₀), limit of detection (LOD) and biosensor induction (IF) were determined and monitored over a storage period of 5 months. In addition, the impact of these parameters was monitored on the biosensor survival rate during freeze-drying and the subsequent storage process. Throughout the 5-month study, the freeze-dried recombinant yeast assay retained comparable dose–response characteristics to those of the freshly prepared counterpart, displaying median values of EC₅₀ in the range of 350 nM to 550 nM and LODs in the range of 20 nM to 45 nM of the reference compound thyroxine (T4). Long-term stabilization is demonstrated using spiked (T4, 2 µM) river water and extracted wastewater effluent. After 5 months of storage, the T4-equivalent activities were 96 ± 38% and 112 ± 15% for river water and wastewater, respectively. In summary, we have successfully demonstrated a proof of principle of a field-deployable yeast thyroid screen (YTS) by using freeze-dried cells and trehalose as a cryoprotectant to achieve storability for up to 5 months at 4 °C. Full article

Shigella is a foodborne bacterial pathogen with a low infectious dose and significant public health impact. Culture-based and molecular techniques provide reliable identification but are time-consuming. Nanoparticle-based biosensors offer sensitive, selective, and compact alternatives. Recent advances in nanoparticle-based biosensors for Shigella spp. (S. flexneri, S. sonnei, S. dysenteriae, and S. boydii) detection have been reviewed in terms of signal amplification, biorecognition, biological targets, sensor types, and performance in real food matrices. Detection strategies rely on gene-level and whole-cell recognition. Targeting virulence genes, invasion plasmid antigen H (ipaH), provides stable genus-level identification, whereas whole-cell recognition facilitates rapid detection without extensive sample preparation. Optical biosensors, including fluorescence-based methods, surface-enhanced Raman spectroscopy (SERS), and localized surface plasmon resonance (LSPR), achieve low detection limits with strong tolerance to complex food matrices. Electrochemical biosensors offer operational simplicity, portability, and suitability for food screening. Lateral flow and hybrid systems provide rapid detection through simplified assay formats and visual readout, with performance influenced by the balance between speed and sensitivity. Validation in real food matrices shows acceptable recoveries, minimal cross-reactivity, and agreement with reference methods. This overview provides a design-oriented framework for nanoparticle-based biosensor selection in food safety by integrating nanomaterial function, biosensor design, and performance characteristics. Full article

Chronic kidney disease (CKD), one of the major global public health burdens, continues to exhibit a rising prevalence worldwide. The growing population of patients with end-stage renal disease (ESRD) has led to an increasing demand for renal replacement therapy (RRT). Although dialysis effectively prolongs survival, it fails to fully replicate kidney function. In addition, the persistent shortage of donor kidneys results in prolonged waiting periods for kidney transplantation. Emerging renal replacement strategies, such as kidney organoids, have demonstrated considerable potential. However, multiple technical limitations continue to hinder their near-term clinical translation. Bioartificial kidneys (BAKs), which integrate engineering and biological technologies, generally consist of artificial filtration membranes and living-cell bioreactors designed to mimic native kidney function. Advances in nanotechnology, biomaterials, and tissue engineering have accelerated the development of implantable bioartificial kidneys (iBAKs), making them an important research direction in renal replacement therapy. These innovations have improved membrane performance, biocompatibility, and cellular integration; however, substantial challenges remain regarding long-term stability, immune compatibility, and clinical validation before translation into human applications. Specifically, limited cell sources and uncertain long-term biocompatibility remain major barriers to iBAK development. In the future, biosensors and artificial intelligence (AI) technologies may be incorporated into bioartificial kidneys to enable personalized precision therapy. This review focuses on the developmental and major challenges of bioartificial kidneys, with detailed discussion of recent progress in implantable artificial kidneys. Full article

Industrial bioprocesses remain constrained by their limited ability to monitor intracellular events in real time. Most rely on external measurements—nutrient or metabolite levels in the culture medium—that provide only delayed and indirect information about the cell’s internal state. Riboswitches, RNA elements that respond to specific small molecules, offer a complementary route to direct intracellular sensing. Acting as genetically encoded biosensors, they bind metabolites with nanomolar-to-micromolar affinity, and ligand binding drives rapid conformational changes in the RNA. When coupled to gene regulatory outputs, riboswitches can, in principle, support dynamic feedback control that allows cells to sense metabolic imbalances and adjust their own metabolism. This Commentary argues that the central opportunity is conceptual: reframing intracellular biosensing as a foundational layer for adaptive, self-regulating cell factories. It distinguishes what riboswitch technology already demonstrates at laboratory scale from what remains a forward-looking vision, and outlines the engineering barriers, specificity, dynamic range, context-dependence, metabolic burden, evolutionary stability, and validation in production settings that must be addressed before autonomous bioprocess control becomes routine. Importantly, the functional response time of such systems is governed not by binding kinetics alone but by transcription, translation and mRNA turnover, a distinction that matters for feedback stability. Full article

Cyclic adenosine monophosphate and cyclic guanosine monophosphate are key regulators of cellular physiology and tissue homeostasis. Conventional experimental models have provided fundamental insights into cyclic nucleotide pathways; however, they often fail to fully recapitulate essential features of in vivo systems. Two-dimensional cell cultures lack spatial organization, while animal models incompletely capture cell–cell interactions and the dynamic microenvironment shaping signaling processes. In recent years, advanced three-dimensional and microengineered systems have emerged as tools to bridge this gap. In this review, we discuss how three-dimensional and organ-on-chip systems are transforming the study of cyclic nucleotide signaling by enabling reconstruction of tissue architecture and signaling niches. Spheroids and organoids provide robust models to investigate compartmentalized signaling and intercellular communication. Complementarily, microfluidic organ-on-chip devices introduce controlled mechanical cues, perfusion, and tissue interfaces, enabling real-time monitoring of signaling dynamics. We highlight recent advances in microphysiological systems for investigating the spatial and temporal dynamics of cyclic adenosine monophosphate and cyclic guanosine monophosphate signaling, including biosensors, live-cell imaging, and genome editing. We further discuss applications in physiological and pathological contexts, including metabolic, cardiovascular and cancer diseases, and outline current challenges and future perspectives for integrating three-dimensional and organ-on-chip technologies. Full article

Reactive oxygen species (ROS) regulate cellular signaling at physiological concentrations and drive tissue damage when their generation exceeds antioxidant defenses. The conceptual reframing of the field into oxidative eustress (low, controlled redox signaling) and oxidative distress (supraphysiological levels causing biomolecular damage), alongside parallel advances in detection chemistry and genetically encoded biosensors, has transformed how investigators measure ROS in living systems. This review provides a critical, methods-focused update covering the contemporary toolkit, with particular emphasis on advances from 2015 to 2026 while incorporating earlier foundational work where it remains indispensable to interpretation. Consistent with the title and reflecting both the maturity of the available chemistry and the weight of the recent literature, our emphasis falls on hydrogen peroxide and mammalian experimental systems; superoxide, the hydroxyl radical, and singlet oxygen are addressed primarily where their detection intersects with the platforms reviewed here, and non-mammalian models are considered only selectively. Readers seeking dedicated coverage of these other species or of plant, microbial, and invertebrate systems are directed to the specialized reviews cited throughout. Five complementary measurement platforms are evaluated: (i) electron paramagnetic resonance spectroscopy with classical nitrone spin traps and the newer cyclic hydroxylamine probes; (ii) small-molecule fluorescent probes, with particular emphasis on the boronate-based, activity-based sensing platform that has supplanted 2′,7′-dichlorofluorescin diacetate for hydrogen peroxide imaging; (iii) genetically encoded biosensors of the HyPer and roGFP families, which now permit ratiometric, organelle-resolved, and longitudinal measurements; (iv) mass-spectrometry-based quantification of oxidation products and radical adducts, including isoprostanes, 2-hydroxyethidium, and redox-modified cysteines via chemical proteomics; and (v) electrochemical and nanosensor approaches enabling real-time single-cell measurements. The selectivity, sensitivity, temporal resolution, spatial resolution, and quantitative capability of each platform are critically compared. Reliance on a single non-specific probe is no longer sufficient as the sole evidence base for quantitative or species-specific claims; contemporary investigators are expected to apply complementary approaches and to validate findings across modalities. Standardization of reporting, integration with single-cell omics, and clinical translation of validated mass-spectrometry biomarkers are identified as priorities for the coming decade. Full article

Effective management of wastewater treatment plants often requires real-time measurements of Biochemical Oxygen Demand (BOD). Conventional methods for determining Biochemical Oxygen Demand (BOD) are often time-consuming, labor-intensive and prone to inaccuracies. Microbial Fuel Cells (MFCs) have emerged as a viable alternative technology for BOD measurement, offering real-time monitoring capability. However, challenges remain in its validity for testing different types of wastewater. This study developed a cost-effective dual-chamber MFC with graphite felt electrodes and a CMI-7000 membrane, inoculated with a microbial consortia grown from anaerobic sludge at optimal conditions (35 °C, pH 7, 1000 Ω external resistance). After one month of biofilm formation, the MFC produced 600 mV. Voltage outputs were measured at six BOD₅ concentrations (36 to 583 mg/L) in synthetic wastewater, showing a strong linear correlation between BOD₅ concentrations and voltage outputs. The MFC was also tested with five domestic wastewater samples with BOD₅ values ranging between 81 and 405 mg/L. The output voltages were inserted into the derived voltage–BOD correlation to obtain BOD₅ values within 2.5% to 11% of conventional laboratory results. These findings confirm the potential of MFC-based biosensors as an efficient and accurate tool for real-time wastewater monitoring. Full article