Redox sensing and regulation are critical to both the survival and virulence strategies used by the pathogenic fungus Cryptococcus neoformans to evade host immunity and establish infection. However, the precise genetic and biochemical mechanisms driving these redox regulation systems in the context of fungal virulence are unclear. To address this limitation, we designed genetically encoded redox sensors optimized for expression in C. neoformans and linked these sensors to cryptococcal redox proteins for real-time monitoring of intracellular redox status. Using these sensors, we established several fluorescence-based techniques for monitoring dose-responsive changes in the intracellular oxidation status of C. neoformans under stress. Specifically, we demonstrated sensor responsiveness to nontoxic doses of peroxide stress and during different stages of cell growth, and we verified sensor responsiveness in a mutant with known sensitivity to oxidative stress. This approach provides a framework for developing and deploying biosensors in pathogenic fungi and in basidiomycetes─a group of microorganisms with relatively few sophisticated genetic tools for molecular and synthetic biology. Overall, our sensors enable real-time insights into the key redox mechanisms driving growth and survival of a globally important pathogen and pave the way for tool development in other fungi.

The photoelectrochemical (PEC) biosensors relying on anodic photocurrent modulation are prone to producing false-positive results due to the interference from reductive species in samples, while the PEC sensors based on cathodic response often exhibit insufficient sensitivity in practical applications. To address this issue, herein we synthesized CdS via a hydrothermal method and encapsulated it with polyaniline (PANI) to create a high-performance CdS/PANI heterojunction photosensitive material. Then, the composite was used as a photoanode, paired with the Cu2O photocathode, establishing a self-powered system, wherein the CdS/PANI photoanode supplied photogenerated electrons to the Cu2O photocathode. Owing to the strong driving force provided by the Fermi-level difference between CdS/PANI and Cu2O for electron migration, the dual-photoelectrode system produced a strong and stable cathodic response signal, which was up to 23 times that of a three-electrode system, laying the foundation for constructing a highly sensitive sensor. On this basis, the Cu2O electrode functioning as a working electrode was modified by electrodeposited gold nanoparticles (Au NPs), followed by the immobilization of recognition element CA125 antibody through Au-N bonds, targeting the model molecule carbohydrate antigen CA125. Consequently, the obtained self-powered dual-photoelectrode immunosensor demonstrated exceptional analytical performance, including a wide quantitative detection range of 0.001-100 ng mL-1, a low detection limit of 0.26 pg mL-1, high stability, reproducibility, anti-interference capability, and practicability. Furthermore, this sensing platform is readily adaptable to monitoring other disease biomarkers.

Glucose and lactate are primary substrates in cerebral energy metabolism. Hyperpolarized [1-13C]pyruvate has become a powerful imaging agent for metabolic neuroimaging due to its central role in glucose and lactate metabolism, ability to cross the blood-brain barrier, and translational utility in neurological disorders. In particular, [1-13C]pyruvate enables an assessment of mitochondrial metabolism in the cerebral cortex through its conversion to [13C]bicarbonate. While it is not yet confirmed that production of [13C]bicarbonate primarily reflects neuronal metabolism, the higher affinity of neuronal transporters for lactate over pyruvate has motivated interest in hyperpolarized lactate as a more physiologic probe of neuronal metabolism. Here, we identify the predominant cellular source of [13C]bicarbonate and evaluate [1-13C]lactate as an imaging agent for neuronal metabolic imaging. Ex vivo NMR and mass spectrometry imaging of brain tissue collected after bolus injection of [U-13C3]pyruvate revealed that pyruvate dehydrogenase dominates pyruvate carboxylase in the cortex, supporting the neuronal origin of [13C]bicarbonate production. Although the bicarbonate fraction among the total 13C products in vivo was higher following hyperpolarized [1-13C]lactate injection, the signal sensitivity was markedly reduced due to lactate's shorter T1 and larger endogenous pool. Isotopomer analysis of brain tissue harvested 2 min after injection of [U-13C3]pyruvate or [U-13C3]lactate showed comparable labeling of mitochondrial intermediates. In glioma-bearing rats, in vivo imaging revealed an elevated pyruvate-to-lactate ratio within the tumor, highlighting altered redox and transport dynamics in malignancy. These findings demonstrate that both hyperpolarized [1-13C]pyruvate and [1-13C]lactate can effectively probe neuronal and glioma metabolism, although pyruvate outperforms lactate in detecting pyruvate dehydrogenase flux.

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are endogenous gaseous signaling molecules, playing crucial roles in a wide range of biological processes. This study presents the fabrication and evaluation of a triple amperometric microsensor capable of the simultaneous and selective detection of NO, CO, and H2S for in vivo applications. The sensor integrates three platinum working electrodes into a single device. Each electrode was independently modified with specific metal deposits and selective membranes optimized to enhance specificity toward its target analyte. The sensor's excellent performance in terms of sensitivity, linearity, and selectivity was confirmed. To demonstrate in vivo applicability, the sensor was positioned on the cortical surface of a living rat brain, where it successfully monitored real-time concentration changes of NO, CO, and H2S during seizure events induced by 4-aminopyridine: NO exhibited the earliest concentration increase, followed sequentially by CO and H2S, providing the first temporally resolved evidence of in vivo gasotransmitter crosstalk during neural hyperactivity. This work establishes a powerful electrochemical platform for probing multigasotransmitter dynamics in real time.

Supercritical angle fluorescence (SAF) is a near-field collection technique used to create surface-sensitive optical transducers. While SAF biosensors require simpler excitation optics compared with total internal reflection fluorescence (TIRF)-based systems, they rely on complex fluorescence collection setups involving large, expensive microscopes to achieve similar sensitivities. In this article, we present a novel interference-based SAF transducer that leverages complementary metal oxide semiconductor (CMOS)-compatible technologies to significantly simplify and miniaturize the collection scheme without compromising sensitivity. The transducer incorporates an interference filter designed to block both excitation light and undercritical angle fluorescence (UAF) while transmitting SAF. We validated its performance using a protein A immunoassay and compared the results to those of the same assay performed on fluorescence well plates. Our SAF transducer achieved a limit of detection (LoD) of 1 pM, compared to 10 pM for the well plates. Furthermore, the transducer enables a washless assay format, significantly reducing the time to result. Its CMOS-compatible materials also support scalable, cost-effective manufacturing by using standard semiconductor fabrication processes.

An innovative off-axis integrated cavity (OAIC) mimicking the tail flagellum of bacteria is proposed to solve the problems of mode interference noise and slow gas exchange caused by the nonuniform gas-flow field in traditional OAIC with large inside airflow fluctuation. The design concept of such a cavity, named bioinspired mode-noise suppressed OAIC, for the first time combines cavity-enhanced spectroscopy with bioinspired design to our knowledge. By redesigning the gas inlets into a pair of bioinspired tangential inlets, the original turbulent flow is transformed into a tangential rotating flow that guides fluid in a manner similar to bacterial flagella. Multiobjective optimization based on a genetic algorithm is used to optimize the bioinspired OAIC parameters, creating an orderly and uniform fluid within the cavity and reducing laser-gas interaction noise. The bioinspired OAIC shows no significant increase in concentration fluctuations within the 200-1500 sccm flow range, with optical mode-noise level reduced by 2.54 times at 800 sccm. The complete gas exchange time is shortened to 12 s. Allan deviation analysis revealed that the detection limit of bioinspired OAIC reached 34.4 parts-per-trillion (ppt) with an average time of 13.5 s. The bioinspired OAIC demonstrates long-term stability in continuous high-airflow gas detection owing to suppressed airflow fluctuation and minimized mode noise. The proposed bioinspired design concept can also be applied to the fabrication of other resonant cavities for fluid measurement.

Advances in artificial intelligence are enabling flexible intelligent sensors with performance rivaling or surpassing human perception. In this work, we have introduced a dual-mode capacitive sensor featuring double-sided microtetrahedral electrodes (DSMEs) for proximity and contact detection. The innovative architecture design effectively minimizes the sensor's viscoelasticity and equivalent modulus, achieving a high pressure sensitivity of 1.29 kPa-1 across a broad linear response range of 0-20 kPa and a detection upper limit of up to 800 kPa. The sensor demonstrates rapid response and recovery times of 125 and 65 ms, respectively, along with stable signal output maintained over 10,000 loading cycles. Moreover, the microtetrahedral structure electrodes produce a nonuniform electric field, which enhances noncontact sensing capabilities through the capacitive fringe effect, allowing the sensor to detect stainless steel plates at distances of up to 100 mm. Leveraging its exceptional dual-mode sensing capabilities, the sensor has demonstrated remarkable performances in human motion monitoring, object shape recognition, and material type perception. With the integration of machine learning, the sensor achieves an impressive material classification accuracy of 98.75%. These results establish a valuable reference for the development of multifunctional intelligent perception systems in the next generation of intelligent robots.

The growing demand for next-generation wearable technologies characterized by high sensitivity, low detection limits, and a broad pressure range drives the need for advanced pressure sensors capable of detecting subtle physiological signals and large-scale mechanical inputs for ergonomic applications. Here, we present an ultrasensitive ionotronic pressure sensor (IPS) based on a cobalt-rich zeolitic imidazolate framework (ZIF-67)-grown, highly porous ionic nanofibrous membrane (INM) as a dielectric separator, paired with a hybrid nanoporous carbon-incorporated laser-induced graphene (HNPC@LIG) and ionic PVDF-HFP@IL as the electrode/electrolyte layer. The ZIF-67-incorporated INM lowers the baseline capacitance and enhances ion transport under pressure, enabling efficient electric double layer (EDL) formation, while the HNPC@LIG offers a high surface area. As a result, the IPS achieves an exceptionally wide, linear detection range (0-1000 kPa) and high sensitivity: 5073 kPa-1 (0-140 kPa), 18,366 kPa-1 (140-300 kPa), 5324 kPa-1 (300-470 kPa), and 1023 kPa-1 (470-1000 kPa). This performance surpasses that of current state-of-the-art sensors, enabling precise detection of lip motion, respiration, pulse, and posture, paving the way for physiological signal and posture monitoring for ergonomic assistance.

Bacterial biosensors represent a promising avenue for detecting gastrointestinal disease biomarkers; however, their direct oral delivery is limited by challenges such as bioavailability, safety, and interactions with the complex gut microbiota. To address these issues, we developed MagGel-BS, a Magnetic hydroGel-encapsulated Bacterial bioSensor platform. This hybrid system combines biocompatible alginate hydrogel to encapsulate both magnetic particles and bacterial biosensors, facilitating precise detection of disease biomarkers. The hydrogel significantly enhances stability, improving bacterial viability in gastric fluid by 10-fold. Utilizing heme-responsive bacteria, MagGel-BS was able to detect gastrointestinal bleeding in mice within only 20 min, a significant improvement compared to unencapsulated biosensors, which took several hours. Importantly, MagGel-BS showed no immune responses or adverse effects in vivo. In summary, this platform provides a rapid, noninvasive approach for gastrointestinal biomarker detection, demonstrating considerable potential for advancing bacterial-based diagnostics and therapeutics applications.

The rapid and accurate detection of Aggregatibacter actinomycetemcomitans (AA), a key pathogen in aggressive periodontitis, remains a critical challenge in point-of-care diagnostics. Here, we report the development of a portable lateral flow device (LFD) using an RNA-cleaving DNAzyme (RCD-AA5) as a highly specific molecular recognition element. Selected via systematic evolution of ligands by exponential enrichment (SELEX) against AA crude extracellular mixture (CEM-AA), RCD-AA5 demonstrated exceptional specificity, distinguishing the target from seven other Gram-negative and Gram-positive bacteria. A truncated 77-nt variant (RCD-AA5t5) retained full functionality while improving practical applicability. The resulting LFD exhibited 100% sensitivity and 100% specificity for identifying AA in clinical saliva samples. This work establishes a novel, DNAzyme-powered diagnostic platform that enables rapid, user-friendly, and accurate detection of AA, offering significant potential for improving aggressive periodontitis diagnosis in resource-limited and clinical setting.