Wastewater-based epidemiology (WBE) has emerged as a powerful surveillance tool used to assess public health by tracking infectious materials shed into sewage systems by infected hosts. To enable a widespread implementation of WBE, advanced analytical technologies are required for timely, efficient, and accurate detection of the viruses from the complex water matrix. This review discusses key advancements in molecular methods and biosensors demonstrated on wastewater samples that largely enhance wastewater surveillance, including improved sensitivity, enhanced portability, shortened turnover time, integration with wastewater sample treatment, multiplexing ability, and the incorporation of artificial intelligence (AI)/machine learning (ML). We also compare the analytical performance of these advanced methods, their advantages, current challenges, and future direction on how they can better enable wastewater surveillance via efficient detection of targeted and emerging/untargeted viruses from wastewater.

Cascade interactions are fundamental to enzyme catalysis and cellular activities, enabling dynamic and adaptive responses to environmental stimuli. DNA-based cascade systems have been widely employed to mimic biological processes, such as immune responses and DNAzyme catalysis, achieved mainly through the hybridization interaction. Herein, we present a cascade DNA system involving single-stranded sequences, noncanonical cofactor-bridged duplexes, and canonical duplexes to construct and dissociate hydrogel matrices. In this work, thymine-rich oligonucleotides (T-strands) exist as single-stranded random coils in a buffer at pH 7.2. Upon the introduction of a low-molecular-weight cofactor, melamine (MA), a supramolecular noncanonical configuration, termed the T-MA-T duplex, is formed. Subsequent addition of adenine-rich oligonucleotides (A-strands) to the system leads to the replacement of MA cofactors and the formation of more energetically favorable canonical A-T duplex structures. These consecutive structural transitions are further utilized as dynamic bridging elements in stimuli-responsive DNA hydrogels, facilitating liquid-hydrogel-liquid phase transitions. Moreover, we demonstrate precisely controlled release profiles of doxorubicin from the DNA hydrogel. This approach, leveraging both noncanonical and canonical DNA configurations in triggered cascade structural transitions, opens avenues for developing molecular switches, electronic nanodevices, adaptive materials, and other advanced applications.

Conventional bacteria detection from wound infections requires costly or time-consuming methods that require either trained personnel, tedious sample preparation, or complex instrumentation. Hence, it is crucial to develop simple and inexpensive methods that enable accurate, point-of-care assessment of wound infections. Herein, we developed a Paper sensor to detect metabolites, i.e. heterocyclic Amine/Carbonyl, Lactate, Moisture, Trimethylamine and Tryptophan derivatives (termed PALM-T2), released from prevalent wound bacterial species. PALM-T2 consists of five sensing zones that are connected via a sampling arm. Each sensing zone contains a colorimetric sensor that generates unique colour response to certain bacteria metabolites. Images of PALM-T2 were captured using a smartphone and ImageJ was used to analyze colour changes in each sensing zones, eventually revealing the type and concentration of prevalent wound bacterial species. Simulated wound fluid and ex-vivo pig skin 'wound' models were used to demonstrate PALM-T2's performance in simultaneous detection of multiple bacteria metabolites within 30 min. The PALM-T2 sensor displays a great potential for point-of-care detection of bacteria at 105 CFU/mL, the lowest concentration observed from an infected wound.

As a broad class of porous nanomaterials, metal organic frameworks (MOFs) exhibit unique properties, such as broad tunability, high stability, atomically well-defined structure, and ordered uniform porosity. These features facilitate the rational design of MOFs as an outstanding nanomaterial candidate in biosensing, therapeutics delivery, and catalysis applications. Recently, novel modifications of the MOF nanoarchitecture and incorporation of synergistic guest materials have been investigated to achieve well-tailored functional design, gradually bridging the fundamental gap between structure and targeted activity. Specifically, the burgeoning studies of MOF-based high-performance biosensors have aimed to achieve high sensitivity, selectivity, and stability for a large variety of analytes in different sensing matrices. In this review, we elaborate the key roles of MOF nanomaterials in biosensors, including their high stability as a protective framework for biomolecules, their intrinsic sensitivity-enhancing functionalities, and their contribution of catalytic activity as a nanozyme. By examining the main structures of MOFs, we further identify varied structural engineering approaches, such as precursor tuning and guest molecule incorporation, that elucidate the concept of the structure-activity relationship of MOFs. Furthermore, we highlight the unique applications of MOF nanomaterials in electrochemical and optical biosensors for enhanced sensor performances. Finally, the challenges and future perspectives of developing next-generation MOF nanomaterials for biosensor applications are discussed.

Noncanonical DNA structures mediated by low-molecular-weight cofactors significantly enrich the arsenal of the DNA toolbox and expand its functional applications. In this study, cyanuric acid (CA), a cofactor with three thymine-like edges, is employed to assemble adenine-rich strands (A-strands) into a parallel noncanonical A-CA triplex configuration through Watson-Crick and Hoogsteen interactions. This assembly occurs at a system pH value below the pKa of the CA cofactor (6.9), where CA is protonated, while its deprotonation at higher pH levels leads to the dissociation of the A-CA triplex into single A-strands and free CA cofactors. The structural transition is fully pH reversible. The A-CA triplex is further utilized as a crosslinking element for reprogrammable macroscopic object assembly, exemplified by hydrogel cubes (5 × 5 × 5 mm), a topic that has been less explored compared to nano- and microscopic constructs. Controlled, modular assembly and disassembly of various configurations, such as square, line, and T-shape, are demonstrated through reversible pH adjustments. This strategy offers a streamlined approach using a single DNA sequence and cofactor for hydrogel modification and complex construction, providing cost-effective, recyclable, and stimuli-responsive functionality, which inspires the development of versatile and adaptive supramolecular systems in chemistry and materials science.

A self-powered triboelectric nanogenerator based pressure sensor (STEPs) is developed via material doping and morphology tuning to achieve sensitive multidirectional sensing, showing great potential for motion monitoring and human–machine interactions.

Innovations in wearable sweat sensors hold great promise to provide deeper insights into molecular level health information non-invasively. Lactate, a key metabolite present in sweat, holds immense significance in assessing physiological conditions and performance in sports physiology and health sensing. This paper presents the development and characterization of stretchable electrodes with ultrahigh active surface area of 648 % for lactate sensing. The as-printed stretchable electrodes were functionalized with an electron transfer layer comprising Toluidine Blue O and multi-walled carbon nanotubes (MWCNTs), and an enzymatic layer consisting of lactate dehydrogenase with β-Nicotinamide adenine dinucleotide as the cofactor for lactate selectivity. This sensor achieves a dual-signal read-out in which both electrochemical and fluorescence signals were obtained during lactate detection, demonstrating promising sensor performance in terms of sensitivity and reliability. We demonstrate the robustness of the dual-signal sensor under simulated conditions of physical deformation and shifted excitation. Under these compromised conditions, the performance of the stretchable electrodes remained largely unaffected, showcasing their potential for robust and adaptable sensing platforms in wearable health monitoring applications.

Continuous and in situ detection of biomarkers in biofluids (for example, sweat) can provide critical health data but is limited by biofluid accessibility. Here we report a sensor design that enables in situ detection of solid-state biomarkers ubiquitously present on human skin. We deploy an ionic–electronic bilayer hydrogel to facilitate the sequential dissolution, diffusion and electrochemical reaction of solid-state analytes. We demonstrate continuous monitoring of water-soluble analytes (for example, solid lactate) and water-insoluble analytes (for example, solid cholesterol) with ultralow detection limits of 0.51 and 0.26 nmol cm−2, respectively. Additionally, the bilayer hydrogel electrochemical interface reduces motion artefacts by a factor of three compared with conventional liquid-sensing electrochemical interfaces. In a clinical study, solid-state epidermal biomarkers measured by our stretchable wearable sensors showed a high correlation with biomarkers in human blood and dynamically correlated with physiological activities. These results present routes to universal platforms for biomarker monitoring without the need for biofluid acquisition. Biomarkers in biofluids are widely used for medical diagnosis, but their use is limited by accessibility. Here the authors present a stretchable wearable sensor allowing in situ detection of solid-state biomarkers on human skin, hence avoiding biofluid acquisition.

Wearable metabolite sensors are often limited by easily denaturable enzymes that only allow short-duration monitoring. Although encapsulating enzymes in metal-organic frameworks (MOFs) shows promise of long-term enzyme protection, it is typically accompanied by significantly decreased activity due to increased diffusion barrier, steric hindrance for enzyme-substrate binding, and poor enzyme-electronic interface. Herein, the co-encapsulation of enzymes and ultrasmall arginine-derived carbon dots (Argdot) into a mesoporous Zeolitic Imidazolate Framework-8 (mZIF-8) matrix and the enhancement effect of Argdot on enzyme stability and activity, which consequently improves the electrochemical sensor's long-term sensitivity are investigated. Specifically, the glucose oxidase (GOx)-Argdot@mZIF-8 nanocomposite consistently exhibits 40% higher electrochemical sensitivity compared to control GOx@mZIF-8, an improvement similarly demonstrated with another model enzyme lactate oxidase (LOx). Furthermore, GOx-Argdot@mZIF-8 displays excellent stability, retaining 100% of initial sensitivity over 30 days of repeated testing at 37 degrees C. A touch-based glucose sensor prototype is demonstrated as an excellent reusable sensor to monitor finger-tip sweat glucose levels over one month at room temperature. This enzyme encapsulation strategy is not only useful for developing reusable sweat sensors with long-term monitoring capability, but also promising to expand the industry use of enzymes under harsh conditions. Herein, co-encapsulation of enzymes and ultrasmall enzyme-mimicking arginine-derived carbon dots into a mesoporous Zeolitic Imidazolate Framework-8 matrix to develop a hybrid-zyme is investigated. This hybrid-zyme achieves simultaneous activity retention and stability enhancement, which consequently improves the electrochemical sensor's long-term sensitivity for continuous monitoring. This generalizable strategy is useful for developing reusable sweat sensors and expanding the industry use of enzymes.image

Wearable devices can provide timely, user-friendly, non- or minimally invasive, and continuous monitoring of human health. Recently, multidisciplinary scientific communities have made significant progress regarding fully integrated wearable devices such as sweat wearable sensors, saliva sensors, and wound sensors. However, the translation of these wearables into markets has been slow due to several reasons associated with the poor system-level performance of integrated wearables. The wearability consideration for wearable devices compromises many properties of the wearables. Besides, the limited power capacity of wearables hinders continuous monitoring for extended duration. Furthermore, peak-power operations for intensive computations can quickly create thermal issues in the compact form factor that interfere with wearability and sensor operations. Moreover, wearable devices are constantly subjected to environmental, mechanical, chemical, and electrical interferences and variables that can invalidate the collected data. This generates the need for sophisticated data analytics to contextually identify, include, and exclude data points per multisensor fusion to enable accurate data interpretation. This review synthesizes the challenges surrounding the wearable device integration from three aspects in terms of hardware, energy, and data, focuses on a discussion about hybrid integration of wearable devices, and seeks to provide comprehensive guidance for designing fully functional and stable wearable devices.

In situ analysis of sweat biomarkers potentially provides noninvasive lifestyle monitoring and early diagnosis. Quantitative detection of sweat rate is crucial for thermoregulation and preventing heat injuries. Here, a skin-attachable paper fluidic patch is reported for in situ colorimetric sensing of multiple sweat markers (pH, glucose, lactate, and uric acid) with concurrent sweat rate tracking. Two sets of fluidic patterns-multiplexed detection zones and a longitudinal sweat rate channel-are directly printed by an automated ink dispenser from a specially developed ceramic-based ink. The ceramic ink thermal-cures into an impervious barrier, confining sweat within the channels. The ceramic-ink-printed boundary achieves higher pattern resolution, prevents fluid leakage, attains pattern thermal stability, and resistant to organic solvents. The cellulose matrix of the detection zones is modified with nanoparticles to improve the color homogeneity and sweat sensor sensitivity. The sweat rate channel is made moisture sensitive by incorporating a metal-salt-based dye. The change in saturation/color of the detection zones and/or channels upon sweat addition can be visually detected or quantified by a smartphone camera. A cost-effective way is provided to fabricate paper fluidic sensor patches, successfully demonstrating on-body multiplexed evaluation of sweat analytes. Such skin wearables offer on-site analysis, meaningful to an increasingly health-conscious population.

Early diagnosis of chronic kidney disease (CKD) and constant monitoring to guide optimal intervention is critical to prevent renal failure and other critical diseases. However, the conventional blood tests in hospital are time-consuming and have poor patient compliance. Herein, we demonstrate a real-time, minimally invasive, and self-administrable approach to detect kidney biomarkers in the skin interstitial fluid (ISF) using a polymeric microneedle coupled electrochemical sensor array (MNESA). Microneedles can readily penetrate stratum corneum and quickly extract ISF onto the sensors. Four biomarkers are simultaneously detected to avoid false positive and provide an accurate assessment of kidney functions. Using an artificial skin model, it is shown that MNSEA gives specific and sensitive responses to these kidney biomarkers in physiologically relevant ranges (phosphate: 0.3-1.8 mM, 3.62 mu A/mM; uric acid: 50-550 mu M, 4.19 nA/mu M; creatinine: 50-550 mu M, 12.58 nA/mu M; urea: 1-16 mM, 44.6 mV/decade). Using a mouse model, we demonstrate that this approach is as reliable as the commercial assays and is feasible to readily monitor the progression of CDK.

Wound healing is a dynamic process with multiple phases. Rapid profiling and quantitative characterization of inflammation and infection remain challenging. We report a paper-like battery-free in situ AI-enabled multiplexed (PETAL) sensor for holistic wound assessment by leveraging deep learning algorithms. This sensor consists of a wax-printed paper panel with five colorimetric sensors for temperature, pH, trimethylamine, uric acid, and moisture. Sensor images captured by a mobile phone were analyzed by neural network–based machine learning algorithms to determine healing status. For ex situ detection via exudates collected from rat perturbed wounds and burn wounds, the PETAL sensor can classify healing versus nonhealing status with an accuracy as high as 97%. With the sensor patches attached on rat burn wound models, in situ monitoring of wound progression or severity is demonstrated. This PETAL sensor allows early warning of adverse events, which could trigger immediate clinical intervention to facilitate wound care management.

Effective wound care and treatment require a quick and comprehensive assessment of healing status. Here, we develop a carbon dot-doped hydrogel sensor array in polydimethylsiloxane (PDMS) for simultaneous colorimetric detections of five wound biomarkers and/or wound condition indicators (pH, glucose, urea, uric acid, and total protein), leading to the holistic assessment of inflammation and infection. A biogenic carbon dot synthesized using an amino acid and a polymer precursor is doped in an agarose hydrogel matrix for constructing enzymatic sensors (glucose, urea, and uric acid) and dye-based sensors (pH and total protein). The encapsulated enzymes in such a matrix exhibit improved enzyme kinetics and stability compared to those in pure hydrogels. Such a matrix also provides stable colorimetric responses for all five sensors. The sensor array exhibits high accuracy (recovery rates of 91.5-113.1%) and clinically relevant detection ranges for all five wound markers. The sensor array is established for simulated wound fluids and validated with rat wound fluids from perturbed wound models. Distinct color patterns are obtained that can clearly distinguish healing vs nonhealing wounds visually and quantitatively. This hydrogel sensor array shows great potential for on-site wound sensing due to its long-term stability, lightweight, and flexibility.

Bacterial infections remain the leading cause of death worldwide today. The emergence of antibiotic resistance has urged the development of alternative antibacterial technologies to complement or replace traditional antibiotic treatments. In this regard, metal nanomaterials have attracted great attention for their controllable antibacterial functions that are less prone to resistance. This review discusses a particular family of stimuli-activable metal-bearing nanomaterials (denoted as SAMNs) and the associated on-demand antibacterial strategies. The various SAMN-enabled antibacterial strategies stem from basic light and magnet activation, with the addition of bacterial microenvironment responsiveness and/or bacteria-targeting selectivity and therefore offer higher spatiotemporal controllability. The discussion focuses on nanomaterial design principles, antibacterial mechanisms, and antibacterial performance, as well as emerging applications that desire on-demand and selective activation (i.e., medical antibacterial treatments, surface anti-biofilm, water disinfection, and wearable antibacterial materials). The review concludes with the authors' perspectives on the challenges and future directions for developing industrial translatable next-generation antibacterial strategies.

Polystyrene, one of the most widely-produced plastics worldwide, is non-biodegradable and has unsustainable life-cycles with only a small fraction recycled presently. Hence, there is considerable effort underway to explore new methods to give post-consumer polystyrene waste a new lease-of-life as functional materials. In this study, we report the synthesis of the first polyanionic fluorescent carbon nanoparticles from sulfonated waste polystyrene food containers via an environmentally-benign route in water. By virtue of their sulfonate groups, these biocompatible and fluorescent nanoparticles show a number of distinct behaviours in the presence of different main group and transition metal cations. Al3+ brings about both fluorescence enhancement and nanoparticle precipitation, whilst fluorescence quenching was observed for paramagnetic and toxic transition metal cations, with Cu2+ eliciting the most sensitive fluorescence response (LoD=26 mu M). These fluorescence intensity perturbations are likely a consequence of direct metal cation coordination to the exposed sulfonate groups on the nanoparticles. Our findings suggest the potential of using post-synthetically modified waste plastics to produce a family of luminescent carbon materials for environmental sensing of these hazardous cations.

Staphylococcus aureus is one of the most prevalent threats to public health. Rapid detection with high sensitivity and targeted killing is crucial to curb its spread. Herein, a metal-bearing nanocomposite, consisting of a bimetallic nanoparticle and a metal-organic framework (Au/Ir@Cu/Zn-MOF) was constructed. Upon conjugation with anti-S. aureus antibody, this nanocomposite (Ab-Au/Ir@Cu/Zn-MOF) was exploited for its dual functions, i.e. as a reporting probe in a lateral flow immunoassay and a high efficiency antibacterial reagent. Benefiting from the enrichment of Au/Ir NPs by the Cu/Zn-MOF, the Au/Ir@Cu/Zn-MOF-based lateral flow immunoassay sensor exhibited a visual limit of detection of 103 CFU/mL, which was100 times more sensitive than Au/Ir-based sensor. Moreover, the Ab-Au/Ir@Cu/Zn-MOF probe possessed synergistic photothermal-chemodynamic bactericidal effect that specifically targeted against S. aureus. Under a co-treatment by H2O2 (0.4 mM) and 808 nm near infrared irradiation (1 W/cm2, 5 min), complete sterilization of 5 × 105-106 CFU/mL S. aureus was achieved at a nanocomposite concentration as low as 6.25 μg/mL. The superior antibacterial efficiency was attributable to the three-fold properties of the Ab-Au/Ir@Cu/Zn-MOF probe: (1) enhanced multi-enzyme mimicking activities that promote reactive oxygen species generation, (2) high photothermal activity (efficiency of 53.70%), and (3) bacteria targeting ability via the antibody coating. By changing the antibody, this nanocomposite can be tailored to target a wide range of bacteria species, for detection and for precise antibacterial treatment.

Skin Interstitial Fluid (ISF) is an alternative source for biomarkers. Herein, a highly swellable microneedle patch (MNP) to rapidly extract ISF painlessly and bloodlessly is presented. The MNP is made of crosslinked methacrylated hyaluronic acid (MeHA) and dissolvable hyaluronic acid (HA) with the optimal balance of mechanical strength (0.6 N/MN) and absorption capability (16.22 μL in 20 min). Incorporated with wax-patterned and sensing-reagent-decorated test paper (TP) for multiplexed colorimetric detection of metabolites (glucose, lactate, cholesterol, and pH), this TP-MNP biosensor gives rapid color change in biomarker concentration-dependent manner based on specific enzymatic reactions, whereby allowing diagnosis by the naked eye or quantitative RGB analysis. Both the in vitro and in vivo experiments demonstrate the feasibility of TP-MNPs to detect multiple biomarkers in skin interstitial fluid within minutes. Such convenient and self-administrable profiling of metabolites shall be instrumental for home-based long-term monitoring and management of metabolic diseases.

In birds, the sperm storage tubules (SST) are dispersed in uterovaginal junction (UVJ) and highly correlated with differential capacity of sperm storage (SS) in and among species with unspecified mechanisms. Here, the SS duration of 252 egg layer breeders was evaluated in 5 rounds with 3 phenotypic traits to screen high- and low-SS individuals, respectively, followed with transcriptome of UVJ tissues and metabolome of serum (high-SS vs. low-SS) to decipher the candidate genes and biochemical markers correlated with differential SS capacity. Histological characterization suggested slightly higher density of SST in UVJ (high-SS vs. low-SS). Transcriptome analyses identified 596 differentially expressed genes (336 upregulated vs. 260 downregulated), which were mainly enriched in gene ontology terms of homeostasis, steroid and lipid metabolism and hormone activity, and 12 significant pathways (P < 0.05) represented by calcium, steroid, and lipid metabolism. Immunohistochemical staining of GNAQ, ST6GAL1, ADFP, and PCNA showed similar distribution in UVJ tissues between 2 groups. Several candidates (HSD11B2, DIO2, AQP3, GNAQ, NANS, ST6GAL1) combined with 4 (11β-prostaglandin F2α, prostaglandin B1, 7α-hydroxytestosterone, and N-acetylneuraminic acid) of 40 differential metabolites enriched in serum metabolome were considered as regulators and biomarkers of SS duration in egg layer breeders. The integrated transcriptome and metabolome analyses of chicken breeder hens will provide novel insights for exploration and improvement of differential SS capacity in birds.

In the broad spectral range, near‐infrared (NIR) plasmonics find applications in telecommunication, energy harvesting, sensing, and more, all of which would benefit from an electrostatically controllable NIR plasmon source. However, it is difficult to control bulk NIR plasmonics directly with electrostatics because of the strong electric‐field screening effect and high carrier concentration required to support NIR plasmons. Here, this constraint is overcome and the observation of NIR plasmonic resonances that can be modulated electrostatically over a range of ≈360 cm –1 in few‐layer NbSe 2 gratings is reported, thanks to the enhanced electrostatics of atomically thin 2D materials and the high‐quality film produced by a solution method. NbSe 2 plasmons also render strong field confinement due to their atomic thickness and provide an extra degree of resonance frequency modulation from the layered structure. This study identifies metallic 2D materials as promising (easily produced and well‐performing) candidates to extend electrostatically tunable plasmonics to the technologically important NIR range.