Flexible and multi-functional three-dimensional scaffold based on enokitake-like Au nanowires for real-time monitoring of endothelial mechanotransduction.

Endothelial cells are sensitive to mechanical force and can convert it into biochemical signals to trigger mechano-chemo-transduction. Although conventional techniques have been used to investigate the subsequent modifications of cellular expression after mechanical stimulation, the in situ and real-time acquiring the transient biochemical information during mechanotransduction process remains an enormous challenge. In this work, we develop a flexible and multi-functional three-dimensional conductive scaffold that integrates cell growth, mechanical stimulation, and electrochemical sensing by in situ growth of enokitake-like Au nanowires on a three-dimensional porous polydimethylsiloxane substrate. The conductive scaffold possesses stable and desirable electrochemical sensing performance toward nitric oxide under mechanical deformation. The prepared e-AuNWs/CC/PDMS scaffold exhibits a good electrocatalytic ability to NO with a linear range from 2.5 nM to 13.95 µM and a detection limit of 8 nM. Owing to the excellent cellular compatibility, endothelial cells can be cultured directly on the scaffold and the real-time inducing and recording of nitric oxide secretion under physiological and pathological conditions were achieved. This work renders a reliable sensing platform for real-time monitoring cytomechanical signaling during endothelial mechanotransduction and is expected to promote other related biological investigations based on three-dimensional cell culture.

CS/PVP Hydrogel-Based Nanocapillary for Monitoring Bacterial Growth and Rapid Antibiotic Susceptibility Testing.

Infection with drug-resistant bacteria poses a significant threat to human health. Judicious use of antibiotics could reduce the likelihood of bacterial resistance, which can be evaluated through antibiotic susceptibility testing (AST). This paper focuses on the application of a needle-like nanocapillary tip filled with chitosan (CS)/polyethylene pyrrolidone (PVP) hydrogel based on its specific pH-sensitive properties. The gel-filled nanocapillary has the potential to be used for electrical pH detection with a sensitivity of 3.06 nA/pH and a linear range from 7.3 to 4.3. Such sensitivity for pH measurement could be extended for monitoring of bacterial (such as Escherichia coli and Streptococcus salivarius) growth because of the relationship between pH and bacterial growth. Bacterial growth curves obtained using the hydrogel-filled nanocapillary showed good agreement with the OD600 method. Moreover, this device could be applied for rapid AST for tetracycline and norfloxacin on E. coli with minimum inhibitory concentrations of 2 and 0.125 µg/mL, respectively. This study expands the application of the hydrogel-based nanocapillary for bacterial research by monitoring changes in pH values.

Bridging Ionic Current Rectification and Resistive-Pulse Sensing for Reliable Wide-Linearity Detection.

As two mainstream ionic detection techniques, ionic current rectification (ICR) suffers from large fluctuations in trace level detection, while resistive-pulse sensing (RPS) encounters easy clogs in high-concentration detection. By rationally matching the nanopore size with the DNA tetrahedron (TDN), this work bridges the two techniques to achieve reliable detection with wide linearity. As a representative analyte, miRNA-10b could specifically combine with and release TDN from the interior wall, which thus induced the simultaneous generation of distinct ICR and RPS signals. The ICR signals could be attributed to the balance between the effective orifice and surface charge density of the inner wall, while the RPS signals were induced by the complex of miRNA-10b and TDN passing through the nanopore. Such an operation contributed to a wide detection range of 1 fM-1 nM with a good linearity. The feasibility of this method is also validated in single-cell and real plasma detection.

Sensitive electrochemical flow injection analysis of H2O2 released from cells with a pass-through mode.

Conventional plate electrodes were commonly used in electrochemical flow injection analysis and only part of molecules diffused to the plane of electrodes could be detected, which would limit the performance of electrochemical detection. In this study, a low-cost native stainless steel wire mesh (SSWM) electrode was integrated into a 3D-printed device for electrochemical flow injection analysis with a pass-through mode, which is different compared with previous flow-through mode. This strategy was applied for sensitive analysis of hydrogen peroxide (H2O2) released from cells. Under the optimal conditions (the applied potentials, the flow rate and the sample volume), the device exhibits high sensitivity toward H2O2. Linear relationships could be achieved between electrochemical responses and the concentration of H2O2 ranging from 1 nM to 1 mM. The excellent analytical performance of the SSWM-based device could be attributed to the pass-through mode based on the mesh microstructure and intrinsic catalytic properties for H2O2 by stainless steel. This approach could be further successfully extended for screening of H2O2 released from HeLa cells with electrochemical responses linear to the number of cells in a range of 3 - 1.35 × 104 cells with an injection volume of 30 µL. This study revealed the potential of mesh electrodes in electrochemical flow injection analysis for cellular function and pathology and its possible extension in cell counting and on-line analysis.

A Bifunctional Wearable Sensor Based on a Nanoporous Membrane for Simultaneous Detection of Sweat Lactate and Temperature.

Wearable sensors for non-invasive, real-time detection of sweat lactate have far-reaching implications in the fields of health care and exercise physiological responses. Here, we propose a wearable electrochemical sensor with gold nanoelectrode arrays fabricated on the nanoporous polycarbonate (PC) membrane by encapsulating lactate oxidase (LOx) in chitosan (CS) hydrogel for detecting body temperature and sweat lactate concurrently. Flexible gold nanoporous electrodes not only enhance electrode area but also offer a nanoconfined space to accelerate the catalytic reaction of LOx and control substrate concentration on the surface of LOx to decrease substrate inhibition. The proposed sensor has a long durability of 13 days and better selectivity for the detection of sweat lactate over a wide linear range (0.01-35 mM) with a low detection limit (0.144 µM). Furthermore, temperature-dependent transmembrane currents passing through the sensor are used to estimate body temperature. We then use multiple linear regression to adjust the effect of temperature on lactate detection and succeed in monitoring lactate molecules in sweat and body temperature during exercise.

An Ultrasensitive and Efficient microRNA Nanosensor Empowered by the CRISPR/Cas Confined in a Nanopore.

This work presents a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas-nanopipette nano-electrochemistry (Cas = CRISPR-associated proteins) capable of ultrasensitive microRNA detection. Nanoconfinement of the CRISPR/Cas13a within a nanopipette leads to a high catalytic efficacy of ca. 169 times higher than that in bulk electrolyte, contributing to the amplified electrochemical responses. CRISPR/Cas13a-enabled detection of representative microRNA-25 achieves a low limit of detection down to 10 aM. Practical application of this method is further demonstrated for single-cell and real human serum detection. Its general applicability is validated by addressing microRNA-141 and the SARS-CoV-2 RNA gene fragment. This work introduces a new CRISPR/Cas-empowered nanotechnology for ultrasensitive nano-electrochemistry and bioanalysis.

Stretchable Sponge-Based Electrochemical Biosensor for Real-Time Sensing of Cells in Three-Dimensional Culture.

For the study of cell biology, real-time information on cell physiological processes will be more accurate and closer to the in vivo condition in a three-dimensional (3D) culture system. Although most reported 3D cell culture scaffolds can better mimic the in vivo dynamic microenvironment, the real-time analysis technique is deficient or lacking. Herein, a stretchable and conductive 3D scaffold is developed to construct an electrochemical biosensor for real-time monitoring of cell release in 3D culture under stimulation of drug stimulant and mechanical force. In our design, the polyurethane sponge (PU) dipped with conductive carbon ink (CC/PU) was used as a conductive scaffold, and gold nanoparticles (nano-Au) were electrodeposited on the CC/PU (nano-Au CC/PU) to improve the electrochemical sensing performance. The prepared nano-Au CC/PU scaffold exhibits a good electrocatalytic ability to H2O2 with a linear range from 20 nM to 43 µM. Due to the great biocompatibility, HeLa cells can be cultured directly on the nano-Au CC/PU and the in situ and real-time tracking of H2O2 secretion from cells was achieved. The results demonstrate that both the drug stimulant and mechanical force can rapidly activate the release of reactive oxygen species. This study indicates that the stretchable 3D sensing scaffold has good potential for cell biology research in an in vivo-like microenvironment and can be extensively used in the fields of tissue engineering, drug screening, and pathological research.

Vibration-enhanced disposable electroanalytical platform for selective analysis of tryptophan in fruits based on molecular imprinting.

Although electrochemical detection based on molecular imprinting polymers (MIP) could dramatically improve the selectivity, the procedure is time-consuming because of the essential incubation step. In addition, current MIP electrochemical detections were not suitable for analysis of microliter-level sample solutions, limiting their applications for real samples. This investigation aims at applying vibration to enhance efficiency of MIP electrochemical detection of 20 µL sample solutions. MIP analysis of Tryptophan (Trp) was used as the model with disposable MIP electrodes prepared by electrochemical polymerization of o-phenylenediamine on carbon ink coated on stainless steel sheets. The MIP electrode was integrated in a 3D-printed analytical device for vibration-enhanced electrochemical detection of Trp. Our results showed that this vibration-enhanced strategy could significantly increase electrochemical responses of Trp at the same incubation time. Such improvement might be attributed to the enhanced mass transfer at the surface of the working electrode brought by vibration. It needs to be emphasized that this strategy is suitable for analysis of sample solutions with the volume of microliters, which is superior to normal stirring in MIP electrochemical detection. Our approach could be successfully utilized for differentiation of Trp in different fruits, opening more opportunities for MIP electrochemical detection of real samples. The enhanced efficiency by vibration could pave foundation for extensive practical MIP detection of sample solutions at the level of microliters.

Janus Metal-Organic Framework Membranes Boosting the Osmotic Energy Harvesting.

The unique ion-transport properties in nanoconfined pores enable nanofluidic devices with great potential in harvesting osmotic energy. The energy conversion performance could be significantly improved by the precise regulation of the "permeability-selectivity" trade-off and the ion concentration polarization effect. Here, we take the advantage of electrodeposition technique to fabricate a Janus metal-organic framework (J-MOF) membrane that possesses rapid ion-transport capability and impeccable ion selectivity. The asymmetric structure and asymmetric surface charge distribution of the J-MOF device can suppress the ion concentration polarization effect and enhance the ion charge separation, exhibiting an improved energy harvesting performance. An output power density of 3.44 W/m2 has been achieved with the J-MOF membrane at a 1000-fold concentration gradient. This work provides a new strategy for fabricating high-performance energy-harvesting devices.

Construction and Evaluation of Zeolitic Imidazolate Framework-Encapsulated Hemoglobin Microparticles as Oxygen Carriers.

Artificial oxygen carriers, such as favorably hemoglobin-based oxygen carriers, have received considerable attention due to some drawbacks of human donor blood. Among all oxygen carriers, the metal organic framework (MOF) exhibits excellent oxygen-carrying capacity due to its good encapsulation efficiency and competitive biocompatibility. Recently, zeolitic imidazolate frameworks (ZIFs) with unique structure have attracted much attention due to their outstanding solvothermal stability. Notably, ZIF-8, the prototypical ZIF, has been utilized to load hemoglobin (Hb) as a potential blood substitute. In this work, another ZIF material, which possesses a high oxygen binding/release capability, suitable safety profile, high stability, and efficiency as a potential oxygen carrier, was used to encapsulate Hb in an environment-friendly condition.

Rational design of mesoporous chiral MOFs as reactive pockets in nanochannels for enzyme-free identification of monosaccharide enantiomers.

Monosaccharides play significant roles in daily metabolism in living organisms. Although various devices have been constructed for monosaccharide identification, most rely on the specificity of the natural enzyme. Herein, inspired by natural ionic channels, an asymmetrical MOF-in-nanochannel architecture is developed to discriminate monosaccharide enantiomers based on cascade reactions by combining oxidase-mimicking and Fenton-like catalysis in homochiral mesoporous CuMOF pockets. The identification performance is remarkably enhanced by the increased oxidase-mimicking activity of Au nanoparticles under a local surface plasmon resonance (LSPR) excitation. The apparent steady-state kinetic parameters and nano-fluidic simulation indicate that the different affinities induced by Au-LSPR excitation and the confinement effect from MOF pockets precipitate the high chiral sensitivity. This study offers a promising strategy for designing an enantiomer discrimination device and helps to gain insight into the origin of stereoselectivity in a natural enzyme.

Stretchable Electrochemical Sensor Based on a Gold Nanowire and Carbon Nanotube Network for Real-Time Tracking Cell-Released H2S.

Hydrogen sulfide (H2S), as the third gas transporter in biological systems, plays a key role in the regulation of biological cells. Real-time detection of local H2S concentration in vivo is an important and challenging task. Herein, we explored a novel and facile strategy to develop a flexible and transparent H2S sensor based on gold nanowire (AuNW) and carbon nanotube (CNT) films embedded in poly(dimethylsiloxane) (PDMS) (AuNWs/CNTs/PDMS). Taking the advantage of the sandwich-like nanostructured network of AuNWs/CNTs, the prepared electrochemical sensing platform exhibited desirable electrocatalytic activity toward H2S oxidation with a wide linear range (5 nM to 24.9 µM) and a low dete ction limit (3 nM). Furthermore, thanks to the good biocompatibility and flexibility of the sensor, HeLa cells can be cultured directly on the electrode, allowing real-time monitoring of H2S released from cells under a stretched state. This work provides a versatile strategy for the construction of stretchable electrochemical sensors, which has potential applications in the study of H2S-related signal mechanotransduction and pathological processes.

Locally superengineered cascade recognition-quantification zones in nanochannels for sensitive enantiomer identification.

As an intriguing and intrinsic feature of life, chirality is highly associated with many significant biological processes. Simultaneous recognition and quantification of enantiomers remains a major challenge. Here, a sensitive enantiomer identification device is developed on TiO2 nanochannels via the design of cascade recognition-quantification zones along the nanochannels. In this system, ß-cyclodextrin (ß-CD) is self-assembled on one side of the nanochannels for the selective recognition of enantiomers; CuMOFs are designed as the target-responsive partners on the other side of the nanochannels for the quantification of enantiomers that pass through the nanochannels. As a proof-of-principle of the cascade design, arginine (Arg) enantiomers are tested as the identification targets. The l-Arg molecules selectively bind in the recognition zone; d-Arg molecules pass through the recognition zone and then interact with the quantification zone via a specialized reduction reaction. As verified by nanofluidic simulations, because of the confinement effect of nanoscale channels combined with the condensation effect of porous structure, the in situ reaction in the quantification zone contributes to an unprecedented variation in transmembrane K+ flux, leading to an improved identification signal. This novel cascade-zone nanochannel membrane provides a smart strategy to design multifunctional nanofluidic devices.

Synergistic Effect of Electrostatic Interaction and Ionic Dehydration on Asymmetric Ion Transport in Nanochannel/Ion Channel Composite Membrane.

Ion transport in nanochannels of a size comparable to that of hydrated ions exhibits unique properties due to the synergistic effect of various forces. Here, we design a nanochannel/ion channel composite (NIC) membrane that shows a high ion current rectification (ICR) ratio in different electrolytes. Experimental and theoretical results demonstrate that the synergistic effect of electrostatic interaction and ionic dehydration plays an important role in regulating the ICR behavior of the NIC membrane. We find that electrostatic attraction between ions and the channel surface in the ultraconfined space increases the probability of ionic dehydarion, resulting in different dehydration energy costs for different ions. This further alters the driving force for ion transport and thus regulates ICR of the NIC membrane. This work provides fundamental knowledge of ion transport in ion channels, which aids in the understanding of the function of biological systems and the design of high-performance nanochannel devices.

PNP Nanofluidic Transistor with Actively Tunable Current Response and Ionic Signal Amplification.

Inspired by electronic transistors, electric field gating has been adopted to manipulate ionic currents of smart nanofluidic devices. Here, we report a PNP nanofluidic bipolar junction transistor (nBJT) consisting of one polyaniline (PANI) layer sandwiched between two polyethylene terephthalate (PET) nanoporous membranes. The PNP nBJT exhibits three different responses of currents (quasi-linear, rectification, and sigmoid) due to the counterbalance between surface charge distribution and base voltage applied in the nanofluidic channels; thus, they can be switched by base voltage. Four operating modes (cutoff, active, saturation, and breakdown mode) occur in the collector response currents. Under optimal conditions, the PNP nBJT exhibits an average current gain of up to 95 in 100 mM KCl solution at a low base voltage of 0.2 V. The present nBJT is promising for fabrication of nanofluidic devices with logical-control functions for analysis of single molecules.

Light-Enhanced Osmotic Energy Harvester Using Photoactive Porphyrin Metal-Organic Framework Membranes.

High ion selectivity and permeability, as two contradictory aspects for the membrane design, highly hamper the development of osmotic energy harvesting technologies. Metal-organic frameworks (MOFs) with ultra-small and high-density pores and functional surface groups show great promise in tackling these problems. Here, we propose a facile and mild cathodic deposition method to directly prepare crack-free porphyrin MOF membranes on a porous anodic aluminum oxide for osmotic energy harvesting. The abundant carboxyl groups of the functionalized porphyrin ligands together with the nanoporous structure endows the MOF membrane with high cation selectivity and ion permeability, thus a large output power density of 6.26 W m-2 is achieved. The photoactive porphyrin ligands further lead to an improvement of the power density to 7.74 W m-2 upon light irradiation. This work provides a promising strategy for the design of high-performance osmotic energy harvesting systems.

Electrochemically Switchable Double-Gate Nanofluidic Logic Device as Biomimetic Ion Pumps.

Biological ion pumps with two separate gates can actively transport ions against the concentration gradient. Developing an artificial nanofluidic device with multiple responsive sites is of great importance to improve its controllability over ion transport to further explore its logic function and mimic the biological process. Here, we propose an electrochemical polymerization method to fabricate electrochemically switchable double-gate nanofluidic devices. The ion transport of the double-gate nanofluidic device can be in situ and reversibly switched among four different states. The logic function of this nanofluidic device is systematically investigated by assuming the gate state as the input and the transmembrane ionic conductance as the output. A biomimetic electrochemical ion pump is then established by alternately applying two different specific logic combinations, realizing an active ion transport under a concentration gradient. This work would inspire further studies to construct complex logical networks and explore bioinspired ion pump systems.

Associations of sleep characteristics with atopic disease: a cross-sectional study among Chinese adolescents.

BACKGROUND: Adolescence, as a transition between childhood and adulthood, is a critical stage for the long-term control of atopic diseases. We aim to determine if sleep characteristics are involved in the increased risk of atopic disease among adolescents. METHODS: Adopting the stratified cluster random sampling method, this cross-sectional survey included 4932 participants aged 12-18 years. The Chinese version of adolescent sleep disturbance questionnaire and the adolescent sleep hygiene scale were used to collect information on sleep problems and sleep hygiene, respectively. Logistic regression models were implemented to examine the associations of sleep with atopic diseases. RESULTS: Sleep duration was not found to be related with allergic diseases. By contrast, sleep-disordered breathing was associated with an increased risk of asthma (adjusted OR = 1.79, 95% CI 1.25-2.55), allergic rhinitis (adjusted OR = 1.95, 95% CI 1.52-2.49), and eczema (adjusted OR = 1.63, 95% CI 1.23-2.16); poor sleep physiology was correspondent to increased odds of asthma (adjusted OR = 1.69, 95% CI 1.24-2.29), allergic rhinitis (adjusted OR = 1.40, 95% CI 1.13-1.73) and eczema (adjusted OR = 1.66, 95% CI 1.32-2.09); non-optimal sleep environment was associated with an increased prevalence of asthma (adjusted OR = 1.52, 95% CI 1.08-2.12), allergic rhinitis (adjusted OR = 1.32, 95% CI 1.04-1.69) and eczema (adjusted OR = 1.53, 95% CI 1.19-1.96). CONCLUSIONS: As sleep-disordered breathing, poor sleep physiology and non-optimal sleep environment were associated with a higher risk of allergic diseases, the results of this study provide a new concept for the adjuvant treatment of allergic diseases in adolescents. Management strategies of allergic diseases should take regular screening and targeted treatment of sleep issues into account.

Reversible Electrochemical Tuning of Ion Sieving in Coordination Polymers.

Membrane-based ion separation is environmentally friendly, energy-efficient, and easy to integrate, being widely used in water desalination and purification systems. With the existing separation technologies, it is yet difficult to achieve real time, in situ, and reversible control of the separation process. Here, we design and fabricate a Prussian blue (PB) coordination polymer based membrane with uniform and electrochemically size-tunable subnanopores. The ion separation can be significantly and reversibly modulated through the electrochemical conversion between PB and Prussian white (PW). The permeation rates of small hydrated metal ions (Cs+ and K+) obviously increase upon switching from PB to PW, while the permeation rates of large hydrated metal ions (Li+, Na+, Mg2+, and La3+) remain constant. The membrane selectivity of small hydrated ions to large hydrated ions can be increased by more than 2 times during the electrochemical switch, which could be assigned to the slightly larger crystal size (e.g., pore window size) of PW than PB. The present approach provides a new strategy for constructing tunable seawater desalination and ion extraction systems.