Search

Hydrogen peroxide (H 2 O 2 ) levels play a vital role in redox regulation and maintaining the physiological balance of living cells, especially in cell mechanotransduction. Despite the achievements on strain-induced cellular H 2 O 2 monitoring, the applied voltage for H 2 O 2 electrooxidation possibly gave rise to an abnormal expression and inadequate accuracy, which was still an inescapable concern. Hence, we decorated an interlaced CuO@TiO 2 nanowires (NWs) semiconductor meshwork onto a polydimethylsiloxane film-supported gold nanotubes substrate (Au NTs/PDMS) to construct a flexible photoelectrochemical (PEC) sensing platform. Under white light irradiation, CuO@TiO 2 NWs synergistically exhibited great stretchability and the PEC platform enabled stable photocurrent responses from the reduction of H 2 O 2 even during mechanical deformation. Moreover, the admirable biocompatibility and an almost negligible open circuit voltage of +0.18 V for the CuO@TiO 2 NWs/Au NTs/PDMS sensor guaranteed human umbilical vein endothelial cells (HUVECs) adhesion tightly thereon even under continuous illumination for 30 min. Finally, the as-proposed stretchable PEC sensor achieved sensitive and true-to-life monitoring of transient H 2 O 2 release during HUVECs deformation, in which H 2 O 2 release was positively correlated to mechanical strains. This investigation opens a new shade path on in situ cellular sensing and meanwhile greatly expands the application mode of the PEC approach.

ATP plays a crucial role in cell energy supply, so the quantification of intracellular ATP levels is particularly important for understanding many physio-pathological processes. The intracellular quantification of this non-electroactive molecule can be realized using aptamer-modified nanoelectrodes, but is hindered by the limited quantity of modification and electroactive tags on the nanosized electrodes. Herein, we developed a simple but effective electrochemical signal amplification strategy for intracellular ATP detection, which replaces the regular ATP aptamer-linked ferrocene monomer with a polymer, thus greatly magnifying the amounts of electrochemical reporters linked to one chain of the aptamer and enhancing the signals. This ferrocene polymer-ATP aptamer was further immobilized onto Au nanowire electrodes (SiC@C@Au NWEs) to achieve accurate quantification of intracellular ATP in single cells, presenting high electrochemical signal output and high specificity. This work not only provides a powerful tool for quantifying intracellular ATP but also offers a simple and versatile strategy for electrochemical signal amplification in the detection of broader non-electroactive molecules involved in different kinds of intracellular physiological processes.

Traditional methods for the detection of pathogenic bacteria are time-consuming, less efficient, and sensitive, which affects infection control and bungles illness. Therefore, developing a method to remedy these problems is very important in the clinic to diagnose the pathogenic diseases and guide the rational use of antibiotics. Here, microfluidic electrochemical integrated sensor (MEIS) has been investigated, functionally for rapid, efficient separation and sensitive detection of pathogenic bacteria. Three-dimensional macroporous PDMS and Au nanotube-based electrode are successfully assembled into the modeling microchip, playing the functions of "3D chaotic flow separator" and "electrochemical detector," respectively. The 3D chaotic flow separator enhances the turbulence of the fluid, achieving an excellent bacteria capture efficiency. Meanwhile, the electrochemical detector provides a quantitative signal through enzyme-linked immunoelectrochemistry with improved sensitivity. The microfluidic electrochemical integrated sensor could successfully isolate Candida albicans ( C. albicans ) in the range of 30-3,000,000 CFU in the saliva matrix with over 95% capture efficiency and sensitively detect C. albicans in 1 h in oral saliva samples. The integrated device demonstrates great potential in the diagnosis of oral candidiasis and is also applicable in the detection of other pathogenic bacteria.

Airborne nanoplastics can enter alveolar cells and trigger intracellular oxidative stress primarily. Herein, taking advantage of the high electrochemical resolution of SiC@Pt nanoelectrodes, we achieved the quantitative discrimination of the major ROS/RNS within A549 cells, disclosed the sources of their precursors, and observed that the NO (RNS precursor) level significantly increased, whereas O 2 ˙ - (ROS precursor) remained relatively stable during the nanoplastics exposure. This establishes that iNOS or mitochondrion-targeted treatment may be a preventive or therapeutic strategy for nanoplastic-induced lung injury.

In the field of three-dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real-time information about mechanically induced cell responses. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real-time monitoring of stretch-induced signaling molecules. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Electrochemical sensing based on conventional rigid electrodes has great restrictions for characterizing biomolecules in deformed cells or soft tissues. The recent emergence of stretchable sensors allows electrodes to conformally contact to curved surfaces and perfectly comply with the deformation of living cells and tissues. This provides a powerful strategy to monitor biomolecules from mechanically deformed cells, tissues, and organisms in real time, and opens up new opportunities to explore the mechanotransduction process. In this minireview, we first summarize the fabrication of stretchable electrodes with emphasis on the nanomaterial-enabled strategies. We then describe representative applications of stretchable sensors in the real-time monitoring of mechanically sensitive cells and tissues. Finally, we present the future possibilities and challenges of stretchable electrochemical sensing in cell, tissue, and in vivo detection., (© 2020 Wiley-VCH GmbH.)

The role of endogenous serotonin (5-HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real-time recording of biomolecules, the dynamic monitoring of 5-HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich-like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real-time monitoring of distension-evoked 5-HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5-HT overflow, and 5-HT level is closely associated with the physiological or pathological states of the intestine., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Electrochemiluminescence (ECL) nanomaterials are usually deposited compactly on the surface of electrodes, which may cause poor mass transfer of reactants, thereby resulting in low ECL efficiency. In this work, we developed a novel kind of luminescent material denoted as C-Au-luminol nanospheres (C-Au-Lum NSs) by high dispersion of luminophores on porous carbon nanospheres (PCNSs). C-Au-Lum NSs were facilely prepared by the in situ reduction of chloroauric acid with the luminescent reagent luminol (Lum) on the nano-pores of PCNSs. Plenty of luminescent Au-Lum NPs were dispersedly concentrated inside the numerous pores and hollow interiors of PCNSs, effectively increasing the mass transfer of reagents and accelerating the electron transport inside the porous nanospheres. This greatly improved the availability of luminophores and endowed C-Au-Lum NSs with excellent ECL emission. After further integrating with enzymatic circulation and strand displacement, an ultrasensitive ECL biosensor was achieved for the ultrasensitive detection of an important tumor biomarker, mucin1. The logarithmically linear range from 0.1 pg mL-1 to 1 ng mL-1 with the detection limit of 47.6 fg mL-1 (S/N = 3) was achieved, demonstrating the superior performance of C-Au-Lum NSs. This work would provide new ideas for the construction of high-performance ECL sensing platforms for diverse applications.

The existence of a homeostatic mechanism regulating reactive oxygen/nitrogen species (ROS/RNS) amounts inside phagolysosomes has been invoked to account for the efficiency of this process but could not be unambiguously documented. Now, intracellular electrochemical analysis with platinized nanowire electrodes (Pt-NWEs) allowed monitoring ROS/RNS effluxes with sub-millisecond resolution from individual phagolysosomes impacting onto the electrode inserted inside a living macrophage. This shows for the first time that the consumption of ROS/RNS by their oxidation at the nanoelectrode surface stimulates the production of significant ROS/RNS amounts inside phagolysosomes. These results establish the existence of the long-postulated ROS/RNS homeostasis and allows its kinetics and efficiency to be quantified. ROS/RNS concentrations may then be maintained at sufficiently high levels for sustaining proper pathogen digestion rates without endangering the macrophage internal structures., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Remarkable progresses have been made in electrochemical monitoring of living cells based on one-dimensional (1D) or two-dimensional (2D) sensors, but the cells cultured on 2D substrate under these circumstances are departed from their three-dimensional (3D) microenvironments in vivo. Significant advances have been made in developing 3D culture scaffolds to simulate the 3D microenvironment yet most of them are insulated, which greatly restricts their application in electrochemical sensing. Herein, we propose a versatile strategy to endow 3D insulated culture scaffolds with electrochemical performance while granting their biocompatibility through conductive polymer coating. More specifically, 3D polydimethylsiloxane scaffold is uniformly coated by poly(3,4-ethylenedioxythiophene) and further modified by platinum nanoparticles. The integrated 3D device demonstrates desirable biocompatibility for long-term 3D cell culture and excellent electrocatalytic ability for electrochemical sensing. This allows real-time monitoring of reactive oxygen species release from cancer cells induced by a novel potential anticancer drug and reveals its promising application in cancer treatment. This work provides a new idea to construct 3D multifunctional electrochemical sensors, which will be of great significance for physiological and pathological research.

Flexible electrochemical (EC) sensors have shown great prospect in epidermal detection for personal healthcare and disease diagnosis. However, no reports have been seen in flexible device for urea analysis in body fluids. Herein, we developed a flexible wearable EC sensor based on surface molecularly imprinted nanotubes for noninvasive urea monitoring with high selectivity in human sweat. The flexible EC sensor was prepared by electropolymerization of 3,4-ethylenedioxythiophene (EDOT) monomer on the hierarchical network of carbon nanotubes (CNTs) and gold nanotubes (Au NTs) to imprint template molecule urea. This sensor exhibited a good linear response toward physiologically relevant urea levels with negligible interferences from common coexisting species. Bending test revealed that this sensor possessed excellent mechanical tolerance and its EC performance was almost not affected by bending deformation. On-body results of human subjects showed that the flexible platform could distinctly respond to the urea levels in volunteer's sweat after aerobic exercise. The new flexible epidermal EC sensor can provide useful insights into noninvasive monitoring of urea levels in various biofluids, which is promising in the clinical diagnosis of diverse biomedical applications.

Stretchable electrochemical (EC) sensors have broad prospects in real-time monitoring of living cells and tissues owing to their excellent elasticity and deformability. However, the redox reaction products and cell secretions are easily adsorbed on the electrode, resulting in sensor fouling and passivation. Herein, we developed a stretchable and photocatalytically renewable EC sensor based on Au nanotubes (NTs) and TiO 2 nanowires (NWs) sandwich nanonetworks. The external Au NTs are used for EC sensing, and internal TiO 2 NWs provide photocatalytic performance to degrade contaminants, which endows the sensor with excellent EC performance, high photocatalytic activity, and favorable mechanical tensile property. This allows highly sensitive recycling monitoring of NO released from endothelial cells and 5-HT released from mast cells under their stretching states in real time, therefore providing a promising tool to unravel elastic and mechanically sensitive cells, tissues, and organs.

Existing methods offer little direct and real-time information about stretch-triggered biochemical responses during cell mechanotransduction. A novel stretchable electrochemical sensor is reported that takes advantage of a hierarchical percolation network of carbon nanotubes and gold nanotubes (CNT-AuNT). This hybrid nanostructure provides the sensor with excellent time-reproducible mechanical and electrochemical performances while granting very good cellular compatibility, making it perfectly apt to induce and monitor simultaneously transient biochemical signals. This is validated by monitoring stretch-induced transient release of small signaling molecules by both endothelial and epithelial cells cultured on this sensor and submitted to stretching strains of different intensities. This work demonstrates that the hybrid CNT-AuNT platform offers a versatile and highly sensitive way to characterize and quantify short-time mechanotransduction responses., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Carbon nanotube (CNT)-based flexible sensors have been intensively developed for physical sensing. However, great challenges remain in fabricating stretchable CNT films with high electrochemical performance for real-time chemical sensing, due to large sheet resistance of CNT film and further resistance increase caused by separation between each CNT during stretching. Herein, we develop a facile and versatile strategy to construct single-walled carbon nanotubes (SWNTs)-based stretchable and transparent electrochemical sensors, by coating and binding each SWNT with conductive polymer. As a polymer with high conductivity, good electrochemical activity, and biocompatibility, poly(3,4-ethylenedioxythiophene) (PEDOT) acting as a superior conductive coating and binder reduces contact resistance and greatly improves the electrochemical performance of SWNTs film. Furthermore, PEDOT protects the SWNTs junctions from separation during stretching, which endows the sensor with highly mechanical compliance and excellent electrochemical performance during big deformation. These unique features allow real-time monitoring of biochemical signals from mechanically stretched cells. This work represents an important step toward construction of a high performance CNTs-based stretchable electrochemical sensor, therefore broadening the way for stretchable sensors in a diversity of biomedical applications.

Stretchable electrochemical sensors are conceivably a powerful technique that provides important chemical information to unravel elastic and curvilinear living body. However, no breakthrough was made in stretchable electrochemical device for biological detection. Herein, we synthesized Au nanotubes (NTs) with large aspect ratio to construct an effective stretchable electrochemical sensor. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allows for the first time, real-time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching-free and stretching states as well as sensing of the inner lining of blood vessels. The results demonstrate the great potential of this sensor in electrochemical detection of living body, opening a new window for stretchable electrochemical sensor in biological exploration., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Electrode fouling and passivation is a substantial and inevitable limitation in electrochemical biosensing, and it is a great challenge to efficiently remove the contaminant without changing the surface structure and electrochemical performance. Herein, we propose a versatile and efficient strategy based on photocatalytic cleaning to construct renewable electrochemical sensors for cell analysis. This kind of sensor was fabricated by controllable assembly of reduced graphene oxide (RGO) and TiO2 to form a sandwiching RGO@TiO2 structure, followed by deposition of Au nanoparticles (NPs) onto the RGO shell. The Au NPs-RGO composite shell provides high electrochemical performance. Meanwhile, the encapsulated TiO2 ensures an excellent photocatalytic cleaning property. Application of this renewable microsensor for detection of nitric oxide (NO) release from cells demonstrates the great potential of this strategy in electrode regeneration and biosensing., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chemical neurotransmission occurs at chemical synapses and endocrine glands, but up to now there was no means for direct monitoring of neurotransmitter exocytosis fluxes and their precise kinetics from inside an individual synapse. The fabrication of a novel finite conical nanoelectrode is reported perfectly suited in size and electrochemical properties for probing amperometrically inside what appears to be single synapses and monitoring individual vesicular exocytotic events in real time. This allowed obtaining direct and important physiological evidences which may yield important and new insights into the nature of synaptic communications., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recent biochemical results suggest that auxin (IAA) efflux is mediated by a vesicular cycling mechanism, but no direct detection of vesicular IAA release from single plant cells in real-time has been possible up to now. A TiC@C/Pt-QANFA micro-electrochemical sensor has been developed with high sensitivity in detection of IAA, and it allows real-time monitoring and quantification of the quantal release of auxin from single plant protoplast by exocytosis., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Electrochemical techniques based on ultramicroelectrodes (UMEs) play a significant role in real-time monitoring of chemical messengers' release from single cells. Conversely, precise monitoring of cells in vitro strongly depends on the adequate construction of cellular physiological microenvironment. In this paper, we developed a multilayer microdevice which integrated high aspect ratio poly(dimethylsiloxane) (PDMS) microfluidic device for long-term automated perfusion culture of cells without shear stress and an independently addressable microelectrodes array (IAMEA) for electrochemical monitoring of the cultured cells in real time. Novel design using high aspect ratio between circular "moat" and ring-shaped micropillar array surrounding cell culture chamber combined with automated "circular-centre" and "bottom-up" perfusion model successfully provided continuous fresh medium and a stable and uniform microenvironment for cells. Two weeks automated culture of human umbilical endothelial cell line (ECV304) and neuronal differentiation of rat pheochromocytoma (PC12) cells have been realized using this device. Furthermore, the quantal release of dopamine from individual PC12 cells during their culture or propagation process was amperometrically monitored in real time. The multifunctional microdevice developed in this paper integrated cellular microenvironment construction and real-time monitoring of cells during their physiological process, and would possibly provide a versatile platform for cell-based biomedical analysis.