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.
Emerging stretchable electrodes open up new opportunities for the real‐time monitoring of biomolecule release from deformed cells, soft tissues, and organisms. In this minireview, we summarize recent advances in the fabrication of stretchable electrochemical sensors and their representative applications in cell, tissue, and in vivo detection.
Perovskite quantum dots (PQDs) have attracted much attention in the field of photoelectrochemical (PEC) sensors owing to their superb optical properties and efficient charge transport, but the ...inherent poor stability severely hinders their PEC applications. Herein, hydrolysis‐resistant CsPbBr3/reduced graphene oxide nanoscrolls (CsPbBr3/rGO NSs) are obtained by solvent‐assisted self‐rolling process toward water‐stable PEC sensors. CsPbBr3 QDs embedded in rGO nanosheets can be prevented from water since the multilayer rGO shell layers, which maintains excellent optical properties. On account of strong interfacial interactions, rGO nanosheets are crimped spontaneously with CsPbBr3 QDs, which offer access to superb structural and long‐term storage stability. Moreover, appropriate band alignment and ultrafast interfacial carrier transfer enable CsPbBr3/rGO NSs to exhibit greatly enhanced anode photocurrent response for subsequent PEC sensing. As a demonstration, the molecular imprinted PEC sensors for two kinds of mycotoxins (aflatoxin B1 or ochratoxin A) presents an ultra‐high sensitivity and good anti‐interference ability. Significantly, this work provides an inspirable and convenient route for hydrolysis‐resistant PQDs‐based optoelectronic and photoelectrocatalytic applications in aqueous ambience.
Water‐stable CsPbBr3/reduced graphene oxide nanoscrolls (CsPbBr3/rGO NSs) are successfully achieved via rGO self‐rolling and CsPbBr3 encapsulation, appropriate band alignment and ultrafast interfacial carrier transfer enable CsPbBr3/rGO NSs to exhibit greatly enhanced anode photocurrent response for subsequent photoelectrochemical sensing. This work provides an inspirable and convenient strategy for hydrolysis‐resistant perovskite‐based further applications in aqueous ambience.
Nanoelectrodes allow precise and quantitative measurements of important biological processes at the single living‐cell level in real time. Cylindrical nanowire electrodes (NWEs) required for ...intracellular measurements create a great challenge for achieving excellent electrochemical and mechanical performances. Herein, we present a facile and robust solution to this problem based on a unique SiC‐core–shell design to produce cylindrical NWEs with superior mechanical toughness provided by the SiC nano‐core and an excellent electrochemical performance provided by the ultrathin carbon shell that can be used as such or platinized. The use of such NWEs for biological applications is illustrated by the first quantitative measurements of ROS/RNS in individual phagolysosomes of living macrophages. As the shell material can be varied to meet any specific detection purpose, this work opens up new opportunities to monitor quantitatively biological functions occurring inside cells and their organelles.
Nanoelectrodes for biology: A facile and robust strategy for the fabrication of high performance nanowire electrodes (NWEs) was developed. The NWEs allowed the measurement of reactive oxygen and nitrogen species (ROS/RNS) within individual phagolysosomes inside living macrophages.
Mitochondria are believed to be the major source of intracellular reactive oxygen species (ROS). However, in situ, real‐time and quantitative monitoring of ROS release from mitochondria that are ...present in their cytosolic environment remains a great challenge. In this work, a platinized SiC@C nanowire electrode is placed into a single cell for in situ detection of ROS signals from intracellular mitochondria, and antineoplastic agent (paclitaxel) induced ROS production is successfully recorded. Further investigations indicate that complex IV (cytochrome c oxidase, COX) is the principal site for ROS generation, and significantly more ROS are generated from mitochondria in cancer cells than that from normal cells. This work provides an effective approach to directly monitor intracellular mitochondria by nanowire electrodes, and consequently obtains important physiological evidence on antineoplastic agent‐induced ROS generation, which will be of great benefit for better understanding of chemotherapy at subcellular levels.
A platinized SiC@C nanowire electrode with excellent electrochemical and mechanical performance is fabricated and inserted into single cells to monitor reactive oxygen species (ROS) generation from intracellular mitochondria. This allows in situ quantification of paclitaxel‐induced ROS production in real time and identification of the site of which paclitaxel induces mitochondrial ROS generation inside single living cells.
The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of ...modifiers. To address this issue, we propose a versatile strategy for large‐scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs‐poly(3,4‐ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real‐time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time.
Versatile and large‐scale synthesis of biomimetic molecular catalyst modified nanowires provides an innovative perspective for simple and stable construction of functionalized electrochemical nanosensors. Such nanosensors enable the sensitive and selective detection of diverse biomolecules, and for the first time achieve real‐time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells.
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.
Single nanowire electrode amperometry was used to establish that the consumption of ROS/RNS in a phagolysosome leads to a ROS/RNS production. This validates the long‐sought ROS/RNS homeostatic mechanism that was hypothesized to regulate the ROS/RNS intravesicular content during pathogens digestion.
Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed ...functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients' survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT-DNA-PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN-ATM-CHK2 signal and ATR-CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.
A strategy for one‐pot and large‐scale synthesis of functionalized core–shell nanowires (NWs) to high‐efficiently construct single nanowire electrodes is proposed. Based on the polymerization ...reaction between 3,4‐ethylenedioxythiophene (EDOT) and noble metal cations, manifold noble metal nanoparticles‐polyEDOT (PEDOT) nanocomposites can be uniformly modified on the surface of any nonconductive NWs. This provides a facile and versatile approach to produce massive number of core–shell NWs with excellent conductivity, adjustable size, and well‐designed properties. Nanoelectrodes manufactured with such core–shell NWs exhibit excellent electrochemical performance and mechanical stability as well as favorable antifouling properties, which are demonstrated by in situ intracellular monitoring of biological molecules (nitric oxide) and unraveling its relevant unclear signaling pathway inside single living cells.
Versatile one‐pot synthesis of functionalized core–shell nanowires breaks through the limitation of nanoelectrode materials to facilely construct high‐performance single nanowire electrodes. Concurrently with excellent electrochemical, mechanical, and antifouling properties, the nanowire electrodes show great superiority in real‐time monitoring of biological molecules and unraveling the relevant signaling pathway inside single living cells.
As an interface between the blood flow and vessel wall, endothelial cells (ECs) are exposed to hemodynamic forces, and the biochemical molecules released from ECs–blood flow interaction are important ...determinants of vascular homeostasis. Versatile microfluidic chips have been designed to simulate the biological and physiological parameters of the human vascular system, but in situ and real‐time monitoring of the mechanical force–triggered signals during vascular mechanotransduction still remains a significant challenge. Here, such challenge is fulfilled for the first time, by preparation of a flexible and stretchable electrochemical sensor and its incorporation into a microfluidic vascular chip. This allows simulating of in vivo physiological and biomechanical parameters of blood vessels, and simultaneously monitoring the mechanically induced biochemical signals in real time. Specifically, the cyclic circumferential stretch that is actually exerted on endothelium but is hard to reproduce in vitro is successfully recapitulated, and nitric oxide signals under normal blood pressure, as well as reactive oxygen species signals under hypertensive states, are well documented. Here, the first integration of a flexible electrochemical sensor into a microfluidic chip is reported, therefore paving a way to evaluate in vitro organs by built‐in flexible sensors.
The first integration of a flexible electrochemical sensor into a microfluidic vascular chip is reported. This allows simulating of in vivo physiological and biomechanical parameters of blood vessels, and simultaneously monitoring the mechanically‐induced biochemical signals in real time.
Quantitative measurements of intravesicular glutamate (Glu) and of transient exocytotic release contents directly from individual living neurons are highly desired for understanding the mechanisms ...(full or sub‐quantal release?) of synaptic transmission and plasticity. However, this could not be achieved so far due to the lack of adequate experimental strategies relying on selective and sensitive Glu nanosensors. Herein, we introduce a novel electrochemical Glu nanobiosensor based on a single SiC nanowire that can selectively measure in real‐time Glu fluxes released via exocytosis by large Glu vesicles (ca. 125 nm diameter) present in single hippocampal axonal varicosities as well as their intravesicular content before exocytosis. These measurements revealed a sub‐quantal release mode in living hippocampal neurons, viz., only ca. one third to one half of intravesicular Glu molecules are released by individual vesicles during exocytotic events. Importantly, this fraction remained practically the same when hippocampal neurons were pretreated with L‐Glu‐precursor L‐glutamine, while it significantly increased after zinc treatment, although in both cases the intravesicular contents were drastically affected.
A nanowire electrochemical biosensor for the quantitative measurement of the intravesicular glutamate (Glu) content inside living neurons and its released fractions was developed. It is shown that only ca. one third to one half of intravesicular Glu molecules are released by individual vesicles during exocytotic events. The sensor opens new possibilities for exploring the regulatory mechanisms of glutamatergic neurotransmission and plasticity.
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