Stretchable Electrochemical Sensor Research Articles

Real-Time Quantification of Nanoplastics-Induced Oxidative Stress in Stretching Alveolar Cells.

Nanoplastics from air pollutants can be directly inhaled into the alveoli in the lungs and further enter blood circulation, and numerous studies have revealed the close relation between internalized nanoplastics with many physiological disorders via intracellular oxidative stress. However, the dynamic process of nanoplastics-induced oxidative stress in lung cells under breath-mimicked conditions is still unclear, due to the lack of methods that can reproduce the mechanical stretching of the alveolar and simultaneously monitor the oxidative stress response. Here, we describe a biomimetic platform by culturing alveoli epithelial cells on a stretchable electrochemical sensor and integrating them into a microfluidic device. This allows reproducing the respiration of alveoli by cyclic stretching of the alveoli epithelial cells and monitoring the nanoplastics-induced oxidative stress by the built-in sensor. By this device, we prove that cyclic stretches can greatly enhance the cellular uptake of nanoplastics with the dependencies of strain amplitude. Importantly, oxidative stress evoked by internalized nanoplastics can be quantitatively monitored in real time. This work will promote the deep understanding about the cytotoxicity of inhaled nanoplastics in the pulmonary mechanical microenvironment.

Flexible and Stretchable Electrochemical Sensors for Biological Monitoring.

The rise of flexible and stretchable electronics has revolutionized biosensor techniques for probing biological systems. Particularly, flexible and stretchable electrochemical sensors (FSECSs) enable the in situ quantification of numerous biochemical molecules in different biological entities owing to their exceptional sensitivity, fast response, and easy miniaturization. Over the past decade, the fabrication and application of FSECSs have significantly progressed. This review highlights key developments in electrode fabrication and FSECSs functionalization. It delves into the electrochemical sensing of various biomarkers, including metabolites, electrolytes, signaling molecules, and neurotransmitters from biological systems, encompassing the outer epidermis, tissues/organs in vitro and in vivo, and living cells. Finally, considering electrode preparation and biological applications, current challenges and future opportunities for FSECSs are discussed.

Stretchable sensor based on NiO-Ni(OH)2 and single-walled carbon nanotubes for in situ and real-time monitoring of dopamine release from cells

As the most abundant catecholamine neurotransmitter in the human brain, dopamine directly facilitates intercellular communication and is closely related to multiple functions of the central nervous system. Here, a flexible and stretchable electrochemical sensor based on NiO-Ni(OH)2 and single-walled carbon nanotubes (SWCNTs) on flexible poly-dimethylsiloxane (PDMS) substrate was fabricated for the sensitive quantification of dopamine released from different cells. The developed NiO-Ni(OH)2/SWCNTs/PDMS film exhibited excellent selectivity and sensitivity to dopamine with a wide linear range from 50 nM to 288 μM and a low detection limit of 12 nM (S/N = 3). The prepared sensor is highly biocompatible, where living cells can grow and proliferate directly on the electrode surface with strong adhesion, allowing for the in situ and real-time tracking dopamine secretion from cells. This work indicated that the flexible NiO-Ni(OH)2/SWCNTs/PDMS can serve as an effective sensing platform for monitoring cellular signal molecules released from living cells during mechanical deformation.

Three-Dimensional Stretchable Sensor-Hydrogel Integrated Platform for Cardiomyocyte Culture and Mechanotransduction Monitoring.

Cardiomyocytes are responsible for generating contractile force to pump blood throughout the body and are very sensitive to mechanical forces and can initiate mechano-electric coupling and mechano-chemo-transduction. Remarkable progress has been made in constructing heart tissue by engineered three-dimensional (3D) culture models and in recording the electrical signals of cardiomyocytes. However, it remains a severe challenge for real-time acquiring of the transient biochemical information in cardiomyocyte mechano-chemo-transduction. Herein, we reported a multifunctional platform by integrating a 3D stretchable electrochemical sensor with collagen hydrogel for the culture, electrical stimulation, and electrochemical monitoring of cardiomyocytes. The 3D stretchable electrochemical sensor was prepared by assembling functionalized conductive polymer PEDOT:PSS on an elastic scaffold, which showed excellent electrochemical sensing performance and stability under mechanical deformations. The integration of a 3D stretchable electrochemical sensor with collagen hydrogel provided an in vivo-like microenvironment for cardiomyocyte culture and promoted cell orientation via in situ electrical stimulation. Furthermore, this multifunctional platform allowed real-time monitoring of stretch-induced H2O2 release from cardiomyocytes under their normal and pathological conditions, as well as pharmacological interventions.

Nanofiber-based Stretchable Electrodes for Oriented Culture and Mechanotransduction Monitoring of Smooth Muscle Cells.

Vascular smooth muscle cells (SMCs) are circumferentially oriented perpendicular to the blood vessel and maintain the contractile phenotype in physiological conditions. They can sense the mechanical forces of blood vessels expanding and contracting and convert them into biochemical signals to regulate vascular homeostasis. However, the real-time monitoring of mechanically evoked biochemical response while maintaining SMC oriented growth remains an important challenge. Herein, we developed a stretchable electrochemical sensor by electrospinning aligned and elastic polyurethane (PU) nanofibers on the surface of PDMS film and further modification of conductive polymer PEDOT:PSS-LiTFSI-CoPc (PPLC) on the nanofibers (denoted as PPLC/PU/PDMS). The aligned nanofibers on the electrode surface could guide the oriented growth of SMCs and maintain the contractile phenotype, and the modification of PPLC endowed the electrode with good electrochemical sensing performance and stability under mechanical deformation. By culturing cells on the electrode surface, the oriented growth of SMCs and real-time monitoring of stretch-induced H2O2 release were achieved. On this basis, the changes of H2O2 level released by SMCs under the pathology (hypertension) and intervention of natural product resveratrol were quantitatively monitored, which will be helpful to further understand the occurrence and development of vascular-related diseases and the mechanisms of pharmaceutical intervention.

Stretchable Oxygen-Tolerant Sensor Based on a Single-Atom Fe-N4 Electrocatalyst for Observing the Role of Oxidative Stress in Hypertension.

Oxidative stress and related oxidative damage have a causal relation with the pathogenesis of hypertension. Therefore, it is crucial to determine the mechanism of oxidative stress in hypertension by applying mechanical forces on cells to simulate hypertension while monitoring the release of reactive oxygen species (ROS) from cells under an oxidative stress environment. However, cellular level research has rarely been explored because monitoring the ROS released by cells is still challenging owing to the interference of O2. In this study, an Fe single-atom-site catalyst anchored on N-doped carbon-based materials (Fe SASC/N-C) was synthesized, which exhibits excellent electrocatalytic activity for the reduction of hydrogen peroxide (H2O2) at a peak potential of +0.1 V and can effectively avoid the interference of O2. Furthermore, we constructed a flexible and stretchable electrochemical sensor based on the Fe SASC/N-C catalyst to study the release of cellular H2O2 under simulated hypoxic and hypertension conditions. Density functional theory calculations show that the highest transition state energy barrier from the oxygen reduction reaction (ORR), i.e., O2 to H2O, is 0.38 eV. In comparison, the H2O2 reduction reaction (HPRR) can be completed only by overcoming a lower energy barrier of 0.24 eV, endowing the HPRR to be more favorable on Fe SASC/N-C compared with the ORR. This study provided a reliable electrochemical platform for real-time investigation of H2O2-related underlying mechanisms of the hypertension process.

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.

Cover Picture

The cover picture depicts the stretchable electrochemical sensor for in‐situ inducing and real‐time monitoring of cell mechanotransduction. The stretchable sensor is mainly fabricated by different nanomaterials including nanoparticles, nanosheets and nanowires/nanotubes, which form continuous pathways for electron transport on elastic substrate. To further achieve the tracking of transient biochemical molecules released during cell mechanotransduction, the stretchable sensing interface is equipped with excellent sensitivity, selectivity and stability by combining functional materials such as natural enzyme, nanocatalyst and biomimetic molecule. More details are given in the review by Liu et al. on page 443—457.image

Stretchable Electrochemical Sensors: From Electrode Fabrication to Cell Mechanotransduction Monitoring†

Comprehensive SummaryElectrochemical sensing faces huge challenges in characterizing the transient release of biochemical molecules from deformed cells, due to the severely mechanical mismatch between rigid electrodes and soft cells. In recent years, the emergence of stretchable electrochemical sensors has made a breakthrough by complying with the deformation of living cells and simultaneous monitoring of mechanically evoked biochemical signals. This review first summarizes two fundamental strategies for the fabrication of stretchable electrodes from the points of structure and material. Next, recent progresses in construction of functionalized interface to improve the performance of stretchable electrochemical sensors are presented. Then, the application of stretchable electrochemical sensors in real‐time monitoring of biomolecules released by mechanically sensitive cells is introduced. Finally, some perspectives and challenges of stretchable electrochemical sensors regarding cell detection are discussed. What is the favorite and original chemistry developed in your research group?The design and construction of electrochemical sensing platform for real‐time monitoring of life activities.What is the most important personality for scientific research?Innovative spirit, strong curiosity and persistence.How do you supervise your students?Encourage students to think much and eager to innovate.What are your hobbies?I like music and playing badminton.Who influences you mostly in your life?My family and collaborators.Could you please give us some advices on improving Chinese Journal of Chemistry?Focusing on the originality of the manuscript.

Redox Homeostasis Alteration in Endothelial Mechanotransduction Monitored by Dual Stretchable Electrochemical Sensors.

In vivo, endothelial cells are permanently subjected to dynamic cyclic stretch and adapt to it through the release of vasoactive substances. Among them, reactive oxygen species (ROS) and nitric oxide (NO) are indispensable redox molecules, the contents of which and their ratio are closely implicated with endothelial redox homeostasis. However, simultaneous and quantitative monitoring of ROS and NO release in endothelial mechanotransduction remains a great challenge. Herein, a stretchable electrochemical device is developed with a dual electrode based on gold nanotubes decorated with uniform and tiny platinum nanoparticles. This hybrid nanostructure endows the sensor with high sensitivity toward both hydrogen peroxide (H2O2) (as the most stable ROS) and NO electrooxidation. Importantly, the two species can be well discriminated by applying different potentials, which allows simultaneous monitoring of H2O2 and NO release in stretch-induced endothelial mechanotransduction by the same device. The results of quantitative analysis suggest that endothelial redox homeostasis and its alteration are strongly related to vascular biomechanical and biochemical milieus. Further investigation reveals that the interplay of ROS and NO signaling has an important role in the regulation of endothelial redox state. This work will greatly facilitate the deep understanding of the molecular mechanism of endothelial dysfunction and vascular disorder.

Stretchable Electrochemical Sensors for Cell and Tissue Detection

AbstractElectrochemical 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.

Stretchable Electrochemical Sensors for Cell and Tissue Detection.

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.

Stretchable Electrode Based on Au@Pt Nanotube Networks for Real-Time Monitoring of ROS Signaling in Endothelial Mechanotransduction.

Vascular endothelial cells (ECs) are natively exposed to dynamic cyclic stretch and respond to it by the production of vasoactive molecules. Among them, reactive oxygen species (ROS) are closely implicated to the endothelial function and vascular homeostasis. However, the dynamic monitoring of ROS release during endothelial mechanotransduction remains a steep challenge. Herein, we developed a stretchable electrochemical sensor by decoration of uniform and ultrasmall platinum nanoparticles (Pt NPs) on gold nanotube (Au NT) networks (denoted as Au@Pt NTs). The orchestrated structure exhibited prominent electrocatalytic property toward the oxidation of hydrogen peroxide (H2O2) (as the most stable ROS) while maintaining excellent mechanical compliance of Au NT networks. Moreover, the favorable biocompatibility of Au NTs and Pt NPs promoted the adhesion and proliferation of ECs cultured thereon. These allowed in situ inducing ECs mechanotransduction and synchronously real-time monitoring of H2O2 release. Further investigation revealed that the production of H2O2 was positively correlated with the applied mechanical strains and could be boosted by other coexisting pathogenic factors. This indicates the great prospect of our proposed sensor in exploring ROS-related signaling for the deep understanding of cell mechanotransduction and vascular disorder.

Integrating Flexible Electrochemical Sensor into Microfluidic Chip for Simulating and Monitoring Vascular Mechanotransduction.

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.

Rhinophore bio-inspired stretchable and programmable electrochemical sensor

Rhinophore, a bio-chemical sensory organ with soft and stretchable/retractable features in many marine molluscs species, exhibits tunable chemosensory abilities in terms of far/near-field chemical detection and molecules' source orientation. However, existing artificial bio-chemical sensors cannot provide tunable modality sensing. Inspired by the anatomical units (folded sensory epithelium) and the functions of a rhinophore, this work introduces a stretchable electrochemical sensor that offers a programmable electro-catalytic performance towards glucose based on the fold/unfold regulation of the gold nanomembrane on an elastic fiber. Geometrical design rationale and covalent bonding strategy are used to realize the robust mechanical and electrical stability of this stretchable bionic sensor. Electrochemical tests demonstrated that the sensitivities of the as-prepared bionic sensor exhibit a linear relationship with its strain states from 0% to 150%. Bio-inspired sensory functions are tested by regulating the strain of the bionic sensor. The sensor achieves a sensitivity of 195.4 μA mM−1 in a low glucose concentration range of 8–206 μM at 150% strain for potentially far-field chemical detection, and a sensitivity of 14.2 μA mM−1 in a high concentration range of 10–100 mM at 0% strain for near-field chemical detection. Moreover, the bionic sensor performs the detection while extending its length can largely enhance the response signal, which is used to distinguish the molecules’ source direction. This proposed bionic sensor can be useful in wearable devices, robotics and bionics applications which require diverse modality sensing and smart chemical tracking system.

(Invited) Stretchable Electrochemical Sensor for Inducing and Monitoring Cell Mechanotransduction in Real-Time

Nearly all kinds of cells within organisms are sensitive to mechanical forces and convert them into specific biochemical responses. This important and sophisticated process is described as mechanotransduction1. Several approaches are classically used to report on the ensuing modifications (gene expression, protein activity, etc.) expressed by cells in response to mechanical stimulations. Nonetheless, acquiring such evidences requires at least tens of minutes preventing any real-time information about the primary biochemical signals underlying mechanotransduction. Monitoring such presumably transient and weak signaling events since very early stages of cell mechanotransduction remains therefore an important challenge. Electrochemical sensing for detecting and quantifying transient release of biochemical molecules by living cells or tissues is widely accepted nowadays. In this regard, flexible and stretchable biocompatible electrochemical sensors should offer ideal platforms for applying mechanical strains and monitoring at the same time electroactive biochemical responses from mechanosensitive cells directly cultured on the sensor. However, up to date, despite several stimulating progresses in stretchable physical sensors and very few emerging successes in wearable electrochemical devices, no breakthrough concept has emerged for inducing cell mechanotransduction and investigating it in real-time by a single electrochemical device. Recently, we reported a high-performance stretchable electrode based on networks of gold nanotubes (Au NTs) deposited on polydimethylsiloxane (PDMS) thin films. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allowed 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.2 However, the sensitivity and stability of the Au NTs/PDMS electrode were not sufficient to detect very weak transient signals triggered from cells by stretching strains only. This limitation was further overcomed by implementing a percolating CNTs network onto the Au NTs backbones through transfer of a free-standing CNTs ultrathin-film onto the Au NTs/PDMS electrode. This hybrid nano-structure provides the sensor with greatly enhanced mechanical and electrochemical performances while granting very good cellular compatibility, which allowed monitoring stretch-induced transient release of vasoactive molecules by endothelial cells cultured on this sensor and submitted to stretching strains. The work represents the first step toward real-time monitoring of cell mechanotransduction by electrochemical techniques, providing a promising way toward many other direct, in real time and in situ measurements of cell mechanotransduction.

A Stretchable Electrochemical Sensor for Inducing and Monitoring Cell Mechanotransduction in Real Time.

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.

A Stretchable Electrochemical Sensor for Inducing and Monitoring Cell Mechanotransduction in Real Time

AbstractExisting 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.

Conductive Polymer-Coated Carbon Nanotubes To Construct Stretchable and Transparent Electrochemical Sensors.

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.

Automation Highlights from the Literature

Automation Highlights from the Literature