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Paralytic shellfish toxins (e.g., saxitoxin, STX; gonyautoxin-2, GTX-2) and tetrodotoxin (TTX) are highly toxic and widely distributed ion channel marine toxins which specifically block the voltage-dependent sodium channels (VDSCs), causing great harm to human health. It is urgent to exploit new detection methods with high specificity and high efficiency. Here, a portable high-throughput cardiomyocyte-based potential biosensor was established with cardiomyocytes, a 16-well microelectrodes (MEs) sensor and a robust 32-channel recording system, which presented high-quality and high-consistency extracellular field potential (EFP) signals in each well with a long duration of 80 h. The feature parameters, including firing rate (FR), spike amplitude (SA), spike slope (SS), spike duration (SD) and field potential duration (FPD), were extracted from EFP to quantitatively assess the toxic effects of these ion channel toxins. Importantly, the biosensor showed temporal specificity and parametric selectivity under toxin treatments, and FR, SS and SD were the optimal parameters to STX, TTX and GTX-2, respectively. This biosensor can rapidly detect 0.29 ng/mL STX, 0.30 ng/mL TTX and 0.16 ng/mL GTX-2 within 5 min, 10 min and 15 min, respectively. Thus, our novel multi-well cardiomyocyte-based biosensor will be a promising tool for high-effective detection of ion channel toxins. [ABSTRACT FROM AUTHOR]

Liver models are vital for the liver diseases and drug research as many novel drugs. However, traditional liver models cannot meet this need, mainly because they cannot replicate the complex physiological structure and microenvironment of the liver, especially the O 2 and nutrient gradients. Liver-on-a-chip (LOC), based on microfluidic technology, can not only closely simulate the physiological structure and microenvironment of the liver through the design of suitable microchannels, but can also incorporate advanced biosensors with high sensitivity and potential for rapid responses to microenvironmental signals and liver function indicators. Nevertheless, LOCs have not been widely exploited for liver disease research or the screening of drugs for hepatotoxicity because of considerable professional barriers. In this review, we comprehensively summarize recent progress in LOC development and the embedding of biosensors into LOCs. We first introduce the physiological characteristics and microenvironment of the liver and then summarize the fabrication process and advantages of LOCs. We subsequently focus on recent advances relating to three-dimensional (3D) hepatocyte organization and the simulation of hepatic sinusoids and lobules in LOCs and further systematically summarize the research progress in biosensor-integrated LOCs. Finally, we discuss the potential value of LOCs and the challenges facing their exploitation. In conclusion, this review provides insights into the design and development of biosensor-integrated LOCs aiming to promote further research into this promising platform. • The integration of various biosensors into LOC is highlighted. • Application of well-designed LOCs and integrated biosensors are systematically reviewed. • The challenges underlying LOC and integrated biosensor are deeply discussed. [ABSTRACT FROM AUTHOR]

The development of new drugs is a lengthy process, while the observation of serious side effects, such as cardiotoxicity, can result in the drug to be withdrawn even after development, leading to heavy burden on human health and social economy. To assess the drug cardiotoxicity, the electrical and mechanical properties of cardiomyocytes are increasingly being used to investigate the mechanisms and potential toxicity of drugs. Conventional non-invasive and label-free recording strategies are not well suited to record the integrated electromechanical signals from the single cell in a high-throughput manner, whereas label-based recordings strategies suffer from phototoxicity and drug side effects, precluding their long-time detection. In this study, we established a new multimodal microelectrode biosensing system to achieve the simultaneous and dynamic interrogation of electromechanical signals from multisite single cardiomyocytes. This multimodal device can detect subtle changes in the electromechanical signals induced by ion channel drugs during the excitation-contraction coupling of cardiomyocytes. The use of electromechanical integrated single cell signals for drug assessment was compared with commercial drug assays, and our multimodal microelectrode biosensing system can afford record electromechanical integrated signals as well as efficiently identify the effects of ion channel-blocking drugs on the electrical and mechanical properties of cardiomyocytes. Our multimodal microelectrode biosensing system is a potential valuable platform in the fields of cardiology and pharmacology. • Multimodal microelectrode biosensing system perform the electromechanical integrated recording of signal cardiomyocytes. • The multimodal device was designed to simultaneously record electromechanical integrated signals in situ. • The biosensing system can sensitively identify the ion channel-blocking drug effect on excitation-contraction coupling. [ABSTRACT FROM AUTHOR]

Electroporation serves as a powerful technique to introduce the exogenous nucleotides, DNA, RNA, proteins, dyes, and virus particles into cells. Through the effect of high intensity of electric field, the permeability of the cell membrane is instantaneously improved to absorb the exogenous molecules in surrounding medium. To protect the cell viability, ultralow-voltage electroporation techniques are well developed by versatile devices, and delivery efficiency is commonly assessed by label-based analysis by microscope-ImageJ or flow cytometry. However, accuracy and complexity of these analytical strategies still hinder efficient and precise biomedical studies in situ. Here we developed an intracellular delivery biosensing system by nanostrawed electroporation array (NEA) that can efficiently assess the universal electroporation performance by cell viability, delivery efficiency, and cell mortality. The intracellular delivery biosensing system consists of NEA, fluorescent microscope, and automated analysis software. Intracellular delivery biosensing system of electroporation quality is based on the enhanced fluorescent watershed segmentation (enhanced FWS) algorithm, which possessed low deviation (~5%) and significantly shortened the operation time (~8 s/10 images) in contrast to high deviation (~13%) and long operation time (~10 min/10 images) of conventional inaccurate, labor-intensive and time-consuming methods. It is believed that the intracellular delivery biosensing system will be a promising universal platform to assess nanodevice electroporation in the fields of cell biology, biotechnology, and medicine. • Intracellular delivery biosensing system by nanostrawed electroporation array was established. • Electroporation quality analysis was based on the enhanced fluorescent watershed segmentation (enhanced FWS) algorithm. • Biosensing system can efficiently assess the electroporation performance by viability, delivery efficiency and mortality. • Intracellular delivery biosensing system possessed accurate and efficient performance in intracellular delivery analysis. [ABSTRACT FROM AUTHOR]

Cardiac arrhythmia and drug-induced cardiotoxicity seriously threaten the human life. To develop antiarrhythmic agents and prevent the drug-induced cardiotoxicity, it is demanded to explore the high-specificity and high-efficiency drug screening platforms for preclinical investigations. Here, a specific electromechanical integrated correlation (EMIC) model was established based on the synchronized signal recording of cardiomyocyte-based biosensing system. The cardiomyocyte-based biosensing system consists of an integrated electromechanical device and a synchronized recording instrument. By extracting the feature points and correlation information of both electrical and mechanical signals, the multi-parameters of EMIC are applied for the drug recognition, showing the good specificity to analyze the typical Na+, K+, Ca2+ channel blockers. Further, visualized analysis of EMIC parameters was performed using the extracted parameters of synchronized recording signals to present the drug specific recognition functions. By heat map, radar map, and principal component analysis (PCA), the specific features and patterns were intuitively displayed to achieve the drug recognition. We believe this high-content and high-specific drug recognition strategy will be a promising and alternative method for the preclinical screening of cardiac safety and drug development in biomedical fields. Image 1 • Cardiomyocyte-based biosensing system records synchronized electromechanical signals. • Electromechanical integrated correlation (EMIC) model was established. • EMIC model was optimized by long-term stability and solvent stability test. • Visualized recognition of EMIC model was developed for ion channel blockers. [ABSTRACT FROM AUTHOR]