Integrated nanoporous electroporation and sensing electrode array for total dynamic time-domain cardiomyocyte membrane resealing assessment

Intracellular electrophysiological research is vital for biological and medical research.Traditional planar microelectrode arrays(MEAs)have disadvantages in recording intracellular action potentials due to the loose cell-electrode interface.To investigate intracellular electrophysiological signals with high sensitivity,electroporation was used to obtain intracellular recordings.In this study,a biosensing system based on a nanoporous electrode array(NPEA)integrating electrical perforation and signal acquisition was established to dynamically and sensitively record the intracellular potential of cardiomyocytes over a long period of time.Moreover,nanoporous electrodes can induce the protrusion of cell membranes and enhance cell-electrode interfacial coupling,thereby facilitating effective electroporation.Electrophysiological signals over the entire recording process can be quantitatively and segmentally analyzed according to the signal changes,which can equivalently reflect the dynamic evolution of the electroporated cardiomyocyte membrane.We believe that the low-cost and high-performance nanoporous biosensing platform suggested in this study can dynamically record intracellular action potential,evaluate cardiomyocyte electroporation,and provide a new strategy for investigating cardiology pharmacological science.

Model Predictive Control for Cascaded H-Bridge PV Inverter with Capacitor Voltage Balance

We designed an improved direct-current capacitor voltage balancing control model predictive control(MPC)for single-phase cascaded H-bridge multilevel photovoltaic(PV)inverters.Compared with conventional voltage balanc-ing control methods,the method proposed could make the PV strings of each submodule operate at their maximum power point by independent capacitor voltage control.Besides,the predicted and reference value of the grid-connected current was obtained according to the maximum power output of the maximum power point tracking.A cost function was con-structed to achieve the high-precision grid-connected control of the CHB inverter.Finally,the effectiveness of the proposed control method was verified through a semi-physical simulation platform with three submodules.

仿生嗅觉感知技术及其在嗅觉障碍疾病筛查中的研究进展

嗅觉障碍是多种疾病的早期症状,如新型冠状病毒感染的症状之一是嗅觉丧失,阿尔茨海默病和帕金森病患者通常伴有嗅觉降低或丧失.研究基于嗅觉功能检测的早期疾病筛查和诊断技术对控制患者病情、改善人类健康具有重要意义.目前嗅觉功能障碍的检测与评价方法尚不能有效地筛查和诊断各类嗅觉障碍相关疾病,而仿生嗅觉感知技术在模拟人类嗅觉感知系统方面具备一定的灵敏度、选择性和准确度,因此在嗅觉障碍相关疾病筛查中具有广阔的应用前景.本文介绍了目前国内外嗅觉功能障碍相关疾病的研究现状,分析了仿生嗅觉感知技术的原理及其在嗅觉障碍与疾病相关性检测与诊断中的研究进展.随着生物医学工程领域多学科交叉融合的发展,细胞网络芯片、类器官仿生芯片以及脑机交互技术的转化应用将促进仿生嗅觉感知技术在嗅觉障碍相关疾病研究中的发展以及临床疾病诊断技术的革新.

Recognition of high-specificity hERG K+ channel inhibitor-induced arrhythmia in cardiomyocytes by automated template matching

Cardiovascular disease(CVD)is the number one cause of death in humans.Arrhythmia induced by gene mutations,heart disease,or hERG K+channel inhibitors is a serious CVD that can lead to sudden death or heart failure.Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals.However,parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats,and it is difficult to achieve automated and efficient arrhythmic recognition with these methods.In this work,we developed a unique automated template matching(ATM)cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system.The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation.The performance of the ATM model under long-term astemizole,droperidol,and sertindole treatment at different doses was determined.The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy(100%for astemizole treatment and 99.14%for droperidol and sertindole treatment)than the ATM model based on arrhythmic multitemplates.We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.

Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment

Cardiovascular diseases have emerged as a significant threat to human health.However,drug development is a time-consuming and costly process,and few drugs pass the preclinical assessment of safety and efficacy.The existing patch-clamp,Ca2+imaging,and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput,limited long-term assessment,or inability to synchronously and correlatively analyze electrical and mechanical signals.Here,we develop a high-content,dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized(EMS)biosensing system.This microfabricated EMS can record both firing potential(FP)and mechanical beating(MB)signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals(FP–MB)for further analysis.This system was applied to test typical ion channel drugs(lidocaine and isradipine),and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed.The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples.Furthermore,a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs.The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines.

Evaluating the efficacy and cardiotoxicity of EGFR-TKI AC0010 with a novel multifunctional biosensor

Non-small cell lung cancer(NSCLC)is a leading cause of cancer mortality worldwide.Although epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)have dramatically improved the life expectancy of patients with NSCLC,concerns about TKI-induced cardiotoxicities have increased.AC0010,a novel third-generation TKI,was developed to overcome drug resistance induced by EGFR-T790M mutation.However,the cardiotoxicity of AC0010 remains unclear.To evaluate the efficacy and cardiotoxicity of AC0010,we designed a novel multifunctional biosensor by integrating microelectrodes(MEs)and interdigital electrodes(IDEs)to comprehensively evaluate cell viability,electrophysiological activity,and morphological changes(beating of cardiomyocytes).The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative,label-free,noninvasive,and real-time manner.AC0010 was found to significantly inhibit NCI-H1975(EGFR-L858R/T790M mutation),while weak inhibition was found for A549(wild-type EGFR).Negligible inhibition was found in the viabilities of HFF-1(normal fibroblasts)and cardiomyocytes.With the multifunctional biosensor,we found that 10μM AC0010 significantly affected the extracellular field potential(EFP)and mechanical beating of cardiomyocytes.The amplitude of EFP continuously decreased after AC0010 treatment,while the interval decreased first and then increased.We analyzed the change in the systole time(ST)and diastole time(DT)within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment.This result probably indicated that the relaxation of cardiomyocytes was insufficient,which may further aggravate the dysfunction.Here,we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations(10μM).This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated.In addition,novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.