In this paper,a hybrid electronic noses’system(HENS)based on MOS-SAW detection units intended for lung cancer diagnosis is proposed.The MOS gas sensors are used to detect the VOC molecules with low molecular weight(L...In this paper,a hybrid electronic noses’system(HENS)based on MOS-SAW detection units intended for lung cancer diagnosis is proposed.The MOS gas sensors are used to detect the VOC molecules with low molecular weight(LMW),and the SAW sensors are adopted for the detection of VOC with high molecular weight(HMW).Thus,the novel combination of these two kinds of gas sensors provides higher sensitivities to more of VOC species in breath than that of using only a single kind of sensor.The signals from MOS-SAW detection units are then recognized by a multi-model diagnosis method.Applying four algorithms,six models were established for diagnosis and tested by leave-one-out cross-validation method.The model by artificial neural network(ANN)was selected as the best model to analyze breath samples.89 clinical samples were tested with MOS-SAW ANN diagnostic model,which takes the features derived from both the MOS and SAW sensors.It shows the highest sensitivity of 93.62%,and the highest selectivity of 83.37%.The study shows that,promisingly,our HENS is effective during screening of lung cancer patients,especially among the people of high risk.展开更多
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 patien...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.展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant No.81027003).
文摘In this paper,a hybrid electronic noses’system(HENS)based on MOS-SAW detection units intended for lung cancer diagnosis is proposed.The MOS gas sensors are used to detect the VOC molecules with low molecular weight(LMW),and the SAW sensors are adopted for the detection of VOC with high molecular weight(HMW).Thus,the novel combination of these two kinds of gas sensors provides higher sensitivities to more of VOC species in breath than that of using only a single kind of sensor.The signals from MOS-SAW detection units are then recognized by a multi-model diagnosis method.Applying four algorithms,six models were established for diagnosis and tested by leave-one-out cross-validation method.The model by artificial neural network(ANN)was selected as the best model to analyze breath samples.89 clinical samples were tested with MOS-SAW ANN diagnostic model,which takes the features derived from both the MOS and SAW sensors.It shows the highest sensitivity of 93.62%,and the highest selectivity of 83.37%.The study shows that,promisingly,our HENS is effective during screening of lung cancer patients,especially among the people of high risk.
基金This study was supported by the National Natural Science Foundation of China(Grant no.62120106004)the China Postdoctoral Science Foundation(Grant no.2022M712783,BX2021265,2021M702859).
文摘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.