Electrochemical Biosensor For Acute Myocardial Infarction Biomarker Based On Nanostructured Materials

Acute myocardial infarction is a very serious cardiovascular disease clinically,which has an acute onset,a high fatality rate and a serious threat to human life.Acute myocardial infarction(AMI)is usually caused by obstruction of the coronary arteries that prevents blood from returning to the heart,which may initiate severe myocardial injuries.Therefore,accurate diagnosis and timely treatment are essential to improve survival rate.Cardiac troponin I(cTnI)has proven to be a golden biomarker for acute myocardial infarction detection.The detection of cTnI in serum can truly and accurately reflect the patient’s condition,and it is an effective method for clinical diagnosis of AMI.Up to now,most reported strategies on cTnI,including colorimetric immunoassay,electrochemical immunoassay,fluorescence immunoassay,surface plasmon resonance spectroscopic sensing,etc.However,these methods still have some problems,such as most of them based on single-signal detection,low sensitivity,and high detection cost.Therefore,there is an urgent need to develop analysis methods that are fast,highly sensitive,highly accurate,and low in detection costs.Based on the above,this work aimed to the development of a novel detection technology of cTnI.From the perspective of improving the sensitivity and accuracy of detection,combining nanotechnology and nucleic acid technology to amplify the signal,we reasonably construct dual-mode sensors for sensitive and accurate detection of cTnI.The main works are summarized as follows:1.Dual-modular aptasensor for detection of cardiac troponin I based on mesoporous silica films by electrochemiluminescence/electrochemical impedance spectroscopyA simple,dual-modular aptasensor for accurate determination of cardiac troponin I(cTnI),a sensitive biomarker of acute myocardial infarction,is reported.It has the parallel output of electrochemiluminescence(ECL)and electrochemical impedance spectroscopy(EIS)based on target-gated transportation of signal probes(luminol/H2O2 or Fe(CN)63-/4-).The sensing capacity is originated from the amino-functionalized mouth margin of the nanochannels in a vertically oriented mesoporous silica film,which was in situ-grown on indium tin oxide-coated glass.With the linkage of glutaraldehyde to couple the aptamer as a trapper,it brings in the high specific target-gated response toward cTnI as decreased ECL or increased EIS.The concentration of cTnI is measurable by the ECL response within a wide linear range from 0.05 pg/mL to 10 ng/mL,as well as the EIS response for a linear range between 0.05 pg/mL and 1 ng/mL.Significantly,the self-verification of these two data from ECL and EIS validated each other with a satisfactory linear correlation(R2=0.999),thereby realizing the more reliable and accurate quantification to avoid false results.The designed strategy is an effective method for detection of cTnI,which is of great potential to apply in clinical detection.2.Ratiometric electrochemical cTnI TDs aptasensors based on HCR and Au/Ti3C2-MXene amplification for screening serious patient in COVID-19 pandemicThe accurate assay of cardiac troponin I(cTnI)is very important for acute myocardial infarction(AMI),it also can be employed is an effective index for screening serious patients in COVID-19 pandemic before fatal heart injury to reduce the mortality.A high accuracy and reproducibility ratiometric sensing strategy was proposed based on an enhanced electrochemical signal of methylene blue(MB)vs.a stable referable electrochemical signal of doxorubicin(Dox).The bio-recognition of cTnI with BFP/Tro4-apatamer/Au@Fe3O4 would release BFP simultaneously and equivalently and succedent initiating of the HCR.The tetrahedral DNA(TDs)not only serves as a carrier of Dox to produce the stable reference electrochemical signal and to prevent the generation of false positive signals,but also regulates the density and orientation of the capture probes to improve the hybridization efficiency.In the electrochemical ratiometric aptasensor platform,only the electrochemical signal of MB increases with the target cTnI existence,while the reference electrochemical signal from Dox changes little,reflecting the real-time state of the electrode surface during the test.The ratio value of electrochemistry of MB/electrochemistry of Dox showed a good linear relationship with cTnI concentration in the range of 0.1 fM to 500 fM with the limit of detection was 0.1 fM.(2.4 fg/mL,S/N=3).The prepared ratiometric electrochemical aptasensor had good selectivity,sensitivity,reproducibility and stability,and had been used for the determination of cTnI in real serum with satisfactory results.It is worth looking forward to be used for screening serious patient of COVID-19 to reduce the mortality,especially in mobile cabin hospital.3.Ratiometric electrochemiluminescence and electrochemistry cTnI TDs aptasensors based on HCR and Au/Ti3C2-MXene amplification for screening serious patient in COVID-19 pandemicA highly sensitive and accurate ratiometric aptasensor strategy for cTnI was developed based on the enhanced electrochemiluminescence(ECL)signal of doxorubicin(Dox)-luminol vs.the stable referable electrochemical(EC)signal of Dox.The bio-recognition of cTnI with Tro4-aptamer on BFP/Tro4-apatamer/Au@Fe3O4 would release the equal amount of BFP and the free BFP was captured by tetrahedral DNA(TDs)anchored on Au/Ti3C2-MXene/ITO electrode by Au-S,fueling HCR,which greatly improved the sensitivity.The tetrahedral DNA(TDs)not only serves as a carrier of Dox to produce the stable reference electrochemical signal and to obviate the false positive results,but also regulates the density and orientation of the capture probes to improve the hybridization efficiency.In the ratiometric ECL/EC platform,only the ECL signal of Dox-luminol increased along with the level of cTnI,while the reference signal of Dox was stable,reflecting the real-time state of the electrode surface.The ECLDox-luminol/CurrentDox linearly regressed to cTnI concentration in the range of 0.1 fM to 1 pM with the limit of detection(LOD)as 0.04 fM(0.96 fg/mL,S/N=3).The proposed ratiometric ECL/EC aptasensors had good specificity,sensitivity,reproducibility and stability and had been applied to determine cTnI in real samples with satisfactory results.It is worth looking forward to be used for screening serious patient of COVID-19 to reduce the mortality,especially in mobile cabin hospital.