Construction Of Novel Electrochemiluminescence Cancer Marker Sensor Based On Semiconductor Quantum Dot

Electrochemiluminescence（ECL）is a chemiluminescence phenomenon excited by electrochemistry,combining electrochemistry and spectroscopy ingeniously.Compared with other optical methods,ECL showed its unique advantages.The ECL technology,which does not require an external light source,avoids scattered light and other impurity luminescence interference,and has the advantages of simple operation,continuous measurability,easy control,and good reproducibility.Therefore,ECL analysis technology has broad application prospects in the fields of clinical laboratory diagnosis,food safety testing,environmental pollution monitoring,and biological imaging.Semiconductor quantum dots（QDs）have been extensively researched and applied in the ECL field due to their unique optoelectronic properties and adjustable size.However,most of the reported QDs contains heavy metal elements,causing environmental pollution and health problems,and restricting their application in the fields of biological testing and clinical diagnosis.In recent years,biocompatible carbon-based QDs have been explored in the ECL field,which overcome the toxicity of heavy metal QDs.Traditional carbon-based QDs have the disadvantage of low ECL efficiency,so the synthesis of QDs or QDs-composite nanomaterials with high ECL efficiency,good biocompatibility,and low toxicity has become a challenging topic.Recently,ECL biosensor based on semiconductor QDs,as a new analytical platform with good selectivity and high sensitivity,has been widely used in the detection and clinical diagnosis of tumor markers.Based on this,this article mainly starts from the inorganic nanomaterial-quantum dots,combined with the unique biological properties of DNA to construct new nanostructured light emitters,and screens out some new quantum dots with excellent ECL performance and high luminous intensity,and explores the enhanced ECL luminescence.mechanism.By using different new quantum dot nanomaterials as ECL luminescent reagents,in combination with co-reaction reagents and co-reaction promoters,ECL signal probes are prepared,and an efficient DNA biological signal amplification strategy is assisted to construct an ultra-sensitive detection of cancer markers.Biosensors have laid the foundation for the application research of semiconductor quantum dots in the fields of ECL clinical diagnosis and ECL imaging.This research work is divided into the following parts:1.Construction of electrochemiluminescence microRNA sensor based on 3D CdTe QDs-DNA nano-reticulationThe introduction of nanomaterials as ECL emitters have greatly improved the performance of ECL and the diversity of ECL system.However,due to the compactness of reported nanomaterials,a serious internal filtration effect is caused,which reduced the ECL efficiency.In this work,we reported a 3D luminous nanomaterial with reticular structure,which not only supported abundant CdTe QDs to avoid the inner filter effect for a high ECL efficiency,but also contained the hemin/G-quadruplex as coreaction accelerator in the 3D CdTe QDs-DNA-NR/S₂O₈^2-system for the enhancement of ECL intensity.Herein,a novel three-dimensional CdTe QDs-DNA nano-reticulation（3D CdTe QDs-DNA-NR）was used as signal probe with the dual-legged DNA walker circular amplification as target conversion strategy to establish a pioneering ECL biosensing strategy for ultrasensitive detection of microRNA-21 form cancer cells.Furthermore,with the target-induced dual-legged DNA walker circular amplification strategy,a mass of output DNA was produced to connect with the 3D CdTe QDs-DNA-NR for the construction of ECL biosensor,which realized the ultrasensitive detection of microRNA-21 from 100 amol/L to 100 pmol/L,and the detection limit was down to 34.0 amol/L.Significantly,this work could be readily extended for the detection of other biomolecules to provide a neoteric channel for disease diagnosis.2.Ultrasensitive detection of microRNA based on BCNO quantum dots as novel ECL emitersAs a class of non-metallic QDs,carbon-based QDs have the advantages of non-toxicity and good biocompatibility,which are widely used in the ECL field.However,most carbon-based QDs as ECL emitters still have the defect of weak ECL emission.Herein,the boron radicals active sites of boron carbon oxynitride quantum dots（BCNO QDs）is electrically excited to produce boron radicals（B^·）for catalyzing peroxydisulfate(S₂O₈^2-)as coreactant to accelerate the generation of abundant sulfate radicals(SO₄^·-)for significant enhancement on the ECL efficiency of BCNO QDs,which overcome the defect of traditional carbon-based QDs with low ECL efficiency.Impressively,under the extremely low concentration of S₂O₈^2-solution,the BCNO QDs/S₂O₈^2-system could exhibited high ECL emission,realizing the environmental friendliness and excellent biocompatibility for sensitive bioanalysis.As a proof of concept,BCNO QDs,a new generation of ECL emitter with high ECL efficiency,was successfully used in ultrasensitive determination of microRNA-21,which pushes the exploration of new ECL emitters and broadens the application in the field of clinical diagnosis,ECL imaging and molecular devices.3.Black phosphorus quantum dots as efficient ECL emitter binding palindrome sequences mediated single-strand amplification for ultrasensitive biosensor constructionWith the continuous development of nanotechnology,the development of new semiconductor quantum dots has always been a research hotspot,and it has also restricted the development of quantum dots in the fields of ECL clinical analysis and ECL imaging.In this study,stable BP QDs were prepared under the protection of n-methyl-2-pyrrolidone（NMP）,which produced cathodic ECL response in a system where S₂O₈^2-was the co-reactant.BP QDs show the excellent ECL response and extremely high biocompatibility in the ECL/S₂O₈^2-system.As a zero-dimensional form of black phosphorous nanomaterials,black phosphorous quantum dots（BP QDs）exhibits unique photophysical and electrochemical properties due to their quantum confinement and edge effects.Then,further study discussed the ECL cathode ECL mechanism of BP QDs.Based on this,this work constructed an ultra-sensitive ECL biosensor to detect cancer marker MUC1,using BP QDs as a high-efficiency ECL emitter and combined with palindrome-mediated single-stranded amplification.Palindrome sequences are popular primers in the field of nucleic acid molecular sensing,which can not only prevent the waste of nucleic acid,but also realize the amplification strategy of nucleic acid with only a single primer.This biosensor has a sensitive response to the cancer marker MUC1 with a concentration range of 100 fg/m L to 10 ng/m L,and its detection limit is 16.5 fg/m L.