Construction Of High Performance Field Effect Transistor Biosensors For Reliable Detection Of Bladder Cancer-associated Nucleic Acid

Bladder cancer is one of the most common malignant tumours in the urinary system with a high and rising trend of mortality.Timely diagnosis of early-stage bladder cancer remains the contributing bottleneck due to its complex pathological types and nonspecific symptoms.In this regard,the exploitation of an approach to accurately diagnose early-stage bladder cancer is in highly demand.As a urine storage organ,bladder lesions have a direct effect on the composition of the urine.Urine,as the metabolic microenvironment of bladder tumor cells,contains abundant bladder cancer biomarkers including DNA,RNA,proteins,and tumour cells,which is crucial for developing a non-invasive diagnosis of the disease.Particularly,micro RNA plays a crucial role in cell metastasis,development,proliferation,apoptosis and carcinogenesis,and it was immediately excreted into urine via the metabolism of bladder tumour cells in case of bladder carcinogenesis.Therefore,the quantitative detection of bladder cancer-associated micro RNA in human urine is an effective strategy to achieve noninvasive diagnosis of early-stage bladder cancer.However,the highly sensitive and selective detection of bladder cancer-associated micro RNA in urine is hindered by their extremely low abundance.Consequently,the exploration of a highly sensitive and selective approach for the detection of a trace amount of micro RNA in human urine is of vital importance for the diagnosis and postoperative of bladder cancer。Nano-biosensors constructed by nanomaterials have been comprehensively employed for the detection of disease-relevant biomarkers.As a type of nano-biosensors,field effect transistor(FET)biosensors exhibit prominent electrical performance,ease to be miniaturized and integrated.Owing to its intrinsic amplification feature,FET biosensors could generate a significant electrical signal change under a tiny local microenvironment change,therefore demonstrating tremendous potential in the highly sensitive detection of disease-relevant biomarkers.In the FET biosensors,semiconductor channel nanomaterials play a central role in the determination of the device performance.Currently,zero-dimensional nanoparticles,one-dimensional nanowires,and two-dimensional nanosheets have been utilized as semiconductor channel nanomaterials of FET biosensors.Among which,two-dimensional indium gallium zinc oxide(IGZO)shows the advantages of ease to scalable and high stability,promising its potential as ideal channel nanomaterial of FET biosensors.To this end,the development of a highly sensitive and selective IGZO FET biosensor is expected to achieve highly sensitive detection of bladder tumour-associated biomarkers and realize early diagnosis of bladder cancer.Herein,we reported the fabrication of high performance indium gallium zinc oxide field effect transistors(IGZO FET).The fundamental electrical performance of IGZO FET was also investigated.Furthermore,the single-stranded DNA-functionalized IGZO(ss DNA-IGZO)FET exhibits high sensitivity,specificity and sensing reproducibility in the detection of micro RNA-21.With the ability to detect trace amount of micro RNA-21 in human urine,the IGZO FET biosensor could be employed to effectively classify urine samples from bladder cancer patients and healthy donors.Our designed IGZO FET biosensor provides a powerful tool for the development of a nanotechnology platform to achieve early diagnosis of bladder cancer,as well as demonstrates great potential in personal health management.(1)The IGZO channel with uniform and smooth structure was prepared by a radio frequency sputtering system and the IGZO FET with outstanding stability and high on/off ratio was further constructed.In addition,we also studied the relationship between the field-effect mobility and deposition time,and explored the electrical properties of IGZO FET under the maximum mobility,which is crucial for the later preparation of highly selective biosensors.(2)IGZO FET biosensor with high selectivity and specificity was constructed by modified with single-stranded DNA(ss DNA)that is specific for micro RNA-21.Particularly,our designed ss DNA-IGZO FET biosensors realized the ultra-sensitive detection of mi RNA-21 extracted from human urine with an ultra-low detection limit of 19.8 a M and could effectively differentiate urine samples between bladder cancer patients and healthy donors.The development of high-performance IGZO FET biosensors provides a powerful tool for the early diagnosis of bladder cancer.