Silicon Nanofield Effect Transistor Biosensors For Detection Of Tumor Markers

Presently,malignant tumors are still seriously threatening human health.Early screening and diagnosis are the main ways to improve the survival rate and quality of life of patients,and the detection of tumor marker is still one of the important means of cancer screening.The methods for detecting tumor markers are time-consuming,complex,low sensitivity and existing the risk of radioactive contamination.With the development and cross-integration of nanotechnology and biomedical technology,a new discipline of nanomedicine has emerged,in which nanobiosensor is the development result of this cross-discipline.Nano-biosensor has the characteristics of fast response,high sensitivity,strong specificity,no label,less sample requirement and so on.It is of great significance for rapid and high sensitivity detection of tumor markers.In this paper,we firstly fabricated of a Silicon Nanowires filed effect transistor(Si NWs FET)biosensor.Then we improved the electrical properties of the device and made the device surface functionalized.Lastly,we simultaneously detected multiple tumor markers in human serum by the biosensor.We developed a novel Nano-biosensor for highly sensitive,fast and low power consumption method for the detection of tumor markers.1.Label-free and real-time detection of alpha-fetoprotein using a nanowire biosensorWe fabricated a Si NW-FET according to “top-down” methodology.The mothed of surface functionalization of Si NW was testified by Au nanoparticles(GNPs)labeled proteins and fluorescent proteins.Si NWs were immobilized by anti-AFP antibodies.Then a polydimethylsiloxane(PDMS)microchannel was integrated to the modified Si NW-FETs.Then various concentrations of AFP were pumped through the sensing area.As low as 0.1 ng/m L concentrations of AFP was detected by employing the Si NW-FETs fabricated in this work.2.A silicon nanoribbon biosensor based on field effect transistor(Si-NR FET)was fabricated and used to detect carcinoembryonic antigen(CEA)We fabricated a Si-NR-FET based on the improvement of traditional silicon nanowires according to “top-down” methodology.By increasing the amount of antibodies modified to the surface of the Si NRs,the sensitivity and stability of the device was improved.Si-NR FETs were immobilized by the anti-CEA antibodies using the same method as before.Then,the CEA was detected by sealing the modified Si-NR FETs with a PDMS microchannel.The lowest detection of the device was 10 pg/ml CEA solutions and was more uniformity and stability than devices fabricated before.The experimental results implicate that the Si-NR FET biosensor could be used for high specificity,sensitivity,label-free and real-time responsive detection of CEA which has promising potential in clinical applications.3.Multiplexed detection of tumor markers by GNPs modified Si NW-FET biosensor in human serumHerein,a Si NW-FET biosensor was fabricated by top-down method and then was modified with 1.4 nm GNPs monoclonal antibodies.Then,the device was integrated with PDMS microfluidic multi-channels.Then,the integrated devices was used to detect AFP and CEA solution simultaneously.The results showed linear AFP solution fitting from 520 fg/ml to 200 ng/ml and CEA solution 256 fg/ml to 100ng/ml,respectively.The limit of simultaneously detection of AFP and CEA solution were 520 fg/ml and 256 fg/ml.Moreover,the detection of tumor markers in human serum by the NW biosensor showed a good correlation with traditional ELISA method.The NW biosensor showed a potential clinical application in the early diagnosis of tumors.4.Fabrication of Dual-gate silicon nanoribbon field effect transistors(DG-Si NR-FETs)and detection of tumor markerIn this study,we fabricated high sensitive DG-Si NR-FETs by the lithography combined with RIE etching method.The device combined source electrode,drain electrode,surface and top gate electrode and the Si NR surface was covered by passivation layer.The test results showed that the DG-Si NR-FETs enhanced the control ability of the device,and improved the sensitivity and stability of the sensor.The basic current value of the device raised to u A level,and both the surface and top gates had good control effect of the FET electrical performance.The detection limit of CEA solution was 10 fg/ml by using this sensor.Compared with previous researches,the sensitivity and stability of the biosensor have been greatly improved.In summary,the silicon-based NWs or NRs FET biosensors fabricated by the "top-down" method in this paper have good electrical properties and biocompatibility.It can meet the requirements of high sensitivity,specificity,rapidity and label-free detection in the detection of tumor markers.By improving the surface modification method and PDMS microfluidic channel,it can be used for simultaneous detection of multiple tumor markers in human serum with high sensitivity.It has wide application prospects in the screening and early diagnosis of tumors.