| New diseases and cancers are gradually showing the characteristics of difficult early diagnosis and incurable late stage.There is an urgent need to develop high-sensitivity detection technology to achieve rapid and accurate diagnosis of ultra-low concentration targets in the early stage of the disease.Due to the characteristics of high sensitivity,fast response speed,low production cost,miniaturization and integration,biosensors based on nano-material semiconductors have attracted much attention,especially molybdenum disulfide(MoS2)nano-film biosensors.MoS2 has suitable band gaps,which is better biocompatibility and lower detection limits for biological targets in biosensor applications,compared with graphene and other bulk semiconductor materials.Hence,MoS2 has natural advantages in the detection of low-concentration complex biological samples.At present,the nano MoS2 biosensor has realized the detection of various biological molecules such as DNA,RNA,and protein,but there are still problems such as poor device repeatability,complex biological functionalization methods,and insufficient target detection limits.This paper has conducted in-depth research on the material synthesis,biological functionalization methods and device structure of MoS2 thin film biosensors,optimized the preparation process of two-dimensional MoS2 nano-films,and prepared high-performance field effect transistor(FET)devices;designed new biological functionalization method improves the sensor's detection performance of biological targets;improves the structure of the sensor to enable it to be reusable.The main research contents and the results obtained are as follows:1.Preparation and microstructure of MoS2 nano film(1)The process of preparing the MoS2 film by the mechanical peeling method is improved,and a small-layer MoS2 film that can be positioned is successfully obtained by using the prepared substrate with a mark.The Raman spectrum shows that the film exhibits a very narrow FWHM at the characteristic peaks of E2g1=382 cm-1 and A1g=404 cm-1,indicating that the film crystal quality is very high.Atomic force microscopy(AFM)shows the film thickness It is controlled at 4?6 nm,indicating that the improved process has improved the uniformity of the film.(2)A patterned MoS2 film array growth method is designed on the basis of the CVD two-step method.The precise control of the shape,size and thickness of the MoS2 film is realized.Raman and AFM showed that the MoS2 film was selectively grown on the area where the molybdenum metal was deposited,and a high-quality rectangular film array with a thickness of 4 nm was obtained,which solved the problem of mass customization of materials in biosensors.2.Biofunctionalization of MoS2-based biosensor for prostate cancer antigen(PSA)detection(1)MoS2-based FET devices were fabricated by photolithography,and the output and transfer characteristics of the devices were studied.The linear Ids-Vds curve shows that the device has good ohmic contact characteristics.The Ids-VG,back curve shows n-type FET characteristics,and the carrier mobility reaches ?=9.8 cm2V-1s-1,the parameter index meets the PSA high-performance test requirements.(2)Design an environmentally friendly DNA tetrahedron-binding biotin-streptavidin system(BSAS),and use it to modify the surface of MoS2-based FET devices,and the functionalized device structure FET/DNA-TSPs/BSAS/anti-PSA.XPS shows that the formation of Au-S bonds between the DNA tetrahedron and the Au film on the surface of the FET device provides a stable basis for biological modification.In addition,the modified system of BSAS's high affinity and multi-stage amplification effect improves the sensor's ability to capture the target detection object.(3)The electrical response of PSA was studied by means of real-time testing,and it was found that the response current is closely related to the PSA concentration.This is due to the fact that the high concentration of antigen reduces the positive potential of the sensor surface due to the binding of the antibody.The response percentages of different concentrations of PSA were fitted,and it was found that the response of the sensor to PSA was linear,and the R2 of the fitted curve was 0.959,indicating that the sensor had an excellent response to the PSA target protein.The linear range of the sensor's response to PSA is 1fg/mL?100 ng/mL,and the detection limit of 1 f g/mL is 10,000 times and 100 times the highest level in the existing literature.(4)It is found that the response percentage ratio of Casein,BSA and IgG&HSA is less than 20%,which is far lower than the response of the target protein in PBS and serum,indicating that the MoS2-based biosensor has excellent specificity and reliability for PSA detection.It shows great potential in detecting PSA in real-time medical applications.3.Bio-separated MoS2-based sensor array(1)A bio-separated sensor array is designed.The Au-S bond is formed by the reaction between the thiol group at the bottom of the DNA tetrahedron and Au,which affects the principle of Au surface potential.The biosensing area of the sensor is isolated.At the same time,a separate MoS2 device array is prepared based on the patterned structure,which realizes the bio-separation type.The construction of the MoS2-based sensor array solves the problem of sensor biological incompatibility and non-reusability.(2)The electrical response of BRCA1 of a 1×4 sensor array is studied.It is found that the response results of different unit devices to the same concentration of BRCA1 are basically at the same current level,indicating that the array uniformity is very good.The linear range of the response concentration of the array unit to BRCA1 is 1fM?1?M,and a very high linear fitting coefficient of R2=0.98 is obtained.Compared with similar methods,this result has a wider detection range.(3)The method of comparing blank and non-complementary DNA samples was used to study the specific selectivity of the sensor and the reliability of detecting low concentrations of BRCA1.It is found that the sensor has a very low noise level%RBlank+3SD=2.5%,and the response to non-complementary DNA is almost negligible,indicating that the sensor has a reliable response percentage to BRCA1 detection,and the specific selectivity meets the demand. |
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