Solid-State Nanopores Based On Two-Dimensional Materials

Solid-state nanopore devices have presented their great potential in single-molecule sensing,showing good performance in biomolecular configuration recognition and signal feature extraction of bases/amino acids etc.Using ionic blockage effect caused by the translocation of biomolecules through the nanochannel,the nanopore device can acquire related information of the molecules.At present,the most common solid-state nanopore device is classic solid-state nanopore based on silicon nitride（Si Nx）.Due to the difficulty of getting the material thinner,the Si Nx nanopore has lower spatial resolution,hence it is hard to realize the detection or identification of the biomolecules in nanometer or even sub-nanometer precision.In addition,in the classic nanopore device,the dwell time of the translocation is usually shorter than 1 ms.When the sampling frequency of the patch clamp cannot be increased further,such dwell time will make it harder to acquire internal information of single molecules and the interaction details with the nanopore.These two aspects,low spatial resolution and fast translocation speed must be improved if nanopore devices are to be utilized to explore the dynamic characteristic in nanopores and more complex structural features of single molecules.The two-dimensional materials have several special features,such as ultra-thin thickness of the monolayer and stronger interaction with biomolecules.Using them in forming nanopore devices will be conducive to improving the spatial resolution and slowing the translocation speed.According to the potential issues of solid-state nanopore biosensors and the features and advantages of two-dimensional materials mentioned above,this thesis will carry out the following work:1.This thesis firstly completed the fabrication of classic Si Nx solid-state nanopores and verified the robustness of existing experimental conditions and methods,preparing in advance for the fabrication design of two-dimensional material nanopore devices and the discovery of possible testing problems.2.This thesis used Molybdenum Sulfide（Mo S2）thin film material to design rapid,efficient,and controllable nanopore fabrication process based on mechanical exfoliation,dry transferring,Focused Ion Beam（FIB）and Transmission Electron Microscopy technique（TEM）.And for the first time we realized the translocation detection of single BSA molecules and verified the feasibility of it.Through statistical investigation,individual signal inspection,and comparative analysis of single-molecule signals,Mo S2 nanopores show high signal-to-noise ratio（SNR）in protein detection and good noise controllability.Furthermore,through the control of nanopore pore sizes and the realization of BSA translocation tests under various pore sizes,it was found that the pore size has influences on the translocation threshold voltage,the translocation dwell time,and the translocation orientation of BSA.3.To further slow the translocation speed of single molecules,this thesis also designed and fabricated nanopore devices based on the heterostructure formed by the stacking structure of Graphene-Mo S₂and conducted translocation tests onλDNA and protein molecules.The experimental results show that,on the premise of ensuring the smooth passage of single molecules and maintaining high spatial resolution,the heterostructure nanopores utilize the difference in van der Waals interaction between two materials and biomolecules so that the speed of protein translocation can be slowed down up to more than 100 milliseconds.Besides,by comparison analysis,the effect of slowing down the translocation time of the heterostructure is confirmed.Meanwhile,in the analysis of single signals we noticed higher orders within some long signals,reflecting the shape of BSA molecules,its structure variation,different interaction strength with the heterostructure and so on.This thesis clearly showed the feasibility and stability of solid-state nanopore devices based on two-dimensional materials in single-biomolecule sensing.Each defect,the low spatial resolution,and the fast translocation has been improved to some degree.Based on the results of this work,it will be possible to use two-dimensional material nanopores to detect more kinds of biomolecules and analyze structural details,providing a new research direction and space for rapid biochemical detection and analysis in the future.