Naopore-based Sensing Of Particles And Biological Molecules

Solid-state nanopore sensing is a rapidly expanding field with many potential applications in single molecule sensing,and has been significantly improved in the past decade with the development of nanotechnology and biotechnology.As particles or biological molecules pass through the nanoscale pore driven by the electric field,the ionic current through the pore is changed which can be used to sense the molecules.Research on transport in nanopores is an interdisplinary field with the contents in nanotechnology,biology,materia ls,mechanics,chemistry etc.Study on the mechanism and applications is of great importance.In this thesis,physics of the translocation through nanopores is studied and the potential applications of nanopore in DNA sensing and DNA identification are shown.Firstly,the ionic current signatures causeed by particle translocation through cylindrical nanoproes is studied using numerical simulation.The current decreases and increases during particle translocation through a nanopore at low salt concentration are studied.The results show the ionic concentration polarization effect enhances or depletes the ion concentration inner and around the pore,which contributes to the ionic current and causes the biphasic resistive pulse.Secondly,the signals during DNA translocation through conical glass nanopores are experimentally studied with different voltage,salt type and salt concentration.The results show the current signature depends on the salt type,salt concentration and translocation direction and show several typical event shapes.Numerical simulation is used to explain the phenomena and this provides references for optimizing the experimental condition.Thirdly,asymmetric dynamics of DNA translocation through conical nanopores is shown: It is found that the DNA translocation time is obviously different when DNA enters or exits the conical pore.Custom-designed DNA with markers is used to study the translocation velocity and a model is given to explain the phenomenon.This also provides a way to slow dow n the DNA for nanopore sensing.Finally,by labelling and mapping of short sequence motifs on DNA molecules,a method for DNA identification with solid-state nanopore is put forward.Methylase is used to label the sequence 5’-TCGA-3’ on DNA with biotin molecules,and then streptavidin is added to bind to biotin molecules.The sample is detected with solid-state nanopores to identify the labelled positon on the DNA.This provides an easy and accurate method for DNA identification.Overall,the underlying physics for nanopore sensing is revealed by experimental and numerical study.The potential applications for DNA sensing and DNA identification are shown in this thesis.