Study On Solid-state Nanopore Fabrication And Ion Transport Mechanism

Compared with biological nanopores,solid-state nanopores have its advantages of adjustable pore size,good acid-base resistance,stable structure at high temperature and compatible semiconductor manufacturing process.It has wide application prospects in the fields of nanofluids,especially in the biomolecules and nanoparticles detections.Single-molecule detections based on nanopores are of low cost,high throughput,no label and simple operation.However,the large current noise of solid-state nanopore is still a huge challenge in DNA sequencing and protein sequencing.Therefore,how to reduce the current noise of solid-state nanopore and improve the signal-to-noise ratio of biomolecular sensing are the key problems to be solved.The ion transport at nanoscale is extremely complex,the ion distribution in Stern layer and diffusion layer,the ion mobility,the dielectric constant of water and surface charge inner pores constantly change with solution concentration,p H and pore size.It is greatly theoretical significant to understand and master the ion transport law inner nanopore for various applications.However,there are still some knowledge-gaps in the theoretical research on the isoelectric point and the surface charge of silicon nitride nanopore,and the mixed ions transport in the TESPMA(Triethoxysilylpropylmaleamic Acid)modified nanopore.Based on the above challenges and problems to be solved in the field of solid-state nanopores,a series of studies have been carried out to reduce current noises and enrich the ion transport theory of nanopore.The Si N_x and Si N_x/Si O₂ thin-film chips were designed and manufactured based on the semiconductor manufacturing process.It is found that the current noise of Si N_x/Si O₂ thin-film chip can be reduced to 50 p A,which is 4 times lower than that of general Si N_x thin-film chip.So the Si N_x/Si O₂ thin-film chip can greatly improve the sensitivity and accuracy of biomolecule detection.Moreover,the Si N_x/Si O₂ thin-film chip has the local thinning area,it obviously improves the mechanical strength and service life of the chip.The manufacturing process of nanopores was studied based on the focused electron beam and focused ions beam,which could realize the cross-scale fabrication of nanopores with diameters ranging from 1 nm to several hundred nanometers.In addition,the Si N_x nanopores were modified using TESPMA,the carboxyl functional groups could effectively reduce diameters of nanopores and could greatly enhance the surface charge density of nanopores.The influence of the relative content of amino and silanol and their dissociation constant on the isopotential point(p H_iep)of nanopore were analyzed comprehensively.The research results indicate that the influence of amine groups on p H_iep is huge that the small number of amine groups can change dramatically p H_iep several p Hs.The p H_iep of Si N_x nanopore was measured as 4.1 and the ratio of amine over silanol was ascertained as 0.013.The calculation method of surface charge of Si N_x nanopore was estabilished,which change not only with p H,but also with the concentration of solution.When the p H of solution is higher than the p H_iep,the surface charge is negative and increases with the increase of salt content.When the p H is lower than the p H_iep,the surface charge is positive and change little with salt concentration.Inspired by biological channels that the sub-m M concentration of calcium or magnesium ions can modulate ion transport,the mixed ion transport based on monovalent and divalent cations were study by TESPMA nanopores.It is first found that nanopores with a diameter larger than 20 nm occurred anomalous mole fraction effect,whereas with a diameter smaller than 20 nm were blocked by calcium ions such that ion current of 4 nm pore in mixtures of KCl and Ca Cl₂ and in Ca Cl₂ was even ten times smaller than that in KCl solution.These phenomena are explained by the decreasing of surface charge and the effect of local charge inversion where accumulated calcium ions switch the effective surface charge from negative to positive,which make the nanopore current great decreases.The study established the relationship between the concentration of Ca²⁺,the diameter of nanopores,the various anomalous phenomena caused by Ca²⁺and the surface charge changes inner nanopoes.In order to better understand the ion transport of Ca²⁺in TESPMA nanopore,the COMSOL Mutiphysics was used to study the transport mechanism of Ca²⁺.The strong correlation liquid theory was used as the boundary condition to describe the variation of the nanopore surface charge with the concentration of Ca²⁺in the Stern layer.The results show that the decreases of the surface charge inner nanopore and the local charge inversion at the orifice caused by Ca²⁺are the main reasons for the anomalous mole fraction effect and the effect of Ca²⁺gating in the TESPMA nanopore.In addition,the influences of the mobility and the dielectric constant of solution caused by concentration and electric field intensity on the pore conductance were also considered.The results demonstrate that the above parameters have little effect on the conductance of nanopores.However,the theoretical model indeed can be improved by considering the change of ion mobility with concentration,which makes the calculated results in the smaller nanopores more consistent with the experimental data.The theoretical model and physical mechanism be further extended to explain the transport of other multivalent ions in the nanopore.