Ji Li

Boron nitride nanopores: Highly sensitive DNA single-molecule detectors

The first electronic measurement of DNA translocation through ultrathin BN nanopores is demonstrated. BN nanopores show much higher detection sensitivity compared with SiN nanopores. BN has a spatial resolution as graphene. The ultrathin BN nanopores provide substantial opportunities in realizing high-spatial-sensitivity nanopore electrical devices for various applications.

The growth mechanism and topography of superconducting YBa2Cu3O7-δ and BiSrCaCuO-2201 films studied by scanning tunneling microscopy

The growth mechanism and surface topography of YBa2Cu3O7 − δ (YBCO) and BiSrCaCuO-2201 (BSCCO) epitaxially grown superconducting films have been studdied by scanning tunneling microscopy. We report here two growth mechanisms: screw dislocation growth and layered growth, and also the surface characterization and surface modification of thin films under a controlled manner. High-quality epitaxial thin films were grown in situ by excimer laser ablation. YBCO thin films were epitaxially grown with the c-axis perpendicular to the SrTiO3 (100) substrate surface. On the flat substrate, the YBCO films were nucleated and grown in the screw dislocation manner. On the titled substrate (α<1 deg.), the films show layered growth. The etching caused by field-induced evaporation has been utilized to observe the initial stage of growth. Epitaxially grown BSCCO-2201 films were firstly synthesized in our laboratory with the c-axis perpendicular to the ZrO2 substrates. Layered growth has been observed by STM. No screw dislocations were identified in our samples. Larger atomic flat areas were present, which are more stable than YBCO films. As a parent phase for the BSCCO 2212, 2223 series, the study of the growth mechanism of 2201 films is very important to the synthesis of superconducting 2212, 2223 or other artificial layered thin films.

Electron microscopy study of C60

The microstructural features of the powder C60 material have been studied by using scanning microscopy, electron diffraction, and high resolution electron microscopy. Scanning electron microscopy observation reveals that the grains in the samples are packed by extensively disordered crystallites as well as amorphous granules. Electron diffraction measurements have identified that the crystals of C60 have two kinds of structure, one is face‐centered‐cubic (fcc) with unit cell parameter a=1.41 nm, and the other has the hexagonal closest packed (hcp) structure with cell parameters a=0.958 nm and c=1.63 nm. High resolution electron microscopy as well as electron diffraction observations clearly show the random crystallites packing in the C60 grains.

Intrinsic and membrane-facilitated α-synuclein oligomerization revealed by label-free detection through solid-state nanopores

α-Synuclein (α-Syn) is an abundant cytosolic protein involved in the release of neurotransmitters in presynaptic terminal and its aberrant aggregation is found to be associated with Parkinson’s disease. Recent study suggests that the oligomers formed at the initial oligomerization stage may be the root cause of cytotoxicity. While characterizing this stage is challenging due to the inherent difficulties in studying heterogeneous and transient systems by conventional biochemical technology. Here we use solid-state nanopores to study the time-dependent kinetics of α-Syn oligomerization through a label-free and single molecule approach. A tween 20 coating method is developed to inhibit non-specific adsorption between α-Syn and nanopore surface to ensure successful and continuous detection of α-Syn translocation. We identify four types of oligomers formed in oligomerization stage and find an underlying consumption mechanism that the formation of large oligomers consumes small oligomers. Furthermore, the effect of lipid membrane on oligomerization of α-Syn is also investigated and the results show that 1,2-dioleoyl-sn-glycero-3-[phospho-L-serine] (DOPS) small unilamellar vesicles (SUVs) dramatically enhances the aggregation rate of α-Syn while do not alter the aggregation pathway.

Structural study on C60 material

Abstract The crystal structure and defect structures of C60 material have been studied by means of X-ray diffraction, high-resolution electron microscopy and electron diffraction. The diffraction measurements show that the C60 crystal has the face-centered cubic (fcc) structure with lattice parameter a=1.42 nm. High-resolution electron microscopy observations, combined with the analyses of selected area electron diffraction, indicate that the coherent twins situated in the {111} planes frequently appear in the C60 crystal. The disordered stacking along the 〈111〉 direction and other kinds of defects appearing in the new material have also been investigated. Upon in situ cooling and heating from 130 K to 700 K, the structural stability of the C60 crystal has been observed.

Tiny Protein Detection Using Pressure through Solid-State Nanopores.

Solid‐state nanopore is a promising tool to detect proteins and its complexes. Small proteins (sub‐35 kDa) translocate very fast which could not be detected by normal patch‐clamp recording instrument due to low temporal resolution. We first introduce pressure into protein study and detection. The pressure‐derived force, combined with the voltage bias, makes very tiny protein (MW < 6.5 kDa) detection possible. Capture rate for Aprotinin is enhanced five times more than that in traditional voltage‐driven method by fine tuning of pressure and voltage. Temporal resolution of Aprotinin detection has improved by decreasing effective driving force. Moreover, we provide potential method to locate the equilibrium range for BSA movement in ionic solution by modulating driving pressure and retard voltage. Our study is of fundamental significance in nanopore research and provides unique platforms to study small proteins and other tiny biomolecules.

Probing surface hydrophobicity of individual protein at single-molecule resolution using solid-state nanopores

Solid-state nanopore is found to be a promising tool to detect proteins and their complexes. Nanopore-protein interaction is a fundamental and ubiquitous process in biology and medical biotechnology. By translocating phi29 connector protein through silicon nitride nanopores, we demonstrate preliminarily probing the surface hydrophobicity of individual protein at single-molecule resolution. The unique “double-level event” observed in the translocation and the ratio of two current drop levels suggest that the position where the interaction occurs is the hydrophobic surface of the protein. We provide a potential method to locate the hydrophobic region of a specific protein surface. This study is of fundamental significance in revealing the important role that hydrophobic interaction plays in nanopore-protein interaction and holds great potential for detecting local surface chemical property of individual protein using solid-state nanopores.中文摘要纳米孔是一种有效的探测蛋白质以及蛋白质复合物的工具. 蛋白质与纳米孔的相互作用是生物和生物医学领域普遍存在的基础过程. 本文通过分析phi29蛋白穿过氮化硅纳米孔产生的电信号, 初步实现了单分子层面对蛋白疏水表面的探测. phi29蛋白穿孔过程中独特的”双层事件”以及双层事件深度的比例表明相互作用发生在phi29蛋白的疏水表面. 本文提供了一种在蛋白表面定位疏水区域的潜在方法, 揭示了疏水相互作用在蛋白和纳米孔的相互作用中扮演着重要的角色. 另外, 该研究在固态纳米孔探测蛋白表面化学性质等领域也具有巨大的潜在意义.

Non-sticky translocation of bio-molecules through Tween 20-coated solid-state nanopores in a wide pH range

Nanopore-based sensing technology is considered high-throughput and low-cost for single molecule detection, but solid-state nanopores have suffered from pore clogging issues. A simple Tween 20 coating method is applied to ensure long-term (several hours) non-sticky translocation of various types of bio-molecules through SiN nanopores in a wide pH range (4.0–13.0). We also emphasize the importance of choosing appropriate concentration of Tween 20 coating buffer for desired effect. By coating nanopores with a Tween 20 layer, we are able to differentiate between single-stranded DNA and double-stranded DNA, to identify drift-dominated domain for single-stranded DNA, to estimate BSA volume and to observe the shape of individual nucleosome translocation event without non-specific adsorption. The wide pH endurance from 4.0 to 13.0 and the broad types of detection analytes including nucleic acids, proteins, and biological complexes highlight the great application potential of Tween 20-coated solid-state nanopores.