Controllable Fabrication of Sub-10 nm Graphene Nanopores via Helium Ion Microscopy and DNA Detection.

Solid-state nanopores have become a prominent tool in the field of single-molecule detection. Conventional solid-state nanopores are thick, which affects the spatial resolution of the detection results. Graphene is the thinnest 2D material and has the highest spatial detection resolution. In this study, a graphene membrane chip was fabricated by combining a MEMS process with a 2D material wet transfer process. Raman spectroscopy was used to assess the quality of graphene after the transfer. The mechanism behind the influence of the processing dose and residence time of the helium ion beam on the processed pore size was investigated. Subsequently, graphene nanopores with diameters less than 10 nm were fabricated via helium ion microscopy. DNA was detected using a 5.8 nm graphene nanopore chip, and the appearance of double-peak signals on the surface of 20 mer DNA was successfully detected. These results serve as a valuable reference for nanopore fabrication using 2D material for DNA analysis.

Novel Microneedle Patch-Based Surface-Enhanced Raman Spectroscopy Sensor for the Detection of Pesticide Residues.

Pesticide residues are a global threat to human health, and conventional sensors fail to simultaneously detect pesticide residues on the surface and inside agricultural products. In this work, we present a new microneedle (MN) patch-based surface-enhanced Raman spectroscopy (SERS) sensor. The needles and the basement of MNs can simultaneously detect pesticide residues on the surface and inside agricultural products. The Ag nanoparticles and sodium hyaluronate/poly(vinyl alcohol) (HA/PVA) hydrogel used in this MN patch-based sensor efficiently amplify the Raman signals of the pesticide residues. In addition, the HA/PVA hydrogel can effectively and quickly collect the residues, allowing this sensor to detect pesticide residues more conveniently. Furthermore, the stepped structure of the MNs increases the sensor's surface area. Experimental results show that the sensor can detect thiram and thiabendazole (TBZ) pesticide residues with detection limits of 10-7 and 10-8 M, respectively. The detection process is minimally invasive and not harmful to agricultural products. The application of this MN patch-based SERS sensor can be extended to the safety and health monitoring of other plants and animals.

Controllable Shrinking Fabrication of Solid-State Nanopores.

Nanopores have attracted widespread attention in DNA sequencing and protein or biomarker detection, owning to the single-molecule-scale detection accuracy. Despite the most use of naturally biological nanopores before, solid-state nanopores are widely developed with strong robustness, controllable sizes and geometries, a wide range of materials available, as well as flexible manufacturing. Therefore, various techniques typically based on focused ion beam or electron beam have been explored to drill nanopores directly on free-standing nanofilms. To further reduce and sculpt the pore size and shape for nano or sub-nano space-time sensing precision, various controllable shrinking technologies have been employed. Correspondingly, high-energy-beam-induced contraction with direct visual feedback represents the most widely used. The ability to change the pore diameter was attributed to surface tension induced original material migration into the nanopore center or new material deposition on the nanopore surface. This paper reviews typical solid-state nanopore shrinkage technologies, based on the careful summary of their principles and characteristics in particularly size and morphology changes. Furthermore, the advantages and disadvantages of different methods have also been compared completely. Finally, this review concludes with an optimistic outlook on the future of solid-state nanopores.

Study on cutting force of reaming porcine bone and substitute bone.

Accurate mechanical feedback systems are critical to the successful implementation of virtual and robotic surgical assistant systems. Experimental measurements of reaming force could further our understanding of the cancellous bone reaming process during hip arthroplasty to help develop surgical simulators with realistic force effects and improve the protection mechanism of robot-assisted surgical systems. In this study, reaming experiments with natural bone (porcine femur) and a bone substitute (polyurethane blocks) were performed on a CNC lathe. This paper proposes using the maximum reaming force of the steady reaming stage to represent the force characteristic. The reaming force is biased to one side in the overlap direction and the maximum reaming force will vary when the reamer is not coincident with the long axis of the bone. The diameter of the reamer has the greatest influence on reaming force, which clearly increases with increasing reamer diameter. During operation, a medium rotation speed and high feed speed can reduce the reaming force. After cutting, the morphology of the cut surface is not flat, but arc-shaped, which will have a significant impact on implantation of the femoral prosthesis. In in vitro cutting experiments, polyurethane blocks can be used as a substitute for cancellous bone.

Chitosan/zinc nitrate microneedles for bacterial biofilm eradication.

Chronic wounds are greatly health threatening owing to the increasing morbidity, and bacterial biofilm is a major cause of chronic wounds. The critical for bacterial biofilm eradication is overcome the barrier of extracellular polymeric substances (EPS) produced by the bacteria, and promote the diffusion of drugs within the biofilm. In this article, composite microneedles (MNs) of chitosan and zinc nitrate (CS-Zn[II] MNs) were investigated to eradicate bacterial biofilm. The CS-Zn(II) MNs combined the structure characteristic of MNs with the antibacterial properties of CS and Zn2+ . The MNs can pierce the EPS due to the needle-like structure, and can transport directly the CS and Zn2+ into the bacterial biofilm. The needle-like structure of MNs also increased the contact area between drug carrier and bacterial biofilm nearly 14-23% comparing with membrane without needle-like structure, and facilitated the diffusion of drugs. What is more, the synergistic effect of CS and Zn2+ make the CS-Zn(II) MNs obtain excellent antibiofilm properties. Counting the colony forming units and bacterial live/dead staining tests confirmed the fascinating antibacterial abilities (up to 100% inhibition) and biofilm eradication properties, respectively, of the CS-Zn(II) MNs. The inhibition zone test shown that the antibiofilm effect of MNs was superior to membrane and the antibiofilm effect of MNs was become increasingly obvious along with the increase of the treatment time. Besides, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays proved that the CS-Zn(II) MNs possess brilliant cytocompatibility. These results indicate that the CS-Zn(II) MNs are promising method for bacterial biofilm eradication.

Modulation of Ionic Current Rectification in Ultrashort Conical Nanopores.

Nanopores that exhibit ionic current rectification (ICR) behave like diodes such that they transport ions more efficiently in one direction than in the other. Conical nanopores have been shown to rectify ionic current, but only those with at least 500 nm in length exhibit significant ICR. Here, through the finite element method, we show how ICR of conical nanopores with lengths below 200 nm can be tuned by controlling individual charged surfaces, that is, the inner pore surface (surfaceinner) and exterior pore surfaces on the tip and base side (surfacetip and surfacebase). The charged surfaceinner and surfacetip can induce obvious ICR individually, while the effects of the charged surfacebase on ICR can be ignored. The fully charged surfaceinner alone could render the nanopore counterion-selective and induces significant ion concentration polarization in the tip region, which causes reverse ICR compared to nanopores with all surfaces charged. In addition, the direction and degree of rectification can be further tuned by the depth of the charged surfaceinner. When considering the exterior membrane surface only, the charged surfacetip causes intrapore ionic enrichment and depletion under opposite biases, which results in significant ICR. Its effective region is within ∼40 nm beyond the tip orifice. We also found that individual charged parts of the pore system contributed to ICR in an additive way because of the additive effect on the ion concentration regulation along the pore axis. With various combinations of fully/partially charged surfaceinner and surfacetip, diverse ICR ratios from ∼2 to ∼170 can be achieved. Our findings shed light on the mechanism of ICR in ultrashort conical nanopores and provide a useful guide to the design and modification of ultrashort conical nanopores in ionic circuits and nanofluidic sensors.

Value of interim 18F-FDG PET/CT for predicting progression-free survival in stage â ¢B/IV EGFR-mutant non-small-cell lung cancer patients with EGFR-TKI therapy.

OBJECTIVES: We retrospectively investigated the prognostic value of FDG-PET performed for patients with Stage ⅢB/IV EGFR-mutant non-small-cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: A total of 78 patients newly diagnosed with Stage ⅢB/IV EGFR-mutant NSCLC who received baseline and interim PET/CT examination and were treated with EGFR-TKI therapy were included. Interim PET was performed after 4-6 weeks of treatment. Cox proportional hazards regression analysis was used to assess the association between quantitative 18F-FDG PET/CT parameters, other clinicopathological factors and progression-free survival (PFS), non-durable clinical benefit (non-DCB). Five interim PET variables were analyzed in this study in the prediction of non-DCB. RESULTS: The one-year and two-year progression-free survival rates of the patients were 33.9% (28.6-39.2%) and 20.7% (16.1-25.3%), respectively. Multivariable analysis indicated that interim PET relevant factors ΔSUVmax (p = 0.002, p = 0.014) and ΔSUVmean (p = 0.000, p = 0.030) were independent risk factors for predicting the PFS or non-DCB of patients receiving EGFR-TKI treatment. The optimal cutoff values of the parameters in the tumor survival analyses were 56.74% for ΔSUVmax (p = 0.002) and 36.48% for ΔSUVmean (p = 0.001). ΔSUVmax had the highest diagnostic value in the prediction of non-DCB. The one-year progression-free survival rates (95% confidence intervals) of patients with ΔSUVmax ≥ 56.74% and ΔSUVmax <56.74% were 59.5% (44.2-74.8%) and 5.7% (0.0-13.3%), respectively (p = 0.000). CONCLUSION: An early PET scan after 4-6 weeks can effectively predict the PFS and non-DCB of patients with Stage ⅢB/IV EGFR-mutant NSCLC receiving EGFR-TKI therapy.

Prewetting Polypropylene-Wood Pulp Fiber Composite Nonwoven Fabric for Oil-Water Separation.

The removal of oil from the water surface is vital to protect the environment and living organisms against the threats posed by industrial oily wastewater and offshore oil spills. High cost, low efficiency, and environmental pollution limit the widespread use of the commercial methods of oil-water separation. In this study, the prewetting polypropylene-wood pulp fiber composite nonwoven fabric (PWNF) has been used in the gravity-driven separation of the oil-water mixture. The prewetting PWNF displayed superior underwater oleophobic properties, and the underwater kerosene contact angle was 137.65° ± 4.27°. The oil-water interfacial tension in the microchannels among the PWNF fibers prevented the oil from passing through the microchannels; however, it allowed the passage of water. The PWNF membrane maintained an excellent oil-water separation performance after repeated separation and long-term soaking cycles. The separation membrane maintained 75% and 50% of the initial separation performance after 40 repeat cycles and water immersion for more than 20 days, respectively. The separation rate of the PWNF membrane was also investigated as a function of salt solution concentration, temperature, and pH. Meanwhile, the influences of prewetting time, prewetting temperature, and different dyeing condition of the mixture on the separation rate were clarified. The destruction of the oil-water contact interface was suggested as the main failure mode of the developed PWNF separation membrane. The maximum kerosene height that the PWNF separation membrane could sustain was 800 mm. The obtained results confirmed that the PWNF separation membrane exhibited the high potential of widespread use in various environments for achieving efficient and stable separations, especially for the oily wastewater treatment.

Controlling DNA Translocation Through Solid-state Nanopores.

Compared with the status of bio-nanopores, there are still several challenges that need to be overcome before solid-state nanopores can be applied in commercial DNA sequencing. Low spatial and low temporal resolution are the two major challenges. Owing to restrictions on nanopore length and the solid-state nanopores' surface properties, there is still room for improving the spatial resolution. Meanwhile, DNA translocation is too fast under an electrical force, which results in the acquisition of few valid data points. The temporal resolution of solid-state nanopores could thus be enhanced if the DNA translocation speed is well controlled. In this mini-review, we briefly summarize the methods of improving spatial resolution and concentrate on controllable methods to promote the resolution of nanopore detection. In addition, we provide a perspective on the development of DNA sequencing by nanopores.

Review: Porous Metal Filters and Membranes for Oil-Water Separation.

In recent years, oil-water separation has been widely researched to reduce the influences of industrial wastewater and offshore oil spills. A filter membrane with special wettability can achieve the separation because of its opposite wettability for water phase and oil phase. In the field of filter membrane with special wettability, porous metal filter membranes have been much investigated because of the associated high efficiency, portability, high plasticity, high thermal stability, and low cost. This article provides an overview of the research progress of the porous metal filter membrane fabrication and discusses the future developments in this field.

Rapid fabrication of solid-state nanopores with high reproducibility over a large area using a helium ion microscope.

The fabrication of solid-state nanopores in an insulating membrane has attracted much attention for biomolecule analysis such as DNA sequencing and detection in recent years. For practical applications and device integration, the challenges include precise size control for sub 10 nm nanopores, excellent repeatability and rapid fabrication over a large area to reduce the cost for mass production. A helium ion beam could provide an effective fabrication approach to produce such solid-state nanopores. It is easy to control the nanopore size and reach sub 10 nm pore size with a simple change in the milling time with an appropriate ion beam current. Here we report new results in a set of experiments demonstrating that with a small range of stage automatized motions and equal mill times one can obtain good fabrication reproducibility in nanopore sizes (<10% variation in size). The automation in the stage motion and milling time opens a door for the rapid mass production of nanopore chips over a wafer size of several inches.

Solid-State Nanopore.

Solid-state nanopore has captured the attention of many researchers due to its characteristic of nanoscale. Now, different fabrication methods have been reported, which can be summarized into two broad categories: "top-down" etching technology and "bottom-up" shrinkage technology. Ion track etching method, mask etching method chemical solution etching method, and high-energy particle etching and shrinkage method are exhibited in this report. Besides, we also discussed applications of solid-state nanopore fabrication technology in DNA sequencing, protein detection, and energy conversion.

Amorphous Silicon Nanowires Grown on Silicon Oxide Film by Annealing.

In this paper, amorphous silicon nanowires (α-SiNWs) were synthesized on (100) Si substrate with silicon oxide film by Cu catalyst-driven solid-liquid-solid mechanism (SLS) during annealing process (1080 °C for 30 min under Ar/H2 atmosphere). Micro size Cu pattern fabrication decided whether α-SiNWs can grow or not. Meanwhile, those micro size Cu patterns also controlled the position and density of wires. During the annealing process, Cu pattern reacted with SiO2 to form Cu silicide. More important, a diffusion channel was opened for Si atoms to synthesis α-SiNWs. What is more, the size of α-SiNWs was simply controlled by the annealing time. The length of wire was increased with annealing time. However, the diameter showed the opposite tendency. The room temperature resistivity of the nanowire was about 2.1 × 103 Ω·cm (84 nm diameter and 21 µm length). This simple fabrication method makes application of α-SiNWs become possible.

Ionic current modulation from DNA translocation through nanopores under high ionic strength and concentration gradients.

Ion transport through nanopores is an important process in nature and has important engineering applications. To date, most studies of nanopore ion transport have been carried out with electrolytes of relatively low concentrations. In this paper, we report on ionic current modulation from the translocation of dsDNA through a nanopore under high ionic strength and with an electrolyte concentration gradient across the nanopore. Results show that in this case, DNA translocation can induce either negative or positive ionic current modulation, even though usually only downward peaks are expected under this high ion concentration. Through a series of experiments and numerical simulations with nanopores of different diameters and concentration gradients, it is found that the positive pulse is due to extra ions outside the electric double layer of the DNA that are brought into the nanopore by the enhanced electroosmotic flow (EOF) with the negatively charged DNA inside the nanopore.

Detection of short single-strand DNA homopolymers with ultrathin Si3N4 nanopores.

A series of nanopores with diameters ranging from 2.5 to 63 nm are fabricated on a reduced Si3N4 membrane by focused ion beam and high energy electron beam. Through measuring the blocked ionic currents for DNA strands threading linearly through those solid-state nanopores, it is found that the blockade ionic current is proportional to the square of the hydrodynamic diameter of the DNA strand. With the nanopore diameter reduced to be comparable with that of DNA strands, the hydrodynamic diameter of the DNA becomes smaller, which is attributed to the size confinement effects. The duration time for the linear DNA translocation events increases monotonically with the nanopore length. By comparing the spatial configurations of DNA strands through nanopores with different diameters, it is found that the nanopore with large diameter has enough space to allow the DNA strand to translocate through with complex conformation. With the decrease of the nanopore diameter, the folded part of the DNA is prone to be straightened by the nanopore, which leads to the increase in the occurrence frequency of the linear DNA translocation events. Reducing the diameter of the nanopore to 2.5 nm allows the detection and discrimination of three nucleotide "G" and three nucleotide "T" homopolymer DNA strands based on differences in their physical dimensions.