Grégory F. Schneider

DNA translocation through graphene nanopores.

Nanopores--nanosized holes that can transport ions and molecules--are very promising devices for genomic screening, in particular DNA sequencing. Solid-state nanopores currently suffer from the drawback, however, that the channel constituting the pore is long, approximately 100 times the distance between two bases in a DNA molecule (0.5 nm for single-stranded DNA). This paper provides proof of concept that it is possible to realize and use ultrathin nanopores fabricated in graphene monolayers for single-molecule DNA translocation. The pores are obtained by placing a graphene flake over a microsize hole in a silicon nitride membrane and drilling a nanosize hole in the graphene using an electron beam. As individual DNA molecules translocate through the pore, characteristic temporary conductance changes are observed in the ionic current through the nanopore, setting the stage for future single-molecule genomic screening devices.

DNA sequencing with nanopores

Major hurdles in the quest to sequence DNA with biological nanopores have now been overcome.

Atomic-scale electron-beam sculpting of near-defect-free graphene nanostructures.

In order to harvest the many promising properties of graphene in (electronic) applications, a technique is required to cut, shape, or sculpt the material on the nanoscale without inducing damage to its atomic structure, as this drastically influences the electronic properties of the nanostructure. Here, we reveal a temperature-dependent self-repair mechanism that allows near-damage-free atomic-scale sculpting of graphene using a focused electron beam. We demonstrate that by sculpting at temperatures above 600 °C, an intrinsic self-repair mechanism keeps the graphene in a single-crystalline state during cutting, even though the electron beam induces considerable damage. Self-repair is mediated by mobile carbon ad-atoms that constantly repair the defects caused by the electron beam. Our technique allows reproducible fabrication and simultaneous imaging of single-crystalline free-standing nanoribbons, nanotubes, nanopores, and single carbon chains.

Functional core/shell nanoparticles via layer-by-layer assembly. investigation of the experimental parameters for controlling particle aggregation and for enhancing dispersion stability.

Gold nanoparticles (AuNPs) with a size of 13.5 nm were synthesized using well-established methods as described earlier by Turkevich (Turkevich, J.; Stevenson, P. C.; Hillier, J. Discuss. Faraday Soc. 1961, 11, 55-75) and Frens (Frens, G. Nature (London), Phys. Sci. 1973, 241, 20-22) using citrate as the reducing agent. It has already been reported that such AuNPs can easily be coated with polymeric shells using electrostatic layer-by-layer assembly of certain polyelectrolytes. Here, we show which parameters, namely, the polyelectrolyte concentration, the contour length of the polyelectrolyte chain, and the ionic strength, are preventing bridging flocculation during polyelectrolyte adsorption and enhancing the stability of the colloidal dispersion. For the preparation of individually coated particles with high yield, we identified optimal conditions such as the degree of polymerization of the polyelectrolytes used, the polyelectrolyte concentration, the nanoparticle concentration, and the concentration of added NaCl during multilayer buildup. Surprisingly, such functional nanoparticles are obtained with highest yield at a moderate excess of polyions. In contrast to expectations, a larger excess of polyions leads again to slight destabilization of the dispersion. The present findings raise our confidence to establish layer-by-layer deposition as a general method for functionalizing even different nanoparticles using a single method.

Multifunctional Cytotoxic Stealth Nanoparticles. A Model Approach with Potential for Cancer Therapy

Here we report on a highly versatile nanoparticle-based core/shell drug delivery system consisting of cytotoxic stealth carrier particles. Their multifunctional shells, mandatory for addressing different diagnostic/treatment requirements, are constructed using a single assembly process in which various different functionalities are incorporated in a modular fashion. More specifically, we discuss a robust electrostatic and covalent layer-by-layer (LBL) assembly strategy as engineering approach toward nanoparticles with multilayer shells that combine all of the following properties: (i) a small size distribution of the nanoparticle carrier, (ii) a high stability in physiological media, (iii) attachment of a pro-drug in covalent form and thus a low toxicity of the carrier system, (iv) the triggered release and activation of the drug only after endocytosis and enzymatic cleavage, and (v) stealthiness and thus protection against uptake by macrophages. The fact that we employ small nanoparticles as carriers is predicted to enhance the accumulation of active drug in the tumor tissue (i.e., enhanced permeability and retention of tumor tissues, EPR). To establish this system as a proof of concept, we use the smallest nanoparticles within the interesting size range of about 25-100 nm for EPR targeting since these are the most difficult to functionalize and because they possess the highest surface area. On the basis of gold nanoparticle cores, our system allows for precise control of particle size and size distribution and also for easy monitoring of the dispersion stability by the naked eye.

Wedging Transfer of Nanostructures

We report a versatile water-based method for transferring nanostructures onto surfaces of various shapes and compositions. The transfer occurs through the intercalation of a layer of water between a hydrophilic substrate and a hydrophobic nanostructure (for example, graphene flakes, carbon nanotubes, metallic nanostructures, quantum dots, etc.) locked within a hydrophobic polymer thin film. As a result, the film entrapping the nanostructure is lifted off and floats at the air-water interface. The nanostructure can subsequently be deposited onto a target substrate by the removal of the water and the dissolution of the polymeric film. We show examples where graphene flakes and patterned metallic nanostructures are precisely transferred onto a specific location on a variety of patterned substrates, even on top of curved objects such as microspheres. The method is simple to use, fast, and does not require advanced equipment.

Tailoring the hydrophobicity of graphene for its use as nanopores for DNA translocation

Graphene nanopores are potential successors to biological and silicon-based nanopores. For sensing applications, it is however crucial to understand and block the strong nonspecific hydrophobic interactions between DNA and graphene. Here we demonstrate a novel scheme to prevent DNA-graphene interactions, based on a tailored self-assembled monolayer. For bare graphene, we encounter a paradox: whereas contaminated graphene nanopores facilitated DNA translocation well, clean crystalline graphene pores very quickly exhibit clogging of the pore. We attribute this to strong interactions between DNA nucleotides and graphene, yielding sticking and irreversible pore closure. We develop a general strategy to noncovalently tailor the hydrophobic surface of graphene by designing a dedicated self-assembled monolayer of pyrene ethylene glycol, which renders the surface hydrophilic. We demonstrate that this prevents DNA to adsorb on graphene and show that single-stranded DNA can now be detected in graphene nanopores with excellent nanopore durability and reproducibility.

Controllable Atomic Scale Patterning of Freestanding Monolayer Graphene at Elevated Temperature

We show that by operating a scanning transmission electron microscope (STEM) with a 0.1 nm 300 kV electron beam, one can sculpt free-standing monolayer graphene with close-to-atomic precision at 600 °C. The same electron beam that is used for destructive sculpting can be used to image the sculpted monolayer graphene nondestructively. For imaging, a scanning dwell time is used that is about 1000 times shorter than for the sculpting. This approach allows for instantaneous switching between sculpting and imaging and thus fine-tuning the shape of the sculpted lattice. Furthermore, the sculpting process can be automated using a script. In this way, free-standing monolayer graphene can be controllably sculpted into patterns that are predefined in position, size, and orientation while maintaining defect-free crystallinity of the adjacent lattice. The sculpting and imaging processes can be fully computer-controlled to fabricate complex assemblies of ribbons or other shapes.

Controlled, Reversible, and Nondestructive Generation of Uniaxial Extreme Strains (>10%) in Graphene

Theoretical calculations have predicted that extreme strains (>10%) in graphene would result in novel applications. However, up to now the highest reported strain reached ∼1.3%. Here, we demonstrate uniaxial strains >10% by pulling graphene using a tensile-MEMS. To prevent it from slipping away it was locally clamped with epoxy using a femtopipette. The results were analyzed using Raman spectroscopy and optical tracking. Furthermore, analysis proved the process to be reversible and nondestructive for the graphene.

1/f noise in graphene nanopores

Graphene nanopores are receiving great attention due to their atomically thin membranes and intrinsic electrical properties that appear greatly beneficial for biosensing and DNA sequencing. Here, we present an extensive study of the low-frequency 1/f noise in the ionic current through graphene nanopores and compare it to noise levels in silicon nitride pore currents. We find that the 1/f noise magnitude is very high for graphene nanopores: typically two orders of magnitude higher than for silicon nitride pores. This is a drawback as it significantly lowers the signal-to-noise ratio in DNA translocation experiments. We evaluate possible explanations for these exceptionally high noise levels in graphene pores. From examining the noise for pores of different diameters and at various salt concentrations, we find that in contrast to silicon nitride pores, the 1/f noise in graphene pores does not follow Hooges relation. In addition, from studying the dependence on the buffer pH, we show that the increased noise cannot be explained by charge fluctuations of chemical groups on the pore rim. Finally, we compare single and bilayer graphene to few-layer and multi-layer graphene and boron nitride (h-BN), and we find that the noise reduces with layer thickness for both materials, which suggests that mechanical fluctuations may be the underlying cause of the high 1/f noise levels in monolayer graphene nanopore devices.