Adam R. Hall

Hybrid pore formation by directed insertion of α-haemolysin into solid-state nanopores

Most experiments on nanopores have concentrated on the pore-forming protein α-haemolysin (αHL) and on artificial pores in solid-state membranes. While biological pores offer an atomically precise structure and the potential for genetic engineering, solid-state nanopores offer durability, size and shape control, and are also better suited for integration into wafer-scale devices. However, each system has significant limitations: αHL is difficult to integrate because it relies on delicate lipid bilayers for mechanical support, and the fabrication of solid-state nanopores with precise dimensions remains challenging. Here we show that these limitations may be overcome by inserting a single αHL pore into a solid-state nanopore. A double-stranded DNA attached to the protein pore is threaded into a solid-state nanopore by electrophoretic translocation. Protein insertion is observed in 30-40% of our attempts, and translocation of single-stranded DNA demonstrates that the hybrid nanopore remains functional. The hybrid structure offers a platform to create wafer-scale device arrays for genomic analysis, including sequencing.

Direct and Transmission Milling of Suspended Silicon Nitride Membranes With a Focused Helium Ion Beam

Helium ion milling of suspended silicon nitride thin films is explored. Milled squares patterned by scanning helium ion microscope are subsequently investigated by atomic force microscopy and the relation between ion dose and milling depth is measured for both the direct (side of ion incidence) and transmission (side opposite to ion incidence) regimes. We find that direct-milling depth varies linearly with beam dose while transmission-milling depth varies with the square of the beam dose, resulting in a straightforward method of controlling local film thickness.

Translocation of Single-Wall Carbon Nanotubes Through Solid-State Nanopores

We report the translocation of individual single-wall carbon nanotubes (SWNTs) through solid-state nanopores. Single-strand DNA oligomers are used to both disperse the SWNTs in aqueous solution and to provide them with a net charge, allowing them to be driven through the nanopores by an applied electric field. The resulting temporary interruptions in the measured nanopore conductance provide quantitative information on the diameter and length of the translocated nanotubes at a single-molecule level. Furthermore, we demonstrate that the technique can be utilized to monitor bundling of SWNT in solution by using complementary nucleotides to induce tube-tube agglomeration.

Highly controllable near-surface swimming of magnetic Janus nanorods: application to payload capture and manipulation

Directed manipulation of nanomaterials has significant implications in the field of nanorobotics, nanobiotechnology, microfluidics and directed assembly. With the goal of highly controllable nanomaterial manipulation in mind, we present a technique for the near-surface manoeuvering of magnetic nanorod swimmers and its application to controlled micromanipulation. We fabricate magnetic Janus nanorods and show that the magnetic rotation of these nanorods near a floor results in predictable translational motion. The nanorod plane of rotation is nearly parallel to the floor, the angle between rod tilt and floor being expressed by θ, where 0° < θ < 20°. Orthogonal magnetic fields control in-plane motion arbitrarily. Our model for translation incorporates symmetry breaking through increased drag at the no-slip surface boundary. Using this method we demonstrate considerable rod steerability. Additionally, we approach, capture, and manipulate a polystyrene microbead as proof of principle. We attach Janus nanorods to the surfaces of cells and utilize these rods to manipulate individual cells, proving the ability to manoeuver payloads with a wide range of sizes.

Measuring Single-Wall Carbon Nanotubes with Solid-State Nanopores

Solid-state nanopores have been used widely to study biological polymers. Here, we expand the technique to analyze single-wall carbon nanotubes. By wrapping them in an amphiphilic layer, individual tubes can be translocated electrically through a nanopore, resulting in temporary interruptions in the trans-pore current reminiscent of measurements on DNA, RNA, and proteins. The technique may find use in discriminating nanotubes by size and thus electrical structure, facilitating their inclusion in electrical devices.

Solid-State Nanopores: From Fabrication to Application

There are relatively few technologies for measurement at the single-molecule scale. Fluorescent imaging, for example, can be used to directly visualize molecules and their interactions, but diffraction limitations and labeling requirements may push the system from its native state. Although recent advances in super-resolution imaging have been able to break this resolution barrier, important challenges remain. Atomic force microscopy (AFM) is capable of imaging molecules at high resolution and at high speed. However, AFM imaging is a surface technique, requiring sample preparation and some immobilization. Other technologies such as optical tweezers and magnetic tweezers are capable of molecular manipulation and spectroscopy to great effect but require a significant apparatus and have limited inherent analytical capabilities.

Molecular Detection and Force Spectroscopy in Solid-State Nanopores with Integrated Optical Tweezers

We describe how individual biopolymer molecules can be captured, detected and manipulated inside a solid-state nanopore using an integrated optical tweezer system. The combination of nanopore and tweezer technologies offers measurement capabilities like size and length discrimination similar to translocation experiments along with arbitrary position control and the ability to perform direct force spectroscopy. We discuss the experimental setup and measurements on two different types of molecules (bare DNA and protein-coated DNA), and we describe a model for the force on a charged molecule in a nanopore.