Lydia L. Sohn

Mesoscopic electron transport

Preface L.P. Kouwenhoven, et al. Introduction to Mesoscopic Electron Transport L.P. Kouwenhoven, et al. Geometric Phases in Mesoscopic Systems - From the Aharonov-Bohm Effect to Berry Phases A. Stern. Delocalization, Inelastic Scattering and Transport Due to Interactions Y. Imry. Electron Transport in Quantum Dots L.P. Kouwenhoven, et al. Magnetotunneling Spectroscopy: Studying Self-Organized Quantum Dots and Quantum Chaology L. Eaves. Shot Noise in Mesoscopic Systems M.J.M. de Jong, C.W.J. Beenakker. Admittance and Nonlinear Transport in Quantum Wires, Point Contacts, and Resonant Tunneling Barriers M. Buttiker, T. Chirsten. Transport Theory of Interacting Quantum Dots H. Schoeller. Transport in a One-Dimensional Luttinger Liquid M.P.A. Fisher, L.I. Glazman. The Proximity Effect in Mesoscopic Diffusive Conductors D. Esteve, et al. Mesoscopic Effects in Superconductivity R. Fazio, G. Schoen. Ultrasmall Superconductors D.C. Ralph, et al. The Superconducting Proximity Effect in Semiconductor-Superconductor Systems: Ballistic Transport, Low Dimensionality and Sample Specific Properties B.J. van Wees, H. Takayanagi. Scanning Probe Microscopes and Their Applications L.L. Soh, et al. Quantum Point Contacts Between Metals J.M. van Ruitenbeek. Conductance Quantization in Metallic Nanowires N. Garcia, et al. Quantum Optics Y. Yamamoto. Topics in Quantum Computers D.P. DiVincenzo.

Direct detection of antibody–antigen binding using an on-chip artificial pore

We demonstrate a rapid and highly sensitive all-electronic technique based on the resistive pulse method of particle sizing with a pore to detect the binding of unlabeled antibodies to the surface of latex colloids. Here, we use an on-chip pore to sense colloids derivatized with streptavidin and measure accurately their diameter increase on specific binding to several different types of antibodies. We show the sensitivity of this technique to the concentration of free antibody and that it can be used to perform immunoassays in both inhibition and sandwich configurations. Overall, our technique does not require labeling of the reactants and is performed rapidly by using very little solution, and the pore itself is fabricated quickly and inexpensively by using soft lithography. Finally, because this method relies only on the volume of bound ligand, it can be generally applied to detecting a wide range of ligand–receptor binding reactions.

Quantitative sensing of nanoscale colloids using a microchip Coulter counter

We have fabricated a microchip Coulter counter on a quartz substrate, and have used it to detect individual nanoscale colloidal particles with a sensitivity proportional to each particles size. We demonstrate the ability of this device to sense colloids as small as 87 nm diameter, and to distinguish between colloids whose diameters differ by less than 10%. Further reductions in the pore size, easily done with current nanofabrication techniques, make our device applicable to measuring biological macromolecules, such as DNA and proteins.

Dielectric spectroscopy for bioanalysis: From 40 Hz to 26.5 GHz in a microfabricated wave guide

We report developing coplanar waveguide devices which can perform dielectric spectroscopy on biological samples within a microfluidic channel or well. Since coupling to the fluid sample is capacitive, no surface functionalization or chemical sample preparation are required. Data on cell suspensions and solutions of proteins and nucleic acids spanning the frequency range from 40 Hz to 26.5 GHz are presented. Low-frequency data are well explained using a simple dispersion model. At microwave frequencies, the devices yield reproducible and distinguishable spectral responses for hemoglobin solution and live E. coli.

Personalized exposure assessment : Promising approaches for human environmental health research

New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a “toolbox” of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure–disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs.

Fabrication of nanostructures using atomic‐force‐microscope‐based lithography

We describe a novel technique for fabricating metallic nanostructures on an arbitrary substrate using an atomic force microscope (AFM). An AFM is used to plow a pattern through the top of two resist layers spun onto a substrate. The resist is then developed to create a mask through which material can be deposited. By changing the applied force, the top resist‐layer thickness, or the development time, the linewidth can be varied. Continuous metallic wires ∼500 A×400 A×15 μm have been fabricated on bare substrates and between contact pads.

Single-molecule sequence detection via microfluidic planar extensional flow at a stagnation point

We demonstrate the use of a microfluidic stagnation point flow to trap and extend single molecules of double-stranded (ds) genomic DNA for detection of target sequences along the DNA backbone. Mutant EcoRI-based fluorescent markers are bound sequence-specifically to fluorescently labeled ds lambda-DNA. The marker-DNA complexes are introduced into a microfluidic cross slot consisting of flow channels that intersect at ninety degrees. Buffered solution containing the marker-DNA complexes flows in one channel of the cross slot, pure buffer flows in the opposing channel at the same flow rate, and fluid exits the two channels at ninety degrees from the inlet channels. This creates a stagnation point at the center of a planar extensional flow, where marker-DNA complexes may be trapped and elongated along the outflow axis. The degree of elongation can be controlled using the flow strength (i.e., a non-dimensional flow rate) in the device. Both the DNA backbone and the markers bound along the stretched DNA are observed directly using fluorescence microscopy, and the location of the markers along the DNA backbone is measured. We find that our method permits detection of each of the five expected target site positions to within 1.5 kb with standard deviations of <1.5 kb. We compare the methods precision and accuracy at molecular extensions of 68% and 88% of the contour length to binding distributions from similar data obtained via molecular combing. We also provide evidence that increased mixing of the sample during binding of the marker to the DNA improves binding to internal target sequences of dsDNA, presumably by extending the DNA and making the internal binding sites more accessible.

Ordered stretching of single molecules of deoxyribose nucleic acid between microfabricated polystyrene lines

A technique for creating arrays of parallel, stretched single molecules of deoxyribose nucleic acid (DNA) on an arbitrary substrate for high-resolution scanning-probe imaging is discussed. The technique consists of lithographically patterning polystyrene lines on a substrate which then provide attachment sites for the ends of individual DNA molecules. Molecular combing is performed to stretch DNA from one polystyrene line to the other. Scanning-tunneling and atomic-force microscope images of single molecules of bacteriophage-lambda DNA are shown to demonstrate the advantages of this technique. Several applications, from high-resolution genomics to molecular electronics, are discussed.

Nanotechnology: A quantum leap for electronics

If electronic devices are to be shrunk from the current micrometre length scale all the way down to the single-atom or molecule scale, we need to know how such tiny constructions will behave. Electrical measurements have now been made on the smallest electronic components possible — single metal atoms. They show that the conductivity depends on the number of valence electrons available in each atom.

Fluorescent marker for direct detection of specific dsDNA sequences

We have created a fluorescent marker using a mutant EcoRI restriction endonuclease (K249C) that enables prolonged, direct visualization of specific sequences on genomic lengths of double-stranded (ds) DNA. The marker consists of a biotinylated enzyme, attached through the biotin-avidin interaction to a fluorescent nanosphere. Control over biotin position with respect to the enzymes binding pocket is achieved by biotinylating the mutant EcoRI at the mutation site. Biotinylated enzyme is incubated with dsDNA and NeutrAvidin-coated, fluorescent nanospheres under conditions that allow enzyme binding but prevent cleavage. Marker-laden DNA is then fluorescently stained and stretched on polylysine-coated glass slides so that the positions of the bound markers along individual DNA molecules can be measured. We demonstrate the markers ability to bind specifically to its target sequence using both bulk gel-shift assays and single-molecule methods.