Carmichael, Stephen W.

Abstract The transmission electron microscope (TEM) was invented in the 1930's, and developments in specimen preparation in the 1950's led to its widespread use as a tool to study structure in biologic systems. Similar in principle to the light microscope, but utilizing a much shorter wavelength for better resolution, the TEM has the image-forming beam pass through the specimen. This results in a two-dimensional image which can be difficult to interpret because features from different depths of the three dimensional specimen are superimposed. Traditionally this was dealt with by cutting sections of plastic-embedded specimens so thin (in the 40 to SO nanometer range) that they effectively had only two dimensions. To allow biologists to examine structures in three dimensions, serial sections are stacked and structures reconstructed. Even though computers have made reconstruction easier, the reality is that resolution in the depth dimension is limited by the section thickness. The technique of electron tomography is emerging as a way to overcome this limitation.

Abstract The use of barcodes on products, combined with the computer technology to read and track the subsequent data, has revolutionized inventory control in our society. Barcodes are commonly seen on items as large as automobiles and as small as pieces of candy. But if you need to track a large number of items that are microscopic in size, such as biologically relevant molecules (think genomics, proteomics, metabolomics, etc), then you need very small barcodes. Sufficiently small rods that can be marked as barcodes have been developed by Sheila Nicewarner-Peña, Griffith Freeman, Brian Reiss, Lin He, David Peña, Ian Walton, Remy Cromer, Christine Keating, and Michael Natan.

Abstract Many animals can walk up vertical surfaces or even along the ceiling. And many studies have examined how flies accomplish this impressive task. Whereas these studies have revealed the anatomy of the contact area and there have been many assumptions about the fly attachment mechanism, the main elements that contribute to the attachment force were unknown. However, Mattias Langer, J. Peter Ruppersberg, and Stanislav Gorb have successfully demonstrated that the fluid secreted from the fly's feet is a critical factor in attaching the fly to the ceiling.

Abstract Laser tweezers take advantage of the forces around converging beams of light to exert slight pressures on small structures. Whereas these optical devices have allowed for some elegant studies of cell biology, wouldn't it be great if we had mechanical tweezers that offered even better manipulation? In a recent paper, Philip Kim and Charles Lieber demonstrated a fabulous device they called “nanotweezers.“ Logically, they used nanotubes as the key structural component for their nanWith nanotubes serving as the tines of the tweezers, Kim and Lieber devised a very clever arrangement for the hub. They took a standard glass tube, 1 mm in diameter, and pulled it to a tapered end of about 100 nm.otweezers. Carbon nanotubes are particularly strong for their size, they conduct electricity, and they can be fabricated as small as 1 nanometer (nm) in diameter. With nanotubes serving as the tines of the tweezers, Kim and Lieber devised a very clever arrangement for the hub. They took a standard glass tube, 1 mm in diameter, and pulled it to a tapered end of about 100 nm. They then evaporated a very thin coat of chromium and then gold on one side, then rotated the rod 180° and deposited metal on the other side. Each coated side operated as an independent electrode.

Abstract When you read the header to this article, you probably thought I made a mistake. Doesn't he mean atomic force microscope, the familiar AFM? And isn't that microscope in our present, not in our future? Well, I'm not confused. The reference is to a beam of atoms that some day may be used in an atomic microscope, just like a beam of electrons is used in an electron microscope. It would be even more accurate to refer to an “atomic de Broglie microscope,” but that's a rather awkward label.

Abstract There are many approaches to obtaining high-resolution images and three dimensional volumetric data sets, but all have limitations. Many techniques involve reconstructing volumes of information from sections, either physical sections or optical sections. Recently, James Sharpe, Ulf Ahlgren, Paul Perry, Bill Hill, Allyson Ross, Jacob Hecksher-Sørensen, Richard Baldock, and Duncan Davidson have developed an optical technique that is analogous to computed tomography (CT). Whereas clinical CT involves an X-ray source and detector rotating around the patient, optical projection tomography (OPT) has the specimen rotating within an optical pathway.

Abstract The atomic force microscope (AFM), the workhorse of scanning probe microscopes, has become even more versatile. Anneliese Raab, Wenhai Han, Dirk Badt, Sandra Smith-Gill, Stuart Lindsay, Hansgeorg Schindler, and Peter Hinterdorfer have demonstrated that the AFM, in the dynamic force mode, can use antibodies as a probe. Dynamic force microscopy uses a magnetized tip that is oscillated in an alternating magnetic field as the tip scans the surface. This provides a very gentile interaction that can be recorded as a high resolution topographic image. Raab et al., showed that more information can be obtained from the specimen.

Abstract The atomic force microscope (AFM) is being utilized in even more clever ways to reveal details of molecular structure and function. As an example, Julio Fernandez and Hongbin Li have used the AFM in the force-clamp mode to monitor the folding trajectory of a single protein. They have demonstrated in a unique way in which a single protein behaves when put under tension, and then what happens when the tension is relieved. Fernandez and Li linked several molecules of ubiquitin, a small protein, together to form a polyubiquitin chain. With one end of the chain attached to a substrate, the tip of a soft cantilever of the AFM attached to a single protein, and from one to nine ubiquitin molecules were picked up.

Abstract Since the discovery of nerve growth factor, it has been thought that neurotrophic factors are released or secreted from target cells. However, more recently it has been suggested that a specific neurotrophic factor known as brain-derived neurotrophic factor (BDNF) may reach target cells directly from pre-synaptic axons. It has not been known how these molecules get from the neuron in which they are produced to the target cells. Keigo Kohara, Akihiko Kitamura, Mieko Morishima, and Tadaharu Tsumoto have demonstrated that BDNF is transported anterogradely from presynaptic neurons to target neurons.

Abstract Nanofabrication is upon us. But engineers require measurements of physical properties of their materials in order to use them appropriately. Because the size of the object is in the nanometer scale, tiny measuring devices are required. Furthermore, there is the problem of reading these tiny devices. Zhong Lin Wang, Philippe Poncharal, and Walter de Heer at Georgia Tech have solved this problem by using the transmission electron microscope (TEM) to read off the measurements. A special device was designed to fit inside the TEM, allowing for simultaneous visualization and manipulation of a nanostmcture. The nanostructure that Wang ef al, used was the carbon nanotube which could be clearly visualized by the TEM and has a well-defined structure. Specifically, they used multiwalled nanotubes with diameters of 5 to 50 nm and lengths of 1 to 20 μm. The device they designed for in situ microscopy was a modified specimen holder that allowed carbon nanotubes to be mounted in a conducting medium and positioned across from a counter electrode, which was a droplet of mercury or gold/ platinum balls.