Carmichael, Stephen W.

Abstract For biologic studies, atomic force microscopy (AFM) has been prevailing over scanning tunneling microscopy (STM) because it has the capability of imaging non-conducting biologic specimens. However, STM generally gives better resolution than AFM, and we're talking about resolution on the atomic scale. In a recent article, Franz Giessibl (Atomic resolution of the silicon (111)- (7X7) surface by atomic force microscopy, Science 267:68-71, 1995) has demonstrated that atoms can be imaged by AFM.

Abstract When physicists of the last century were studying the nature of light and its application to the newly-refined microscopes, they devised certain laws relating to physical limitations to resolution. These laws had something to do with the wavelength of light being proportional to the limit of resolution. Lately these laws haven't just been broken, they've been shattered! But in all fairness to our predecessors, light is being used now in a manner that they could not have imagined. The scanning interferometric apertureless microscope (SIAM) recently refined by a team led by H. Kumar Wickramasinghe with colleagues Frederic Zenhausern and Yves Martin is a prime example.

Abstract It has long been appreciated that communication between the nucleus and the cytoplasm of a cell occurs through the nuclear pores. Regulation of this communication has remained a mystery. A breakthrough in our understanding of this regulation was recently presented by Carmen Perez- Terzic, Jason Pyle, Marisa Jaconi, Lisa Stehnc-Bittel, and David Clapham of Mayo Clinic. Using field emission scanning electron microscopy (FESEM), transmission electron microscopy, and atomic force microscopy (AFM), they demonstrated the presence of a small plug within the nuclear pore that was present under certain physiologic circumstances. This “plug“ may regulate the movement of molecules through the pore.

Abstract Microscopes are being used to obtain more and more information from a specimen. We are all acquainted with various ways to visualize structures, whether on the surface or embedded within a relatively translucent specimen. There are many ways to “tag” a molecule of interest so that the molecule can be positively identified within the specimen. Traditional microscopes are not able to identify a molecule for us. Other analytical tools are used for that. For example, the nuclear magnetic resonance (NMR) spectrum of a molecular species yields a “fingerprint” that gives a reliable identification. Wouldn't it be great to combine the sensitivity of a state-of-the-art microscope with the molecular analytical capabilities of NMR? Well you guessed it, this has been done. This approach was first suggested by John A. Sidles at the University of Washington and has recently been demonstrated by Dan Rugar and colleagues at the IBM Almaden Research Center in San Jose.

Abstract In general terms, parasites that cause malaria are injected into the skin by mosquitoes. They then travel into the bloodstream and then to the liver where they invade liver cells and mature into forms called schizonts. Within each schizont, cell division produces thousands of tiny new forms called merozoites, each of which, when released into the bloodstream, is capable of infecting a red blood cell. This “traditional” pathway for malarial parasites may not be the only way these parasites travel through the body. Using some increasingly more powerful immuno-imaging tools, Rogerio Amino, Sabine Thiberge, Béatrice Martin, Susanna Celli, Spencer Shorte, Friedrich Frischknecht, and Robert Ménard have demonstrated an additional route that could have profound implications for developing effective vaccines for this major worldwide disease.

Abstract Coal is remnants of plant matter that were compressed and held at a high temperature for eons. However, if plants are charred first, they become hard and brittle, and may resist compression. Under appropriate circumstances, anatomic detail can be elegantly retained. Ian Glasspool, Dianne Edwards, and Lindsey Axe have performed detailed studies on plant fossils recovered in England, near the Welsh border, that can be considered to be evidence for the earliest wildfire yet described on our planet. They examined a series of mesofossils, about one millimeter in size, which required microscopic study. It is well known that chemical and structural changes occur to organic tissues during charring. This can mean that charcoal is resistant to decay and compression and it is also more reflective than non-charred material. Glasspool et al. used incident light and scanning electron microscopy to reveal 3-dimensional cellular detail of the specimens. Additional specimens were embedded and polished for reflectance microscopy. The results indicated that the specimens were charcoal.

Abstract Would you believe it might be possible to build organs using an ink-jet printer? In a remarkable pair of articles, Thomas Boland and his collaborators describe a modified printer that promises to be abie to do exactly that. The first article of this pair describes the software and hardware to arrange cells in two dimensions, just as a printer arranges droplets of ink on a fiat piece of paper. The software that normally controls the position of a drop of ink is modified to position a drop containing one or two cells in suspension onto a substrate.

Abstract The atomic force microscope (AFM) has been used in many ways to extract information from biologic specimens. Now Gerry Leatherman, Edgar Durantini, Devens Gust, Tom Moore, Anna Moore, Simon Stone, Ziniu Zhou, Peter Rez, YangZhang Liu, and Stuart Lindsay have used conduction atomic force microscopy (CAFM) to demonstrate that a molecule of carotene can function as a molecular wire. Leatherman et al., synthesized carotene and then examined the molecules with the scanning tunneling microscope (STM), They could image spots that averaged 2 nm in diameter, although the size of the spots varied widely due to the geometry of the probe tip. Interestingly, the number of spots increased with the concentration of carotene, but the average size of the spots did not change. This made it clear that they were able to image carotene molecules with the STM, and that the carotene did not form large aggregates.

Abstract In addition to concerns about the appearance of a display, curators of art galleries are also concerned about conservation of the artwork and their authenticity. Microscopes have played a role in these latter activities since the 1930s. Various imaging techniques, including X-radiography, infrared reflectography, macrophotography, UV-fluorescence and raking light (light source at a low angle to the surface) imaging have their advantages and disadvantages. Confocal microscopy is most useful compared to the other methods for the purpose of examination of subsurface structure, but the close working distance (a few mm) makes it precarious to use on valuable masterpieces. More recently, Haida Liang, Marta Cid, Radu Cucu, George Dobre, Adrian Podoleanu, Justin Pedro, and David Sauders have demonstrated the usefulness of optical coherence tomography (OCT) for non-destructive examination of artwork. OCT, as discussed previously in this column, is more commonly used to examine biological specimens.

Abstract How do the right cells get to the right place in lymph nodes? It is known that lymphocytes known as B cells (that originate in the bone marrow) migrate to follicles within the nodes, whereas T cells (that originate in the bone marrow and migrate to the thymus gland) reside in an adjacent region known as the paracortex. By combining confocal, electron, and intravital microscopy, Marc Bajénoff, Jackson Egen, Lily Koo, Jean Pierre Laugier, Frédéric Brau, Nicolas Glaichenhaus, and Ronald Germain have demonstrated a role for the stroma of the node in directing these cells to the appropriate location. The stromal cells that are critical in the B cell follicles are follicular dendritic cells (FDCs) and in the paracortex it's the fibroblastic reticular cells (FRCs).