Method images surfaces of biological materials - C&EN Global

A team of German scientists has used scanning tunneling microscopy (STM) to ... The team showed that an ultrathin water film coating an insulator's su...
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hnanishi-Kari shown in 1990 photo.

book to those of other researchers who had worked in her lab and neighbor­ ing labs. They concluded that pages she claimed she prepared in 1984 and 1985 were actually cobbled together in 1986, about the time OToole first raised allegations. A draft report in 1991 of NIH's sec­ ond probe relied heavily on the Secret Service's evidence to conclude Imanishi-Kari fudged data to meet O'Toole's challenges. The final NIH report was delayed while the Justice Department, at Dingell's behest, weighed bringing criminal charges. The U.S. attorney's office in Baltimore decided in 1992 not to prosecute, saying the case was too complicated for a jury of nonscientists. Meanwhile, NIH's much criticized fraud office was moved to HHS, ulti­ mately becoming ORI. ORI's final in­ vestigative report adds additional counts of misconduct to those in the 1991 draft report and will form the ba­ sis of the government's case at Imanishi-Kari's appeals hearing. Imanishi-Kari tells C&EN she is in­ nocent and has duplicated the ques­ tioned experiments. Since her grants were cut off by NIH in 1990, her re­ search has been funded by the Ameri­ can Cancer Society. Tufts removed her from her position as assistant professor of pathology as a result of ORI's mis­ conduct finding, she says, and she is now a research associate there. Baltimore—never himself accused of

S misconduct—initially defended Iman­ s ishi-Kari vigorously. After the NIH draft report became public in 1991, he distanced himself, indirectly apologiz­ ing to OToole for not taking her mis­ givings seriously. In 1992, he shifted again, saying that the paper's conclu­ sions were valid after all. He resigned as president of Rockefeller University under the weight of the controversy and is currently professor of biology at MIT. C&EN could not reach him for comment. Unable to find work in her field for several years, whistleblower OToole is now a researcher at Genetics Institute in Cambridge, Mass. "Here is a case where the evidence is overwhelming," she says, "a complete misrepresenta­ tion in an important article in a firstrate peer-reviewed journal. It's taken nine years of fighting to establish there was misconduct and that it matters. This is what people who bring forth evidence are up against."

provides enough conductivity to obtain a good STM image." The team consists of four scientists at the institute and two at Munich Technical University. Biological materials exhibit "notori­ ously poor conductivity" for STM imag­ ing, the team's paper notes. Good STM images can normally only be obtained for organic samples sufficiently thin to allow electrons to tunnel through the material. Specimens thicker than 1 nm must be coated with a metal to a thick­ ness of at least 1 nm to obtain an STM image. However, high-resolution images cannot be obtained with such a coating. Thus, many scientists turn to atomic force microscopy (AFM) for surface to­ pography of biological samples. AFM depends not on electrical conductivity of a surface but on variations in the force between a probe and a surface. "The information on topography we obtain is similar to that obtained by AFM," says Guckenberger, but the res­ olution may be better. For example, the paper shows an Pamela Zurer STM image of plasmid DNA: The plas­ mid has an apparent diameter of 3.5 nm, close to the known diameter of about 2.5 nm. "We hope to get better resolution at higher humidities," Guck­ enberger adds. The scanning tunneling A team of German scientists has used microscope will need modifications to scanning tunneling microscopy (STM) achieve such resolution. to image surfaces of biological materi­ The team performed two types of ex­ als supported on insulators. The new periments. First, it measured the sur­ technique, which depends on air hu­ face conductivity of bulk insulators as a midity around a sample, "opens up a function of ambient air humidity. The wide field of new applications for researchers find the current between STM" in materials science and biology, probe tip and surface increases with in­ the researchers say. creasing relative humidity. "The thick­ STM uses a probe with a sharp con­ ness of the water layer depends on the ducting tip to scan a sample and pro­ relative humidity," Guckenberger duce an image of its surface with notes. Using published data on the re­ nanometer precision. The method de­ lationship of relative humidity to wa­ pends on electric current flow between ter-layer thickness, the team can con­ tip and surface. Conventional STM thus trol the thickness of the adsorbed film cannot be used directly to image insulat­ by controlling relative humidity. ing materials. The researchers next imaged the sur­ The team showed that an ultrathin faces of several biological samples pre­ water film coating an insulator's sur­ pared on mica. Their paper focuses on face provides sufficient electrical con­ plasmid DNA, but collagen and the to­ ductivity to image the surface by STM bacco mosaic virus "are also easily im­ [Science, 266,1538 (1994)]. The materials aged by the same STM technique." are examined in humid air and include One unanswered question concerns hydrophilic insulators such as glass and the mechanism of the water film's mica, as well as plasmid DNA support­ "surprisingly high" humidity-depen­ ed on mica. dent conductivity. The team suggests Team leader Reinhard Guckenberg­ protons may hop along structured wa­ er, a physicist with the Max-Planck In­ ter. "But other ions may also be in­ stitute for Biochemistry in Martinsried, volved," Guckenberger says. tells C&EN that "a monolayer of water Michael Freemantle

Method images surfaces of biological materials

DECEMBER 5, 1994 C&EN

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