news and views Acoustic physics 50 Vibrating cylinder Suspended by sound 40 ++ ++ E. H. Brandt 30 + Ultrasound waves can levitate heavy balls of tungsten. This contact-free method of keeping items suspended in the air can be applied to the mm 20 investigation and processing of new materials. + It is well known that radiation can exert a in space experiments, where there is no 10 force. The solar wind, for example, is gravity. They have also been used to process + + caused by sunlight blowing away micro- materials where it is important to avoid the 0 scopic dust particles, and its force on a contamination of samples by the container Concave reflector sunbather is equal to the weight of a fly. It wall - for example, for growing ice parti- -20 -10 0 10 20 is probably less well known that sound cles4, undercooling liquids far below their mm waves also exert a force. The radiation force freezing point5, and heating liquid crystals6 on a tiny sphere from a travelling sound and ceramics5 to high temperatures. Figure 2 Contour lines of the acoustic potential wave is weak, proportional to the sixth Xie and Wei3 have managed to increase computed by Xie and Wei3. Tiny objects can be power of the ratio of the sphere radius to the the force and stability of single-axis acoustic levitated in the four potential wells (or minima) wavelength of the sound. But it can become levitation, and so were able to levitate balls denoted by crosses. The middle two wells are more substantial - proportional to the of tungsten, which has a density of 18.9 g located on the central symmetry axis, and the third power of this ratio - in a standing cm 3. They achieved this by optimizing the top and bottom wells are ring shaped. The sound wave, of the sort that occurs near diameter of the vibrating cylinder and the separation of the cylinder (top) and concave reflecting walls. It has previously been distance, radius and curvature of the con- reflector (bottom) in the resonance mode is shown that a siren operating at 3,260 Hz and cave reflector. To understand the relation- approximately two wavelengths, which is 20.3 an appropriate reflector can freely levitate ship between these geometric parameters mm for sound with a frequency of 16.7 kHz. drops of liquid and bubbles1, or even a steel and the observed enhancement, the authors ball 1 cm in diameter2. As Xie and Wei3 show developed a detailed model. tive Bernoulli pressure, which is proportional in Applied Physics Letters, the levitating force They began by computing the sound to the velocity squared. (Negative Bernoulli of ultrasound (which has a frequency too wave generated in their levitator from pressure provides the lifting force on an high for humans to hear) can be enhanced hydrodynamic theory to give the time- airplane wing.) But the acoustic force is a even further by carefully designing the averaged mean square pressure and mean nonlinear effect; with a linear approxima- shape of the reflector. This allows them to square velocity of the vibrating air at each tion of the model, any sound wave oscillates levitate balls of high-density tungsten. point in space. They inserted these values symmetrically over time, so all time aver- The strongest acoustic forces are exerted into a general expression for the time- ages would be zero and there would be no by the standing sound waves formed inside averaged potential of the acoustic radiation radiation force. an almost closed box. But the `single-axis force acting on a small rigid sphere. This The acoustic potential calculated by Xie geometry', in which a concave circular reflec- expression was first derived by Lev Gor'kov and Wei3 is shown as a contour plot in Fig. 2. tor faces a vibrating cylinder that emits ultra- in an ingenious paper7 in 1962 (see also the This configuration corresponds to the reso- sound at a frequency of 16.7 kHz (Fig. 1), discussion and application of this formula in nant state in which the distance between is more convenient and provides easy access ref. 8). It says that the sphere is attracted to emitter and reflector is approximately two to the levitating samples. Such levitators can regions with large air velocities and repelled sound wavelengths, which at 16.7 kHz is be used to simulate the microgravity condi- by regions with high pressures. This seems 20.3 mm for air at room temperature. The tions of space in a terrestrial laboratory. intuitive - the sphere avoids places at high minima of the acoustic potential are marked Conversely, they are used to position samples pressure and prefers places with large nega- by six crosses. As expected, these minima occur at four heights, close to the maxima of the velocity amplitudes, and their vertical spacing is approximately half a wavelength. If the sound intensity is large enough, each of these minima (or potential wells) can trap and levitate a small sample when the maximum vertical gradient of the potential (slope of the potential well) exceeds the gravitational force. Xie and Wei3 show that the resonance frequencies and positions of stable levitation given by their model are in good agreement with the observed locations of the levitated spheres. The contours of the potential in Fig. 2 show that the two middle potential Figure 1 Acoustic levitation by ultrasound. In Xie and Wei's latest experiment3 the force produced by a wells sit on the vertical axis of symmetry, but standing wave of 16.7-kHz ultrasound, which forms between a vibrating cylinder (top) and a concave the wells next to the emitter and reflector reflector (bottom), is enough to levitate small objects. The freely floating objects are: a, three polymer form larger rings around the symmetry axis. spheres; b, four liquid crystal samples; c, a water drop deformed to a pancake shape by the uneven This theoretical finding explains why the acoustic pressure; and d, a heavy tungsten sphere levitated in the lowest resonance mode, which has two samples at the top and bottom in Fig. 1b one potential minimum. are located slightly off the central axis. 474 NATURE |VOL 413|4 OCTOBER 2001|www.nature.com © 2001 Macmillan Magazines Ltd news and views Apart from acoustic levitation, there are new materials that cannot be formed by unaffected people (100% enzyme activity), several other types of contact-free levi- normal cooling, such as metallic glass and unaffected individuals who were carriers tation9: aerodynamic levitation (by a fluid new superconductors. The improvements of the mutant gene (50­60% activity) and jet), optical levitation (by a laser beam), of the single-axis acoustic levitator achieved TTP patients (2­7% activity). It also gave electrical levitation (in a quadrupolar alter- by Xie and Wei3 - increasing the levitation them the opportunity to undertake a `link- nating electric field), radio-frequency levi- force with greater stability and predictability age' study to pinpoint the chromosomal tation (by the eddy currents induced in a - may offer researchers the same opportu- location of the defective gene, and at the conducting sample by a conical coil), mag- nities as experiments in microgravity, but at same time to identify mutations that cause netic levitation (in the strong field of an a fraction of the cost. I TTP. Linkage analysis needs families (pedi- electromagnet, which famously levitated a E. H. Brandt is at the Max-Planck-Institute for grees) with several generations of affected young frog10,11), and superconducting levi- Metals Research, D-70569 Stuttgart, Germany. and unaffected people for study, as well as a tation (by combining superconductors and e-mail: ehb@mf.mpg.de phenotypic marker - in this case the pro- permanent magnets). In all these types of 1. Trinh, E. H. Rev. Sci. Instrum. 56, 2059­2065 (1985). teinase activity. Armed with good pedigrees free flotation, the main aim is to achieve 2. Gammel, P. M., Cronquist, A. P. & Wang, T. G. J. Acoust. Soc. and a good marker, Levy et al. embarked on good vertical and horizontal stability, other- Am. 83, 496­501 (1988). 3. Xie, W. J. & Wei, B. Appl. Phys. Lett. 79, 881­883 (2001). a search for patterns of inherited genes in wise a small perturbation may cause the 4. Bauerecker, S. & Neidhart, B. J. Chem. Phys. 109, 3709­3712 families with TTP, matching these patterns levitating sample to fall. (1998). with enzyme levels until they homed in on a Acoustic levitation has the advantage 5. Weber, J. K. R. et al. Rev. Sci. Instrum. 65, 456­465 (1994). single gene, ADAMTS13, on chromosome 9. that it is simple and can levitate both non- 6. Xie, W. J. & Wei, B. Chin. Phys. Lett. 18, 68­70 (2001). 7. Gor'kov, L. P. Sov. Phys. Dokl. 6, 773­775 (1962); transl. (with In a single, elegant study they identified the magnetic and non-conducting materials. misprints) from Dokl. Akad. Nauk SSSR 140, 88­91 (1961). enzyme, the gene, and the mutations in that Experiments in microgravity in which met- 8. Barmatz, M. & Collas, P. J. Acoust. Soc. Am. 77, 928­945 (1985). gene that cause TTP. Other investigators, als and alloys are heated and cooled, without 9. Brandt, E. H. Science 24, 349­355 (1989). 10.Berry, M. V. & Geim, A. K. Eur. J. Phys. 18, 307­313 (1997). using protein-purification methods, have touching any container walls, have produced 11.Brandt, E. H. Phys. World 10, 23­24 (1997). confirmed that ADAMTS13 is the enzyme that processes VWF7,8. ADAMTS13 is a newly discovered mem- Human genetics ber of a relatively new family of enzymes - the first ADAMTS protein was found only four years ago9. The name (which stands for To clot or not `a disintegrin-like and metalloproteinase Amanda J. Fosang and Peter J. Smith with thrombospondin motifs') reflects the various modules, or motifs, that are found in In multicellular animals, there has to be a balance between the free flow these proteins (Fig. 1, overleaf). Each mod- and clotting of blood. One molecule involved is von Willebrand factor, and ule is thought to contribute in some way to the enzyme that cuts it down to size is now unveiled. the protein's overall function. This must be true of ADAMTS13 too, as the TTP-causing the development of TTP. Then came the mutations found by Levy et al. are not clus- discovery that the activity of an enzyme tered in one region, but are spread along Thrombotic thrombocytopenic purpura is a potentially fatal human disease. It results from the widespread, abnormal that cleaves these large multimers into more or less the entire length of the gene. aggregation of platelets and a protein, called smaller fragments is markedly reduced in It is likely that one or more of the throm- von Willebrand factor, in the small blood the blood of patients with TTP3. In some bospondin motifs in ADAMTS13 helps it to vessels of many organs, including the brain forms of the disease, patients produce an dock onto VWF, while the metalloprotein- and kidneys. The accumulated clots of antibody that blocks the enzyme4; in others, ase domain, which contains the active site, platelets and proteins obstruct blood flow the activity is missing altogether3. These does the business of cleaving VWF. The role and cause red blood cells to fragment, lead- observations pointed to the malfunctioning of the disintegrin-like domain is unknown. ing to serious neurological and renal mal- of a VWF-cleaving `proteinase' as the under- Disintegrins are molecules that bind integrin functioning as well as anaemia, fever and a lying cause of the disease. Levy et al.1 have proteins on the surface of cells. Many snake low platelet count (thrombocytopenia). On now identified the gene, ADAMTS13, that venoms contain disintegrin domains that page 488 of this issue, Levy and colleagues1 encodes this proteinase, and show that bind to integrins on platelets, leading to describe how they tracked down the gene mutations in this gene lead to an inactive either haemorrhaging or clotting, depend- that is mutated in patients with the heredi- enzyme and to TTP. ing on the venom. The disintegrin-like tary form of this disorder. Their work adds The first clues to the identity of the domain of the ADAMTS enzymes is about significantly to our understanding of the VWF-cleaving proteinase came about five 40% identical to those of snake venoms. molecules involved in blood clotting. years ago when the enzyme was partially So far, no ADAMTS protein has been found Von Willebrand factor (VWF) is a large purified, revealing that it requires zinc to have a disintegrin-like function. But, protein that circulates in the blood as multi- ions for full activity and is inhibited by given the relationship between platelets and mers of varying sizes. One of its main func- metal-ion chelators5,6. This partially puri- VWF, it will be interesting to determine tions is to mediate interactions between fied enzyme could cleave VWF between the whether this region of ADAMTS13 interacts platelets, and between platelets and the walls amino acids tyrosine at position 842 and with platelets. of blood vessels. Both types of interaction are methionine at position 843, generating We still have much to learn about the vital in maintaining the balance between characteristic fragments. Levy et al.1 fol- ADAMTS family. For example, deregulated bleeding and clotting. lowed this proteinase activity to track down expression of several ADAMTS proteins Thrombotic thrombocytopenic purpura the affected gene in families with TTP. They is implicated in disease (Fig. 1), but (TTP) was first described2 in 1924. But it developed an assay to measure how much ADAMTS2 and ADAMTS13 are the only was only recently linked to an increase in of the cleavage product was present in members of the family for which there is the number of unusually large multimers patients' blood plasma. a clear association between an inherited of VWF in the blood, which suggests that This assay was critical to the authors' suc- disorder and a disturbed enzymatic pro- these abnormal forms might contribute to cess. It allowed them to distinguish between cess. Decreased levels of ADAMTS2 prevent NATURE |VOL 413|4 OCTOBER 2001|www.nature.com 475 © 2001 Macmillan Magazines Ltd