The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements quantified binding constants for vancomycin-sensitive and vancomycinresistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions affected by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also impact on our understanding of antibiotic drug action in bacteria.When biochemically specific interactions occur between a ligand immobilized on one side of a cantilever and a receptor in solution, the cantilever bends due to a change in surface stress [1][2][3][4][5][6][7][8][9] . The general applicability of this novel nanomechanical biosensing transduction mechanism has been shown for sequence-specific DNA hybridization [1][2][3][4][5]8

Nature © Macmillan Publishers Ltd 1998 8 letters to nature 566 NATURE | VOL 391 | 5 FEBRUARY 1998X-ray microprobe, our CRL could be used to guide and focus the neutron beam to explore local crystallography and magnetic domains. In addition, two other uses are possible. The first is to reduce neutron beam divergence and enhance the resolution limit of Bragg reflection rocking curves. The second possibility would be to magnify the pattern of scattered neutrons from a sample. Because area detectors for neutrons have a relatively low spatial resolution (5 mm), small-angle experiments use long (up to 40 m), expensive, evacuated paths to spread the diffraction pattern over the detector. Magnifying optics could be used to shorten this flight path. We are at present exploring new materials and achromatic lens designs. Such a system could provide significant new opportunities for the present generation of reactor-based neutron sources.

We describe a highly sensitive new type of calorimeter based on the deflection of a ‘‘bimetallic’’ micromechanical sensor as a function of temperature. The temperature changes can be due to ambient changes, giving a temperature sensor or, more importantly, due to the heat absorbed by a coating on the sensor, giving a heat sensor. As an example we show the results of using the sensor as a photothermal spectrometer. The small dimensions and low thermal mass of the sensor make it highly sensitive and we demonstrate a sensitivity of roughly 100 pW. By applying a simple model of the system the ultimate sensitivity is expected to be of the order of 10 pW. The thermal response time of the cantilever can also be determined, giving an estimate of the minimum detectable energy of the sensor. This we find to be 150 fJ and again from our model, expect a minimum value of the order of 20 fJ.

Atomic force microecopy is used to measure force profiea and friction forces for the block copolymer PEO/PS physisorbed on mica in xylene, 2-propanol, n-dodecane, and air. The force profiles show the distinctive repulsive forces associated with brushlike confiiations in good solvents and shorter range attractive forces in poor solvents. The brushlike profiles show that in addition to being compressed between the surfaces, the polymer chains can also bend out of the tip-surface contact region. The friction data show that the tip is beet regarded as a single asperity contact and on solid polymer surfacea there is a transition to plowing type friction as the applied force is increased which can be associated with the yielding of the polymeric material. No friction signal could be measured within the polymer brush in a good solvent. Topographic images of the adsorbed polymer in poor solvents are also shown. At submonolayer coverages the polymer agglomerates and during imaging the agglomerates were either broken up or moved if the tip scanning speed was too slow. The polymer could be more eaily imaged by adding 2-propanol which further collapsed the polymer chains and thus strengthed the agglomerate structures. In good solvents the tip tends to displace the molecules along the surface and it is concluded that further studies on these systems will be best undertaken with polymers chemisorbed onto the surface.

Three differently charged nanoscale features were constructed by sequential nanografting of 6mercaptohexan-1-ol, N-(6-mercapto)hexylpyridinium bromide, and 3-mercaptopropionic acid into a selfassembled monolayer resist of an alkanethiol terminated with a hexa(ethylene glycol) group on an atomically flat template stripped gold surface. The immobilization of three proteins, lysozyme, rabbit IgG, and bovine carbonic anhydrase (II), onto these different charged nanopatches was studied at a variety of pH values. At pH 4.5, all three proteins adsorbed onto the charged nanosurfaces. At higher pH, the proteins behaved differently, depending on the pH and relative surface charge of the nanosurface. A surface charge distribution model was employed to explain the unusual adsorption behavior of carbonic anhydrase. Finally, an approach that combines electrostatic immobilization and specific protein-protein interactions to fabricate multiplelayered (protein G/rabbit IgG/anti-IgG) three-dimensional (3D) protein nanostructures is presented, demonstrating that the combination of nanografting, electrostatic immobilization, and specific protein interaction is a powerful tool for construction of novel 3D protein surface nanostructures.