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Characterization of Grafted Poly(ethylene glycol) on Si Wafers Using Scanning Probe Microscopy.

The uniformity and surface topography of grafted poly(ethylene glycol) (PEG) coatings were characterized at the microscale as a function of grafting temperature (grafting density) using scanning probe microscopy. Images of PEG-coated silicon wafers show isolated domains which decrease in size and increase in surface density with increasing grafting temperature. Domain sizes appeared to correlate with the polarity of the solvent used for imaging. Roughness measurements of the PEG layers were obtained. The results are relevant in relation to the biomedically significant ability of PEG coatings to mask surface features such as charge detected via zeta potential measurements. Copyright 1998 Academic Press.

Journal Article↗

High resolution imaging of native biological sample surfaces using scanning probe microscopy.

The possibility of acquiring high resolution topographs using scanning probe microscopes under physiological conditions allows the observation of biomolecules at work. Progress has recently been made in imaging protein-DNA complexes, individual oligomers and protein arrays. Scanning probe microscopes are now tools that complement X-ray crystallography and electron microscopy.

Bacterial Outer Membrane Proteins↗

The role of scanning probe microscopy in drug delivery research.

The success of a drug delivery system is often dependent on the surface properties of the device. These surface properties will determine the complex dynamic interfacial events that occur when the system is introduced into the aqueous environment of a patient. Development of the scanning probe microscopes has provided a number of very powerful new surface analytical techniques that are making a significant contribution to the characterization of drug delivery systems and the interfacial processes that occur when such systems are exposed to aqueous living environments. In this review, we describe the design and attributes of these instruments and discuss the impact of the techniques on a wide range of drug delivery research. The scanning probe microscopes are providing new insights into important problems concerning drug delivery, including the molecular structure of polymeric biomaterial surfaces, the conformation of target biomolecules, the influence of morphology on biodegradation, the adsorption of proteins to synthetic surfaces, and the structure and interactions of colloidal particles. As the whole field of scanning probe microscopy continues to advance, drug delivery research is set to benefit; in the final section of the review, the future potential derived from the ability to characterize new surface properties under aqueous conditions is discussed.

Drug Delivery Systems↗

Detecting H+ in ultrafine ambient aerosol using iron nano-film detectors and scanning probe microscopy.

Recent epidemiological evidence strongly suggests that ambient-particle-associated acidity is more closely correlated with total mortality and hospital admissions for respiratory disease than indices of total particulate mass. In addition, evidence is accumulating to support the hypothesis that the number of ultrafine (d < or = 200 nm) acid particles, rather than ambient mass, is an important determining factor affecting lung injury. Both outdoor and indoor air environments are dominated by nanometer-sized particles. However, no data are currently available on the size distribution or number concentration of acidic ambient ultrafine particles largely because there are no suitable methods for measuring these important quantities. We have developed a method to accomplish these measurements based on the use of iron nano-films for detection of acid droplets. Detectors were prepared by vapor deposition of iron onto 12-mm-diameter glass cover slips. The detectors develop reaction sites when exposed to H2SO4 or NH4HSO4 particles. Exposures to non-acidic particle (NaCl and [(NH4)]2SO4) result in no detectable surface deformations. The nano-films are examined with scanning probe microscopy (SPM) for the enumeration of reaction sites. Until recently, direct visualization of individual objects smaller than 200 nm has been possible only with electron microscopy. The advancement of SPM provides the opportunity to examine the detector surface features with high quality three dimensional imaging.

Aerosols↗

Scanning probe microscopies for high-resolution characterization of electrochemical sensors. Plenary lecture.

A better understanding of tailored electrodes and electrochemical sensors requires a more detailed picture of their surfaces. New scanning probe techniques, such as scanning tunnelling or scanning bioelectrochemical microscopies, offer unique opportunities for high-resolution in situ characterization of tailored electrodebased sensors. Scanning tunnelling microscopy provides valuable information on the topography of pre-treated surfaces, the heterogeneity of composite electrodes, the morphology of electropolymerized films, the packing arrangement of adsorbed monolayers and the microdistribution of immobilized biological components. Scanning bioelectrochemical microscopy is shown to be extremely useful for the mapping of localized biological activity and the monitoring of dynamic biological events. Valuable insights are achieved by correlating the structural features with the preparation/modification conditions and the subsequent sensing performance. Such correlations can facilitate the predictive design of increasingly better sensors.

Biosensing Techniques↗

The scanning probe microscopy of metalloproteins and metalloenzymes.

In recent years, the concept of microscopy and the ability to study processes at a truly molecular level have been revolutionised by the development of a family of instruments based on acquiring data through the scanning of a proximal probe across a surface. Scanning Probe Microscopes (SPMs) enable surface-confined structures to be resolved at ångstrom-resolution, in real time, and under a variety of controllable conditions. Despite initial difficulties, much progress has been in the application of this technology to the high-resolution analysis of biological systems; these have varied from complex cellular systems to molecular biopolymers. Studying the interactions of protein with surfaces has been intrinsic to the development of our understanding of blood coagulation, fibrinolysis, thrombus formation and the synthesis of biocompatible materials. The specific interactions of metalloproteins and enzymes with electrode surfaces remains central to the understanding of the bioelectrochemical processes and to the development of biosensing devices. Though ellipsometry, Raman, microcalorimetry, surface plasmon resonance, and other spectroscopic methods, can provide much information on these interfaces, the acquired data are averaged over a large number of molecular species with a low spatial resolution. Proximal probe methods have much to offer in this regard and have revolutionized our ability to monitor such interactions.

Animals↗

Correction for piezoelectric creep in scanning probe microscopy images using polynomial mapping.

We describe a method for using polynomial mapping to correct scanning probe microscope images for distortion due to piezoelectric creep. Because such distortion varies from image to image, this method can be used when the actual locations of some features within an image are known absolutely, or in a series of images in which the actual locations of some features are known not to vary. While the general case of polynomial mapping of degree N requires the determination of 2(N+ 1)2 matrix elements by regression, we find that by understanding the mechanism by which piezoelectric creep distorts scanning probe microscope images, we can fix most of these coefficients at 0 or 1 a priori, leaving only 2(N+ 1) coefficients to be determined by regression. We describe our implementation of this strategy using the Interactive Data Language (IDL) programming language, and demonstrate our technique on a series of atomic force microscopy (AFM) images of diblock copolymer microdomains. Using our simplified scheme, we are able to reduce the effects of distortion in an AFM image from 5% of the scan width to a single pixel, using only five reference points.

Journal Article↗

Surface ultrastructure of pit organ, spectacle, and non pit organ epidermis of infrared imaging boid snakes: A scanning probe and scanning electron microscopy study.

Boid snakes possess unique infrared imaging pit organs. The ultrastructure of the surfaces of these organs scatter or reflect electromagnetic radiation of specific wavelengths. Pit organ epidermal surfaces of boid snakes are covered with arrays of pore-like structures called micropits. In order to determine the dimensions of this complicated surface structure, we have performed the first ultrastructural analysis on snake epidermis by high-resolution microscopy techniques. Using scanning probe microscopy and scanning electron microscopy, we found that the epidermis of pit organ, maxillary non pit organ, spectacle, and ventral scales contain arrays of micropits. These scale surfaces also contain major surface features of overlapping plate-like structures. Pit organ micropits averaged 319 nm in diameter and 46 nm in depth and were spaced an average of 808 nm from each other. These micropits were significantly deeper, of greater diameter, and spaced at greater distances apart than those of the other scales. Plate structures of the pit organs had a mean distance between plates of 3.5 microm and a mean plate step height of 151 nm. These differences serve to strengthen the argument that arrays of micropit and plate surface structures function as spectral filters or anti-reflective coatings with respect to incident electromagnetic radiation.

Animals↗

Electrochemical deposition of molecular adsorbates for in situ scanning probe microscopy.

We have studied gold and graphite electrodes in an electrochemistry cell under various solutions using the scanning tunneling microscope (STM). The gold (111) surface yields quite reproducible images and cyclic voltammograms. In situ voltammograms show that, under certain conditions, nanomolar quantities of DNA fragments can suppress the adsorption of a buffer salt of millimolar concentration. When the DNA concentration is reduced below that required for a monolayer coverage, the salt adsorption is restored. We show images of bare gold, gold covered with an adsorbate produced by the buffer salt, and gold prepared with a concentration of DNA fragments close to that required for monolayer coverage added to the buffer. Under these conditions, the surface is found to be uniformly covered with a characteristic structure.

Adsorption↗

Potential-induced resonant tunneling through a redox metalloprotein investigated by electrochemical scanning probe microscopy.

The redox metalloprotein azurin self-chemisorbed onto Au(1 1 1) substrates has been investigated by electrochemically controlled scanning tunneling (STM) and scanning force/lateral force microscopy (SFM/LFM) and cyclic voltammetry (CV) in aqueous solution. The combined use of STM and SFM/LFM under electrochemical control in the negative side of the azurin redox midpoint (+116 mV vs. SCE) has delivered unique information on the nature of the STM images. While in STM the bright spots, believed to be associated with azurin molecules, are visible only for potential values higher than -125 mV, the concurrent electrochemical SFM results show adsorbed proteins over the whole potential range investigated (from -225 to +75 mV). Stepping the potential back and forth (between -25 and -125 mV) in STM imaging, it has been possible to make bright spots appearing and disappearing repeatedly, indicating that STM image formation arises possibly through resonant tunneling via the redox levels of azurin. These results represent the first clear evidence of potential-dependent tunneling in proteins adsorbed onto a conductive substrate.

Journal Article↗

Study of inhomogeneities in sources prepared for alpha-particle spectrometry using scanning probe microscopy.

For high-resolution alpha-particle spectrometry, sources of high quality must be prepared by methods giving the thinnest and most homogeneous deposit possible on a suitable support. Surface characteristics of several types of alpha-particle sources were studied using a scanning probe microscope. Major inhomogeneities were observed, which means that the materials and techniques used for thc preparation of sources must be improved.

Journal Article↗

Characterization of High Resolution Resists and Metal Shims by Scanning Probe Microscopy.

Technologies such as compact disc (CD) manufacturing, hologram embossing, and security printing rely on the reproduction of micro-patterns generated on surfaces by optical or electron-beam lithographic writing onto electron-beam or photoresists. The periodicity of such patterns varies from sub-micron to several microns, with depths up to 0.5 µm. The scanning probe microscope (SPM) is becoming a routine tool for analysis of these micro-patterns, to check on depths and lateral dimensions of features. Direct scanning of resist-covered plates is now possible, without damage, using resonant low-contact force SPM with etched silicon cantilevers. Metal shims produced from the master resist plates can also be scanned and checked for defects prior to production of embossed foils. The present article discusses examples of the use of a Digital Instruments 3100 microscope in analysis of production electron-beam lithography plates with a 0.5 µm resist thickness. We also examine features of nickel replicas ("father" and "mother" shims) produced by electroforming from the original plate. With SPM measurements of the development profile of a particular plate, corrections can be made to exposures and development times during production to correct errors. An example is given of such a feedback process.

Journal Article↗