Detecting the presence of a given substance at the molecular level, down to a single molecule, remains a considerable challenge for many nanotechnology sensor applications that range from nanobiotechnology research to environmental monitoring and antiterror or military applications. Currently, chemical functionalization techniques are used to specify what a nanoscale detector will sense. For biological molecules, this might mean developing an antibody/antigen pair, or an alternative synthetically generated ligand. For chemical gases, it is much more challenging to develop the right 'glue' that sticks a given gas to a substrate. The advantage of spectroscopic techniques such as Raman, infrared, and nuclear magnetic resonance spectroscopy is that they are label-free, i.e. they require no preconditioning in order to identify a given analyte. They are also highly selective, capable of distinguishing species that are chemically or functionally very similar. On the downside, spectroscopic methods face enormous challenges in measuring dilute concentrations of an analyte and generally involve the use of large, expensive equipment. This article describes a novel chemical detection technique called nanomechanical resonance spectroscopy.
X-rays are at the short wavelength, high energy end of the electromagnetic spectrum (only gamma rays have shorter wavelength and carry more energy) and this form of radiation is primarily used for crystallography and diagnostic radiography. Due to the high energy they carry, and because their wavelengths are on the order of the size of atoms, X-rays can penetrate deeply into a material. X-rays play an important role in microscopy and X-ray microscopes have become very powerful scientific instruments for domains such as nanotechnology, materials and life sciences, microelectronics, and chemistry. Depending on the level of energy they carry, X-rays are termed 'hard' - highest energy rays, typically between 8-100 thousand electron volts (keV) - or 'soft' - lower energy rays from roughly 1-8 keV - however this distinction is not well defined. By combining the magnifying power of optical microscopy with the penetrating power of X-rays, X-ray microscopes can generate highly detailed two-dimensional images of features down into the nanoscale, including their internal structure and quantitative chemical information.
More than half a century ago, Erwin Schroedinger, nobel laureate in physics, claimed that it is 'impossible to carry out experiments on single molecules or atoms'. Today, the detection, tracking and study of single molecules and atoms has become an omnipresent tool in biology, chemistry and physics alike. For example, sequencing DNA one base pair (or letter) at a time currently provides the most likely solution to fulfill the quest for a $1,000 human genome. Nevertheless, observation of a single molecule, especially with standard light microscopes requires a good deal of laboratory skills. This is mostly due to the fact that a single molecule only gives a miniscule amount of detectable signal. In fact, people using light as a probe have relied exclusively on the use of fluorescence, the emission of lower energy light following absorption of radiation at a certain energy. In this scheme, the signal from the molecule of interest can be easily separated from residual excitation light or background fluorescence simply by filtering the detected light spectrally and only detecting the color that is emitted by the molecule. In this way, it is possible to suppress unwanted signals from the billions of other molecules that are in the vicinity of the molecule of interest. As powerful as this approach has been, it also has one major limitation: it is only possible to study molecules that are highly fluorescent, i.e. emit lower energy light with high efficiency. Scientists from the ETH Zurich have recently demonstrated a major step towards the detection and study of single molecules in absorption.
Nanomaterial-based drug-delivery and nanotoxicology are two of the areas that require sophisticated methods and techniques for characterizing, testing and imaging nanoparticulate matter inside the body. Especially the potential risk factors of certain nanomaterials have become a heated topic of discussion recently. Most, if not all, toxicological studies on nanoparticles rely on current methods, practices and terminology as gained and applied in the analysis of micro- and ultrafine particles and mineral fibers. The development of novel imaging techniques that can visualize local populations of nanoparticles at nanometer resolution within the structures of cells - without destroying or damaging the cell - are therefore important. Researchers in the U.S. have now demonstrated that at ultrasonic frequencies, intracellular nanomaterial cause sufficient wave scattering that a probe outside the cell can respond to. This ultrasonic holography technique provides a non-invasive way of looking inside a cell.
'Reverse engineering' is the process of discovering the technological principles of a device or system through analysis of its structure, function and operation, often by taking it apart and analyzing its workings in detail. This approach is a common practice among industrial companies who use it to analyze the competition's products, be it cars or MP3 players, to understand where the latest product improvements come from and how individual components are made. An increasing number of scientists apply a similar approach to nature's own 'micro- and nanotechnology' systems. They believe that learning from nature's designs and engineering successes is more likely to provide the cues for designing practical nanodevices than by simply applying a 'trial and error' approach. The basic idea is that natural materials and systems can be adopted for human use beyond their original purpose in nature. Some examples of 'reverse' biophysics work and have already proven quite useful, for instance the use of individual red blood cells as reliable, ultrasensitive mechanotransducers.
With the advance of nanotechnologies the demand for ever more precise instruments that measure, map and manipulate details at the nanoscale increases as well. For instance, the study of potential distributions with nanoscale resolution becomes increasingly important. In the early days of atomic force microscopy (AFM) the scanning force microscope was used to measure charges, dielectric constants, film thickness of insulating layers, photovoltage, and electrical potential of a given surface. Then, in 1991, the concept of a scanning contact potential microscope was introduced, allowing the simultaneous measurement of topography and contact potential difference. Named the scanning surface potential microscope (SSPM) - also often referred to as Kelvin probe force microscope - this is a variation of the AFM that measures the electrostatic forces (potential) between the probe tip and the surface of a material. Compared with other AFM techniques, the lateral resolution of traditional SSPM, from submicron down to 10 nm, is much lower.
Understanding and manipulating cellular function at the level of individual molecules is within reach. One of the requirements of single molecule techniques is the ability to follow an individual molecule for sufficiently long times in solution. However, it is a challenge to cope with the effects of Brownian motion (the random motion of small particles suspended in a gas or liquid) on this time scale. To meet this challenge, more recently, biomolecules have been encapsulated inside lipid vesicles, which are themselves tethered to a surface. Now, a novel nanocontainer offers controlled permeability functionality which not only is desirable for single molecule imaging but also is a very important property for micro- and nanodevices and for delivery of drugs or imaging agents in vitro and in vivo.
Whenever you read an article about nano this or nano that, chances are you come across a large number of confusing three-letter acronyms - AFM, SFM, SEM, TEM, SPM, FIB, CNT and so on. It seems scientists earn extra kudos when they come up with a new three-letter combination. One of the most important acronyms in nanotechnology is AFM - Atomic Force Microscopy. This instrument has become the most widely used tool for imaging, measuring and manipulating matter at the nanoscale and in turn has inspired a variety of other scanning probe techniques. Originally the AFM was used to image the topography of surfaces, but by modifying the tip it is possible to measure other quantities (for example, electric and magnetic properties, chemical potentials, friction and so on), and also to perform various types of spectroscopy and analysis. Today we take a look at one of the instruments that has it all made possible. So far, over 20,000 AFM-related papers have been published; over 500 patents were issued related to various forms of scanning probe microscopes (SPM); several dozen companies are involved in manufacturing SPM and related instruments, with an annual worldwide turnover of $250-300 million, and approx. 10,000 commercial systems sold (not counting a significant number of home-built systems).