Researchers from the University of Bristol have assembled tools at nanometer scales that can be manipulated with laser tweezers to probe extremely small particles, surfaces and membranes. These so-called holographically trapped nanotools can now be calibrated to directly measure ultrasmall forces, supporting a novel form of force microscopy. Optical tweezers (single-beam gradient force traps) use a highly focused laser beam to provide an attractive (trapping) or repulsive force, depending on the refractive index mismatch, to physically hold and move microscopic dielectric objects. Optical tweezers have been used to study biological systems in recent years. The forces involved are typically on the order of piconewtons, and it has been shown that the forces acting on a microsphere in an optical trap can be modeled as a Hookean spring. The knowledge of the exact forces involved in trapping microparticles can be used to measure tiny forces occurring in nature – for example, how much bonding exists between a molecule and its environment. To do this quantitatively, however, the so-called optical trap constant (equivalent to the spring constant) has to be calibrated for each axis of the trap. There are several methods for doing this, but to date these are limited to either very small parts (nanoparticles) or simple shapes, such as microspheres or nanorods. But the Bristol researchers (with co-workers in Osna-brück, Germany, and Glasgow) have directed their attention to nanotools, which are combinations of simple shapes that generate nanoscopic assemblies offering additional functionalities. Nanotools are assembled at Bristol University using a dynamic holographic assembler. It uses a Ti:sapphire laser and a high-resolution spatial light modulator to generate hundreds of optical traps, which enable manipulation of numerous nanoparticles at the same time. To visualize the process, a multitouch table-user interface has been developed. It not only permits large-scale visualization of the manipulated parts but also controls the optical traps, thereby allowing users to intuitively move particles under the microscope with their fingers. The researchers envision these nano-tools forming small machines that can build even smaller nanotools, with which even smaller nanostructures can be built, until eventually individual atoms can be controlled. This will allow the micromanipulation of things such as DNA or brain cells to better understand how they respond to the forces applied to them when, for example, the need to insert or attach a drug arises. Using a nanotool, researcher Dr. David Carberry says he can “feel” the force being applied and knows how hard to push to control nanostructures precisely. Nanotools can be used not only as actuators but also as sensors. However, to quantitatively measure (or exert) forces, again the optical probe must be calibrated. For arbitrarily shaped assemblies, in contrast to simple shapes, this is not straightforward. This led the researchers working with professor Mervyn Miles to develop a generalized theory for the calibration and to verify it using an optical probe that can act as a cantilever tip of a scanning probe microscope. This nanotool was constructed by bringing together two 2-µm streptavidin-coated silica microspheres in contact with a biotin-coated silica nanorod, with the coatings making the parts stick together. Details of the work were published in the April 30, 2010, issue of the journal Nanotechnology. Nanotools, especially when calibrated, are expected to have a great deal of potential. For example, because the properties of a cancerous cell are very different from those of a healthy one, researchers should be able to poke it and determine whether they can obtain more information about its surface properties. The nanotools may even be capable of modifying cells via nanosurgery. The scientists, who have won research grants, have begun to collaborate with biomedical groups working on neurons and cardiac stem cells.