A revolution in optical manipulation

Abstract

A new generation of techniques that use the forces exerted by carefully sculpted wavefronts of light offers precisely the level of access and control needed for rapid progress at the frontiers of several branches of science and engineering. In particular, optical forces are ideally suited to manipulating mesoscopic systems, which are characterized by length scales ranging from tens of nanometres to hundreds of micrometres, forces ranging from femtonewtons to nanonewtons and time scales ranging upward from a microsecond. In biology, this range covers many of the inter-and intracellular processes responsible for respiration, reproduction and signalling. In physics and chemistry, it corresponds to the still-puzzling interface between classical and quantum mechanical behaviour, which is made all the more perplexing by the general inapplicability of statistical many-body theory in this realm. Fulfilment of the promise of mesoscopic engineering has been held back by the need for tiny motors to drive micromachines and for robust human-scale interfaces with atomic-scale nanotechnology. Until quite recently, the options for manipulating, analysing and organizing mesoscopically textured matter have been limited. The advent of flexible multifunctional optical traps meets this need. Many of the most powerful optical manipulation techniques are derived from single-beam optical traps known as optical tweezers (see Fig. 1), which were introduced by Arthur Ashkin, Steven Chu and their coworkers at AT&T Bell Laboratories 1,2 . An optical tweezer uses forces exerted by a strongly focused beam of light to trap small objects. Although the theory behind optical tweezers is still being developed, the basic principles are straightforward for objects either much smaller than the wave-length of light or much larger. Small objects develop an electric dipole moment in response to the light's electric field, which, generally speaking, is drawn up intensity gradients in the electric field toward the focus. Larger objects act as lenses, refracting the rays of light and redirecting the momentum of their photons. The resulting recoil draws them toward the higher flux of photons near the focus 3 . This recoil is all but imperceptible for a macroscopic lens but can have a substantial influence on mesoscopic objects. Optical gradient forces compete with radiation pressure result-ing from the momentum absorbed or otherwise transferred from the photons in the beam, which acts like a fire hose to blow parti-cles down the optical axis. Stable trapping requires the axial gra-dient force to dominate, and is achieved when the beam diverges rapidly enough away from the focal point. For this reason, opti-cal tweezers are usually constructed around microscope objective lenses, whose high numerical apertures and well corrected aber-rations focus light as tightly as possible. Optical tweezers can trap objects as small as 5 nm (refs 4,5) and can exert forces exceeding 100 pN (refs 6–8) with resolutions as fine as 100 aN (refs 9–11). This is the ideal range for exerting forces on biological and macromolecular systems and for measuring their responses. Biological and medical applications of optical tweezers have been reviewed extensively 2,12,13 , and so just a few examples of their uses will be outlined. Optical tweezers have been used to probe the viscoelastic properties of single biopolymers (such as DNA), cell membranes, aggregated protein fibres (such as actin), gels of such fibres in the cytoskeleton, and composite structures (such as chroma-tin and chromosomes). They have also been used to characterize the forces exerted by molecular motors such as myosin, kinesin, proces-sive enzymes and ribosomes. These measurements have revealed that cells use mechanical forces not only for mobility, motility and chro-mosome sorting during reproduction but also for regulating gene transcription, inter-and intracellular signalling and respiration. As a natural extension of these studies, optical tweezers offer great prom-ise for intracellular surgery, for instance, in modifying the chromo-somes of living cells 14 . On a larger scale, optical tweezers are useful for selecting individual microbes from heterogeneous populations. In addition, their ability to transport and modify cells precisely has led to clinical applications in such areas as in vitro fertilization 15 . In the physical sciences, the unique ability of optical tweezers to organize matter non-invasively has led to a burst of activity in A revolution in optical manipulation