What Are Optical Tweezers?

Optical tweezers are instruments that hold and move microscopic objects using the momentum carried by a tightly focused laser beam. A single beam brought to a diffraction-limited spot through a high numerical aperture objective creates a three-dimensional potential well in which a dielectric particle sits, and translating the focus drags the particle with it. Because the trapping force is generated by light rather than by contact, the technique manipulates living cells, bacteria, and individual biomolecules without mechanical damage or physical tethering to a probe.

Arthur Ashkin at Bell Laboratories established the field, reporting acceleration and trapping of micron-sized neutral particles by laser radiation pressure in 1970 and identifying the gradient force that makes stable trapping possible. The single-beam gradient trap that defines the modern instrument followed in 1986, and trapping of viruses and bacteria came shortly after. Ashkin received a share of the 2018 Nobel Prize in Physics for the work, and his contribution is surveyed in a retrospective on the origins of optical trapping.

Gradient and Scattering Forces

The optical force on a trapped particle separates into two components. The scattering force acts along the direction of beam propagation and pushes the particle downstream. The gradient force points toward the region of highest intensity and, for a particle with refractive index above that of the surrounding medium, pulls it into the focus. Stable trapping requires the axial gradient force to overcome the scattering force, which is why a steeply converging beam from an objective of numerical aperture near 1.2 or higher is essential. For particles much smaller than the wavelength the physics is well described by treating the particle as an induced dipole in a field gradient, while for particles much larger than the wavelength a ray-optics picture based on momentum transfer at refracting surfaces applies. Typical traps deliver forces from a fraction of a piconewton to about 100 piconewtons, a range that happens to match the forces generated by molecular motors and by the unfolding of nucleic acid structures.

Instrument Design and Calibration

A working optical tweezer combines a near-infrared laser, usually around 1064 nm to limit absorption and photodamage in biological samples, with an inverted microscope, beam-steering optics, and a position detector. Steering is done with galvanometer mirrors, acousto-optic deflectors, or a spatial light modulator, the last of which can create dozens of independently addressable traps from one beam. Position is usually read by back-focal-plane interferometry on the forward-scattered light, though dual-trap designs using confocal detection of back-scattered light avoid the need for optical access on both sides of the sample. Force calibration converts detector voltage into piconewtons by fitting the Lorentzian power spectrum of the particle's Brownian motion in the trap, by applying a known viscous drag, or by equipartition analysis of positional variance.

Single-Molecule Force Spectroscopy

The dominant scientific use of optical tweezers is measuring forces and displacements on individual molecules. A DNA or protein molecule is tethered between two beads, one held in a trap and one on a pipette or in a second trap, and the tether is stretched while force and extension are recorded. This geometry has resolved the stepping of kinesin and myosin along cytoskeletal filaments, the translocation of RNA polymerase base by base, and the folding and unfolding trajectories of individual proteins, as reviewed in accounts of optical tweezers as a tool in cell biology and of single-molecule experiments using optical traps.

Applications

Optical tweezers have applications in a range of fields, including:

• Molecular biophysics, for studying motor proteins and nucleic acid mechanics
• Cell biology and microrheology of the cytoplasm and membranes
• Assisted reproduction and clinical sperm selection
• Colloid science and the assembly of microstructures
• Atomic physics, including optical tweezer arrays of neutral atoms for quantum computing
• Microfluidic sorting of cells and particles