David McGloin and Jonathan P. Reid
Optical injection of a gold nanoparticle into a cell. The nanoparticle is first trapped by continuous wave optical tweezers. Once in position at the surface of the cell, a pulsed femtosecond beam is applied; this forces the cell through the cell membrane.
The field of molecular motor research is now relatively mature. Work on cells is perhaps not as developed. However, as optical physicists start to cross-train in biology, there is significant growth in this area. There is a growing body of work evaluating the properties of blood cells, as these are relatively easy to trap, as well as bacteria. Another growth area is in the spectroscopy of trapped cells, with the easy combination of optical tweezers with any spectroscopic technique that can be put through a microscope. Raman spectroscopy, which often involves long integration times, is of specific interest for those using traps. An additional advantage is that, with trapped cells, it becomes easier to probe sub-cellular and specific sites of interest on the cell membrane.
One of the most interesting developments has been the optical stretcher, in which deformations of cells can be studied in a dual-beam fiber trap. This is particularly useful because the health or properties of a cell can often be linked to the properties of its cytoskeleton. In the case of cancer, it is well known that, in order to proliferate, cells become more “squashy.” The alterations in the cytoskeleton can be detected by the optical stretch, and this makes it possible to use the technique to analyze material from biopsies. Jochen Guck’s group in Cambridge University has recently shown that the optical stretcher can be used to diagnose oral cancer; the researchers simply measured the deformability of the cells. No molecular markers are needed—just a simple mechanical measurement.
Another applied technique that is being invigorated by optical tweezers is that of cell poration—which is typically used for drug delivery. This process primarily involves blasting a cell with a high-intensity pulse of light, typically from a femtosecond laser source. Optical techniques are unlikely to have direct applications for drug delivery in vivo, but they can open the possibility of looking at controlled experiments in vitro and potentially being able to transfect cell lines that are traditionally hard to manipulate. In addition to the transfection of molecular material, these techniques can also be used to controllably introduce nanoparticles into cells—another area of great interest for imaging enhancements and drug delivery.
The technique was developed by Kishan Dholakia’s group at the University of St. Andrews in Scotland. A gold nanoparticle is trapped using optical tweezers and then positioned on the cell surface and injected into the cell using a 100-fs Ti:sapphire laser. This approach opens new avenues in cell microrheology and enhanced Raman spectroscopy, and it may lead to novel strategies for deploying and developing biosensors.
The aerosol carousel. Five aerosol water droplets are trapped in a ring. The droplets can be rotated, using holographic optical tweezers, to move through the “interrogation zone” denoted by the dashed box on the left-hand side. Here a Raman spectra is taken (right-hand image) and can be used to analyze the droplet composition as well as to gain information on its size. Using this technique, one can make comparative measurements between the different droplets
Trapping aerosols
To end, we come full circle. In some of the very first papers published on optical forces in the early 1970s, Ashkin looked at trapping particles in air: aerosols. This optical levitation work did not receive much attention when optical tweezers were developed, and it has remained a niche area that was far removed from mainstream optical manipulation research. It was not until very recently that any airborne particle was actually trapped within a conventional (high-numerical-aperture) optical trap.
Clearly, however, as our need to understand climate change grows, the work on airborne particles is becoming increasingly relevant. Optical tweezers provide a unique way of studying aerosol properties. They are able to localize a range of particle sizes in a simple way that other techniques, such as the electrodynamic balance, cannot match. They are particularly useful in the study of particle dynamics, as they are a non-destructive mechanism—unlike, say, a mass spectroscopy measurement.
In the figure above, we show the combination of some of the techniques we discussed to form an optical carousel for aerosols. Here, a holographic optical tweezers system is used to rotate trapped aerosols through a Raman spectroscopy probe region, so that particles can be analyzed in a comparative fashion, keeping the environment the same but the aerosol size different, for example. Our groups have led the way in analyzing aerosol dynamics, both in understanding the basic physics and technology and in developing techniques to probe atmospherically interesting aerosol properties, such as size, temperature, hygroscopicity, chemical aging and mass accommodation.
These sensitive measurements are made possible by the unique combination of trapping stability, precision control and the optical properties of aerosols themselves. Clearly, the study of aerosols has a long way to go; while we have successfully trapped submicron particles, which are of greater atmospheric interest than the 1-to-10-µm-diameter particles we typically deal with, they are proving a challenge to routinely trap and analyze. The other major challenge will be to examine whether non-spherical transparent liquid particles can be easily trapped. Some evidence indicating that photophoresis works can be used to back up the claim that light can be used to trap such particles, but heating may compromise this approach. Research that evaluates small, opaque particles such as soot would help shed light on ice nucleation and aerosol aging.
The past four decades have seen this optical subfield mushroom into a widely used technique across all the sciences. This explosion of work is unlikely to slow down as more and more physicists become interdisciplinary scientists and move into applied areas in biophysics and chemistry. Technology development continues as well. However, it is the applications—in biology, medicine, atmospheric science, and other areas—that are driving this exciting field. Look for more groundbreaking discoveries in the microworld over the next 40 years.
David McGloin is with the electronic engineering and physics division at the University of Dundee, Dundee, United Kingdom. Jonathan P. Reid is with the School of Chemistry, University of Bristol, Bristol, United Kingdom.
References and Resources
>> MicroTetris
>> Smallest Strip the Willow in the World
>> A. Ashkin. “Acceleration and Trapping of Particles by Radiation Pressure,” Phys. Rev. Lett. 24, 156 (1970).
>> A. Ashkin et al. “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11, 288 (1986).
>> M.J. Lang and S.M. Block. “Resource letter: LBOT-1: Laser-based optical tweezers,” Am. J. Phys. 71, 201 (2003).
>> D. McGloin. “Optical Tweezers: 20 years on,” Phil. Trans. Roy. Soc. A 364, 3521 (2006).
>> K. Dholakia et al. “Optical Micromanipulation,” Chem. Soc. Rev. 37, 42 (2008).
>> M. Dienerowitz et al. “Optical manipulation of nanoparticles: a review,” J. Nanophot. 2, 021875 (2008).
>> H. Zhang and K.K. Liu. “Optical tweezers for single cells,” J. Roy. Soc. Interface 5, 671 (2008).
>> T. Perkins. “Optical traps for single molecule biophysics: a primer,” Laser & Photon. Rev. 3, 203 (2009).
>> J.B. Wills et al. “Optical Control and Characterisation of Aerosol,” Chem. Phys. Lett. 481, 153 (2009).
