Laser revolution

The 2018 Prize in Physics is awarded to Arthur Ashkin for his invention of optical tweezers and to Gérard Mourou and Donna Strickland for developing techniques to generate high-intensity, ultrashort optical laser pulses.

Arthur Ashkin, who won the 2018 Nobel Prize Physics for inventing “optical tweezers”.

THIS year’s Nobel Prize in Physics recognises a trio of scientists who have invented simple yet remarkable techniques to harness the power of lasers that now enable extremely tiny objects, on the one hand, and incredibly fast processes, on the other, to be viewed in a new revealing light. Both inventions have revolutionised the use of laser in basic scientific research, applications and industry. Apart from physics, other fields, including chemistry, biology, medicine and technology, have benefited immensely from the high-precision methods and instruments that have resulted from these two award-winning works.

The American physicist Arthur Ashkin (96), formerly with Bell Laboratories in Holmdel, New Jersey, received half the award of nine million Swedish krona ($1.1 million) for his invention of “optical tweezers”. As the name implies, optical tweezers enable one to grab and manipulate the tiniest elements of matter—atoms, molecules, viruses, bacteria, living cells and bits of DNA—with laser beams without any damage to the material being studied. What was the stuff of science fiction, soon after the invention of the laser in 1960, is now reality.

The Nobel citation for Ashkin reads, “for the optical tweezers and their application to biological systems”.

The French physicist Gérard Mourou (74) of École Polytechnique, Palaiseau, France, and the Canadian physicist Donna Strickland (59) of the University of Waterloo, Canada, who had been Mourou’s doctoral student while doing this award-winning work at the University of Rochester, New York, share the other half of the Nobel Prize for developing techniques to generate high-intensity laser pulses that can stimulate targets at femtosecond (fs, a millionth of a billionth of a second or 10—15 s) timescales.

Today it is possible to generate petawatts (a million billion watts) of laser power packed into pulses at incredibly short timescales of attoseconds (billionth of a billionth of a second, 10—18 s). Besides, the method has enabled applications in diverse fields including table top terawatt (1012 watt) or T3 lasers, particle accelerator technology and high-intensity applications in industry and medicine, including precision retinal and corneal surgery.

The Nobel citation for Mourou and Donna Strickland says, “for their method of generating high-intensity, ultrashort optical pulses”.

Optical tweezers

Optical tweezers are a laser-based technique for trapping and manoeuvring objects, making use of the fact that light can exert force, which is called “radiation pressure”. That light can exert force was suggested 400 years ago by Johannes Kepler, the astronomer who gave us Kepler’s laws that govern planetary motion, when he argued that the tails of comets always point away from the sun because of the pressure of light from the sun. In 1873, the scientist James Clerk Maxwell showed that his theory of electromagnetism implied the existence of radiation pressure. However, because radiation pressure is so weak, experimental verification of its existence was difficult and had to wait until the early 1900s.

With the invention of the laser, detailed study of radiation pressure became possible. Unlike ordinary light, where light of many colours (wavelengths) and their phases are randomly mixed, the laser is an intense and coherent collimated beam of monochromatic light. Soon after the advent of the laser, Ashkin realised that the laser would be ideal for getting light to move small particles and started experimenting with the new equipment at Bell Laboratories. In an interview to the journal Nature Photonics in 2011, Ashkin said that he first became interested in radiation pressure forces during the Second World War when he was at the Columbia Radiation Laboratory. “We worked on microwave magnetrons. For fun, I tried an experiment to detect the radiation pressure of a 3-cm-wavelength megawatt magnetron, and it worked.”

Ashkin focussed light from the laser on micrometre-sized transparent latex beads for his experiments. In a landmark experiment in 1970, he showed that force due to light from the laser could actually move particles in air or water. The particles, he found, were accelerated by the forward force in the direction of the light from the laser. But, to his surprise, he also found that the spheres were drawn to the high-intensity region at the centre of the beam.

Since the intensity falls from the centre towards the periphery of the beam, the radiation pressure of the light on the spheres also correspondingly varies spatially, pushing them towards the middle of the beam, which holds the particles at the beam centre (Figure 1). In his 2011 interview, Ashkin said: “This demonstrated very large pushing forces and, surprisingly, a strong transverse gradient force due to basic scattering and gradient forces that pulled the particles into the high-intensity region of the light. These observations showed how laser light could trap particles on a glass plate.”

To achieve trapping, Ashkin initially devised a scheme with a counter-propagating laser beam so that the push of the two opposing beams could be made to cancel out the motion of the beads and particles could be trapped. This development came in 1970 itself. In the following year came the optical levitation trap in air, the first single beam 3D trap where the force of a vertical laser beam on a bead is balanced by the counterforce of gravity, and the particle is trapped at a point in air.

By 1978, Ashkin had developed his idea of an all-optical single-beam 3D trap. In a paper published in Physical Review Letters in 1978, Ashkin offered a description of such a device and also proposed how it could be used to trap atoms, cool them down to very low temperatures (to minimise thermal fluctuations) and manipulate them—an idea that the American physicist Steven Chu and others realised much later in a work that went on to win the Nobel Prize in 1997.

The first attempts by Ashkin and associates to trap atoms were not successful. It would take another eight years for the researchers (including Chu) to implement the concept first on dielectric particles. They demonstrated that this method could trap dielectric particles in water, ranging in size from a few tens of nanometres to tens of micrometres. Around the same time, similar ideas had been developed by V.S. Letokhov and associates in the former Soviet Russia (see box). “That was a time of many exciting discoveries, but I don’t recall jumping out of my bathtub and running down the street naked yelling ‘eureka’! One highlight of the discovery was the realisation that it might also be possible to trap atoms and molecules—after all, atoms are just small dielectric particles,”Ashkin has said.

Optical tweezer traps typically refer to single-beam gradient traps as described by Ashkin. Here a laser beam is focussed through a strong lens, which creates a component of the gradient force opposite to the direction of propagation of the beam (Figure 1.4). Trapping is achieved when the gradient force component is strong enough to cancel the forward scattering force, which requires a large convergence angle of the beam. In practice, the objective lens of a microscope is powerful enough to do this job.

“I invented tweezer traps in 1978,” Ashkin told Nature Photonics . “Tweezer trap depths are orders of magnitude greater than those of the atom traps proposed earlier by Letokhov and others. Tweezers are single-beam traps and are therefore easily manoeuvrable in space. Interestingly, optical tweezers were first applied in 1986, at a time of difficulty in our first atom-trapping experiment. The demonstration of trapping sub-micrometre-sized Rayleigh particles [where the particle sizes are smaller than the wavelength of the light incident on them] at that time was proof of the validity of tweezer traps.” The work was groundbreaking enough to grab the headlines of the Sunday New York Times . Soon afterwards the method began to be successfully applied for atom cooling and trapping, which got the 1997 Nobel Prize in Physics (see box).

Ashkin soon realised that the technique that he had invented had great potential for use in manipulating biological systems. But, as he said in his interview: “I was concerned at that time about the potential damage that strong laser beams could cause to living tissue. This problem was later solved by using infrared lasers.” Indeed, in their first experiment, when Ashkin and colleagues were trapping sub-micrometre particles of the tobacco mosaic virus (TMV), they left the samples under the microscope for a day or so. When they returned, they discovered “strange particles that seemed to be self-propelled”, which they later realised were bacteria. However, the tweezers’ intense green light quickly killed them, a process Ashkin dubbed as “opticution”. But once they switched to infrared laser, the bacteria could be kept alive indefinitely in the trap.

This innovation paved the way for the possibility that one could really study biological systems using optical tweezers. Ashkin’s subsequent experiments included manipulating plant cell components and estimating the force involved in organelle transport in amoeba cells. His pioneering studies triggered the use of optical tweezers for new biological studies by other scientists as well. The first quantitative application of optical tweezers to biological systems was in the study of the mechanics of bacterial flagella, the helical filament that propels the bacterium by connecting to a molecular rotary motor, by Steven Block, David Blair and Howard Berg. The flagellum was first tethered to a substrate so that its action set the bacterium spinning. Then they paralysed the flagellum and used the optical tweezers to gently pull the bacteria sideways. By measuring its return to position, they determined the elasticity of the specialised protein complex that connects the flagellum to the cell.

Basically, an optical tweezer experiment involves attaching a biomolecule to a trapped bead, pulling on it and determining the force one must apply to dissociate a molecular complex. The distance the bead moves is directly proportional to the force applied and is referred to as “trap stiffness”. As Block has explained, it is an optical equivalent of Hooke’s law and the trap is a three-dimensional spring made out of light. If the “spring” is calibrated for whatever force is put on it, optical tweezers can be used as a measuring tool. Highly accurate measurements of the motion of the bead, the motions of the molecule attached to the bead can be inferred to that level of accuracy.

“There are two major advantages of optical tweezers,” pointed out Pramod Pullarkat of the Raman Research Institute (RRI), Bengaluru, who uses the technique to investigate the elastic properties of the cell membrane and generation of forces in subcellular structures. In his email response to Frontline , he said: “Firstly, because the force exerted by light on a particle is very weak, it allows for the measurement of very weak forces acting at microscopic lengths. Thus it can measure tiny forces, for example, the Brownian kicks experienced by a suspended particle due to the collisions with water molecules or the force exerted by a single molecular motor protein. These forces are of the order of 0.000000000001 newton (piconewton). The second major advantage is that light can pass through transparent media. Thus one can easily manipulate organelles of a living cell without piercing the cell wall.”

Optical tweezers have now become a basic tool in biological physics and related areas, and the canvas of its applications is ever-widening. The basic optical tweezers instrument for trapping micrometre-sized particles is relatively simple. But accurate measurement of the motion of trapped objects, say in fluids, requires advanced instrumentation. This has now enabled optical trapping experiments where even a single base-pair rung along the helical DNA ladder can be detected, which means a spatial resolution at the angstrom (or tenth of a billionth of a metre) level.

The method is used for non-invasively trapping and manipulating single cells and organelles and for performing single-molecule force and motion measurements. The latter involves tagging them to “handles” that can be easily trapped with tweezers, such as micrometre-sized plastic or silica beads. The beads also serve as probes to monitor motion and measure force. Early single-molecule studies with such optical traps included physical properties of DNA, such as relaxation, elasticity and a sharp force-induced transition to an extended form of DNA.

The study of mechanics of molecular motors is an area that developed during the 1990s in which optical tweezers have been particularly useful. Roop Mallik of the Tata Institute of Fundamental Research (TIFR), Mumbai, who studies biological systems with tweezers, explained in an email to Frontline : “These motors are molecular machines present in all cells of our body, which generate the tiny forces that allow us to move around, for the heart to beat, and almost every conceivable biological motion that you can imagine.” They essentially convert chemical energy into linear or rotary motion. Linear motor proteins, for example, play an essential role in intracellular transport, muscle contraction and cell division.

A linear molecular motor is characterised by its step size, dwell time and the force generated, but these parameters are not accessible to any of conventional biophysical methods. Optical tweezers have enabled the determination of trajectories of single linear molecular motor proteins with sufficient resolution to obtain information on all the parameters. A breakthrough was the first direct observation of the stepping motion of kinesin, a motor involved in transportation of cellular cargo along microtubules (Figure 2).

“We can now exert a very precise calibrated force on a single molecule, for example a piece of DNA or a protein,” said Mallik. “Right after the discovery of the optical trap by Ashkin, it was not easily possible to prepare such molecules in isolated and purified form. Some of these molecules (like kinesin) had not even been discovered at that time. The parallel development of biological and chemical methods to purify these molecules has allowed us to use optical traps on them, and measure the very tiny forces generated during all kinds of biological and other processes, which are about a million-million times smaller than the forces that we are used to in our daily lives,” he added.

Mallik’s own work has involved a particular motor called dynein (belonging to the same family as kinesin) which he showed can “shift gears” when you pull it backward using an optical trap. As Mallik said: “This motor slows down but generates a proportionately larger force when you try to stop it with an optical trap. This ability, which is unique to dynein, allows it to work in very large teams inside the cells of our body. Almost all known bacteria and viruses hijack the dynein motor to infect and multiply in cells of the body.”

Pullarkat and colleagues have built an optical trap in-house at the RRI to investigate the mechanical properties of neuronal cells and other cell types. As Pullarkat pointed out, although optical traps are now commercially available and can be easily operated by researchers from any discipline, they can be very expensive. “Construction requires a good knowledge of the physics involved,” Pullarkat said. “It is much cheaper [at a total cost of a few lakhs] to build one’s own system. Typically, people with physics training build their own, and researchers at a few Indian universities as well as research institutes have, indeed, built their own optical tweezers. Apart from cost advantage, a self-built trap allows for easy implementation of specific trapping requirements,” he added.

From the earliest and simplest optical tweezers of Ashkin, the technique, too, has considerably evolved in recent times. According to Pullarkat, steerable optical tweezers have now been developed that use electrically rotatable mirrors. He said: “These allow for manipulation of living cells or other suitable particles as they could be trapped and moved from one location to the other. Steerable systems also allow for generating multiple traps by switching the focus of the laser beam between two or more locations at a very fast rate using acousto-optic deflectors, which enable the creation of a large number of traps with a single laser. With such ultra-fast steering, extended traps can also be generated, allowing particles to be confined to a line or a circle. Even more complex trap geometries can be generated using holographic or diffraction techniques.”

Ashkin’s basic idea of using radiation pressure to trap and manipulate particles, his invention of the optical tweezers and his pioneering applications of the technique of biological systems have thus opened up a new window through which, aided by technological innovations, the molecular foundations of biology can be investigated in unprecedented detail today.

In developing the technique for generating high-power ultrashort laser pulses, Mourou and Donna Strickland were inspired by a popular Scientific American article about radars that produced long wavelength radio waves. However, adopting the method used for radio waves for the shorter optical light waves was far from easy, both theoretically and practically. The breakthrough was described in their joint paper in December 1985, which was Donna Strickland’s first scientific publication that has now been found worthy of the Nobel award.

According to the background document on the work put out by the Nobel Committee, when Donna Strickland moved from Canada to Rochester, New York, to do research in physics, she became attracted by the green and red lights that lit up the laser lab like a Christmas tree and not least, by the vision of Mourou, who became her supervisor, which was to amplify short laser pulses to high intensity levels. In her post-announcement telephonic interview with the website Nobelprize.org, she said: “It was just a fun thing to do, and so I enjoyed putting many hours into it. It is the one time in my life that I worked very, very hard! It was fun time in the field of short-pulse lasers, and it was a fun group to be in and it was fun most of the time!”

From the time lasers were invented, scientists have attempted to make more intense pulsed laser beams. However, by the mid 1980s, it was the end of the road, it seemed. The development of short duration pulses was not followed by techniques to make the pulses carry more energy. There was only a marginal increase in the number of photons in each pulse between 1970 and 1985 (Figure 3). The problem was that increasing the peak power per pulse beyond a point resulted in either distortion to the shape of the pulse or worse, damage to the laser amplification medium or optical components of the apparatus.

The breakthrough and the Nobel Prize-winning work in 1985 of Mourou and Donna Strickland was the development of the chirped pulse amplification (CPA) technique for optical pulses. CPA essentially involves three steps: first, the ultrashort laser pulse is stretched in time by several orders of magnitude so that its peak power is correspondingly reduced; second, it is amplified—time-stretching enables huge amplification—in a laser material without damaging the amplifier; and third, it is compressed back in time to its original duration, resulting in very high peak power packed in that ultrashort period.

The stretching in time in the first step is actually achieved by introducing a “chirp” into the signal, that is, by using some kind of dispersive medium like a prism or a diffraction grating which decomposes the pulse into all of its constituent frequencies in such a way that low frequency (red) components propagated faster than the high frequency (blue) components (positive dispersion or “up-chirp”). This naturally reduces the intensity of the pulse; it is a way of “diluting” the light.

In the original experiment, Mourou and Donna Strickland used a 1.4-km-long optical fibre. The first improvement of the set-up by others saw the fibre being replaced by a pair of gratings (Figure 4). Pulse amplification saw an increase by nine orders of magnitude in the energy—nanojoule to joule—per pulse. Shortly after Mourou and Donna Strickland invented this simple and elegant method, CPA-based lasers with peak powers of more than 1 terawatt (1 TW, or a million-million watt) were built and the intensity of rapid laser pulses saw a giant leap (Figure 3) thereafter. In 1999, the Lawrence Livermore National Laboratory (LLNL) built a petawatt (1 PW, or a million billion watt) laser.

The invention of CPA triggered the development of several new areas of research and applications. One joule pulse, with a typical duration of one picosecond (ps, a billionth of a second), was produced with the first neodymium-glass laser. Shorter pulses with width below 100 femtoseconds were produced using titanium-sapphire lasers.

One of the early and important uses of ultrashort intense pulses was the rapid illumination of the fast processes between molecules and atoms, which happen so quickly that one could earlier describe it only as a transition between a “before” state and an “after” state. Now with femtosecond pulses, it is possible to see events during this near-instantaneous transition in detail. Imaging with a femtosecond laser pulse would make it the world’s fastest camera.

Drilling holes or cutting material, including living matter, with great precision, is now possible with ultra-sharp laser beams. By drilling minute holes deep into the storage medium, lasers can now be used to develop more efficient data storage systems. The technology is also being used for making surgical stents, micrometre-sized stretched metal cylinders that widen and reinforce blood vessels, the urinary tract and other passages in the body. In recent years, femtosecond lasers have been used in refractive surgical procedures to treat myopia and astigmatism. In LASIK (laser-assisted in situ keratomileusis), a femtosecond laser enables access to corneal stroma and enables its reshaping with high precision.

One of the new areas of research that ultrashort intense laser pulses have enabled is called attosecond physics (Figure 5). With laser pulses shorter than 100 attoseconds (one attosecond is a billionth of a billionth of a second), scientists can now explore the world of electrons. Electrons are basically responsible for all of chemistry—the chemical bonds and optical and electronic properties of matter. The chemical process can now be studied at the electron level.

Now visions for higher than petawatt lasers have emerged. For example, the Extreme Light Infrastructure (ELI) beamlines facility in Prague will have a 10-PW system—equivalent to an incredibly short flash from a hundred thousand billion electric bulbs—which will be completed in a few years’ time. A further tenfold increase in power is already being envisaged. Focussed intensity levels are expected to exceed a mind-boggling level of 1023 W/cm2 .

Thus the Nobel Prize-winning work by Mourou and Donna Strickland has opened many avenues for research in basic and applied sciences, even as the CPA is continually being improved upon and its frontiers are constantly expanding.