Laser Microscalpel Created

Femtosecond lasers have just become more accurate and versatile, thanks to Adela Ben-Yakar, mechanical engineering assistant professor at The University of Texas at Austin.

By nature, Femtosecond lasers produce extremely brief, high-energy light pulses that can sear a targeted cell so quickly and accurately that the lasers’ heat has no time to escape and damage nearby healthy cells.

However, the very same laser systems, typically used in LASIK and other eye surgeries, have been too bulky - until now. Ben-Yakar’s laboratory has developed a femtosecond laser microscope system that includes a tiny, flexible probe that focuses light pulses to a spot size smaller than a human cell.

Ben-Yakar dubbed her creation the Microscalpel.

The Microscalpel can destroy a single cell while leaving nearby cells intact, which could improve the precision of surgeries for cancer, epilepsy and other diseases.

"You can remove a cell with high precision in 3-D without damaging the cells above and below it," Ben-Yakar says. "And you can see, with the same precision, what you are doing to guide your microsurgery."

As a result, the medical community envisions the lasers' use for more accurate destruction of many types of unhealthy material. These include small tumors of the vocal cords, cancer cells left behind after the removal of solid tumors, individual cancer cells scattered throughout brain or other tissue and plaque in the arteries.

Within a few years, Ben-Yakar expects to shrink the probe's 15-millimeter diameter by three-fold, so it would match endoscopes used today for laparoscopic surgery. The probe tip she has developed also could be made disposable -- for use operating on people who have infectious diseases or destroying deadly viruses and other biomaterials.

To develop the miniature laser-surgery system, Ben-Yakar worked with co-author
Olav Solgaard at Stanford University's Electrical Engineering Department to incorporate a miniaturized scanning mirror. Ben-Yakar and her graduate student Chris Hoy, another co-author, also used a novel fiber optic cable that can withstand intense light pulses traveling from an infrared, femtosecond laser.

To make the intensity more manageable, they stretched the light pulses into longer, weaker pulses for traveling through the fiber. Then they used the fiber's unique properties to reconstruct the light into more intense, short light pulses before entering the tissue.

For the study, Ben-Yakar directed laser light at breast cancer cells in three-dimensional biostructures that mimic the optical properties of breast tissue. She has since studied laboratory-grown, layered cell structures that mimic skin tissue and other tissues.

Ben-Yakar is also investigating the use of nanoparticles to focus the light energy on targeted cells. In research published last year, she demonstrated that gold nanoparticles can function as nano-scale magnifying lenses, increasing the laser light reaching cells by at least an order of magnitude, or ten-fold.

"If we can consistently deliver nanoparticles to cancer cells or other tissue that we want to target, we would be able to remove hundreds of unwanted cells at once using a single femtosecond laser pulse," Ben-Yakar says. "But we would still be keeping the healthy cells alive while photo-damaging just the cells we want, basically creating nanoscale holes in a tissue."

Ben-Yakar's experimental system is described in the June 23 issue of Optics Express.

Grants from the National Science Foundation and the National Institute of Health funded the research.

Thin-disk laser yields energetic femtosecond pulses

Ursula Keller's group at ETH Zurich in Switzerland has built the first Yb:YAG thin-disk laser to deliver femtosecond pulses with energies above 10 µJ. The team believes that the design could yield a compact source of high-power ultrashort pulses for applications such as high-resolution imaging and precision micro- and nanomachining.

"Our motivation was to increase the pulse energy of femtosecond oscillators," team member Thomas Südmeyer told optics.org. "In this way, many experiments and applications that previously relied on complex and expensive amplifier systems are now within the reach of simple and cost-efficient diode-pumped solid-state lasers."

Generating high-energy femtosecond pulses is a crucial requirement for many scientific and industrial applications. The normal approach in these applications is to exploit a laser amplifier system, but the repetition rate is typically limited to the kilohertz regime – which in turn affects the signal-to-noise ratio and also restricts the throughput and precision of materials processing applications.

Other techniques are capable of delivering microjoule pulses at megahertz repetition rates, but these require complex amplifier systems with a seed laser and multiple amplification stages. In contrast, the new laser developed by Südmeyer and colleagues produces femtosecond pulses directly using a high-power oscillator, eliminating the need for any external amplification.

The laser delivers up to 45 W of average power at a repetition rate of 4 MHz. This yields 11.3 µJ pulses with a duration of 800 fs and a peak power of 12.5 MW, which Südmeyer says is sufficient for driving high-field experiments.

According to Südmeyer, the latest results are the culmination of several years' work on thin-disk lasers, which enable high average powers to be achieved with good beam quality. The Swiss team use a multiple-pass cavity to extend the length of the resonator to 37 m, while stable femtosecond pulses are produced by passive modelocking using a semiconductor saturable absorber mirror (SESAM). "This results in a power-scalable solution for the generation of pulses with durations in the femtosecond regime," said Südmeyer.

Until now, however, the pulse energies that could be produced from this set-up were limited to a few microjoules. "Our initial effort to increase the pulse energy was limited by some excess nonlinearity, which initially was not identified," commented Südmeyer. "We found that the source of the additional instabilities was the nonlinearity of the air atmosphere inside the laser cavity."

The solution, says Südmeyer, is to flood the laser cavity with helium, which has a negligible nonlinearity compared with air. The repetition rate was reduced to 4 MHz in order to produce pulses with energies greater that 10 µJ.

The team now plans to increase the average power to beyond 500 W and the pulse energy towards 100 µJ. "We will also investigate in collaboration with Professor Huber from the University in Hamburg new thin disk materials, which will allow us to achieve shorter pulse durations," said Südmeyer.

The researchers reported their work in Optics Express.

Attosecond angular streaking

Petrissa Eckle, Mathias Smolarski, Philip Schlup, Jens Biegert, André Staudte, Markus Schöffler, Harm G. Muller, Reinhard Dörner & Ursula Keller(Department Physik, ETH Zurich, Wolfgang-Pauli-Str. 16, 8093 Zurich, Switzerland)

Ultrashort measurement-time resolution is traditionally obtained in pump–probe experiments, for which two ultrashort light pulses are required; the time resolution is then determined by the pulse duration. But although pulses of subfemtosecond duration are available, so far the energy of these pulses is too low to fully implement the traditional pump–probe technique. Here, we demonstrate 'attosecond angular streaking', an alternative approach to achieving attosecond time resolution. The method uses the rotating electric-field vector of an intense circularly polarized pulse to deflect photo-ionized electrons in the radial spatial direction; the instant of ionization is then mapped to the final angle of the momentum vector in the polarization plane. We resolved subcycle dynamics in tunnelling ionization by the streaking field alone and demonstrate a temporal localization accuracy of 24 as r.m.s. and an estimated resolution of approximately 200 as. The demonstrated accuracy should enable the study of one of the fundamental aspects of quantum physics: the process of tunnelling of an electron through an energetically forbidden region.

Nature Physics
Published online: 30 May 2008 | doi:10.1038/nphys982

Brightest X-ray Vision at the Nano-scale

X-ray beams from an energy-recovery linac (linear accelerator) could be both a thousand times brighter and a thousand times faster--with pulses as brief as one ten-thousandth of a billionth of a second--than current state-of-the-art synchrotron X-ray sources.

"We're closer than ever to building a kind of universal toolkit for all the science and engineering disciplines," says Joel D. Brock, a Cornell University professor of applied and engineering physics.

"To date, the best-existing X-ray diffraction machines like CHESS (the Cornell High Energy Synchrotron Source) have given us ‘snapshots' of life--still pictures, for instance, of a particular virus. ERL will give us 3-D movies as the virus moves, grabs on to a cell and propagates disease. We will have X-ray vision at the nano-scale," Brock predicts, suggesting some questions to be answered:

-- Can excited-state studies of photosynthesis yield less expensive, more efficient solar energy?

-- If deep-earth pressures and temperatures turn ordinary carbon into diamond, what will those forces do to carbon nanotubes?

-- What really happens in the split second when a stem cell "decides" to become heart muscle?

But an equally pertinent question for Brock and other advocates of the next-generation of X-ray sources is this: How much longer can biomedical researchers, chemists, materials and environmental scientists, engineers, nanotechnologists and biophysicists maintain their competitive advantages without an instrument like ERL?

How ERLs Work

Moving beyond traditional X-ray crystallography systems--where the arrangement of atoms in crystalline material is revealed by analyzing the way X-ray beams are scattered from electrons in the crystal--the energy-recovery linac offers significant advantages. For one, materials subjected to ultrabright X-ray pulses need not be in crystalline form. And the tightly focused beam allows studies at much smaller scales.

As envisioned and invented by experimental physicists at Cornell, energy-recovery linear accelerators produce high-energy, pulsed X-ray beams by injecting electrons into the electromagnetic fields of a series of superconducting microwave cavities in a linear accelerator. Then, in a return loop, the electron beam is turned into X-rays by passing through undulators, which force the beam to oscillate to the right and left of its mean path with horseshoe magnets of alternating orientations. The pulsed X-rays are now ready for studies in multiple stations at the facility.

While the ERL X-ray beam loses about 0.04 percent of its energy during oscillation, 99.98 percent of its remaining energy is recaptured into the electromagnetic fields when the electrons are re-injected into the linac for deceleration--providing energy to accelerate subsequent bunches of electrons.

Compared to a traditional storage-ring X-ray source, such as CHESS, which recycles electrons billions of times but suffers from a compromised beam size, ERLs send each bunch of electrons through the undulators only once. Again and again, ERLs recover and reuse energy that accelerates electron bunches, while maintaining very small beam size--the key to the brilliance needed to study intimate details at the nano-scale.

The superconducting microwave cavities, which are cooled to -456 degrees Fahrenheit to produce hardly any heat during continuous operation, are among the novel components that proved their worth during the prototype-testing stage of the ERL project. Another component was the photocathode gun that produces electrons--in extremely intense short-duration bunches--for acceleration in the superconducting microwave cavities.

What Comes Next?

Development of ERL technologies, as well as prototype production and testing, was made possible by about $18 million in support from the National Science Foundation (NSF) and $12 million from New York State (for civil engineering feasibility studies, plus technology and infrastructure development). Cornell University has invested some $10 million in the project, with additional investment planned. ERL technology-development studies were conducted in conjunction with physicists at Jefferson Laboratory (the Thomas Jefferson National Accelerator Facility) in Newport News, Virginia.

Because ERL technology was developed with public money, it is now available to any institution that hopes to build a next-generation X-ray source--including Cornell University, which will propose assistance from federal and state sources.

Construction of an ERL X-ray facility--with national and international availability to researchers in all fields of science and engineering--is estimated to cost between $300 million to $400 million. Just as an ERL recovers energy, building an ERL in Ithaca, New York, Cornell officials observe, would save money by repurposing parts of CHESS and the Wilson Synchrotron Laboratory that were built at Cornell with public resources.

ERL for All

Cornell's Joel Brock wants an ERL, wherever it is built, because his particular line of research needs better X-rays.

"I'm trying to understand the growth of thin films of electronic materials, and it certainly would help to watch--in atomic detail--as we form exotic new materials for advanced optoelectronic applications," he says.

"But the beauty of ERL beams is that they can be used, simultaneously, for every form of science, from archaeology to zoology. In one station on the beam line on any given day you might have an environmental scientist working next to an art historian and a biophysicist--from Minneapolis or Beijing or Amsterdam. ERL really can become a universal toolkit."

Source: NSF, by Tracy Vosburgh

Laser sets heart beating to a new rhythm

Researchers in Japan have shown that a train of femtosecond laser pulses can cause heart muscle cells to contract and synchronize to the laser exposure. This optical pacemaker effect could provide crucial insights into abnormal heart rhythms and be combined with anti-fibrillation drugs to understand these effects at the cellular level. (Optics Express 16 8604)

"Calcium regulates the contraction of cardiomyocytes (heart muscle cells)," Nicholas Smith from Osaka University told optics.org. "We knew that if we could artificially perturb the calcium levels in the cell, we could control the beating and change its frequency. We used periodic femtosecond laser irradiation to synchronize the cell beat frequency and effectively create a laser pacemaker for the cells."

The team used a Ti:sapphire laser operating at 780 nm and emitting 80 fs pulses at a repetition rate of 82 MHz to stimulate the contraction. The optimal conditions were found to be average powers of between 15 and 30 mW and 8 ms exposures applied periodically at 1–2 Hz using a mechanical shutter.

The laser synchronization works by causing a transient leak from the cell's calcium stores. When the cells are cultured (in this case neonatal rat cardiomyocytes), the team introduces a fluorescent tag called Fluo-4, which it monitors using fluorescence microscopy to see the cells contracting.

Smith and his colleagues carried out over 200 experiments on single as well as groups of cardiomyocytes using different laser powers and periodicities. The synchronization of the cell contraction to the laser periodicity occurred in approximately 25% of all trials for average laser powers of between 15 and 30 mW.

"The laser contractions are as strong as the spontaneous contractions without the laser," said Smith. "We did not expect that whole cell groups would so easily synchronize with the laser periodicity."

When the laser is switched off, the researchers say that the target cells continue contracting for around 64 seconds or 20 laser cycles. But when the laser is switched back on, the cell cannot contract because of the high intracellular calcium levels. "Short-term damage can be negligible for a range of laser powers but long-term degradation of cell health can and will occur," commented Smith.

There are now several avenues of research that the team is hoping to pursue. "We want to understand why not all target cells synchronize with laser and why it is so easy to use the laser as a pacemaker for a large group of cells," said Smith. "We could also use the technique to introduce new contraction periodicities into individual cells within heart tissue, or within a whole heart. We could then study how asynchronous contractions might propagate through the heart."

Source: Optics.org

Extreme UV light made easy

A new system to generate coherent extreme-ultraviolet (EUV) light has been developed by researchers in Korea. The device, based on a nanostructure made of bow-tie shaped gold "antennas" on a sapphire substrate, is smaller and cheaper than existing systems and might allow an EUV source the size of a laptop computer to be made. Potential applications for the source include high-resolution biological imaging, advanced lithography of nanoscale patterns and perhaps even "X-ray clocks".

EUV light has a wavelength of between around 5 and 50 nm (100–10 times shorter than that of visible light). It can thus be used to etch patterns at tiny length scales and is ideal for spectroscopic applications because the wavelength is the same as that of many atomic transitions.

However, EUV radiation is currently produced in a very complicated process involving the use of amplified light pulses from an oscillator (a source of laser light) to ionize noble gas atoms. The electrons freed during this process are accelerated in the light field and their surplus energy is freed as attosecond (10^–18 s) pulses of light of different wavelengths. The shortest wavelengths of light can then be "filtered out" to produce a single EUV pulse.

Scientists would ideally like to produce EUV light directly from the oscillator without the need for expensive and bulky amplifiers. In this way, EUV-light generation could be simplified and the size of the source significantly reduced to tabletop dimensions. In contrast, current devices usually measure around 2–3 m across. Now, Seung-Woo Kim of KAIST in Daejeon and colleagues have shown that this might be possible.

The researchers report that a bow-tie nanostructure of gold – measuring around 20 nm across – can enhance the intensity of femtosecond laser light pulses by two orders of magnitude. This is high enough to generate EUV light with a wavelength of less than 50 nm directly from a small pulse with an energy of 10^11 W/cm^2 injected into argon gas (Nature 453 757). The energy needed is about 100 times less than in traditional approaches.

Surface plasmons

The technique works thanks to "surface plasmons" (surface excitations that involve billions of electrons) in the "gap" of the bow-tie gold nanostructures (see figure). When illuminated with the correct frequency of laser light, the surface plasmons can begin to resonate in unison, greatly increasing the local light field intensity. This phenomenon, known as resonant plasmon field enhancement, is already exploited in imaging techniques, such as surface-enhanced Raman scattering, which is sensitive enough to detect individual molecules on a metal surface.

Immediate applications include high-resolution imaging of biological objects, advanced lithography of nanoscale patterns and making X-ray clocks. These exploit a frequency-stabilized femtosecond laser and are being investigated worldwide to replace the current caesium atomic clocks for better time precision.

"This new method of short-wavelength light generation will open doors in imaging, lithography and spectroscopy on the nanoscale," commented Mark Stockman of the Georgia State University in a related article (Nature 453 731). The spatially coherent, laser-like light could have applications in many areas: spectroscopy; screening for defects in materials; and, if extended to X-ray or gamma-wavelengths, detecting minute amounts of fissile materials for public security and defence.

The team now plans to improve the conversion efficiency of the generated light by modifying the design of their nanostructure – for example, by making 3D cones with sharper tips. These will not only enable higher local field enhancement but also better interaction of the femtosecond light pulses with injected gas atoms. The team will also test the spatial and temporal coherence of the generated EUV light.

Source: Physicsworld.com; Phtonics.com; Optics.org

Moving EUVL From Lab to Fab

MAUI, Hawaii, June 3, 2008 -- More than 100 leading lithographers will meet in Maui next week to begin developing a plan to speed the introduction of extreme ultraviolet lithography (EUVL) into high-volume semiconductor manufacturing.

The effort will take place June 10-12 at the 2008 International Workshop on EUV Lithography, being held at the Wailea Beach Marriott. Keynote speaker will be retired IBM senior scientist Eberhard Spiller, PhD, whom many consider the "father of EUVL" because of his pioneering work on EUVL mirrors. Spiller is owner of Spiller X-Ray Optics in Livermore, Calif., and will speak on "Imaging in the EUV Region."

Optical lithography, which has dominated chip manufacturing for more than three decades, involves the direction of light onto a mask -- a sort of stencil of an integrated circuit pattern -- which projects the image of the pattern onto a semiconductor wafer covered with light-sensitive photoresist. The process has allowed more and more features to be crammed onto a computer chip, but current techniques have pushed the method about as far as it can go. Creating faster circuits with smaller and smaller features requires using shorter and shorter wavelengths of light -- such as those in the EUV range -- but technical difficulties and its cost continue to keep EUVL from becoming commercially viable for high-volume manufacturing.

In focused sessions at the International Workshop on EUV Lithography, key researchers from North America, Europe and Asia will present findings aimed at solving the most critical EUVL challenges in source power, mask defects and resist performance.

Special emphasis will be placed on the power scaling potential of discharge-produced plasma (DPP) and laser-produced plasma (LPP) as potential EUV power sources. LPP-based sources using high-power lasers are strong candidates for delivering 180 W of EUV power, enough to meet manufacturing requirements.

Single-module high-power laser supplier Gigaphoton will describe its high-power pulsed CO2 lasers, while researchers from MIT's Lincoln Lab in Lexington, Mass., will document the performance of Yb:YAG lasers as an alternate high-power laser technology. Additional candidates for high-power source technology also will be reviewed.

Six papers on enhancing the performance of current EUVL resists and highlighting new approaches for developing new resists will be presented. Other papers will cover EUVL source, optics, optics design, contamination, reticle protection, mask and mask metrology. Also, many leading researchers will give invited talks to highlight potential solutions to EUVL challenges.

Interspersed among the presentations will be three expert panels on EUVL source, mask, and general research and development issues. Panelists will identify areas where additional R&D is needed to solve the challenges to bringing EUVL into the factory.

Preceding the workshop, several courses will be offered June 9-10 on the fundamentals and underlying physics of EUVL. These courses recognize that EUVL is a multidisciplinary science, and are designed for technologists whose expertise lies outside lithography.

Organizing the workshop is EUV Litho Inc., an organization dedicated to promoting and accelerating introduction of EUVL into high-volume manufacturing through workshops and education. SPIE is co-sponsoring the event and will publish its proceedings.

Registration details and additional information are available at: www.euvlitho.com

3D microscopy images cells with nanoscale resolution

The highest resolution 3D images of the inside of single cells have been generated by scientists at the Max Planck Institute in Germany. The group says that its scanning fluorescent microscope obtains a spatial resolution far below the wavelength of light, allowing it to image the interior of cells with unprecedented detail (Nature Methods DOI:10.1038).

"We have produced the smallest focal spots that have been attained so far in a scanning fluorescent microscope, and thus attained the best 3D resolution inside a transparent object such as a cell," Stefan Hell, from the Department of NanoBiophotonics in Göttingen, told optics.org. "Contrary to previous systems, the focal spot, which measures 40–45 nm in diameter, is both spherical and of subdiffraction dimensions enabling isotropic 3D resolution on the nanoscale."

The resolution of a standard confocal system is limited to over 200 nm in the focal plane and over 500 nm along the optic axis. "We have achieved a resolution of 40–45 nm in all directions and this can be improved even further since our scheme allows further confinement of fluorescent spot (i.e. the effective PSF of the microscope)," commented Hell.

3D microscopy offers the only method of non-invasively visualizing the interior of cells. According to Hell, the level of 3D resolution is approaching that of an electron microscope but with the advantage of being able to use fluorescent tags to identify specific proteins.

The group's setup is a lens-based fluorescence microscope that merges the fundamentals from two existing microscopy techniques. "We have developed an effective microscopy scheme called isoSTED, which combines elements of stimulated emission depletion (STED) and 4Pi microscopy to compress the fluorescent spot to subdiffraction dimensions," explained Hell.

In STED microscopy, very short laser pulses excite a fluorescent tag attached to the sample under observation. This excitation pulse is immediately followed by a depletion pulse, tuned to an emission line of the fluorescent tag. The depletion pulse causes stimulated emission, which moves electrons from the excited state from which fluorescence occurs to a lower energy state. This decreases the effective spot size of the excited region resulting in higher resolution imaging.

The idea behind 4Pi microscopy is to illuminate the sample with a pair of synchronized laser pulses in such a way that the pulses interfere constructively. This is equivalent to increasing the total aperture of the system.

Source: optics.org