Lasers have been used to conduct academic research nearly since their invention in 1960, and these sources of coherent light quickly found diverse, if not precisely directed, applications. “Some of the earliest research was simply zapping anything within reach of a laser to see what happened,” laser historian Jeff Hecht said. “One result was the development of industrial applications, and the same approach was used in medical research.” Of course, early lasers were not only expensive to build, they also required a team of scientists to operate and maintain them. Recent trends indicate that as lasers have become less costly, more reliable, smaller in size, and easier to use, they’ve also become increasingly commonplace in the lab, where they can replace and improve upon existing technologies in a variety of disciplines. Researchers at the University of Colorado Boulder built a microflow reactor to identify molecules in combustion reactions using an ytterbium-fiber vacuum ultraviolet light source that effectively serves as a more accessible alternative to synchrotron instruments. ID: inside diameter; L: length; SCCM: standard cubic centimeters per minute; VUV: vacuum ultraviolet. Courtesy of Nicole Labbe. Marco Arrigoni, director of marketing for the scientific market at Coherent Inc., sees this particular trend persisting. “Traditionally, research teams would have to build their own lasers,” he said. “Today, you see lasers in the scientific community as more of a black box — the user will not have to know anything about the laser.” Synchrotron replacement While spectroscopy and microscopy dominate research applications for lasers, the technology is also employed in myriad other fields by scientists, some of whom have limited experience in optics or photonics. Nicole Labbe, an assistant professor of mechanical engineering at the University of Colorado Boulder is one such scientist. Her training in theoretical chemical engineering did not require her to “take data,” although she worked closely with experimentalists in the past. When she started at Boulder in 2016, Labbe inherited a retiring professor’s research group, which required her to get up to speed on laser technologies. “I’m definitely more of a laser user than a laser scientist,” Labbe said. BRAIN directly increased research laser sales, because it was focused on looking at the brain in nondestructive ways. Multiphoton imaging and optogenetics benefitted from this wave of funding. — Marco Arrigoni, director of marketing for the scientific market at Coherent Inc. Her lab examines the chemicals produced by combustion reactions, with an eye toward designing more efficient engines and fuels that could potentially lower pollution. “Tens of thousands of unique molecules emerge from your car’s tailpipe,” Labbe said. “They are the result of hundreds of thousands of different reactions — all happening in concert, very quickly.” To better understand this “complicated web of chemistry,” as she called it, Labbe’s team built a microflow reactor that allows the researchers to take a snapshot of combustion reactions using mass spectrometry. Mass spectrometry works by ionizing a mix of molecules and assessing their mass-to-charge ratio to identify particular chemical species. Initially, Labbe’s group ionized the chemical products in the microreactor with an Nd:YAG laser that delivered a fixed energy output of about 10.5 eV, operating on the ninth harmonic. “However, that laser’s energy was the biggest limitation with the experiment,” Labbe said. Because mass spectrometry relies on a certain amount of energy to ionize molecules, a laser’s output is crucial. If a molecule’s ionization energy does not correspond to the laser’s output, the molecule will go undetected — either because it is not ionized, or because it is blown apart. One alternative to using mass spectrometry is to travel to a synchrotron facility, Labbe said, which she had done in the past. Synchrotrons can output varied light energies and offer a more nuanced analytical approach than many tabletop lasers commercially available to researchers. But there are drawbacks to this approach, Labbe said: “Unless you’re a lab scientist at a synchrotron and have a dedicated beam line, you have to apply for time, which is highly competitive.” KMLabs’ Henry Kapteyn and Margaret Murnane use lasers that leverage high harmonic generation to produce wavelengths of light that are able to characterize the mechanical properties of ~5-nm films and investigate the influence of dopants and surfaces. They found that as the layers thin, the mechanical properties dramatically deteriorate, becoming nearly 10× flimsier than expected. Courtesy of JILA. She was able to avoid this process, however, through a fortuitous introduction to her University of Colorado colleagues — physicists Henry Kapteyn and Margaret Murnane, whose company, KMLabs, has been designing ultrafast, tabletop lasers since 1994. Labbe teamed up with KMLabs to test prototypes of what would become its Hyperion vacuum ultraviolet (VUV) laser, an ytterbium fiber light source that allows researchers the ability to modulate energy output from 6.0 to 10.8 eV in discrete intervals. “All of a sudden we had the ability to adjust the power,” Labbe said. “This allowed us to see more products of our reactions. It opened a whole new world.” KMLabs’ Hyperion laser, Kapteyn said, works through high harmonic generation — the nonlinear process by which laser light is converted to various wavelengths at harmonic frequencies of the fundamental. High harmonic generation can help produce x-ray and extreme-UV laser pulses at femtosecond or faster speeds. Traditionally, lasers operate at a single harmonic that produces a fixed output. A study — which compared the efficacy of a CO2 laser (a), a CO laser (b), and a thulium fiber laser (c) for fractional skin ablation — found that the CO laser generated greater coagulation while maintaining deep ablation holes, when compared to using the CO2 and thulium fiber lasers. The additional coagulation could enhance the skin-tightening effects of the treatment. The thermal damage is highlighted with black lines. Courtesy of Linh Ha. Coherent’s Arrigoni said ytterbium fiber lasers typically produce high average power with fast repetition rates, allowing researchers to capture data quickly. The lasers have become the standard, he added, in multiphoton imaging and optogenetics, either when used directly or as a pump for tunable accessories such as optical parametric oscillators and amplifiers. Labbe said, “It’s not a complete replacement for a synchrotron, of course, but now we have the leisure to test new things in-house.” She further pointed out that lasers that are able to act as synchrotron sources have a wide applicability in research, from atmospheric and interstellar science to investigations of materials. Probing nanoscale materials The use of lasers to detect and measure imperfections in materials is not new. Hand-held laser-induced breakdown spectroscopy devices, for example, are now commonly deployed in the field to analyze soils, polymers, food, and other bulk materials. But as nanoscale materials have entered the mix, engineers have sought to expand the capabilities of these systems by leveraging more powerful lasers that can probe samples with shorter wavelengths. “For decades, we have been probing nanoscale materials using visible laser sources with wavelengths that are too large to be very sensitive to their structural and functional properties,” Murnane said. Sources that generate high harmonic frequencies seem well-poised to take advantage of this need. For studies on heat transport at the nanoscale and on charge, spin, and phonon dynamics in nanoparticles, Kapteyn and Murnane use ultrafast, high-repetition-rate laser systems that generate extreme UV and soft x-ray light spanning wavelengths from 1 to 10 nm1,2. Murnane said it is important to investigate material properties at the nanoscale because such properties can be vastly different from the bulk properties of the same material. Kapetyn said, “Although we are analyzing these materials with ultrafast pulses to study quantum phenomena, we’re actually affecting the system in a way that evolves over a much longer period of time.” To help design and fabricate microelectronics that leverage quantum properties such as spin, KMLabs recently joined the Belgium-based Interuniversity Microelectronics Centre (IMEC). Cutting out surgery Coherent’s Arrigoni said that, while the market growth for industrial lasers typically follows the economy, the market for research lasers follows publicly funded national science budgets, which grow about 3% each year. New project programs can occasionally further spur growth. The Obama administration’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative provided one such boost in 2013. “BRAIN directly increased research laser sales,” Arrigoni said, “because it was very focused on looking at the brain in nondestructive ways.” Multiphoton imaging and optogenetics benefitted from this wave of funding, he said. The ease with which output power and pulse speed can be modulated on many lasers has also prompted research beyond brain imaging — for example, using lasers to rapidly diagnose cancers and bacterial infections3,4, or as an alternative to surgery. A team at Columbia University, for example, is using femtosecond pulses from Ti:sapphire lasers to cross-link corneal proteins as an alternative to more invasive lasik procedures for vision correction5. Another recent line of research is exploring the use of mid-infrared carbon monoxide (CO) lasers as surgical alternatives. Although these lasers have been used in research labs since the late 1960s, their CO2 counterparts — which output 9- to 11-µm light — became the standard for many industrial and medical processes over time. “The advances in compact, fully sealed CO2 laser technology have enabled commercially viable CO lasers now,” said Dan Attanasio, a senior product line manager at Coherent. This new generation of CO lasers deploys 5.5-µm wavelengths, which provides multiple advantages, including 3× greater optical penetration into tissue compared to CO2 lasers, said Linh Ha, a clinical scientist at the Institute of Biomedical Optics at the University of Lübeck in Germany. Water also has lower absorption at 5.5 µm, which allows better coagulation in tissue. And shorter-wavelength CO lasers can also produce tighter spots, which can promote greater surgical precision. Ha and colleagues from the University of Lübeck and Harvard Medical School sampled three types of lasers for fractional ablation on ex vivo human skin: a CO2 laser, a prototype CO laser, and a 1.9-µm wavelength thulium fiber laser6. Fractional skin ablation is a dermatological technique that resurfaces and rejuvenates the skin. Dermatologists typically use CO2 lasers or 3-µm-wavelength erbium-doped YAG lasers for this procedure. Ha’s study found that the CO laser generated greater coagulation while maintaining deep ablation holes, as compared to CO2 and thulium fiber lasers. The additional coagulation could enhance the skin-tightening effects of the treatment. Ha believes that in the future tunable laser systems operating in the infrared will allow physicians the ability to tailor treatment to patients’ needs. “The ‘perfect’ laser system for fractional laser therapy would offer an adjustable ratio of ablation to coagulation,” she said. CO lasers, Attanasio said, provide research clinicians with a new tool at their disposal. “This laser technology will emerge as a platform for new investigations, just as CO2 laser technology did before it.” www.linkedin.com/in/farooqtheahmed Acknowledgments The author would like to thank Jeff Hecht; Marco Arrigoni and Dan Attanasio, Coherent Inc.; Nicole Labbe, the University of Colorado Boulder; Henry Kapteyn and Margaret Murnane, KMLabs; and Linh Ha, the University of Lübeck. References 1. T.D. Frazer et al. (2019). Engineering nanoscale thermal transport: size- and spacing-dependent cooling of nanostructures. Phy Rev App, Vol. 11, Issue 2, 024042, www.doi.org/10.1103/physrevapplied.11.024042. 2. P. Tengdin et al. (2020). Direct light-induced spin transfer between elemental sublattices in a spintronic Heusler material via femto- second laser excitation. Sci Adv, Vol. 6, eaaz1100, www.doi.org/10.1126/sciadv.aaz1100. 3. G. Balasundaram et al. (2020). Biophotonic technologies for assessment of breast tumor surgical margins—a review. J Biophotonics, e202000280, www.doi.org/10.1002/jbio.202000280. 4. B. Lorenz et al. (2020). Discrimination between pathogenic and non-pathogenic E. coli strains by means of Raman microspectroscopy. Anal Bioanal Chem, Vol. 412, pp. 8241-8247, www.doi.org/10.1007/s00216-020-02957-2. 5. C. Wang et al. (2018). Femtosecond laser crosslinking of the cornea for non-invasive vision correction. Nat Photonics, Vol. 12, pp. 416-422, www.doi.org/10.1038/s41566-018-0174-8. 6. L. Ha et al. (2020). First assessment of a carbon monoxide laser and a thulium fiber laser for fractional ablation of skin. Lasers Surg Med, Vol. 52, Issue 8, www.doi.org/10.1002/lsm.23215.