July 1, 2018 (Vol. 38, No. 13)
Laser-Based Mid-IR Spectroscopy Developed to Provide Accurate and Practical Microsecond Measurements
Ordinary Fourier-transform infrared (FTIR) spectroscopy, which enables label-free techniques, is versatile enough to study most substances—except biologics. When biologics entered the biopharma scene as therapeutics, scientists found that their tissue and water densities were too great for FTIR wavelengths to adequately penetrate. The weak signals that were returned, therefore, had poor signal-to-noise ratios. To further exacerbate the problem, FTIR spectroscopy lacked the speed to measure the fast-occurring reactions, like protein folding or enzymatic activity, which are common with biologic substances.
As scientists struggled with this problem, three Swiss researchers were putting their heads together to craft a solution. Newly minted Ph.D.s Andreas Hugi, Markus Mangold, and Markus Geiser had worked together at university on aspects of the problem. Soon after graduating, they combined their expertise in physics with insights from the field of instrumentation to create a laser-based mid-IR spectrometer that made mid-range IR measurements fast, accurate, and practical. The resulting spectrometer is based on semiconductor quantum cascade laser (QCL) frequency combs in the mid-infrared spectral range—the subject of Dr. Hugi’s doctoral thesis.
Drs. Hugi, Mangold, and Geiser spun their technology out of their labs in ETH Zurich and Empa (Swiss Federal Laboratories for Materials Testing and Research) and into their new company, IRsweep, in 2014.
High-Resolution and Microsecond-Range Measurements
“Our solution has two main advantages: very high brightness and very high time resolution,” Dr. Mangold says. “Using lasers as a light source gives more light than the conventional lights used in other spectrometers. So, when it comes to tissue or water, you still get a strong signal,” Dr. Mangold explains.
The new spectrometer also enables a high, 1-MHz spectral resolution that minimizes cross absorption and resolves closely spaced features. As a dual-comb spectrometer, it measures multiple wavelengths in parallel. “We can measure the entire spectrum in less than one microsecond,” he says.
Such speed makes this approach to mid-IR spectrometry particularly useful for measuring quickly occurring instances, like protein folding, which occurs in micro- to milliseconds, and for studying biological substances such as rhodopsin, which transports protons across a membrane within milliseconds upon illumination. “No other technology lets researchers measure the spectrum of substances needing microsecond-range measurements without repeating those measurements potentially thousands of times.”
The second generation of this spectrometer, the IRisF1, was introduced this spring. It enables researchers to measure the full IR spectrum simply by changing lasers. The technology works best at the 7-µm wavelength, and IRSweep is currently developing devices with center wavelengths ranging from 5 to 10 µm.
Learning Business, Post-Doc Style
“We’re a very young team, and that brings challenges,” Dr. Mangold says. Like many spinoffs, the founders have deep technological expertise but had no management experience before founding IRsweep. Each of the founders is a physicist. Dr. Hugi and Dr. Geiser are experts in quantum cascade lasers, while Dr. Mangold has completed post-doc studies focused on developing high-sensitivity trace gas sensors for environmental applications at Empa. Their scientific backgrounds are the company’s strong suit. As a company, “we combine the knowledge to build the laser spectrum systems with application knowledge,” Dr. Mangold says.
“We recognized we had a lot to learn, so we put together a strong advisory team that has the business knowledge we were lacking,” he adds. Advisors include Timothy Day, co-founder and CEO of the photonics company Daylight Solutions; angel investor Philip Bodmer, principle at the consulting firm Bodmer & Partner; and Christoph Harder, principle at Harder & Partner and president of Swissphotonics. All three are analytical-instrument industry veterans, with years of business experience in addition to their technical expertise. As for Drs. Mangold, Hugi, and Geiser, they’re each active in the running of the company. Dr. Hugi holds the title chairman of the board, and Dr. Mangold and Dr. Geiser are managing directors, but no other management titles have been assigned. Instead, the three work collaboratively, as a team, to build and manage the company.
“We founded the company in the very way people say you shouldn’t found a company,” Dr. Mangold admits. “We developed the technology first and then found applications. It took quite a bit of work to find our place, to learn where our technology could be most useful.” The environmental monitoring industry, which aligned with Dr. Mangold’s research experience, was one of the first identified. The biotech industry was next, based upon the spectrometer’s abilities with biologics.
In 2014, Dr. Mangold recalls, “the cofounders had the impression the technology was ready to leave the lab and be commercialized. We wanted people to have access to it.” At the time, the spectrometer was far from being a product. It was still more of a table-top collection of components that were being optimized. It wasn’t until early 2017—two and a half years later—that the company had developed a working prototype.
IRsweep’s cofounders waited until this point to begin talking with potential funders. “We wanted to have a prototype ready when we started talking with potential investors,” Dr. Mangold explains, believing that an actual prototype would generate more positive results than would mere plans.
The first investment rounds closed July 2017, with a significant investment from an undisclosed Swiss industrial company. Although that organization provides notable financial backing, IRsweep also has received support from the European Space Agency Business Incubation Center Switzerland, the Swiss National Competence Center for Research Quantum Science and Technology, Eurostars, DARPA, and Volkswirtschaftstiftung (the Swiss Federal Foundation for Promotion of the National Economy through Scientific Research).
As a new company with only recently commercialized products—the IRisF1 and the IRcell (a component for spectroscopic gas measurements)—IRsweep’s distribution is still somewhat limited. “We don’t have a distributor yet (for the IRisF1),” admits Dr. Mangold. Anyone interested in the technology must contact the company directly. “That limits distribution to Europe and the U.S.,” he notes. The IRcell, however, is available in the U.S. through MenloSystems.
Today, IRsweep markets its IRisF1 mainly to academic researchers who need to understand very fast processes, but it also has applications in industrial labs that need high-throughput measurements. “Ours is a very broadly applicable technology. It’s not only for biotech,” Dr. Mangold insists.
One of the greatest market challenges IRsweep faces is one that is common to disruptive technologies everywhere. It must help potential users overcome their concerns about trying technology that is so different from the spectrometers they have used throughout their careers.
“They usually understand what our spectrometer is good for, but are concerned it won’t perform as well as the 60-year-old technology they already know,” Dr. Mangold explains. “IR laser spectrometers don’t yet have a long track record.”
The company’s solution is to conduct trials and publish scientific papers detailing the results. Scientific studies are expected to be published soon, detailing the technology’s capabilities in concurrently recording time and spectral data of biomolecular kinetics. Additional papers are likely to follow. In the meantime, IRsweep has a growing presence at scientific conferences throughout Europe and North America, with the goal of helping researchers to become aware of, and comfortable with, this new mid-range IR spectroscope.
As the company advances, Dr. Mangold says, IRsweep is focusing on broadening the spectral coverage of the existing instrument to make it useful for more spectroscopists. It also plans to identify additional, industrial, applications, and thus expand its customer base. Once again, IRsweep is seeking challenges that its technology can solve, wherever they exist.