Genetic Engineering & Biotechnology News

JUL 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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8 | JULY 2018 | Genetic Engineering & Biotechnology News | GENengnews.com Gail Dutton Ordinary Fourier-transform infrared (FTIR) spectroscopy, which enables label-free tech- niques, is versatile enough to study most substances—except biologics. When biolog- ics entered the biopharma scene as thera- peutics, 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 spectros- copy 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 prob- lem, 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 prob- lem. 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 Zu- rich 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 advan- tages: very high brightness and very high time resolution," Dr. Mangold says. "Us- ing 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 measur- ing quickly occurring instances, like protein folding, which occurs in micro- to millisec- onds, and for studying biological substances such as rhodopsin, which transports protons across a membrane within milliseconds upon illumination. "No other technology lets re- searchers measure the spectrum of substanc- es needing microsecond-range measurements without repeating those measurements po- tentially thousands of times." The second generation of this spectrom- eter, 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 wave- length, 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 tech- nological 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 environmen- tal 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 ap- plication 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 lack- ing," he adds. Advisors include Timothy Day, co-founder and CEO of the photonics company Daylight Solutions; angel inves- tor Philip Bodmer, principle at the consult- ing 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 addi- tion to their technical expertise. As for Drs. Mangold, Hugi, and Geiser, they're each ac- tive 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 man- age the company. "We founded the company in the very way people say you shouldn't found a com- pany," Dr. Mangold admits. "We developed the technology first and then found appli- cations. 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 co- founders had the impression the technology was ready to leave the lab and be commer- cialized. 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 compa- Laser-Based Mid-IR Spectroscopy Developed to Provide Accurate and Practical Microsecond Measurements IRsweep Tackles Biologics Challenge with Spun-Out Lab Method On Your Radar IRsweep's IRspectrometer can accelerate Fourier-transform infrared (FTIR) spectroscopy measurements to capture fleeting processes, such as protein folding, or facilitate high-throughput applications, such as drug-quality screening. The instrument uses quantum cascade laser frequency comb technology to emit multiple colors at the same time, allowing samples to be probed at different wavelengths simultaneously. IRsweep's founders (left to right): Markus Mangold, Ph.D., Andreas Hugi, Ph.D., and Markus Geiser, Ph.D. These scientists applied their expertise in physics to create a new paradigm for spectroscopy. They develop optical sensing solutions in the mid-infrared range (the fingerprint region of most molecules) that offer broad spectral coverage and speed in combination with high brightness.

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