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Time-of-Flight Continues to Soar as New Applications Emerge

In June 1997, IBO published an article on the market for time-of-flight (TOF) mass spectrometry instrumentation. The article predicted rapid growth and major changes in the competitive makeup of the sector. One year later, much has changed and the fast-growing market for TOF/MS systems is much more clearly defined, growing even faster now than IBO predicted last year, and finding a wide variety of new variants and applications.

A year ago the TOF market was nascent, still considered by many an experimental technique. The leading position in the technology was up for grabs, and manufacturers were struggling to get a clear focus on how to address the market strongly. This has changed markedly in the last twelve months, and a new phase of the TOF market has begun, as was clearly evident at the recent ASMS conference on mass spectrometry (see show review on page 8).

Time-of-flight mass spectrometry is a technology that analyses the chemical makeup of substances by sending ions down a flight tube to a detector, then measuring the time the various ions take to "fly" the length of the tube. This yields the molecular weight of the molecule in question and allows researchers to determine its composition with high accuracy. The technique compares favorably to competitive techniques in that it is relatively fast, accurate and sensitive. It is most commonly used in biological applications involving large molecules, since it is one of the techniques most capable of testing them without breaking them apart. But because of its speed and flexibility, TOF has potential for a very wide range of analytical applications in many different industries.

TOF mass spectrometry systems are generally divided into categories based on the techniques they use to ionize samples. They are also often used in "hybrid" configurations with other analytical instruments including liquid and gas chromatographs and other forms of mass spectrometers including secondary ion mass spectrometers (SIMS) and magnetic sector mass spectrometers.

By far the most common type of TOF instrument is matrix assisted desorption ionization (MALDI). The rapid acceptance of MALDI is due primarily to its usefulness in biotechnology and drug discovery research. That continues to drive its growth now, and it is clear that MALDI is no longer considered an experimental technique, but is a well-accepted and established technology. MALDI's estimated share of the TOF market has dropped from 85% last year to around 70%. That is not a reflection on the success of the technique, which experienced growth of 14% in the last year, but an indication of how other forms of TOF are beginning to gain acceptance. While biotechnology continues to be the driving force behind MALDI-TOF, the ASMS conference revealed how the technique is also finding numerous new applications such as enzyme analysis for commercial detergents, chiral analysis, and analysis of pesticides.

MALDI-TOF is the first sector of the TOF market to begin to experience a shakeout period in which marginal companies fall by the wayside and the dominant leaders emerge. The competitive market for MALDI has gained a fairly clear shape in the last year. The biggest factor in this solidification was the merger of Perkin-Elmer with PerSeptive Biosystems last January. Two of the biggest questions last year were how these two companies would approach the market. P-E at that time was the major force in biotechnology, but had made no significant entry into the MALDI market. PerSeptive was a relatively small company with good MALDI products but limited marketing capability, especially outside of the biotechnology market. With the merger, the combined operations of P-E and PerSeptive have moved decisively into the forefront of the MALDI market. P-E is now the leader in MALDI-TOF and appears to be pulling away from the pack and making its leading position more secure.

Shimadzu is in second place in the race for dominance of MALDI through its Kratos operations, but doesn't seem to be growing as fast as the market as a whole and may not be able to hold that position long. The Kratos operation has never appeared to have the full weight of the Shimadzu organization behind it, and Shimadzu has still not been able to gain a reputation as a major force in MALDI-TOF. Hewlett-Packard has dropped out of the MALDI-TOF competition, and Micromass has chosen to focus only on the high end of the market, leaving the rest-where the bulk of the sales are-to other players. Other current players in MALDI-TOF are Bruker and Thermo BioAnalysis, whose TOF line was split off from the Finnigan operation of ThermoQuest. The current players in MALDI-TOF have survived the first part of the shakeout, and should be able to keep their

MALDI operations viable, although there could be more shakeout to come as new products hit the market and competitors jockey for position.

The fastest growing area of time-of-flight is LC-TOF, which includes electro-spray ionization (ESI) and atmospheric pressure ionization (API). The market for LC-MS really began in 1997 with the introduction of several products that took sales from an estimated $7.5 million in 1996 to around $26 million in 1997. The popularity of the LC-TOF systems comes largely from researchers discovering them as an alternative to quadrupole MS systems, over which they have some technical advantages.

While rapid growth was expected in this sector, the market took to the technique with unexpected alacrity, bringing a growth rate of better than 250%. This feverish pace should simmer down considerably this year, but it will still remain in the high double-digit range of a market in an initial rapid growth phase. Still too young for a shakeout, this remains a market still unformed, where virtually any company with a good product has a chance at becoming one of the key players. Several companies now have LC-TOFs on the market, including P-E (PerSeptive Biosystems), Micromass (now a part of Waters), Larson-Davis/Sensar, and Analytica of Bradford.

While nothing close to the skyrocketing growth of LC-TOF, gas chromatography time-of-flight (GC-TOF) is also experiencing the steep growth curve of a young market gaining rapid acceptance. Still in an embryonic state, GC-TOF has high potential, especially for process applications, and is expected to see high double-digit annual growth for the next few years. LECO, Larson-Davis/Sensar, Thermedics Detection, and HD Technologies have already introduced products. Micromass is now developing a system, which will put its parent company, Waters, in the GC-TOF business.

Although hardly a mature market, the slowest growing sector of the TOF market is instruments used with secondary ion mass spectrometers (SIMS). TOF-SIMS are useful in both process and research applications, and can often be used as alternatives to magnetic sector and quadrupole instruments. Growth of sales of these instruments is expected to be in the low double digits. Time-of-flight instruments can also be used in tandem with other forms of mass spectrometers such as quadrupole LC-MS and magnetic sector instruments. In tandem with magnetic sector systems, TOF constitutes a real competitive threat to quadrupole systems.

The last year has been a critical one in the formation of the market for time-of-flight instrumentation. The next few years will likewise be important as the market takes shape. There will be more shakeout as market leaders emerge and less competitive companies drop out or focus on niches. P-E is the clear leader in TOF at this point, and has the potential to widen its lead. Micromass and Thermo are both leading MS companies, but their stakes in the TOF market are still relatively small. Micromass has ceded all but the high end of the MALDI-TOF market and will concentrate on gaining more substantial share in LC and GC hyphenates. The Thermo BioAnalysis TOF operations were split off from ThermoQuest, which is the world leader in mass spectrometry, when all forms of the technology are counted. Thermedics Detection is another Thermo subsidiary designing, manufacturing and marketing TOF systems. In this instance Thermo's fragmented structure seems to have been an inhibiting factor for the company in trying to gain a strong foothold in TOF, which they might have been able to do more effectively had all MS operations been unified.

H-P has an agreement with Bruker to develop other forms of MS, and since Bruker has time-of-flight technology, H-P could conceivably get a beachhead through Bruker. Such an effort could take several different forms, and H-P could bring its strong presence in GC and HPLC to establish itself as a force in TOF.

Whether H-P follows this course or not, the next year will almost certainly see more acquisition, merger and alliance activity among companies involved in time-of-flight mass spectrometry, as the swelling market attracts companies eager to stake their claim in the rapid growth and promised profits.

Column Graph: Global Time-of-Flight MS Demand by Technique ($m)

 1997 1998 1999

ICP-TOF - 1.5 2.4

GC-TOF 7.5 13.1 22.5

TOF-SIMS 14.3 15.8 17.5

LC-TOF 7.5 26.3 71.1

MALDI-TOF 96.0 109.2 121.2

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Publication:Instrument Business Outlook
Article Type:Article
Geographic Code:1USA
Date:Jun 15, 1998
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