World affairs don't normally intrude on Pittcon. But President Clinton's decision to help Israel combat the recent wave of terrorist bombings focused attention on a small booth in Chicago's vast McCormick Place. As the U.S. military was flying Thermedics Detection's Egis explosive detectors to Israel, the company was unveiling a fast gas chromatography (GC) unit based on the same once-classified technology. The instrument was chosen best new product in an informal poll of editors and reporters covering Pittcon '96.
Thermedics Detection's Flash-2D-GC (circle 201 on Reader Service Card) employs fast temperature programming to analyze mixtures in a fraction of the time required by conventional GC instruments. For example, project engineer Clayton Wood demonstrated a 70-second analysis of a standard mixture of hydrocarbon fire accelerators that normally takes about 16 minutes to run. "It's bomb detection repackaged in a way that's so versatile everybody can use it," he said.
The key technology is a special heating tube surrounding the GC columns. Usually, columns are heated in an oven. "Our oven is the GC column itself," said Senior Vice President David H. Fine. "We can heat as fast as 100°C per second. The fastest conventional GC is around 30°C per minute.
"The technology is new to the analytical instrument field, but it is tried and true." It was developed for bomb detectors in the late 1980s with funding from the State Department and the Federal Aviation Administration.
The Flash-2D-GC has six independent temperature-programmable zones, including as many as four "cold spots" that can be used for high-speed injection or purge-and-trap procedures. As a fraction comes off the first column, it can be routed to a second column for further analysis - "two-dimensional" chromatography.
The columns can be cooled rapidly, too, allowing an analysis to be momentarily stopped. And fast cooldown means the instrument is quickly ready for the next sample. "Methods development that would have taken a good chromatographer a couple of weeks can be optimized in an hour or two," Fine said. Thermedics Detection believes the payoff in productivity offsets the higher cost of the Flash-2D-GC, which starts at about $60,000.
The instrument can gather data from up to four detectors simultaneously. It can use conventional detectors or unique, compound-specific chemiluminescence detectors developed by Thermedics Detection. Conventional scanning mass spectrometry (MS) is not fast enough to keep up with the new GC instrument. "You must use time-of-flight (TOF) instruments," Fine said.
Just down the aisle, LECO was demonstrating its fully automated Pegasus TOF/MS unit (circle 202), designed specifically to work with current high-resolution capillary GC systems and emerging fast GC systems. Its proprietary fast detection system can acquire up to 500 spectra per second, according to technical specialist Mary Jane Phinney.
LECO's Pegasus TOF/MS
system"The thing that allows fast analysis is time-array detection," Phinney said. "All the ions pulsed out of the source hit the detector. It's virtually instantaneous for each sample."
The base price of the Pegasus is $160,000, including a data system with acquisition, calibration, quantitation, library searching, and presentation capabilities. "That's everything you need except the GC," said Phinney.
Another type of detector that can keep up with the Flash-2D-GC, according to Thermedics Detection's Wood, is Valco Instruments' Pulsed Discharge Detector (PDD, circle 203). Valco's detector uses a stable, low-powered, pulsed direct current discharge - "spark" - in helium as an ionization source.
Valco Instruments' Pulsed
Discharge DetectorThe PDD is the first commercial electron capture detector to eliminate completely the radioactive source, according to marketing manager Jack Frank. A stand-alone version was introduced two years ago at Pittcon. Besides electron capture, that universal model also can operate in helium ionization or photon ionization modes simply by switching gas mixtures. Both Air Products & Chemicals (circle 204) and Air Liquide (circle 205) are now offering gas blends specially formulated for PDDs at much lower prices than earlier, Frank said.
This year, Valco was showing off its dedicated versions of the PDD, which cost $2,000 to $3,000. Attracting the most attention was Model D-2-HP, a helium and photoionization detector designed to be retrofitted to Hewlett-Packard's ubiquitous 5890 GC unit.
"We expect PDD will completely replace" older technologies such as thermal conductivity and flame ionization detectors, Frank said. Users in the petrochemical and other industries particularly like the Valco detectors for process analyses, he said, because there's no flame or hydrogen involved.
Like gas chromatography, high-performance liquid chromatography (HPLC) is often thought of as a mature technology that is unlikely to experience major advances. "HPLC has been considered as about as good as you can get," said Waters' Vice President for Market Development Robert F. Pfeifer, but "Waters is going to raise the bar."
Waters' Alliance Systems (circle 206) bridges the gap between flexible modular systems that are difficult to validate and integrated systems that are hard to upgrade, Pfeifer said. The Alliance offers a constant platform, he said, so that chemists can choose the most appropriate detector for a given analysis while maintaining the system's internal volume, a key requirement for consistency.
The heart of the system is Waters' 2690 Separations Module, which combines solvent delivery and sample handling. Instead of a single motor connected to both pistons, the module incorporates two independent, digitally controlled piston drives and two independent motors. That increases the precision of flow and of solvent proportionality. "You don't need compensation devices like mixers or pulse dampers," Pfeifer said.
Routine maintenance like changing the high-pressure seals can be done without tools or breaking the fluid connections. "This is a killer feature that has people here saying 'Wow,'" Pfeifer told C&EN.
The separations module can handle 120 sample vials, divided among five, 24-position sample carousels. The carousels can be accessed individually while the others are in use, like a stereo's compact disc player.
The Alliance also incorporates a disk drive so that users can easily transfer methods from other instruments. The system's size is only about three-quarters of traditional "strung-out-on-the-bench" HPLC units, Pfeifer said. Prices range from $25,000 to $50,000.
Hewlett-Packard also introduced an HPLC system. The Hewlett-Packard 1100 Series (circle 207) garnered second place in the Pittcon editors' awards.
The 1100 Series is a family of products consisting of stackable, fully interchangeable hardware modules and software. "We're offering higher performance at lower cost - cheaper, better, faster," said John R. Jaskowiak, product manager for liquid chromatography. "We've considered the entire cost of the system, not just purchase cost but operating costs, maintenance costs, training costs, validation costs."
Among the new features of the series are binary and quaternary pumps, an autosampler, a thermostatted column compartment that allows operation from temperatures below ambient up to 80°C, and a new manual injector. All the modules are fully functional either with Hewlett-Packard or other vendors' components, Jaskowiak said.
A new palm-top control module accepts personal computer cards, which can be used to transfer methods from one system to another. Hewlett-Packard also exhibited a column ID module, a small memory-storage device that clips onto any liquid chromatography (LC) column and tracks information. The device stores records of what conditions - temperature, pressure, flow - the column actually experienced, not just what had been expected to occur, Jaskowiak said.
In a unique twist, Hewlett-Packard also showed how its 3-D capillary electrophoresis (CE) system (circle 208) now can perform capillary electrochromatography (CEC), a hybrid separation technique combining features of HPLC and CE. The method offers separation efficiencies two to three times better than conventional HPLC, allowing separation of compounds with closely related structures.
In CEC, a capillary packed with a typical HPLC stationary phase like C18 replaces the usual bare or fused-silica-coated CE capillary. The mobile phase - about 80% organic - is driven electrically, not hydraulically as in HPLC. The resulting electroosmotic flow produces an extremely uniform profile. And with no hydraulic resistance, particles of less than 3 &mgr;m can be used, yielding columns with more than 200,000 plates per meter.
Hewlett-Packard's 3-D CE is the first commercially available system capable of CEC. To prevent microbubbles from forming as a consequence of the high voltages across the packed capillaries, the system applies inert gas pressure to both the inlet and outlet vials. The same instrument - which starts at under $50,000 - can be used for traditional CE.
A new chromatographic product line for protein purification was introduced at Pittcon by Beckman Instruments. ProScale (circle 209) promises rational optimization and pain-free scale-up of protein purification.
In moving from research scale to production scale, the polymeric-based ion-exchange gels usually used in protein separation become compressed as flow increases. So methods have to be changed at each stage. But the ProScale system uses the same HyperDiffusion media, licensed from BioSepra, for all stages. BioSepra's "gel in a shell" retains the high binding capacity of a gel while protecting it within a porous ceramic shell, said Jeff Chapman, product manager for protein purification and capillary electrophoresis.
Beckman's new BioSys 500 and 2000 Series workstations are designed to work with the HyperDiffusion media. Also, the ProScale optimization software on the 2000 can save time and money by simulating experiments that would otherwise have to be physically performed. "You only do a couple of runs that teach the software," Beckman said. "The rest of the runs are done virtually." The ProScale family of instruments costs between $30,000 and $60,000.
Last year at Pittcon, Finnigan MAT introduced its GCQ instrument for benchtop GC-MS. This year, Finnigan was highlighting its new compact LCQ (circle 210), which it claims allows the addition of MS to LC labs at a fraction of the cost of a traditional research-grade instrument.
"The LCQ is absolutely unique, a benchtop detector for HPLC based on ion trap technology," said Ian Jardine, director of marketing. The company is characterizing the LCQ as an MSn instrument, because it can go beyond tandem MS/MS to MS/MS/MS and as far as MS10. It has a mass/charge range of 50 to 2,000.
"It's an unbelievably powerful tool for dissecting organic molecules piece by piece and determining organic structure," Jardine said. "The user doesn't have to worry about anything. The screen asks, Do you want to do MS? MS/MS? and so on."
Two inlets are available, both atmospheric pressure ionization (API) techniques. Electrospray ionization (ESI) is more suitable for large, highly polar molecules such as peptides and proteins, Jardine said. The atmospheric pressure chemical ionization (APCI) inlet is better for nonpolar compounds such as steroids or carbohydrates.
"The LCQ is at the juxtaposition of where LC-MS is going," said Jardine. "For biotechnology, proteins can be identified by doing MS/MS and searching databases. In the pharmaceutical industry, where time to market is everything, LCQ is the perfect detector for combinatorial chemistry."
Another LC mass detector was showcased by Perkin-Elmer Sciex, a joint venture between Perkin-Elmer and Sciex - the instrumentation division of MDS HealthGroup of Toronto. Its new API 100LC (circle 211), is a scaled-down version of the API 100 introduced last year. Both are single-quadrupole instruments, but the mass range of the API 100LC is limited to 1,200 amu.
Designed for the pharmaceutical marketplace, the API 100LC is priced at about $120,000 complete with an ion spray (Perkin-Elmer's term for electrospray) source and data system. The instrument will work with any manufacturer's HPLC units, said technical sales specialist Wayne R. Heacock, but additional software packages available for about $5,000 may be required.
In the area of GC-MS, Varian introduced its new benchtop instrument, the Saturn 2000 (circle 212). Winner of third place in the Pittcon editors' poll, the Saturn 2000 features a simplified, innovative ion trap with internal ionization that Varian says delivers increased sensitivity.
That improvement comes from ionizing the sample within the same ion trap that will be used for mass analysis a few milliseconds later, according to marketing manager John Mills. "We get the highest sensitivity because we do everything inside the ion trap," he said.
The ionization mode can be switched from electron ionization (EI) to chemical ionization (CI) without hardware changes. With a mass range to 650 amu, the Saturn 2000 is capable of sophisticated MS/MS experiments. It incorporates automated methods development to help the user find the best conditions for parent ion fragmentation.
"Our biggest market is environmental analysis," said Mills. "It's a fantastic trace detection technique that picks needles out of haystacks."
A complete system, including computer but without CI, is available for less than $58,500. Another $4,000 adds CI capability, which can use not only the normal compressed gases but also solvents such as methanol or acetonitrile.
A drastically different system for GC-MS/MS was showcased by Bear Instruments. The new company has constructed an extremely compact benchtop triple-quadrupole MS unit, the Cub 800 (circle 213), based on patented rounded hyperbolic quadrupoles.
Bear INstruments' Cub 800 MS
unitWith a mass range to 800 amu, the Cub is designed to appeal to customers that want more than an ion trap MS but have shied away from expensive conventional triple quadrupoles. The whole system - complete with GC unit, EI/CI ion source, and data system - sells for $150,000.
JEOL U.S.A. exhibited an unusual accessory for its mass spectrometers: a CCD (charge-coupled device) array detector designed to improve sensitivity for recording spectra by at least a factor of 50 over the standard detector system. Instead of a photodiode array detector that jumps from point to point, the JUS-CCD (circle 214) scans many masses simultaneously. The detector has a wide dynamic range and can be operated at scan speeds compatible with LC-MS/MS techniques. The JUS-CCD costs $95,000.
Researchers attending Pittcon were buzzing about the extraordinary resolution Bruker has achieved with improvements to its Reflex II series of research MALDI-TOF mass spectrometers (circle 215). The powerful matrix-assisted laser desorption ionization (MALDI) technique uses a matrix to protect biomolecules from fragmentation as a laser desorbs the sample, producing intact molecular ions.
Bruker's MaldiAuto PrepThe enhanced mass resolution stems from using gridless delayed ion extraction into a two-stage gridless reflectron (reflector), according to Executive Vice President Frank H. Laukien. For example, resolution up to 20,000 has been measured for insulin at 5,733 amu.
Gridless delayed ion extraction "focuses the distribution of kinetic energies that occurs during the MALDI event in the source," Laukien said. "Instead of one big hump, customers can resolve isotopic patterns." Synthetic polymer spectra also benefit from improved resolution, because the fragmentation pattern can be followed monomer by monomer.
Laukien said the added features have not increased the price of the Reflex II, which remains less than $300,000. Older instruments can be retrofitted.
PerSeptive Biosystems has also added delayed extraction technology to its benchtop MALDI-TOF instrument. "This is a big advantage for nucleotides, which are weak molecules that tend to fall apart," said Paul O. Danis, BioSpectrometry product manager. "We now get performance on benchtop instruments that is the same as on older, larger instruments." The Voyager-DE BioSpectrometry Workstation (circle 216) lists for around $150,000.
Bruker introduced a new MALDI-TOF MS unit at Pittcon, the Proflex (circle 217). The easy-to-use instrument is compact and inexpensive yet still offers advanced research-grade capabilities. The basic system starts at just under $100,000. It can be easily upgraded by adding options such as a two-stage gridless reflectron, delayed ion extraction, and high-sensitivity postsource decay - particularly useful for peptide and protein structural analysis. A model with all the optional features sells for less than $200,000.
As MALDI-TOF MS moves from research labs to higher volume applications like quality control, there's a growing need for higher sample throughput and automation. Currently, preparing samples for MALDI-TOF instruments is time consuming, with large variability from user to user. Bruker claims to have cracked the difficult problem of sample preparation with its new MaldiAutoPrep (MAP) system (circle 218).
The unique automated robotics system can process 50 to 100 samples per hour. "It's perfect for the enormous amount of samples generated by combinatorial chemistry and peptide sequencing," Laukien said. "The rate-limiting step had been sample preparation. MAP removes the key obstacles."
The turnkey, stand-alone unit sells for $38,000. Various protocols, programmed either by Bruker or the customer, can be tailored for peptides, oligonucleotides, or synthetic polymers.
A simple manual device for reproducibly preparing MALDI-TOF samples was introduced in Chicago by Lab Connections. The Target (circle 219), priced in the $15,000 range, can be configured to hold circular, rectangular, and strip MALDI sample targets from any commercial MALDI-TOF spectrometer.
Three companies exhibited devices at Pittcon that allow MS analysis of samples too tiny for conventional ESI. "Many times, the most interesting research problems in biology labs have only very minute amounts of precious samples," noted Bruker's Laukien.
Bruker acquired an exclusive license for the nanoelectrospray technology developed at the European Molecular Biology Laboratory in Heidelberg, Germany, by Matthias Mann and Matthias Wilm. Bruker's NanoSpray (circle 220) cuts sample consumption by a factor of 40, Laukien said. It allows multiple stages of MS/MS from less than 1 &mgr;L of total sample, handling flow rates as low as 25 nL per minute.
"The user can get several hours of signal from small amounts," Laukien said. "You can go through all the granddaughter ions. It's a key enabling technology." The NanoSpray option can be added to new or existing Bruker Esquire MS instruments for $20,000.
Perkin-Elmer Sciex says its MicroIonSpray (circle 221) is a derivative of Mann and Wilm's technology. It allows sample sizes of 2 &mgr;L and above, providing acquisition times greater than 10 minutes. The equipment to convert existing Perkin-Elmer ion spray sources costs $5,000.
And Micromass showed its new NanoFlow probe (circle 222). Micromass just came into existence March 1 - a company formed by a senior management buyout of part of the VG divisions of Fisons Instruments. The Federal Trade Commission and comparable agencies in Europe had objected to the sale of Fisons - announced last year - to Thermo Instruments Systems, because Thermo already owned Finnigan MAT, a major MS manufacturer. With the divestment of much of Fison's MS business to Micromass, the Fisons sale is now expected to go through.
A standard ESI source can be simply converted to NanoFlow operation, Micromass said. The probe can be configured for either continuous-flow operation or the introduction of discrete nanovials. The nanovials, containing about 1 &mgr;L of sample, can be used as microreaction vessels to monitor reactions in real time. NanoFlow prices range from $15,000 to $20,000.
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