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SFC IN FLUX As a separation technique, supercritical fluid chromatography (SFC) Ms somewhere between LC and GC, offering advantages of each. In LC, the composition of the mobile phase is varied to achieve the desired separation; in GC, the mobilephase temperature is varied. The composiiion, temperature and pressure of the mobile phase all be varied with SFC providing more ways to alter the solute retention time and selectivity than with conventional LC and GC methods Although more parameters must be optimized with SFC than with traditional chromatographic methods, rapid equilibration and re-equilibration times greatly reduce the method developmenttime.Lower temperatures are used in SFC than in GC, making SFC particularly useful for separating nonvolatile and thermally unstable analytes. In addiiion, higher molecular weight compounds can be separated wiih SFC than with traditional GC. Finally, ,FC offers setter resolution of complex mixtures and faster analysistimesthan general LC techniques. SFC is found in a wide variety of applications. According to Susan Olesik, a professor at Ohio State University, "Almost every pharmaceutical industry around
New faces emerge When Analytical Chemistry reviewed the SFC market in 1994 (Anal. Chem. .994, 66,369 A), four manufacturers were represented: Hewlett Packard, Dionex, Suprex, and Gilson. Since then, the SFC industry has undergone significant changes. Of the four companies, only Gilson still manufactures SFC systems. According to Olesik "The commercial activity is in flux." In reference to the early SFC models, Olesik told Analytical Chemistry "Most of the instruments were overpriced and so they didn't get a lot of use" The Gilson Series SF3 System was developed with Ciba Geigy (Basel, Swiizerland) in 1992 for analytical scale separations of natural products and chiral compounds. Their packed-column SFC system is now available in a dual analyttcal and preparattve configuration. In the latter case, sample throughputs of 50 to 500 mg/h are typically achieved. Hewlett Packard (HP) sold the rights to its SFC instrument in September of 1995 to Terry Berger, a former HP employee, who launched Berger Instruments. Berger's SFC was released in De-
Newer designs emerge with more flexibility and lower price tags.
S0003-2700(97)09044-6 CCC: $14.00 © 1997 American Chemical Society
uses SFC substantially, so there is a permanent niche." SFC has been used extensively for the separation of enantiomers in chiral molecules. The technique reduces costs and increases productivity in other areas as well, including the agrochemical and petrochemical industries. Analytical Chemistry has contacted several companies that currently manufacture SFC systems, to provide potential buyers with information on what is commercially available. The specifications and various options for the selected SFC systems are given in Table 1. This summary is not intended to be a comprehensive review of all manufacturers currently in the SFC business; rather ii ts designed to represent the types of instruments that are available today.
Analytical Chemistry News & Features, November 1, 1997
683 A
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Table 1 . S u m m a r y of s e l e c t e d SFC i n s t r u m e n t s
Model
Berger SFC
Series SF3 System
Isco SFC modular system
Manufacturer
Berger Instruments 31 Waterloo Ave. Berwyn, PA 19312 610-695-3045
Gilson 3000 W. Beltline Hwy. Middleton, Wl 53562 800-445-7661
Isco 4700 Superior St. Lincoln, NE 68504 800-228-4250
URL or e-mail Type Software
[email protected] Analytical Chemstation
www.gilson.com Analytical/preparative UniPoint System Software
www.isco.com Analytical ChemResearch 150
Column type
Packed (2-4.6 mm)
Packed (1-20 mm)
Packed (1-mm microbore)
Fluid delivery
Single-pump module for GC detection only; dual reciprocating pump module for addition of modifier for UV detection
Pump A module for CO2; Pump B module for organic modifier (0-100% in C02)
Digital syringe pump
Dual pumps (C02 and modifier), compatible with HPLC
Pressure control
Electronic back-pressure regulator
Electronic back-pressure regulator; programmable
Model 880-01 back-pressure regulator
Compatible detectors Number of detectors
UV-vis (DAD, VWD), FID, NPD, and ECD Space for two GC detectors inside oven; more than one LC detector can be attached externally Ambient + 7 to 150 °C (with cyrogenic cooling, down to -50 °C) Up to 400 bar
UV-vis (DAD, VWD, scan), ELSD, and FID Multiple detectors can be configured
Programmable pressure controller (Model 100DM syringe pump) UV-vis (VWD, scan), FID, ECD, and NPD One
Ambient + 3 to 200 °C (optional sub-ambient conditions) 90-400 bar
Up to 150 °C
CO-965: ambient + 10 to 80 °C; CO-966; ambient - 15 to 80 °C Up to 350 bar
0.001-5 mL/min
0.2-10 mL/min
0.1 u.L/min-25 mL/min
Special features
Autosampler with solid-state heating and cooling
Independent programming of mobile-phase pressure, composition and flow-rate; components are compatible with HPLC
Reader service number
401
402
Temperature range
Pressure range at outlet Total liquid flow rate
cember of 1996, and according to Olesik appears to be getting a lot of interest. Berger Instruments focuses exclusively on packed-column SFC. Several modules are currently offered, allowing consumers to choose the configuration. Components can be added or removed to fit specific applications. The instrument is essentially the same as the original HP model, "except that some of the features were eliminated in order to get the price down," added Tom Chester of Procter and Gamble.
Up to 690 bar
www.jascoinc.com Analytical/preparative Jasco/Borwin control and data acquisition, 32 bit for Windows '95 Packed (4.6 mm)
UV-vis (DAD or VWD), chiral, and MS Up to two
PU-980: 0.1-10 mL/min; PU-986: 0.1-20 mL/min
Using standard HPLC components, the Jasco system performs HPLC and SFC; analytical system can be scaled up for preparative work; cassette-type flow cells allow easy inspection and cleaning 403
The SFC license formerly owned by Dionex is now in the hands of Sensar Larson-Davis, who currently are building a new instrument. Officials at Sensar Larson-Davis told Analyttcal Chemistry they expect to have the instrument on the market by the first quarter of 1998. Information on the new instrument is expected to be released at the Eastern Analytical Symposium (EAS) later this month. Officials at Sensar Larson-Davis claim that the new instrument will accommodate both packed and open-tubular columns
684 A Analytical Chemistry News & Features, November 1, 1997
LC-900 series modular system Jasco 8649 Commerce Dr. Easton, MD 21601 800-333-5272
404
with a full range of detectors including flame ionization (FID) and UV-vis. Suprex was bought by Isco in August of this year, and the SFC system originally manufactured by Suprex is no longer commercially available. Isco does provide a complete SFC system; however, the company focuses predominantly on a modular type of approach. Isco's primary SFC activity has been in providing theffuiddelivery system necessary for upgrading an existing GC into an SFC. In addition to a pressureprogrammable syringe pump, the delivery
3101 SFC On-Line Process GC ABB Process Analytics 843 North Jefferson St. Lewisburg, WV 24901 304-647-4358
SuperC 20 and SuperC 10
Prochrom 5, rue Jacques Monod 54250 Champigneulles FRANCE (33) 3 83 31 22 44 sfarren @ analytics.abb.com
[email protected] Process monitoring Preparative/semi-prep VistaNet ChromSoft
SFC-200 (preparative) and SFC-50 (semi-prep) Thar Designs 730 William Pitt Way Pittsburgh, PA 15238 412-826-3939 www.thardesigns.com Preparative/semi-prep Process control
Fused-silica open tubular or packed
Packed (4.6-20 mm)
Single pump, syringe type
Membrane pump for CO2; piston reciprocating pump for modifier; piston reciprocating pump for automated injections
Frit restrictor
Computer-controlled backpressure regulator
Electronic back-pressure regulator
FID
UV-vis (VWD)
One
UV-vis as standard; compatible with all types of SFC detectors One
One
30-180°C
10-90°C
Upto150°C
Up to 450 bar
Up to 300 bar
Up to 405 bar
10 mL/min
10-75 mL/min (SuperC 20); 5-30 mL/min (SuperC 10)
5-50 g/min of CO2 and up to 20 mL/min modifier (semi-prep), 20-200 g/min of CO2 and up to 100 mL/min modifier (prep)
On-line process monitoring
Specially designed for preparative purposes in laboratory and for scaleup studies; CO2 recycling; automated for continuous runs and unattended operations; quantitative sample recovery
Modular system with customizable features and equipment allowing scaleup to user requirements; automated for continuous runs and unattended operations
406
407
405
system includes an injection valve, a C02 supply valve with pump refill, and all lhe necessary plumbing connections. A complete SFC system, consisting of a syringe pump, a column with GC oven as heater, and a variable wavelength UV-vis detector, can be purchased through Isco and, with only minor adjustments, can be converted into a microbore LC. Many of the components can also be used for other applications; for example, the syringe pump can also be used with Isco extractors for supercritical fluid extraction (SFE).
Packed, user-provided (20-75 mm for prep; up to 20 mm for semi-prep) High-pressure CO2, modifier and injection pumps
Jasco is another manufacturer that focuses primarily on a modular type of approach, using components of its LC-900 series with the addition of a unique programmable back-pressure regulator. The system is versatile in nature and lets the consumer configure the system to meet specific application requirements. Combinations such as HPLC/SFE/SFC can be constructed from the various components. A wide range of detection systems are available, including chiral, MS, UV-vis, and photodiode array.
In addition to analytical-scale SFC systems, some manufacturers also focus on preparative and process SFC. Gilson and Jasco offer analytical and preparative SFC systems. ABB Process Analytics is one of the only manufacturers of an on-line process monitoring SFC system. ABB focuses primarily on the refining industry, providing SFC instrumentation for the analysis of hydrocarbons and other petroleum products. Thar Designs manufactures preparative and semipreparative SFC systems. The difference between the two systems is the size of the column that be accommodated The similarity in the two systems provides means for scaleup says the company Thar Designs also provides larger process-scale SFC systems on a custom design basis Prochrom is a company dedicated to high-performance preparative chromatography, including HPLC, GC, and SFC. Industrial-scale preparative SFC has been developed by Prochrom and its partners since 1982, and itfirstappeared in their catalog in 1990. Instrumentation provided by Prochrom ranges from laboratory scale (SuperC 10 and 20) to large production scale with the SuperC 500 (500-mm column for production of tens of tons per year). Customers for laboratory-scale equipment are primarily pharmaceutical industries interested in preparative SFC at large scale because of its clean tin d cco~ nomical features. Pharmaceutical nies use preparative SFC to produce hundreds of milligrams or grams of pure samples for early testing of compounds Here their interest is in the speed of method develooment and production and the lower auantity of solvents needed What's behind SFC?
In SFC, the mobile phase is a substance raised above its critical temperature and pressure, referred to as a supercritical fluid. When depicted in a phase diagram, the so-called supercritical fluid region is often designated as its own separate region. This portrayal is misleading, as it suggests that a substance entering this critical zone undergoes a distinct phase change. When the critical pressure and temperature of a substance are exceeded the substance does not suddenly change into a unique phase; rather it becomes a single fluid phase, retaining properties of a gas and a liquid. Supercriticalfluidshave a lower viscosity and greater diffusion rate than their liquid counterparts, and as a result exhibit gaslike transfer properties. Analogous to a
Analytical Chemistry News & Features, November 1, 1997 6 8 5 A
Just Published! CHIRAL SEPARATIONS
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Chiral Separations: Applications and Technology This 11-chapter book chronicles the theory and practical applications of chiral technology by focusing on the efficient preparation, isolation, and separation of chiral molecules in optically pure forms. Asymmetric synthesis and chiral resolution, the basic approaches to obtaining chiral c o m p o u n d s are discussed in a variety of contexts including enantioselective reactions and additions enzyme-catalyzed reactions chromatographic methods with various chiral stationary phases or chiral discriminators and enmrioselective membrane transnort Industrial, academic, and governmental chemists working in pharmaceutical, agricultural, biological, and synthetic organic chemistry will find this concise reference volume to be invaluable and essential reading. Satinder Ahuja, Editor ACS Professional Reference Book 368 pages (1996) Clothbound ISBN 0-8412-3407-8 S99.95 ORDER FROM American Chemical Society 1155 Sixteenth Street, NW Washington, DC 20036 Or CALL TOLL FREE 1-800-ACS9919 and use your credit card! FAX: 202-872-6067. ACS Publications Catalog now available on Internet: URL http://pubs.acs.org or http://www.ChemCenter.org ^^^^^^^m
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gas, they are highly compressible and will expand tofillthe space that they occupy. When the density of a supercriticalfluidis increased, by raising the pressure, it takes on liquidlike solvent properties. Supercriticalfluidtechnology has evolved as a result of the extraordinary dissolving capabilities of supercriticalfluids.The main feature of SFC is that the solvating power of the mobile phase can be adjusted by varying the applied pressure. Cosolvents can also be added to the mobile phase to obtain the solvent behavior desired for a specific application The most commonly used mobile phase in SFC is supercritical C02. Relatively inexpensive, nontoxic, and nonflammable, supercritical C0 2 has advantages over other solvents commonly used in LC methods. Moreover, as laboratories cut down on organic solvents, alternative solvents, such as supercritical C02, gain appeal. Thefirstcommercial instruments for SFC were developed in the early 1980s. At the onset, instruments were designed to accommodate either packed columns, open-tubular (capillary) columns, or both. With a capillary column SFC (cSFC) system, pressure is controlled at the column inlet (that is, upstream) using a pump. Automated programming of the mobile-phase composition is not available. Theflowrate is not actively controlled but depends on the pressure and a passive flow restrictor at the column outlet. Adjusting the flow rate is difficult, so column efficiency is rarely optimal. The restrictor is also prone to clogging. Generally, a cSFC system is equipped with a FID; other GC detectors such as thermionic nitrogen-phosphorus (NPD) and electron capture detectors (ECD) have also been used in these systems Analogous to LC systems, with a packed-column SFC (pSFC) system the composition of the mobile phase can be programmed to obtain the desired composition gradient. In the beginning stages of the development of pSFC, pressure changes were achieved manually by adjusting a pressure relief valve. This method, however, did not yield reproducible pressure gradients. The advent of automated downstream pressure control in 1992 was a major development for pSFC. These newer instruments are equipped with an automatic back-pressure regulator which can generate pressure gradients independent of the mobilephase flow rate and composition According to Chester, "The focus to-
686 A Analytical Chemistry News & Features, November 1, 1997
day tends to be on packed columns because of speed and cost considerations, rather than capability. Most of the time things that are either done by nonaqueous reversed-phase or by normal-phase chromatography can be done much faster by SFC using packed columns. With opentubular columns run times are still about an hour; with packed columns run times can be as short as a couple of minutes." Typically pSFC systems are equipped with UV-vis detectors. Many manufacturers offer a choice of either a diode array detector (DAD) or the less-expensive variable wavelength detector (VWD). Some instruments can also accommodate GC detectors in addition to a UV detector. In the last few years, "evaporative light scattering detectors (ELSD) (see Anal. Chent. 1997,69,561 A) have come on the scene in a much bigger W3V, cind they work really well with SFC " says Chester. He added that "ELSD acts like a pseudouniversal detector." According to Chester ELSD is not as universal as FID but it is compatible with almost everything and has adequate sensitivity Several researchers including Olesik have SFC systems interfaced with MS detection systems Other detectors that have been used with SFC include electron captiire flame phntomptrir fluorescent chemiliiminescent FT-TR and many others
The trend in SFC technology over the past few years has been to provide instruments with more versatility. Most companies have taken on a modular type of approach, letting the purchasers decide what options they want. By letting the consumer choose the instrument's configuration, unwanted costly options are eliminated, resulting in much more affordable SFC systems. As the costs of SFC systems decrease and preconfigured systems become obsolete SFC will begin to have widespread use. Researchers will configure systems to meet their applications and with a little creativity can interface them with just about any tvoe of detection _„_!•„m
Britt Erickson
Upcoming Product Reviews for 1998 March 1: ICP-AES April 1: FT-IR May 1: Supercritical fluid extraction If your company manufactures instruments for these techniques, please let us know. E-mail (
[email protected]) or call us (202-872-4570) at least three months prior to the listed date of publication.
