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(12) United States Patent ao) Patent No.: us 6,561,767 B2
Berger et al. (45) Date of Patent: May 13,2003
(54) CONVERTING A PUMP FOR USE IN SUPERCRITICAL FLUID CHROMATOGRAPHY
(75) Inventors: Terry A. Berger, Newark, DE (US);
Kimber D. Fogelman, Hockessin, DE
(US); L. Thompson Staats, III,
Lincoln University, PA (US); Mark
Nickerson, Landenburg, PA (US); Paul
F. Bente, III, Landenburg, PA (US)
(73) Assignee: Berger Instruments, Inc., Newark, DE (US)
( * ) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days.
(21) Appl. No.: 09/918,436
(22) Filed: Aug. 1, 2001
(65) Prior Publication Data
US 2003/0026704 Al Feb. 6, 2003
(51) Int. CI.7 F04B 19/24; F04B 23/00;
(52) U.S. CI 417/53; 417/313; 417/279
(58) Field of Search 417/53, 313, 279;
(56) References Cited
U.S. PATENT DOCUMENTS
4,373,864 A * 2/1983 Massey et al 417/213
5,089,124 A * 2/1992 Mahar et al 210/101
5,281,406 A * 1/1994 Stalling et al 423/455 B
5,305,232 A * 4/1994 Chimowitz et al 210/386
"chromatography" Encyclopedia Britannica <http:www.search.eb.com/eb/article?eu=119265>.*
* cited by examiner
Primary Examiner—Charles G. Freay
Assistant Examiner—-Timothy P. Solak
(74) Attorney, Agent, or Firm—ZITO tip; Joseph J. Zito;
Kendal M. Sheets
A method for converting a pump for use in a flow stream containing a mixture of highly compressed gas, compressible liquid or supercritical fluid wherein the pump delivers a compressible fluid against a back-pressure regulator which in turn delivers a controllable flow rate downstream of the regulator without performing variable compressibility compensation adjustments on the pump. By using a pressurized source of compressible fluid combined with isocratic conditions, the delivery pressure from the pump is controlled at a rate higher than the downstream gradient with the back-pressure regulator, and an inexpensive pump may be used in place of specialized, expensive pumps and compressibility compensation systems for use in stems operating at or near supercritical fluid levels of compressible fluids. Significant capital and operating laboratory costs are saved through a simpler and cheaper system for accurately delivering compressible fluids into mobile phase flow streams.
12 Claims, 2 Drawing Sheets
CONVERTING A PUMP FOR USE IN
BACKGROUND OF THE INVENTION
Pumps used in SFC Supercritical Fluid Chromatography control the mass-flow of each component of the mobile phase, and therefore control the composition of the mobile phase through the column. Pumping compressible fluids, 10 such as carbon dioxide (C02), at high pressures in SFC systems while accurately controlling the flow, is more difficult than that for a liquid chromatography system. SFC systems use two pumps to deliver two different source streams into a single mobile phase flow stream. Each pump 15 on each flow stream adds pressure, flow ripples, and variances that cause baseline noise. The two pumps also operate at different frequencies, different flow rates, and require separate compressibility compensations, further adding to the complexity of flow operations. 20
Pumps used for supercritical fluid chromatography typically require an extended compressibility compensation range plus a dynamically variable compressibility compensation range to accurately deliver a desired flow rate and ^ fluid composition. When a compressible fluid is mixed with an incompressible fluid, the viscosity of the mixture depends on the mole fraction of the modifier, or incompressible fluid, in the compressible fluid. In combi-chem analysis and purification by SFC, the concentration of modifier can be 3Q varied from 2.5 to 55% over a few minutes. This can result in a major change in the viscosity of the fluid and in the pressure drop across a chromatographic column that can change over an order of magnitude from approximately 9 bar to greater than 250 bar. 35
Normally, an unmodified high performance liquid chromatography (HPLC) pump would deliver an unknown and varying amount of a compressible fluid under such conditions. As the column head pressure increases during the gradient, a larger percentage of each pump stroke would be 40 used up compressing the fluid instead of delivering flow. With an uncompensated pump, the delivery rate becomes a smaller fraction of the flow setpoint. When a second pump is added to a system to deliver an incompressible fluid under high pressure, its delivery rate is unaffected by the increas- 45 ing pressure. Subsequently the two pumps deliver inaccurate flow and composition to the mobile phase. As the pressure in the system rises, the total flow drops below its setpoint, but the concentration of the modifier increases beyond the modifier setpoint. The temperature of the compressible fluid 50 in the pump head must be controlled to prevent the delivered mass flow from changing even further.
When compressed, a pumping fluid heats up and attempts to expand. For highly compressible carbon dioxide at outlet pump pressures above 200 bar, temperature rise of more than 55 ten degrees centigrade are possible within the fluid. The rapid compression of the pumping fluid causes the fluid to heat up and expand and the density to decrease. When heat is transferred to the pump body, the pumped fluid cools and the fluid density increases. go
Reciprocating pumps are typically used in HPLC and SFC. These pumps are more accurate than syringe pumps and can deliver essentially an infinite volume before refilling. A reciprocating pump has an inlet and outlet check valve. During a fill stroke, the outlet check valve closes, 65 isolating the pump from the high pressure in the downstream column (PCJ). The pressure from a filling cylinder of source
fluid, such as compressed C02, (Pcy) forces open the inlet check valve and fills the pump chamber. After the pump is filled at Vcyl, the piston reverses direction, compressing the fluid in the pump until Vpurnp>Ycyl, which closes the inlet valve. On the compression stroke, the piston moves rapidly until Vpurnp>Ycol at which point the outlet valve opens and the fluid moves downstream of the pump and into the column. The piston slows down to the delivery speed when enough extra fluid has been pushed into the column to compensate for lack of flow during the fill stroke. The distance the piston must travel just to compress the fluid to Vcol is calculated based on the known volume of the components and a characteristic of the fluid being pumped, called the compressibility factor Z. With the correct Z, a pump can be controlled to nearly eliminate flow or pressure ripple.
Without a correct Z, the pump either under- or overcompresses the fluid causing characteristic ripples in flow and pressure. Either under- or over-compression results in periodic variation in both pressure and flow with the characteristic frequency of the pump (ml/min divided by pump stroke volume in ml). The result is noisy baselines and irreproducibility. To compensate for this, the more expensive and better liquid chromatography pumps have compressibility adjustments to account for differences in fluid characteristics.
High-pressure SFC pumps have an extended compressibility range and the ability to dynamically change the compression compensation. While these pumps are used as flow sources and the pressure and temperature of the delivered fluid may be measured. The pumps can change the length of compression to account for changes in compressibility with pressure and temperature. Methods in the prior art calculate ideal compressibility based on measured temperature and pressure using a sophisticated equation of state. The method then uses dithering around the setpoint to see if a superior empirical value can be found. This approach is described in U.S. Pat. No. 5,108,264, Method and Apparatus for Real Time Compensation of Fluid Compressibility in High Pressure Reciprocating Pumps, and U.S. Pat. No. 4,883,409, Pumping Apparatus for Delivering Liquid at High Pressure. Other prior art methods move the pump head until the pressure in the refilling cylinder is nearly the same as the pressure in the delivering pump head. One method in U.S. Pat. No. 5,108,264 Method and Apparatus for Real Time Compensation of Fluid Compressibility in High Pressure Reciprocating Pumps, adjusts the pumping speed of a reciprocating pump by delivering the pumping fluid at high pressure and desired flow rate to overcome flow fluctuations. These are completely empirical forms of compressibility compensation. The prior art methods require control of the fluid temperature and are somewhat limited since they do not completely compensate for the compressibility. The compensation stops several hundred psi from the column inlet pressure.
The compressibility of the pumping fluid directly effects volumetric flow rate and mass flow rate. These effects are much more noticeable when using compressible fluids such as carbon dioxide in SFC rather than fluids in liquid chromatography. The assumption of a constant compressibility leads to optimal minimization of fluid fluctuation at only one point of the pressure/temperature characteristic, but at other pressures and temperatures, flow fluctuations occur in the system.
If the flow rate should be kept as constant as possible through the separation column. If the flow rate fluctuates, variations in the retention time of the injected sample would