Liquid purification or separation – Processes – Chromatography
Reexamination Certificate
1999-09-13
2001-01-09
Therkorn, Ernest G. (Department: 1723)
Liquid purification or separation
Processes
Chromatography
C210S198200
Reexamination Certificate
active
06171502
ABSTRACT:
The invention relates to an endpiece for chromatography columns, in particular for columns for HPLC.
In the outlet part of chromatography columns, the column endpiece, the cross-sectional area through which flow takes place decreases by several orders of magnitude. This is accompanied by a corresponding change in the flow speed of the column eluate, with additional radial flow components being created. This entails the problem that chromatography bands separated in the column bed are not eluted separately since mixing effects are created by influences at the column outlet. Because of the better separation effects which can be obtained with high performance liquid chromatography (HPLC), the problem is particularly pronounced in HPLC. In preparative HPLC, where column diameters of more than five centimeters are usual, this problem is further exacerbated since the connection lines are particularly small compared with the column diameters.
Known solutions to the problem are presented in standard works for HPLC, for example in “Handbuch der HPLC” [Handbook of HPLC] (ed. K K Unger, 1994, GIT-Verlag). It is customary, for example, to arrange a cylindrical cavity, in which the eluate can flow radially to the column outlet, under a bed support frit. Depending on the position of a volume element in terms of the cross section of the column (i.e. the distance of this element from the column axis), this liquid element will take a different length of time when flowing through the column endpiece. These differences lead to the aforementioned broadening of the eluate bands, and therefore to the deterioration in the separation performance. This deterioration in the separation performance is interpreted by prevalent opinion as being due to the void volume. It is therefore proposed, as a remedy, to use a zero void volume endplate, as can for example be seen from the picture on page 62 of the said handbook. This endplate contains radial indentations in the central region, which do not extend over the entire cross section. The required transverse flow must therefore take place essentially through the dispenser frit; the latter has the form of a planar cylinder. In this embodiment, the described problem of differing propagation times of the volume elements is therefore unresolved.
FIG. 4
of EP 0 106 746 schematically represents a column endpiece which has a funnel-shaped outlet. Various chromatography columns are schematically represented on page 105 of J. Chromatogr. Library (Elsevier (1975) volume 3; Liquid Column Chromatography). In this case, there are also column endpieces with a curved profile. However, the problem of flow conditions at the transition between the column and the outlet tube is not discussed in these publications. During the hydrodynamic model calculations which have been described in more detail below, another phenomenon contributing to the band broadening became clear: during these calculations, it was found that the pressure profile is not planar, so that a differing pressure increase occurs in the column endpiece as a function of distance from the column axis. This distorted pressure profile has repercussions on the flow in the column packing.
SUMMARY OF THE INVENTION
The object of the invention is to improve the configuration of endpieces of chromatography columns so that the mixing of boundary regions and concomitant band broadening when the eluate flows through the column outlet are reduced, with the further intention, in particular, of avoiding the repercussions of a distorted, that is to say non-planar, pressure profile on the flow situation on the column packing.
The object is achieved by providing column endpieces whose cross section is configured in such a way that separation surfaces between eluted bands pass in parallel through the column outlet, without becoming excessively distorted. To that end, a column endpiece for a chromatography column is provided which has a cross section that is derived from a cone, the side surface more preferably having a curved contour instead of a straight one. The curved contour is obtained on the basis of hydrodynamic analysis, the equation system resulting in a parabola equation, that is to say a concavely curved contour, or in the equation of an exponential function, that is to say a convexly curved contour, depending on the chosen boundary conditions. It was found that hybrid shapes with sigmoid curvature, which changes over from a concave part into a convex part, are also advantageous. In order to avoid the said repercussions of the distorted pressure profile, pressure decoupling is provided according to the invention between the sorbent bed of the chromatography column and its outlet part. To that end, the discharge frit (
2
) is configured in such a way that the pressure drop per unit length in the frit is at least twice as great as in the sorbent packing. Measures which make it possible to increase the pressure drop in a frit are known to the person skilled in the art. They include, for example, reducing the porosity of the frit. Although, according to prevalent opinion, the flow resistance in a terminal frit should be kept as small as possible, so that the pressure drop is not increased unnecessarily, the present invention teaches that this pressure drop in the terminal frit should be increased, so that the separation performance of the chromatography column is increased.
When use is made of a terminal frit which causes strong pressure decoupling, a boundary layer is kept substantially undistorted even with a conical contour. In order to obtain sufficient pressure decoupling, the pressure drop per unit length in the frit is at least twice as great as in the sorbent packing.
The invention relates to a column endpiece for a chromatography column, through which eluent flows, comprising a base part (FIGS.
1
b,
1
c
and
3
;
1
,
1
a,
1
b
), a discharge tube, whose inner profile is denoted by (
4
) and a frit (
2
), the base part having an essentially funnel-shaped contour, and, when the eluent is flowing through, the said frit producing a pressure drop per unit length that is at least twice as great as the pressure drop per unit length which is created in the sorbent packing when the eluent is flowing through. In preferred embodiments, the base part has a curved region (FIGS
1
b,
1
c
and
3
;
1
,
1
a,
1
b
). This curvature may be concave, convex or sigmoidal.
The invention also relates to the use of an endpiece according to the present invention in a chromatography column.
REFERENCES:
patent: 4354932 (1982-10-01), McNeil
patent: 4422860 (1983-12-01), Feinstein
patent: 4966696 (1990-10-01), Tehrani et al.
patent: 5322626 (1994-06-01), Frank
patent: 9514220 (1995-05-01), None
Delp Axel
Harders Hans-Dieter
Mueller Hans Daniel Jakob
Pelz Peter F.
Spurk Joseph H.
Merck PatentGesellschaft
Millen White Zelano & Branigan
Therkorn Ernest G.
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