DE19902697A1 - Dynamic mixing chamber for high pressure liquid chromatography process has minimum dwell volume and exactly reproduces liquid gradients - Google Patents

Abstract

In a high pressure liquid chromatography (HPLC) process a low dwell-volume mixer unit continually prepares a supply of an elution agent. The dynamic mixer operates at pressures of up to 500 bar. The liquids are mixed by a rotating mixer assembly which has the same geometric shape as the mixer chamber, but is fractionally smaller than the chamber, leaving a tiny gap between the two. In a high pressure liquid chromatography (HPLC) process a low dwell-volume mixer unit continually prepares a supply of an elution agent. The dynamic mixer operates at pressures of up to 500 bar. The liquids are mixed by a rotating mixer assembly which has the same geometric shape as the mixer chamber, but is fractionally smaller than the chamber, leaving a tiny gap between the two. The fluid ingredients are able to flow through the gap when the rotor is turning at high speed. The mixing action between the fluids is effected by the tangential forces existing between the two faces, and by turbulence generated by milled surface irregularities in the cylindrical, ellipsoid or conical rotor. The liquid ingredients enter the mixer chamber at A and emerge at B. the mixing process takes place between the chamber wall W and mixer face R. The average gap width is 0.1 mm.

Description

It is known to rotate liquids in stirred vessels Mixing bodies continuously or discontinuously, which is usually the case Stirring bars serve, their dimensions in relation to the used Mix volumes are comparatively small. You will be through external magnetic fields set in rotation.

In liquid chromatography, mixing is used flowing liquids working on the same principle closed mixing vessels, so-called dynamic mixing chambers.

Another possibility for liquid chromatography practiced Mixing flowing liquids is the application special tees or frits. They are called the ones based on it Devices static (literature on the prior art: relevant Monographs on HPLC).

Dynamic mixing chambers result in much more effective liquid mixing than static mixers. However, they have the great disadvantage that, depending on the effective mixing chamber _volume V _Keff (mixing chamber _volume minus _{stirring body volume} ), there is always a more or less exponential dilution effect. As a result, when using such devices for the production of eluent gradients for chromatography (eluent gradient is to be understood as the continuous change in the concentration of the eluent by mixing several solvents), there is a delay in the onset and a distortion of the actual gradient actually effective in the apparatus compared to the given one and desired target gradients.

The effective so-called Dwell volume V _D and the so-called Dwell time t _D are linked to the solvent total volume flow according to t _D = V _D /. Approximately one can set VD ≈ V _Keff , since the other contributions to the Dwell volume in modern devices are negligible compared to V _Keff .

V _Keff must always be significantly smaller than the volume flow required for the intended chromatographic separation column, otherwise the disadvantages mentioned above become very relevant. Since increasingly small volume flows are required today, the usual dynamic mixing chambers, which generally have mixing chamber volumes of a few tenths of a milliliter to one milliliter, cannot be used (Table 1).

The present invention avoids those discussed above Disadvantages and problems due to the implementation of the invention with regard to those necessary for chromatography today Volume flows of sufficiently small effective mixing chamber volumes (Table 1). In this way, a good match can be made always achieve between target and actual gradients. However, are for very small mixing chamber volumes high quality, low pulsation promotional pumps required.

Another advantage of the invention is that the Dynamic designed according to the invention for low volume flows Mixing chambers with significantly higher flows if required, for example, operated at several milliliters per minute can, whereby a flexible use is achieved.

An embodiment of the invention is illustrated in Fig. 1.

The sketch (sectional view) illustrates the principle of the invention.

The rotating body, inside of which there is a small magnet or steel body, is designed as a rotating cylinder in the example. This is kept in suspension by the liquids entering A unmixed and leaving M mixed B and is set in rapid rotation by a strong external magnetic field, which was indicated by the circular arrow. The mixing processes take place in the gap system between chamber wall W and stirring body wall R. Each of the gaps formed is only about 0.1 mm wide. The effective chamber volume V _{Keff, which} is decisive for the Dwell volume of the dynamic mixing chamber, is in this way, depending on the chamber _size , for example 0.03 ml (30 μl), 0.02 ml (20 μl) or 0.01 ml (10 μl). Effective chamber volumes below 10 μl are also possible according to the invention, but their practical implementation is relatively complex.

Table 1

Claims (2)

1. Device for low dwell volume continuous mixing of liquids for the production of eluents for liquid chromatography (HPLC), preferably up to 500 bar, using the principle of the dynamic mixing chamber, characterized in that a minimum effective mixing chamber volume is realized in such a way that the Stirring body used to mix the liquids is designed as a rotating body and receives the same geometric shape as the mixing chamber, the rotating body volume should only be so much smaller than the mixing chamber volume that a very narrow gap system is created between the mixing chamber wall and the rotating body wall, through which the liquids at high Flow speed of the rotating body. 2. Device according to claim 1, characterized in that the Liquid mixing between the parallel gap surfaces of Mixing chamber wall and rotating body wall not only through Tangential forces comes about, but also through turbulence due to milled surface profiles on the preferred cylindrical, ellipsoidal or spherical Rotational body.