DE202011004909U1 - Device for online UV sterilization in LC and FFF systems - Google Patents

Abstract

Device intended for online UV sterilization of solvents in liquid chromatography and / or field flow fractionation, with: - a UV radiation source (1), - one or more solvent capillary (s) (2), - a capillary holder (3) and - a housing (4), wherein the eluent capillary (s) is / are connected to one or more eluent storage container (s) outside the housing and a liquid chromatography system or a field flow fractionation system, characterized in that the UV radiation source (1) in the housing (4) is attached, the capillary holder (3) is arranged essentially concentrically to the UV radiation source (1) in the housing (4), and the solvent capillary (s) (2) is / are wound around the capillary holder (3) .

Description

Technical area

The invention relates to a device which is provided for the on-line UV sterilization of solvents in liquid chromatography (LC) and / or field-flow fractionation (FFF).

State of the art

The sterilization / sterilization of liquid substances as well as corresponding devices and methods are well known.

So z. For example, by the addition of sodium azide to an aqueous solvent in liquid chromatography or field flow fractionation, the growth of microorganisms in the respective mobile phase can be prevented.

Sodium azide, however, is toxic in higher concentrations and in countries such as Japan. B. not allowed.

Without biocidal additives, however, the growth of microorganisms in the respective eluents accelerates, which in turn leads to a contamination of the corresponding chromatography or Feldflussfraktionierungssysteme. The consequence of microbial contamination is shorter maintenance and cleaning intervals with the corresponding effects on productivity and correspondingly higher costs.

Furthermore, the contamination leads to a deterioration of the signal-to-noise ratio of the detectors used. This is particularly true for light scattering detectors, which are often downstream of both liquid chromatography and field flux fractionation.

An alternative is the UV irradiation for the sterilization of liquids.

The UV radiation sources used are usually UV immersion probes or UV lamps, which are directly surrounded by the substance to be disinfected.

From the WO 00/79246 is z. B. an encapsulated UV radiation source is known, which is placed directly in a reservoir of the liquid to be sterilized.

When using such UV sterilization systems, at the interfaces between the liquid to be sterilized, for. As an eluent for liquid chromatography and / or the Feldflussfraktionierung, and the UV radiation source salt crystals. This leads to a change in the composition of the eluent. Furthermore, there may be an uncontrolled redissolution of the salt crystals, which u. U. leads to a disturbance of the detector signal.

Furthermore, devices are known in which a liquid to be sterilized flows past a UV radiation source. The US 2007/0045561 discloses z. B. a chamber having a reflective inner surface, and in which a UV radiation source and a passing through the chamber UV-translucent tube through which flows a liquid to be sterilized, are arranged.

From the WO 2010/097499 Furthermore, a photoconductive capillary is known. This is a polymer capillary, which is coated, inter alia, with a UV-transparent material. A liquid flowing through the capillary is sterilized by means of UV radiation, in that the UV radiation which is introduced into it through one of the two open ends of the capillary, due to total reflection on the UV-translucent coating along the capillary and through the capillary sterilizing liquid is passed.

However, the devices described are mostly used in process technology and are designed for high volume flows of> 100 mL / min. The presence of large dead volumes and the uncontrolled formation of salt crystals in these devices therefore play only a minor role.

Large dead volumes and uncontrolled salt crystal formation, however, complicate the filling and flushing / cleaning of the respective systems with fresh mobile phase in the field of liquid chromatography and field-flow fractionation.

A device for the sterilization of solvents for liquid chromatography and / or field-flow fractionation is described in DE 20 2008 017 762 described. It is a device for sterilizing a solvent, which is located in a reservoir, in particular a solvent containing alkali phosphates for performing a liquid chromatography or Feldflussfraktionierung, wherein the reservoir is provided with a lid on which a coaxial in the interior the UV-translucent and sealed against the solvent protective tube is attached to the reservoir, and a UV lamp is disposed within the protective tube.

To avoid the problems resulting from the formation of dead volumes and uncontrolled salt crystal formation in the reservoir revealed, in this device, in addition to the conventional UV probe a stirring device such. B. a magnetic stirrer, in the storage vessel.

Due to the additionally required components, however, this is accompanied by an increased expenditure on equipment and the possibility of an increased failure rate of the respective chromatography or Feldflussfraktionierungssysteme.

Incidentally, the immersion probe, which is encapsulated in a watertight manner but is still located in the working area of the user, can lead to a higher risk for the user when frequently changing the running medium. If only a certain solvent is used over a longer period of time, this can indeed be refilled without removing the UV probe, however, when changing the solvent, it is necessary to completely open the storage vessel and remove the UV probe to the vessel and also thoroughly clean the probe from the previous solvent.

Presentation of the invention

The object of the invention is to provide a device for ultraviolet sterilization of eluents in liquid chromatography and / or field flux fractionation (FFF) in which the eluent to be sterilized flows past a UV radiation source, i. H. in which an online UV sterilization takes place, and which avoids the problems described above with regard to the formation of dead volumes and uncontrolled salt crystal formation and at the same time is characterized by a safe and user-friendly design or a safe and user-friendly handling.

This object is achieved by the device according to claim 1. According to the invention, a device is provided which is suitable for the on-line UV sterilization of mobile phase and / or field-flow fractionation media comprising a UV radiation source, one or more mobile capillary (s), a capillary holder and a housing, wherein the mobile phase capillary (n ) is connected to one or more fluid reservoirs outside the housing and a liquid chromatography system or a field flow fractionation system, characterized in that the UV radiation source is mounted in the housing, the capillary holder is arranged substantially concentric with the UV radiation source in the housing and the solvent capillary (s) is / are wrapped around the capillary holder.

By this construction, the modular character of the liquid chromatography or Feldflussfraktionierungssysteme used is maintained, which allows individual components such. As pumps, degasifiers or different detectors, exchange or (temporarily) to remove from the solvent circuit of the respective chromatography or Feldflussfraktionierungssysteme. Thus, the device according to the invention can be integrated as required between the pumps and one or more eluent storage vessel (s) in the eluent circuit of a liquid chromatography or Feldflussfraktionierungssystems or removed therefrom.

The structure of the device according to the invention also makes it possible for the mobile phase of a liquid chromatography or Feldflussfraktionierungssystems can be changed without the device has to be removed or opened.

Furthermore, the user does not come into contact with the UV radiation source due to the encapsulation of the UV radiation source in the housing of the device according to the invention.

The encapsulation of the UV radiation source in the housing also ensures that no UV radiation is emitted to the outside during the operation of the device according to the invention.

The internal diameter of the solvent capillary (s) used in the device according to the invention is chosen such that a laminar flow is maintained even at low volume flows below 0.05 mL / min. By maintaining a laminar flow within the capillaries, the formation of non-perfused areas, i. H. Dead volumes, prevented. At the same time, the uncontrolled formation of salt crystals at the interfaces of non-moving mobile phase and the elution of salt crystals are prevented and possibly already existing salt crystals can be dissolved again.

The internal diameter and the length of the mobile phase capillary (s) used are furthermore selected such that even at high flow rates the flow resistance and the resulting pressure drop across the capillary (s) do not influence the delivery rate of the pump used in each case and the mobile phase has been expelled by the UV Radiation source is irradiated to achieve the killing of existing microorganisms in the mobile phase.

In a preferred embodiment, the solvent capillary (s) used in the apparatus of the invention has an inside diameter of 1.0-1.6 mm and a length of up to 1 m.

In addition, the wall thickness and thus the outer diameter of the mobile phase capillary (s) are adjusted so that there is only a very small absorption of UV radiation through the capillary material. Preferably, less than 10%, and more preferably less than 5, of the emitted UV radiation is absorbed.

In a preferred embodiment, the solvent capillary (s) used in the apparatus according to the invention has an outer diameter of 3.2 mm.

The material used for the capillary (s) must be UV-transparent but UV-resistant. The capillary material must also be chemically inert to the various aqueous and organic solvents used in liquid chromatography and / or field-flow fractionation, and must have some thermal stability.

In one embodiment, the mobile phase capillary (s) consist of pure or high purity perfluoroethylene propylene (FEP), such as. FEP HP and FEP HP +, or perfluoroalkoxy (PFA).

These materials ensure a very good transmission of UV rays with simultaneously high chemical and thermal resistance and good mechanical flexibility. The good mechanical flexibility of the capillaries also allows cost-effective production of capillary spirals.

In a preferred embodiment, the mobile phase capillary (s) consist of perfluoroalkoxy (PFA).

A preferred capillary holder of the device according to the invention consists of four metal rods, which are arranged in a cage with an approximately square cross section and which are connected to each other at both ends via a metal ring.

Preferably, the metal rods and the metal ring made of aluminum.

In a further embodiment, a correspondingly shaped injection-molded component can also be used as a capillary holder.

Preferably, the capillary holder of the device according to the invention is removable from the housing.

In one embodiment, the distance of the solvent capillary (s) wound around the capillary holder from the UV radiation source is 10-30 mm, preferably 10-20 mm.

In a preferred embodiment, the solvent capillary (s) are spirally wound with a uniform spacing of the individual turns around the capillary holder. The pitch of the individual turns is preferably 0-10 mm, more preferably 0-5 mm, and most preferably 0-2 mm.

In one embodiment, the UV radiation source of the device according to the invention is an ozone-free low-pressure mercury lamp. Preferably, a UV radiation source having a wavelength of 254 nm is used.

In another embodiment, an excimer radiator having a wavelength in the range of 174 nm can be used as the UV radiation source.

Preferably, the UV radiation source has a rod-shaped structure.

In order to allow easy replacement of the UV radiation source, this is removably mounted in the housing of the device according to the invention.

The housing of the device according to the invention is preferably cylindrical with a round or square cross-section. Preferably, the housing of the device according to the invention has a square cross-section.

The housing of the device according to the invention is preferably made of metal and in a particularly preferred embodiment of aluminum.

The housing has rubber rings, which serve to absorb the UV radiation source shockproof. Furthermore, the housing comprises a removable end plate, with which the housing is closed on one side and which secures the UV radiation source against slipping out. The endplate has a central round hole to accommodate a rubber ring and one end of the UV radiation source. On the opposite side of the housing is a round centrally located recess for receiving another rubber ring and the other end of the UV radiation source. The UV radiation source and the capillary holder are arranged substantially concentrically in the housing.

In a preferred embodiment, the housing is made of black anodized aluminum. The operation of the UV radiation source Resulting UV-C and heat radiation is absorbed by the coating. The aluminum housing acts like a heat sink and dissipates the resulting heat to the outside, so that the temperature in the interior of the housing at not more than 35-50 ° C, preferably not more than 40 ° C, can be maintained. This temperature stabilization significantly increases the life of the UV radiation source, especially when it is a low-pressure mercury lamp.

The mobile phase capillary (s) of the device of the invention leaves / leaves the housing through lateral openings in the longitudinal side of the housing and is connected to one or more mobile storage reservoirs outside the housing and to a liquid chromatography system or a field flow fractionation system.

In a preferred embodiment, the device according to the invention is provided for on-line UV sterilization of mobile phase field fraction fractionation. In particular, the device according to the invention for on-line UV sterilization of mobile phase in the symmetrical flow Feldflussfraktionierung, the asymmetric flow field flow fractionation, the sedimentation Feldflussfraktionierung such. B. the centrifugal Feldflussfraktionierung, as well as the thermal Feldflussfraktionierung and preferably in the Fluß Feldfeldt fractionation.

Short description of the figures

1 shows a UV radiation source ( 1a ), a capillary holder with two capillaries wound around it ( 1b ) and a housing for receiving the UV radiation source and the capillary holder ( 1c ).

2 shows the structure of a preferred embodiment of the device according to the invention

3 shows the structure of a Feldflussfraktionierungssystems, in which the device according to the invention is integrated.

Ways to carry out the invention

1a shows a rod-shaped UV radiation source ( 1 ) for use in the device according to the invention.

1b shows a capillary holder ( 3 ) for use in the device according to the invention. In the capillary holder ( 3 ) Four metal bars are arranged in a cage with a square cross-section and connected at both ends via a metal ring.

To the capillary holder ( 3 ) is one or two FEP or PFA eluent capillary (s) ( 2 wrapped).

1c shows the front view of a housing ( 4 ) for use in the device according to the invention. The housing ( 4 ) has on the left transverse side a removable end plate ( 5 ) with a central round bore. The opposite transverse side is firmly connected to the housing and contains a central round recess.

The housing has openings on the front ( 7 ) for the passage of the eluent capillary (s) ( 2 ) on.

The central round hole in the removable end plate ( 5 ) serves to receive a first rubber ring ( 6 ) and one end of the UV radiation source ( 1 ). The central round recess in the opposite transverse side serves to receive a second rubber ring ( 6 ) and the other end of the UV radiation source ( 1 ) (see. 2 ).

2 shows a housing ( 4 ) for use in the device according to the invention, in which the capillary holder ( 3 ) with the capillary (s) wound thereon ( 2 ) as well as a rubber ring ( 6 ) and the UV radiation source ( 1 ) were inserted. The housing ( 4 ) is with the end plate ( 5 ), in which a rubber ring ( 6 ) is attached, closed.

3 schematically shows a typical integration of the device according to the invention ( 9 ) into a field flow fractionation system. The in the solvent reservoir ( 8th ) is removed by means of the corresponding pumps ( 11 ) and ( 12 sucked). In this case, the eluent first flows through the device according to the invention ( 9 ), in which the eluent is sufficiently long through the UV radiation source ( 1 ) is irradiated, so that the microorganisms present in the eluent are killed and the subsequent system components are protected against microbial contamination. Thereafter, the now sterilized solvent for reducing the dissolved oxygen flows through a degasser ( 10 ). Then the eluent is removed by means of the pumps ( 11 ) and ( 12 ) into the field-flow fractionation unit ( 13 ), such. For example, a field flow fractionation unit for symmetric or asymmetric flow field flow fractionation or sedimentation field flow fractionation is pumped. After sample fractionation within the field flow fractionation unit ( 13 ), the eluent is further passed through one or more detectors (s) ( 14 ) and finally into a waste container ( 15 ).

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• WO 00/79246 [0009]
• US 2007/0045561 [0011]
• WO 2010/097499 [0012]
• DE 202008017762 [0015]

Claims (11)

Apparatus intended for the on-line UV sterilization of solvents in liquid chromatography and / or field-flow fractionation, comprising: - a UV radiation source ( 1 ), - one or more eluent capillary (s) ( 2 ), - a capillary holder ( 3 ) and - a housing ( 4 ), wherein the mobile phase capillary (s) is / are connected to one or more mobile storage reservoir (s) outside the housing and to a liquid chromatography system or a field flow fractionation system, characterized in that the UV radiation source ( 1 ) in the housing ( 4 ), the capillary holder ( 3 ) substantially concentric with the UV radiation source ( 1 ) in the housing ( 4 ) and the mobile phase capillary (s) ( 2 ) around the capillary holder ( 3 ) is / are wound. Apparatus according to claim 1, wherein the UV radiation source ( 1 ) is an ozone-free low-pressure mercury lamp. Device according to claim 1 or 2, wherein the mobile phase capillary (s) ( 2 ) each have an inner diameter of 1.0-1.6 mm and a length of up to 1 m / have. Device according to one of claims 1 to 3, wherein the mobile phase capillary (s) ( 2 ) consists of pure or ultrapure perfluoroethylene propylene (FEP) or perfluoroalkoxy (PFA). Apparatus according to claim 4, wherein the mobile phase capillary (s) ( 2 ) consists of perfluoroalkoxy (PFA) / exist. Device according to one of the preceding claims, wherein the mobile phase capillary (s) ( 2 ) spirally with a uniform spacing of the individual turns around the capillary holder ( 3 ) is / are wound. Device according to one of the preceding claims, wherein the distance between the capillary holder ( 3 ) wound solvent capillary (s) ( 2 ) from the UV radiation source ( 1 ) Is 10-30 mm. Device according to one of the preceding claims, wherein the housing ( 4 ) Rubber rings ( 6 ) for shock-proof recording of the UV radiation source ( 1 ) and a removable end plate ( 5 ) and the UV radiation source ( 1 ) with the help of rubber rings ( 6 ) is secured in the housing. Device according to one of the preceding claims, wherein the housing ( 4 ) is made of black anodized aluminum and the ambient temperature in the housing ( 4 ) during operation of the UV radiation source ( 1 ) is not more than 35-50 ° C. Device according to one of the preceding claims, wherein the device for on-line UV sterilization of eluents in the Feldflussfraktionierung is provided. The device of claim 10, wherein the device is for on-line UV sterilization of mobile agents in flow field-flow fractionation or sedimentation field-flow fractionation.

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