WO2013034242A1

WO2013034242A1 - Device and method for filtering a liquid sample

Info

Publication number: WO2013034242A1
Application number: PCT/EP2012/003474
Authority: WO
Inventors: Franziska Jonas; Bernhard Diel
Original assignee: Sartorius Stedim Biotech Gmbh
Priority date: 2011-09-05
Filing date: 2012-08-16
Publication date: 2013-03-14
Also published as: DE102011112291A1; DE102011112291B4

Abstract

The invention relates to a method and to a device for filtering a liquid sample, wherein in a first step the liquid sample is filled into a sample container by means of a vacuum, in a second step the sample holder is connected to a filter attachment, and in a third step the liquid sample is fed to the filter by means of high pressure, wherein a filtration aid suitable for settlement filtration is fed to the sample container and suspended with the liquid sample before the sample holder is filled with the liquid sample.

Description

Apparatus and method for the filtration of a

fluid sample

description

Field of the invention

The invention relates to a device for filtering a liquid sample with a pressurizable

Sample container for receiving the liquid sample and with a connectable to a connection of the sample container filter attachment, a filter and to the his

Sample container facing away filtrate side one

Filtrate connection has.

The invention further relates to a method for filtering a liquid sample, wherein in a first step, the liquid sample with a negative pressure in a

Sample container is filled, in a second step, the sample container is connected to a filter attachment, and in a third step by overpressure the liquid sample is fed to the filter.

State of the art

For example, from DE 203 01 787 Ul a filter attachment is known, which can be acted upon with a pressure

Sample container, such as a syringe, connected can be. This filter attachment has a filter and a filtrate connection facing away from the sample container on its filtrate side.

However, these known filter attachments, which have basically proven themselves, are not suitable for filtering turbid solutions in a single step and, in particular, for carrying out cell separation without prematurely blocking or achieving a sterile filtrate.

Liquid samples containing, for example, mammalian cells or microorganisms and a high proportion of

Particulate substances are usually supplied for particle-free clarification of a centrifugation or sedimentation and / or direct filtration.

Such conventional treatment methods are complex in terms of time and equipment due to the multiple stages. Especially for small sample volumes, they are relatively expensive or uneconomical.

task

Object of the present invention is therefore, in particular an apparatus and a method for the filtration of

specify a smaller volume, which is a simple and

cost-effective filtration of cloudy solutions with high

Allow biomass shares. Presentation of the invention

The object with respect to the device is achieved in conjunction with the preamble of claim 1, characterized in that the sample container contains a filter aid suitable for precoat filtration, and in that the filter attachment has a filter facing the sample container

Unfiltratseite out upstream dead space for receiving a forming filter or Anschwemmkuchens.

While the expert has been trying so far as possible to the unfiltrate side in the filter attachment no dead space

form, the filter attachment now has a

Unfiltratseite out upstream dead space on, virtually all of the forming filter cake one out

Liquid sample and filter aid existing

Suspension can absorb.

As a result, a precoat filtration can be carried out, which makes it possible, without further aids, such as pump,

Centrifuges and vessels to prepare the sample in a single step in the laboratory. Thus, a multi-step approach is unnecessary.

According to a preferred embodiment of the invention, the sample container is partially filled with the filter aid before receiving the liquid sample. It is not

necessary that filter aid in a submitted

Liquid sample to suspend, but rather

vice versa. The liquid sample is suspended in the submitted filter aid, a dry powder mass. According to a further preferred embodiment of the

Invention is the sample container with kieselguhr, perlite,

Diatomaceous earth, with a particulate (an) organic

Adsorbent or partially filled with a combination of the aforementioned materials as a filter aid. The handling of fine dust filter aids, especially with

Diatomaceous earth, is subject to special requirements for the protection of the user, because certain components can be hazardous to health. Therefore, appropriate precautions are usually required when handling these substances. By the present device with the partially filled

Sample container, which is already pre-filled, ensures dust-free work safely.

According to another preferred embodiment of the invention is on the sample container to the filter attachment out

Hose connection with a valve and a sterile connector arranged to fill the sample container. This makes it possible to use storage tanks, such as bioreactors

Cell cultures, via the sterile connector and the

Hose connection with open valve one cell

To remove fluid sample containing without a risk of contamination of the sample by germs from the

Environment exists, since after removal of the

Liquid sample from a pre-sterilized arrangement

Sample container, filter attachment, sterile connector and

Hose connection via the sterile connector can be separated sterile from the reservoir.

According to a further preferred embodiment of the

Invention is the sample container as a syringe

educated. About the piston of the syringe can be the Apply pressure to sample container, wherein in a known manner by retraction of the piston, a negative pressure to

Recording the liquid sample and by inserting the piston an overpressure for filtration is generated.

According to a further preferred embodiment of the invention, the filter is as a pulp-based depth filter, as a membrane filter, as a plastic fleece or a

Layer composite of several of the aforementioned filter media formed with graduated deposition rates.

The object with regard to the method is achieved in conjunction with the preamble of claim 7 in that, prior to filling the sample container with the liquid sample, a filter aid suitable for precoat filtration is supplied to the sample container and suspended with the liquid sample.

Centrifuges and vessels, the sample in a single-stage

Process in the laboratory. This makes a multi-step approach superfluous.

According to a preferred embodiment of the invention, the filter aid is suspended with the liquid sample in the sample container by shaking. Without further aids is by simply shaking the sample container a

Suspension of the filter aid in the liquid sample possible. According to a further preferred embodiment of the

In the invention, turbid solutions are filtered by the precoat filtration; in particular, by the precoat filtration, cell separation can be effected simply, quickly and safely.

According to a further preferred embodiment of the

Invention is for filling the sample container with the liquid sample of the sample container via a

Hose connection, which has a valve and connected to a reservoir sterile connector, connected to the filter attachment, wherein the negative pressure

Liquid sample via the sterile connector, the

Hose connection and the open valve in the

Sample container is filled, and wherein before the third step, the hose connection and the valve through

Disconnect the sterile connector to be separated from the reservoir sterile.

In this method, it is thus possible from a

To remove reservoir, such as a bioreactor with cell cultures, via the sterile connector and the hose connection with the valve open, a cell-containing liquid sample from the reservoir without a

Contamination risk for the liquid sample by germs from the environment, since after the removal of the liquid sample from a pre-sterilized arrangement

Sample container, filter attachment, sterile connector and

Hose connection via the sterile connector can be separated sterile from the reservoir. Further details of the invention will become apparent from the following detailed description and the accompanying drawings in which preferred embodiments of

Invention are exemplified.

Brief description of the drawings In the drawings:

Figure 1: a side view of a reservoir, to the for taking a liquid sample

Sample container is connectable (in a reduced scale);

Figure 2: a side view of an apparatus for

Filtration, consisting of sample container and attached filter attachment, partly in

Cut with partially filled filter aid;

Figure 3: a side view corresponding to Figure 2 with

Suspension of filter aid and liquid sample;

Figure: a side view corresponding to Figure 2 with

Alligator cake in the dead space and

Figure 5: a side view of an apparatus for

Filtration with attached filter attachment and a hose attachment with valve and a

Sterile connector for filling the

Sample container, partly in section. Description of the embodiments

A device 1 for filtering a liquid sample 2 consists essentially of a sample container 3 and a filter attachment 4.

The sample container 3 is formed in the embodiments of Figures 1 to 3 as a syringe 5. The syringe 5 has in known manner a syringe body 6, in which a piston 7 is guided longitudinally displaceable. At its end facing the filter attachment 4, the syringe body 6 has a syringe port 8.

The filter attachment 4 has at its end facing the sample container 3 a with the syringe port. 8

corresponding terminal 9 on. At its end facing away from the terminal 9, the filter attachment 4 has a

Filtrate 10 on. The filter attachment 4 has a housing lower part 11 carrying the filtrate connection 10, in which a filter 14, which is laterally sealed, rests on the support surface 13 which has filtrate channels 12.

The filter 14 may be used as a pulp or polymer based depth filter, as a membrane filter, as a

Plastic filter fleece, plastic filter screen, metal mesh or as a combination of several of the above

Be formed materials. Towards the sample container 3, the housing lower part 11 or the filter attachment 4 has a dead space 15. To the syringe port 8 is the

Dead space 15 covered by a housing upper part 16. Of the

Dead space 15 communicates via an inflow channel 17 with the connection 9 in connection. The dead space 15 has a volume, the so is that he measures the dry matter of a

Filter aid 18 and the particles to be removed from the liquid sample 2 can be used as alluvial cake 19. For example, kieselguhr is used as filter aid 18.

According to Figure 5, the sample container has a

Hose connection 23 with a valve 24 for filling the sample container 3. This embodiment allows the implementation of a method in which in a first step, the sample container (3) via the hose connection (23), which the valve (24) and one with the

Reservoir (21) connected sterile connector (20)

is connected to the filter attachment (4), in a second step by negative pressure, the liquid sample (2) via the sterile connector (20), the hose connection (23) and the open valve (24) by negative pressure in the

Sample container (3) is filled, in a third step, the hose connection (23) and the valve (24) by

Disconnecting the sterile connector (20) from the

Reservoir (21) are separated sterile and in a fourth step by positive pressure, the liquid sample (2) is fed to the filter (14), wherein prior to the first step the sample container (3) for a precoat

suitable filter aid (18) is supplied.

In this method it is possible to choose from a

Reservoir (21), for example, a bioreactor with cell cultures, via the sterile connector (20) and the

Hose connection (23) with open valve (24) to remove a cell-containing liquid sample (2) from the reservoir (21) without any risk of contamination for the Liquid sample (2) consists of microorganisms from the environment, since after removal of the liquid sample (2) a pre-sterilized arrangement of sample container (3),

Filter attachment (4), sterile connector (20) and hose connection (23) over the sterile connector (20) sterile from the

Reservoir (21) can be separated.

In the method according to Figures 1, 3 and 4, the

Filtration in the form of a precoat filtration of

Sample container 3, for example the syringe 5,

for example, via a sterile connector 20 with a

Reservoir 21, z. As a bioreactor, connected and in a first step, the liquid sample 2 is sucked with a negative pressure in the sample container 3. In a second step, the sample container 3 with the

Filter attachment 4 connected and by shaking the

Sample container 3 with the filter attachment 4 is the

Filter aid 18 suspended with the liquid sample 2. In a subsequent step, the suspension 22 is made

Liquid sample 2 and filter aid 18 by pressure, namely by pushing the piston 7 in the syringe body 6, pressed through the filter 14. In this case, the precoat cake 19 deposits on the filter 14 towards the side of the unfiltrate.

LIST OF REFERENCE NUMBERS

1 device

2 fluid sample

3 sample containers

4 filter attachment

5 syringe

6 syringe bodies of 5

7 pistons of 5

8 syringe port of 6

9 connection of 4

10 filtrate connection of 4

11 housing base

12 filtrate channel

13 bearing surface

14 filters

15 dead space

16 housing upper part

17 inflow channel of 4

18 filter aids

19 alluvial cake

20 sterile connectors

21 storage tank

22 suspension

23 hose connection

24 valve

Claims

Patent claims

Device (1) for filtering a liquid sample

(2) with a pressurized sample container

(3) for receiving the liquid sample (2) and with a filter attachment (4) which can be connected to a connection of the sample container (3), which has a filter (14) and a filtrate connection (10) on the filtrate side facing away from the sample container (3). having,

characterized,

that the sample container (3) is one to one

Precoat filtration contains suitable filter aid (18), and

that the filter attachment (4) has a dead space (15) in front of its filter (14) towards the unfiltrate side facing the sample container (3) for receiving a filter cake (19) that is forming.

Device according to claim 1,

characterized,

that the sample container (3) before receiving the

Liquid sample (2) is partially filled with the filter aid (18).

Device according to claim 1 or 2,

characterized,

that the filter aid (18) consists of diatomaceous earth, perlite,

Diatomaceous earth, a particulate (an)organic adsorbent or a combination of the aforementioned materials

4. Device according to one of claims 1 to 3, characterized in

that a hose connection (23) with a valve (24) and a sterile connector (20) for filling the sample container (3) is arranged on the sample container (3) towards the filter attachment (4).

5. Device according to one of claims 1 to 4,

characterized,

that the sample container (3) acts as a syringe (5)

is trained.

6. Device according to one of claims 1 to 5,

characterized,

that the filter (14) is a pulp-based depth filter, a membrane filter, a plastic fleece or a

Layer composite consisting of several of the aforementioned

Filter media with graduated separation rates.

7. Method for filtering a liquid sample (2), in which in a first step the liquid sample (2) is filled into a sample container (3) with a negative pressure,

in a second step the sample container (3) is connected to a filter attachment (4), and

in a third step by overpressure

Liquid sample (2) is fed to the filter (14), characterized in that

that before filling the sample container (3) with the liquid sample (2), a filter aid (18) suitable for precoat filtration is supplied to the sample container (3) and suspended with the liquid sample (2). becomes.

8. Method according to claims 7,

characterized,

that the filter aid (18) is suspended with the liquid sample (2) by shaking.

9. Method according to claim 7 or 8,

characterized,

that the precoat filtration produces cloudy solutions

be filtered.

10. Method according to one of claims 7 to 9,

characterized,

that the precoat filtration results in cell separation.

11. Method according to claim 7,

characterized,

that for filling the sample container (3) with the

Liquid sample (2) of the sample container (3) via a hose connection (23), which has a valve (24) and one connected to a storage container (21).

Has a sterile connector (20) with which the filter attachment (4) is connected,

that the liquid sample (2) is filled into the sample container (3) via the sterile connector (20), the hose connection (23) and the opened valve (24), and

that before the third step, the hose connection (23) and the valve (24) by disconnecting the Sterile connector (20) is separated from the storage container (21) in a sterile manner.