DE102020129201A1 - Method for preparing a sample concentrate and kit for carrying it out - Google Patents

Abstract

A method for providing a sample concentrate is disclosed, with the steps: providing a filter module; providing a source of a sample optionally containing microbes; connecting the source of a sample optionally containing microbes to the one retentate compartment port of the filter module; Closing the other retentate space access of the filter module; passing the sample into the retentate compartment of the filter module; passing a portion of the sample from the retentate space through a membrane wall into the filtrate space of the filter module; Enrichment of sample concentrate in the retentate space, microbes optionally being enriched in the retentate space and/or microbes being attached to and/or in the membrane wall; Deriving the part of the sample from the filtrate space, characterized in that the following further steps are carried out: providing a flushing gas source; providing a collection container; Closing the access to the filtrate space; opening the other retentate space access and collecting sample concentrate in the collection container; connecting the purge gas source to a retentate space port; directing purge gas into the retentate space via a retentate space port; dissolving the sample concentrate and optionally microbes from and/or out of the membrane wall; optional accumulation of microbes in sample concentrate; Deriving the sample concentrate from the retentate space via the other retentate space access; Collecting the sample concentrate in the collection container.

Description

field of invention

The invention relates to a method for providing a sample concentrate and a set for carrying it out.

State of the art

Various filter systems are known, with which fluid is filtered, for example for industrial purposes, and the filtered fluid is discharged again. In order to determine microbiological properties of the fluid to be filtered in the areas of environmental control, dirt and sewage control or water quality control, components filtered out with the filter, in particular microbial components, are analyzed, among other things. A suitable method for this is, for example, in WO 2019/052989 A1 disclosed. The invention relates to a method for processing protein-containing suspensions or solutions, for example for enriching or purifying the protein-containing particles or dissolved protein-containing substances contained in the suspensions or solutions, the protein-containing suspensions or solutions being filtered using a filter module and the protein-containing retained in the filter module Particles or the dissolved protein-containing substance is derived from the filter module with a backwash liquid.

However, the disadvantages of existing solutions for providing samples from filter systems are that the samples are obtained as a by-product of the cleaning process or backwashing process that is primarily taking place. During cleaning or backwashing, the primary attempt is to achieve a maximum cleaning effect. Accordingly, backwashing is carried out with backwashing liquid until the filter has reached the desired level of cleanliness. Depending on the degree of contamination, a large amount of backwash liquid may be necessary. The sample, which is a by-product, is therefore partially highly diluted and can only be analyzed with great effort. This also makes the analysis potentially more susceptible to errors. As a result, the informative value of the analysis results also decreases accordingly.

Presentation of the invention

The object of the invention is to specify a method for providing a sample concentrate, in which the sample concentrate is to be provided effectively and with little effort and a high concentration of microbes in the sample concentrate is to be achieved. The method with water to be analyzed is preferably used, since this often contains microbes.

This object is solved by a method according to claim 1 and by a set according to claim 10. Further features embodying the invention are contained in the dependent claims.

A method according to the invention for providing a sample concentrate has the following steps. First, a filter module is provided which has an interior space which is divided by a membrane wall into a retentate space and a filtrate space, the retentate space having two retentate space accesses and the filtrate space having at least one fluid space access. A source of a sample optionally containing microbes is then provided. The microbes can be viruses, bacteria or protozoa, but also proteins or protein complexes.

In the following, volumes and volume rates are given as examples for individual process steps. These proved to be advantageous when using a filter module with a filter area in the range of 0.1-5.0 m ² , in particular 0.25-3.50 m ² and particularly preferably 0.5-2.5 m ² . Such filter modules are conventionally used for dialysis purposes, for example. In contrast, conventional filter modules with a filter area of 30-100 m ² are used for industrial filtration. For filter modules with a different filter area, it is assumed that changed volumes and volume rates corresponding to the change in filter area prove to be advantageous.

Thereafter, the source of an optional microbe-containing sample is connected to one retentate space port. Then the other retentate space access is closed. The actual filtration operation then begins, in which the sample is conducted from the source of a sample optionally containing microbes via the one access to the retentate space into the retentate space. As a result, a part of the membranous A large part of the sample is conducted from the retentate space over the membrane wall into the filtrate space. In this case, sample concentrate is enriched in the retentate space, microbes optionally being enriched in the retentate space and/or microbes being attached to and/or in the membrane wall. Finally, the part of the membrane-penetrating part of the sample is derived from the filtrate space via the filtrate space access. A membrane-permeable part of the sample is preferably water. Membrane permeability is to be understood as meaning that the substance which permeates the membrane can diffuse through the membrane wall or membrane pores or can be transported convectively through the membrane wall or membrane pores.

During the filtration operation, the passage of the sample containing optional microbes can be started at a volume rate of 250 ml/min, after which the volume rate can be increased as much as possible to increase the process efficiency. A filtration pressure in the range from 0.0 bar to 2.0 bar is preferably selected, in particular from 0.1 bar to 1.5 bar and particularly preferably from 0.2 bar to 1.0 bar. This allows a high process stability to be achieved.

The method according to the invention is characterized in that the following additional steps are carried out. The access to the filtrate space is closed. Then the other access to the retentate space is opened and sample concentrate is collected in the collection container. A purge gas source is then provided. The purge gas source is then connected to a retentate chamber access and purge gas is conducted from the purge gas source via a retentate chamber access into the retentate chamber, with the aid of the purge gas sample concentrate and microbes being able to be detached from and/or out of the membrane wall and the microbes in the sample concentrate being able to be accumulated. A flushing gas volume in the range from 10 ml to 500 ml, in particular in the range from 20 ml to 300 ml and particularly preferably in the range from 30 ml to 200 ml, is preferably passed into the retentate space. Then the sample concentrate is derived from the retentate space via the other access to the retentate space. Finally, the sample concentrate is collected in a collection container. Based on the volume of the sample concentrate collected in the collection container, conclusions can be drawn as to how heavily the filter module is clogged. In addition, the use of a gaseous fluid for rinsing has the advantage that this does not remain in the collection container and dilute the sample concentrate. This simplifies subsequent analysis of the sample concentrate.

In a further embodiment, between the provision of the filter module and the provision of the source of an optionally microbe-containing sample for priming, a rinsing solution source is provided, the rinsing solution source is connected to a retentate chamber access, the filtrate chamber access is closed, rinsing solution is routed from the rinsing solution source via one retentate chamber access into the retentate chamber and the rinsing solution is derived from the retentate space via the other access to the retentate space. This prepares the filter module for the actual filtration operation by means of moistening with the rinsing solution. At the same time, air in the filter module is removed, which increases the process efficiency of the subsequent filtration operation.

In a further embodiment, between the provision of the filter module and the provision of the source of an optionally microbe-containing sample for priming, a rinsing solution source is provided, the rinsing solution source is connected to a retentate chamber access, the other retentate chamber access is closed, rinsing solution from the rinsing solution source is routed via one retentate chamber access into the retentate chamber , the rinsing solution is conducted from the retentate chamber via the membrane wall into the filtrate chamber and the rinsing solution is derived from the filtrate chamber via the filtrate chamber access. In this way, the filter module is also prepared for the actual filtration operation by means of moistening with the rinsing solution. At the same time, air in the filter module is removed, which increases the process efficiency of the subsequent filtration operation.

In a preferred embodiment, both of the above-described preparatory intermediate steps for priming, in which the filter module is preliminarily moistened by means of the rinsing solution, are carried out one after the other. This ensures that the air is removed from all areas that are located around a retentate room access or filtrate room access, whereby the process efficiency of the subsequent filtration operation is increased again. If there are additional accesses to the retentate space or filtrate space, this rinsing solution can also be used. Preferably, the rinsing solution is administered at a volume rate in the range from 50 ml/min to 500 ml/min, in particular in the range from 100 ml/min to 300 ml/min and particularly preferably in the range from 150 ml/min to 250 ml/min through the filter module passed. The filter module is particularly preferably completely filled with rinsing solution, with only as much rinsing solution as necessary being used. Accordingly, for example wise, with a free inner volume of the filter module of 100 ml, ideally only 100 ml of rinsing solution is used.

In a further embodiment, a buffer solution source is or will be provided following the collection of the sample concentrate in the collection container, the filtrate space access opened, the buffer solution source connected to the filtrate space access, buffer solution from the buffer solution source via the filtrate space access into the filtrate space, the buffer solution from the filtrate space conducted via the membrane wall into the retentate space, optionally microbes are released from and/or out of the membrane wall with the buffer solution, optionally the microbes are accumulated in the buffer solution, the buffer solution optionally containing microbes is derived from the retentate space via the access to the retentate space, and the buffer solution optionally containing microbes is in the Collection container collected as an extension of the sample concentrate already present in the collection container. This makes it possible, in addition to detaching the microbes from and/or from the membrane wall by means of the flushing gas starting from the retentate side, and also detaching the microbes from and/or from the membrane wall starting from the filtrate chamber side. As a result, potentially more microbes are released from the membrane wall overall, which simplifies later analysis of the sample concentrate. A flushing solution volume in the range from 25 ml to 1000 ml, in particular in the range from 50 ml to 750 ml and particularly preferably in the range from 100 ml to 500 ml, is fed into the filtrate space. A volume rate in the range from 25 ml/min to 1000 ml/min, in particular in the range from 50 ml to 750 ml and particularly preferably in the range from 100 ml/min to 500 ml/min, is preferably used here.

In a further embodiment, after the buffer solution optionally containing microbes has been drained off via the retentate room access from the retentate room, the filtrate room access is or are closed, the buffer solution is removed from the buffer solution source with the purge gas source, the buffer solution contained in the purge gas source is removed from the purge gas source via a retentate room access into the retentate room guided, optionally microbes are released from and/or out of the membrane wall with the buffer solution, optionally the microbes are accumulated in the buffer solution, the optionally microbe-containing buffer solution is drained from the retentate chamber via the other access to the retentate space, and the optionally microbe-containing buffer solution is in the collection container as an extension of the in collected from the sample concentrate already present in the collection container. This routing of a buffer solution through the filter module via a retentate chamber access starting from the retentate side potentially additionally releases microbes from and/or out of the membrane wall, which further simplifies the subsequent analysis of the sample concentrate. A buffer solution volume in the range from 10 ml to 500 ml, in particular in the range from 15 ml to 350 ml and particularly preferably in the range from 20 ml to 200 ml, is fed into the retentate space.

In a further embodiment, after the buffer solution has been passed through the filter module by means of the purge gas source and the associated steps, purge gas is or are enriched in the purge gas source, the purge gas contained in the purge gas source is/are conducted from the purge gas source via a retentate space access into the retentate space, the buffer solution and optionally Microbes are released from and/or out of the membrane wall with the aid of the flushing gas, optionally microbes are accumulated in the buffer solution, the optionally microbe-containing buffer solution is drained from the retentate chamber via the other access to the retentate space, and the optionally microbe-containing buffer solution is in the collection container as an extension of the one already in the collection container existing sample concentrate collected. This renewed blast of flushing gas from the retentate side potentially releases more microbes from and/or out of the membrane wall, which further simplifies the subsequent analysis of the sample concentrate. A flushing gas volume in the range from 10 ml to 500 ml, in particular in the range from 15 ml to 350 ml and particularly preferably in the range from 20 ml to 200 ml, is preferably passed into the retentate space.

In a further embodiment, between the connection of the purge gas source to a retentate chamber access and the routing of the purge gas from the purge gas source via a retentate chamber access into the retentate chamber, the filter module and the purge gas source are positioned in such a way that the purge gas source is arranged vertically above the one retentate chamber access and that in the purge gas source contained fluid can be passed vertically downwards into the retentate space via the one retentate space access, wherein the one retentate space access corresponds to the retentate space access to which the flushing gas source is connected. This ensures that the maximum amount of microbes potentially present on and/or in the membrane wall is released from and/or out of the membrane wall with the aid of the first flushing gas pulse. This simplifies subsequent analysis of the sample concentrate. When positioning the filter module and the purge gas source, the filter module can be rotated as required. For example, the filter module can be rotated by 180° around a horizontal axis to change the access to the retentate space at the top.

In a further embodiment, a pump is also provided and the solution or solutions are/are conveyed with the aid of the pump. The pump is preferably a positive-displacement pump, the solution or solutions to be conveyed being particularly preferably pushed through the hose by external mechanical deformation of the hose. A peristaltic pump can be used for this, for example. This ensures that the microbes potentially contained in the solutions are damaged to the smallest possible extent. This further simplifies the subsequent analysis of the sample concentrate.

The invention also relates to a set for carrying out a method for providing a sample concentrate, comprising a filter module having an interior space which is divided by a membrane wall into a retentate space and a filtrate space, the retentate space having two retentate space accesses and the filtrate space having one filtrate space access; and an optionally microbially containing sample source comprising an optionally microbially containing solution. The set is characterized in that it further comprises a purge gas source comprising a purge gas; and a collection container. This set enables the method according to the invention for providing a sample concentrate and the associated advantages.

in die entsprechende Porengröße umgerechnet werden kann.The membrane wall is preferably porous and can be designed, for example, as a hollow-fiber membrane. This type of membrane is particularly suitable for filtering out microbes. Depending on the size of the microbes to be detected, the pore size of the membrane wall is selected in such a way that the microbes are reliably retained. For example, a maximum pore size of 1 nm to 5 nm, preferably 2 nm to 4 nm, has proven advantageous for the reliable retention of viruses that have a size of 20 nm to 60 nm. The maximum pore size means that a so-called molecular weight cut-off (10% permeation) is determined in a sieve coefficient measurement according to DIN EN ISO 8637-1:2016-05 with an aqueous dextran solution with a broad molecular weight distribution, which is determined using the equation $$\text{pore size}\ddot{\text{O}}\text{ß}\left[\text{nm}\right]=0.04456\cdot \left(\text{Molecular Weight of Dextran at Cut-Off}\right)0.43821$$

can be converted into the corresponding pore size.

The retentate space access and the filtrate space access allow both the introduction and the discharge of fluid. In the simplest case, the access to the retentate space and the access to the filtrate space are designed as a hole. If fluid sources are connected to the filter module via the retentate chamber inlets or filtrate chamber inlets and safe inlet and outlet of the fluids is to be enabled, for example cylindrical parts with a thread or other longitudinally circumferential depressions can be used, which enable a fluid-tight connection.

Furthermore, the set can have a rinsing solution source having a rinsing solution. This enables the preparation of the retentate space of the filter module according to the invention and the preparation of the filtrate space of the filter module according to the invention, as well as the associated advantages.

Furthermore, the set can have a buffer solution source having a buffer solution. This enables the inventive routing of a buffer solution through the filter module via a filtrate space access and the inventive routing of the buffer solution through the filter module via a retentate space access and the associated advantages.

Furthermore, the set can have a pump, for example a peristaltic pump. This enables the solution or solutions to be conveyed according to the invention with the aid of the pump and the advantages associated therewith.

In a further embodiment, all accesses to the retentate space and all accesses to the filtrate space can be closed. This makes it possible to store the filter for later re-use. As a result, sample concentrates can be provided continuously and repetitively, so that reference samples can be provided again and again over a long period of time with a single filter module. This increases the quality of analysis and reduces process costs.

In a further embodiment, the filtrate space of the filter module has a second filtrate space access. As a result, the membrane wall is used over a larger area and accordingly more efficient filtration operation is made possible, whereby process times and thus process costs can be minimized.

In another embodiment, the purge gas source is a syringe. This enables simple and rapid handling of the purge gas source, which can increase process efficiency. The syringe volume is preferably in the range from 10 ml to 500 ml, in particular in the range from 15 ml to 350 ml and particularly preferably in the range from 20 ml to 200 ml volume of flushing gas or buffer solution with a single syringe stroke into the retentate space of the filter module.

In another embodiment, the purge gas is air. As a result, there is no need for a flushing gas that is complicated to handle, which means that the process stability can be increased and process costs can be reduced. If the sample to be flushed out is at risk of oxidation, non-oxidizing flushing gas such as nitrogen or carbon dioxide can alternatively be used.

character list

• In 1 a method according to the invention for providing a sample concentrate is shown schematically.
• In 2 According to the invention, the filtration operation of a filter module is shown schematically.
• In 3a According to the invention, the process step of preparing a retentate space of a filter module is shown schematically.
• In 3b According to the invention, the process step of preparing a filtrate chamber of a filter module is shown schematically.
• In 4a According to the invention, the step of flushing out a sample concentrate is shown schematically, with a first flushing gas pulse being carried out via a retentate chamber access.
• In 4b According to the invention, the step of rinsing out a buffer solution optionally containing a sample concentrate is shown schematically, with a buffer solution being passed through a filter module via a filtrate chamber access.
• In 4c According to the invention, the step of rinsing out a buffer solution optionally containing a sample concentrate is shown schematically, a buffer solution being removed from a buffer solution source using a rinsing gas source.
• In 4d According to the invention, the step of rinsing out a buffer solution optionally containing a sample concentrate is shown schematically, with a buffer solution being passed through a filter module via a retentate chamber access.
• In 4e According to the invention, the step of flushing out a buffer solution optionally containing a sample concentrate is shown schematically, with a further flushing gas pulse being carried out via a retentate chamber access.
• In 5 a set according to the invention for carrying out a method for providing a sample concentrate is shown schematically.
• In 6a a filter module according to the invention is shown schematically, the filtrate chamber having two filtrate chamber accesses.
• In 6b a filter module according to the invention is shown schematically, the filtrate space having two filtrate space accesses and all filtrate space accesses being closed.

Description of the Preferred Embodiments

The present invention is described in detail in the following, without the embodiments explained by way of example unnecessarily limiting the scope of protection.

In 1 an inventive method for providing a sample concentrate 200 is shown schematically, which is divided into three consecutive main method steps. These are the first taking place preparation of a filter module 210, the subsequent filtration operation of a filter module 220 and the last taking place rinsing of a filter module 230.

The main process step of preparing a filter module 210 consists of two process steps, namely the preparation of a retentate space 212 and the preparation of a filtrate space 214. The exact sequence of the process steps of preparing a retentate space 212 and the preparation of a filtrate space 214 within the main process step of preparing a filter module 210 is irrelevant for the correct implementation of the method according to the invention for providing a sample concentrate 200 . Thus, both the process step of preparing a retentate space 212 and the process step of preparing a filtrate space 214 can be carried out first.

The main process step for flushing out a filter module 230 consists of five process steps, namely the implementation of a first flushing gas pulse 232, the passage of a buffer solution through a filter module via a filtrate chamber access 234, the removal of a buffer solution with a flushing gas source 236, the passage of a buffer solution through a filter module via a Retentate chamber access 238 and the implementation of a further flushing gas burst 233. Their sequence is - in contrast to the main process step of preparing a filter module 210 - relevant for the correct implementation of the method according to the invention for providing a sample concentrate 200, which is explained in detail below.

Before the method according to the invention for providing a sample concentrate 200, for example with the in 3a Schematically illustrated step of the preparation of a retentate space 212 (see 1 ) of a filter module 110 is started, any closure caps 119 on the retentate chamber accesses 115 to be connected or on the filtrate chamber access 117 to be connected are removed from the filter module 110. A rinsing solution source 150 is then connected to one retentate chamber access 115 . A pump 120 and a manometer 122 are also connected to the source 150 of the rinsing solution. According to the invention, a rinsing solution 152 is fed from the rinsing solution source 150 into the filter module 110 by means of the pump 120 . The pressure at which the rinsing solution 152 is fed into the filter module 110 is determined using the manometer 122 . The rinsing solution 152 is introduced into the filter module 110 via one retentate chamber access 115 and is discharged again from the filter module 110 via the other retentate chamber access 115 . The exit of the rinsing solution 152 from the filter module 110 via a filtrate space access 117 is prevented in that the filtrate space accesses 117 are each closed by means of a closure cap 119 . The method step of preparing a retentate space 212 is carried out at least until the rinsing solution 152 emerges from the other retentate space access 115 . This ensures that the retentate space 114 is completely wetted and prepared for the filtration operation of a filter module 220 .

The preparation of the filtrate space 116 is carried out using the in 3b schematically illustrated method step according to the invention of the preparation of a filtrate space 214 (see 1 ) of a filter module 110. Up to and including the introduction of the rinsing solution 152 into the filter module 110, this method step is carried out in the same way as in 3a schematically illustrated method step of the preparation of a retentate space 212. After the rinsing solution 152 has entered the filter module 110, the rinsing solution 152 is passed from the retentate space 114 via the membrane wall 112 into the filtrate space 116. The rinsing solution 152 is then drained back out of the filter module 110 via the one filtrate chamber access 117 . The exit of the rinsing solution 152 from the filter module 110 via the other filtrate space access 117 and via the other retentate space access 115 is prevented in that the other filtrate space access 117 and the other retentate space access 115 are each closed by means of a sealing cap 119 . The process step of preparing a filtrate space 214 is carried out at least until the rinsing solution 152 emerges from one filtrate space access 117 . This ensures that the filtrate space 116 is completely wetted and prepared for the filtration operation of a filter module 220 . If the filtrate chamber 116 has several filtrate chamber entrances 117, it is advantageous to prepare each of these filtrate chamber entrances 117 individually by leaving the filtrate chamber entrance 117 to be prepared open and closing all filtrate chamber entrances 117 that are not to be prepared at this moment with a sealing cap 119.

After the filter module 110 has been completely prepared, according to the invention, the diagram shown in 2 illustrated filtration operation of a filter module 220 (see 1 ) be performed. A sample 132 optionally containing microbes is fed into the filter module 110 from a source of a sample 130 optionally containing microbes by means of a pump 120 . The sample 132 optionally containing microbes is introduced into the filter module 110 via the one retentate chamber access 115 . After entering the After the sample 132 optionally containing microbes into the filter module 110 , part of the part of the sample 132 optionally containing microbes that passes through the membrane is conducted from the retentate space 114 via the membrane wall 112 into the filtrate space 116 . In this case, microbes are optionally enriched in the retentate space 114 and/or microbes are attached to and/or in the membrane wall 112 . The part of the part of the sample 132 which can optionally contain microbes and which can pass through the membrane is then discharged again from the filter module 110 via the one filtrate chamber access 117 . The escape of the part of the part of the sample 132 that penetrates the membrane, optionally containing microbes, from the filter module 110 via the other filtrate space access 117 and via the other retentate space access 115 is prevented in that the other filtrate space access 117 and the other retentate space access 115 are each closed by means of a sealing cap 119.

If during the main process steps of preparing a filter module 210 (see 1 ) or during the subsequent filtration operation of a filter module 220 has accumulated air in the filter module 110, this can be released from the filter module 110, for example, by carefully loosening the sealing caps 119 located at the retentate chamber entrances 115 or filtrate chamber entrances 117.

The pressure with which the sample 132 optionally containing microbes is fed into the filter module 110 is determined with the aid of the manometer 122 during the filtration operation of a filter module 220 . With the help of the current pressure and the pressure profile, conclusions can be drawn as to how heavily the filter module 110 is currently clogged with clogging components or how quickly the filter module 110 is clogged with clogging components. The service life of the filter module 110 that can be derived from this can be increased by diluting the sample 132 optionally containing microbes or by reducing the volume rate at which the sample 132 optionally containing microbes is fed into the filter module 110 .

If the filter module 110 is clogged with clogging components in such a way that reliable filtration operation of a filter module 220 can no longer be guaranteed, the filter module 110 must be cleaned. If it is to be checked at the same time which clogging components have been accumulated in the filter module 110, the 4a-e schematically illustrated main process step of rinsing out a filter module 230 performed. The in the 4a-e Schematically shown main process step of rinsing out a filter module 230 (see 1 ) can also be carried out when the filter module 110 is still filtering reliably in order to provide a sample concentrate 180 .

Before this last main method step according to the invention can be carried out, the source of a sample 130 optionally containing microbes, which is no longer required for the time being, is separated from the filter module 110 .

During the schematic in 4a illustrated method step of carrying out a first flushing gas pulse 232 (see 1 ) a purge gas source 140 having a purge gas 142 is provided. Furthermore, a collection container 170 is provided, with which a sample concentrate 180 can be collected. Any accesses 117 to the filtrate space are closed with sealing caps 119 . Any retentate room entrances 115 are opened if they are not already open. The flushing gas source 140 is then connected to a retentate chamber access 115 . During the closing, opening and connection process, the filter module 110 can be positioned in such a way that the solution still in the filter module 110 does not escape from the filter module 110 unintentionally. The flushing gas 142 is then conducted from the flushing gas source 140 via the one retentate space access 115 into the retentate space 114 . If during the filtration operation of a filter module 220 (see 1 ) Microbes have accumulated in the retentate space 114 and/or on and/or in the membrane wall 112, these are now additionally accumulated in the sample concentrate 180 still in the filter module. The sample concentrate 180 is then discharged from the retentate space 114 via the other retentate space access 115 and collected in the collection container 170 .

As the next step in the process, the schematic in 4b illustrated method step of conducting a buffer solution through a filter module via a filtrate chamber access 234 (see 1 ) accomplished. A buffer solution source 160 is provided for this purpose. Then one filtrate space access 117 is opened and the buffer solution source 160 is connected to the filtrate space access 117 . Then buffer solution 162 is fed from the buffer solution source 160 via the filtrate space access 117 into the filtrate space 116 . The buffer solution 162 is then conducted from the filtrate space 116 via the membrane wall 112 into the retentate space 114 . In the process, microbes are optionally detached from and/or out of the membrane wall 112 with the buffer solution 162 , microbes optionally being accumulated in the buffer solution 162 . The optional Mic The buffer solution 162 containing the sample is derived from the retentate space 114 via the retentate space access 115 and collected in the collection container 170 as an extension of the sample concentrate 180 already present in the collection container 170 .

As the next step in the process, the schematic in 4c illustrated method step of removing a buffer solution with a purge gas source 236 (see 1 ) accomplished. For this purpose, the buffer solution source 160 is first separated from the filter module 110 and all filtrate chamber accesses 117 that are still open are closed by means of sealing caps 119 . Buffer solution 162 is then removed from the buffer solution source 160 with the purge gas source 140 .

As the next step in the process, the schematic in 4d illustrated method step of conducting a buffer solution through a filter module 110 via a retentate space access 238 (see 1 ) accomplished. For this purpose, the buffer solution 162 contained in the rinsing gas source 140 is conducted from the rinsing gas source 140 via the one retentate chamber access 115 into the retentate chamber 114 . Subsequently, microbes are optionally detached from and/or out of the membrane wall 112 with the buffer solution 162 . At this time, microbes are optionally accumulated in the buffer solution 162 . The buffer solution 162 optionally containing microbes is then drained from the retentate space 114 via the other retentate space access 115 and collected in the collection container 170 as an extension of the sample concentrate 180 already present in the collection container 170 .

As the last, optional process step, the diagram in 4e illustrated method step of carrying out a further flushing gas pulse 233 (see 1 ) accomplished. For this purge gas 142 is first enriched in the purge gas source 140 . The flushing gas 142 contained in the flushing gas source 140 is then conducted into the retentate space 114 via the one retentate space access 115 . If, during the filtration operation of a filter module 220, microbes have accumulated in the retentate space 114 and/or on and/or in the membrane wall 112 and these are still present on and/or in the membrane wall 112, these are now in the still in the Filter module 110 located buffer solution 162 accumulates. The buffer solution 162 optionally containing microbes is then drained from the retentate space 114 via the other retentate space access 115 and collected in the collection container 170 as an extension of the sample concentrate 180 already present in the collection container 170 .

Over the in the 4a-e In the method steps shown schematically, sample concentrate 180 is fed into the collection container 170 up to three times or the sample concentrate 180 already present in the collection container 170 is expanded. This process is corresponding to the change from 4a on 4b and when changing from 4d on 4e an increase in the sample concentrate 180 in the collection container 170 is shown.

In 5 a set according to the invention for carrying out a method for providing a sample concentrate 100 is shown schematically. In the illustration, this has a pump 120; a sump 170; a purge gas source 140 having a purge gas 142; a filter module 110 having an interior which is divided by a membrane wall 112 into a retentate space 114 and a filtrate space 116, the retentate space 114 having two retentate space accesses 115 and the filtrate space 116 having a filtrate space access 117; a source of an optionally microbe-containing sample 130 comprising an optionally microbe-containing sample 132; a rinse solution source 150 containing a rinse solution 152; and a buffer solution source 160 containing a buffer solution 162 .

In 6a a filter module 110 according to the invention is shown schematically, which is equipped with the in 5 shown filter module 110 is almost identical. The only difference is that the filtrate space 116 of the in 6a shown filter module 110 has two filtrate chamber accesses 117 .

In 6b a filter module 110 according to the invention is shown schematically, which corresponds to that in 6a corresponds to the filter module 110 shown, with all retentate chamber accesses 115 and all filtrate chamber accesses 117 being closed with sealing caps 119 .

Reference List

100

Set for carrying out a method for providing a sample concentrate

110

filter module

112

membrane wall

114

retentate dream

115

retentate room access

116

filtrate space

117

filtrate space access

119

sealing cap

120

pump

122

manometer

130

Source of a sample optionally containing microbes

132

Optional sample containing microbes

140

purge gas source

142

purge gas

150

rinsing solution source

152

rinsing solution

160

buffer solution source

162

buffer solution

170

collection container

180

sample concentrate

200

Method of providing a sample concentrate

210

Preparation of a filter module

212

Preparation of a retentate room

214

Preparation of a filtrate room

220

Filtration operation of a filter module

230

Flushing a filter module

232

Execution of a first flushing gas burst

233

Execution of another flushing gas burst

234

Conduction of a buffer solution through a filter module via a filtrate chamber access

236

Taking a buffer solution with a purge gas source

238

Conduction of a buffer solution through a filter module via a retentate chamber access

QUOTES INCLUDED IN DESCRIPTION

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Patent Literature Cited

• WO 2019/052989 A1 [0002]

Claims (15)

Method for providing a sample concentrate (200) comprising the steps: i. Providing a filter module (110) having an interior space which is divided by a membrane wall (112) into a retentate space (114) and a filtrate space (116), the retentate space (114) having two retentate space entrances (115) and the filtrate space (116 ) has at least one fluid chamber access (117); ii. providing a source of an optional microbe-containing sample (130) iii. connecting the source of an optional microbe-containing sample (130) to the one retentate space port (115); IV. closing the other retentate space access (115); v. passing the optional microbe-containing sample (132) from the source of an optionally microbe-containing sample (130) via the one retentate compartment access (115) into the retentate compartment (114); vi. passing a portion of the sample (132), optionally containing microbes, from the retentate space (114) over the membrane wall (112) into the filtrate space (116); vii. Enriching sample concentrate (180) in the retentate space, microbes optionally being enriched in the retentate space (114) and/or microbes being attached to and/or in the membrane wall (112); viii. Deriving the part of the sample (132) optionally containing microbes via the filtrate space access (117) from the filtrate space (116) , characterized in that the following further steps are carried out: ix. Closing the filtrate space access (117); x. opening the other retentate space access (115) and collecting sample concentrate (180) in a collection container (170); xi. providing a purge gas source (140); xiii. connecting the purge gas source (140) to a retentate space port (115) and directing purge gas (142) from the purge gas source (140) via a retentate space port (115) into the retentate space (114); xiii. Deriving the sample concentrate (180) from the retentate space (114) via the other retentate space access (115) and collecting the sample concentrate (180) in the collection container (170). procedure after claim 1 characterized in that the following intermediate step ii for priming is carried out between steps i and ii: ii providing a rinsing solution source (150), connecting the rinsing solution source (150) to a retentate chamber access (115), closing the filtrate chamber access (117), conducting rinsing solution ( 152) from the rinsing solution source (150) via the one retentate space access (115) into the retentate space (114) and deriving the rinsing solution (152) from the retentate space (114) via the other retentate space access (115). procedure after claim 1 characterized in that the following intermediate step i.ii for priming is carried out between steps i and ii: i.ii. Providing a rinsing solution source (150), connecting the rinsing solution source (150) to a retentate space access (115), closing the other retentate space access (115), conducting rinsing solution (152) from the rinsing solution source (150) via the one retentate space access (115) into the retentate space (114), conducting the rinsing solution (152) from the retentate space (114) via the membrane wall (112) into the filtrate space (116) and discharging the rinsing solution (152) from the filtrate space (116) via the filtrate space access (117). procedure after claim 2 and 3 characterized in that both intermediate steps ii and i.ii are carried out for priming, these being carried out in succession. Method according to one of the preceding claims , characterized in that the following step xiv is carried out after step xiii: xiv. Providing a buffer solution source (160), opening the filtrate space access (117), connecting the buffer solution source (160) to the filtrate space access (117), conducting buffer solution (162) from the buffer solution source (160) via the filtrate space access (117) into the filtrate space (116 ), Conducting the buffer solution (162) from the filtrate space (116) via the membrane wall (112) into the retentate space (114), optionally dissolving microbes from and/or out of the membrane wall (112) with the buffer solution (162), optional accumulation of the microbes in the buffer solution (162), deriving the buffer solution (162) optionally containing microbes via the retentate compartment access (115) from the retentate compartment (114) and collecting the buffer solution (162) optionally containing microbes in the collection container (170) as an extension of the in sample concentrate (180) already present in the collection container (170). procedure after claim 5 characterized in that after step xiv the following step xv is carried out: xv. Closing the filtrate chamber access (117), removal of buffer solution (162) from the buffer solution source (160) with the purge gas source (140), conducting the buffer solution (162) contained in the purge gas source (140) from the purge gas source (140) via a retentate chamber access (115 ) into the retentate space (114), optionally dissolving microbes from and/or out of the membrane wall (112) with the buffer solution (162), optionally accumulating the microbes in the buffer solution (162), deriving the buffer solution (162) optionally containing microbes the other retentate space access (115) from the retentate space (114) and collecting the buffer solution (162) optionally containing microbes in the collection container (170) as an extension of the sample concentrate (180) already present in the collection container (170). procedure after claim 6 characterized in that after step xv the following step xvi is carried out: xvi. Enrichment of purge gas (142) in the purge gas source (140), conducting the purge gas (142) contained in the purge gas source (140) from the purge gas source (140) via a retentate space access (115) into the retentate space (114), dissolving the buffer solution (162 ) and optionally microbes from and/or out of the membrane wall (112) using the flushing gas (142), optionally accumulation of the microbes in the buffer solution (162), deriving the buffer solution (162) optionally containing microbes via the other retentate chamber access (115) from the retentate space (114) and collecting the buffer solution (162) optionally containing microbes in the collection container (170) as an extension of the sample concentrate (180) already present in the collection container (170). Method according to one of the preceding claims , characterized in that the following intermediate step xi.i is carried out between steps xi and xii: xi.i. Positioning the filter module (110) and the purge gas source (140) in such a way that the purge gas source (140) is arranged vertically above the one retentate chamber access (115) and that the fluid contained in the purge gas source (140) flows vertically downwards via the one retentate chamber access (115). can be routed into the retentate space (114), wherein one of the retentate space accesses (115) corresponds to the retentate space access (115) to which the flushing gas source (140) is connected. Method according to any one of the preceding claims , characterized in that a pump (120) is also provided and the solution is conducted with the aid of the pump (120). Set for carrying out a method for providing a sample concentrate (100) having the following components: a filter module (110) having an interior which is divided by a membrane wall (112) into a retentate space (114) and a filtrate space (116), the Retentate space (114) has two retentate space accesses (115) and the filtrate space (116) has at least one filtrate space access (117); a source of a sample (130) optionally containing microbes, characterized in that the set has the following further components: a purge gas source (140) having a purge gas (142); and a collection container (170); set after claim 10 characterized in that it further comprises a rinsing solution source (150) comprising a rinsing solution (152). Set after one of Claims 10 or 11 characterized in that it further comprises a buffer solution source (160) comprising a buffer solution (162). Set after one of Claims 10 - 12 characterized in that it further comprises a pump (120). Set after one of Claims 10 - 13 characterized in that all accesses to the retentate space (115) and all accesses to the filtrate space (117) can be closed. Set after one of Claims 10 - 14 characterized in that the filtrate space (116) of the filter module (110) has a second filtrate space access (117).

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