Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
  • B01D63/08—Flat membrane modules
  • B01D63/087—Single membrane modules
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
  • B01D61/14—Ultrafiltration; Microfiltration
  • B01D61/18—Apparatus therefor
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
  • B01D63/08—Flat membrane modules
  • B01D63/081—Manufacturing thereof
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
  • B01D63/16—Rotary, reciprocated or vibrated modules
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
  • B01L3/5021—Test tubes specially adapted for centrifugation purposes
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N1/00—Sampling; Preparing specimens for investigation
  • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
  • G01N1/34—Purifying; Cleaning
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/06—Auxiliary integrated devices, integrated components
  • B01L2300/0681—Filter
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N1/00—Sampling; Preparing specimens for investigation
  • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
  • G01N1/40—Concentrating samples
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N1/00—Sampling; Preparing specimens for investigation
  • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
  • G01N1/40—Concentrating samples
  • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N1/00—Sampling; Preparing specimens for investigation
  • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
  • G01N1/40—Concentrating samples
  • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
  • G01N2001/4016—Concentrating samples by transferring a selected component through a membrane being a selective membrane, e.g. dialysis or osmosis

Definitions

• This invention relates to a device for concentrating and / or purifying macromolecules in a solution and a method for producing such a device.
• the device comprises a chamber or section for the sample to be processed and a chamber for the filtrate, which is separated by means of at least one membrane. More specifically, the invention relates to a new way of attaching the membrane in a pressure-resistant sealing relationship at the interface between the two chambers.
• Devices manufactured according to the invention can be used in centrifuges, as tangential flow modules, as gas pressure cells or with hand-operated syringes, etc.
• the filtration is used as a sterilization step for removing bacteria, as a clarification step for removing suspended solids and contaminants, as a concentration step for proteins and other macromolecules or as a cleaning step for eliminating unwanted micromolecules, such as salts.
• Alternative filtration methods, devices and membrane shut-offs are used in certain applications and process requirements. Centrifugal forces, gas or liquid pressure, or vacuum are typically used to create the vector or gradient to push or pull solvent and small micromolecules through a membrane while retaining solution components that are larger than the membrane's exclusion limit become. In most applications, the higher the pressure or vacuum applied, the greater the filtration speed in relation to the membrane area used. Generally, small area, high speed devices are preferred.
• Typical devices of the type mentioned here contain a chamber for the sample to be processed and a chamber for the filtrate. These chambers communicate through at least one common opening in which a porous membrane, e.g. a microporous, ultrafiltration or reverse osmosis membrane is arranged. The periphery of the membrane is sealingly attached to the opening either on the peripheral surface of the concentration or the filtrate chamber or on both.
• a porous membrane e.g. a microporous, ultrafiltration or reverse osmosis membrane
• the membrane is usually held on the permeate side to withstand the pressure.
• An inlet is provided for introducing a liquid sample into the concentration chamber and an outlet for the filtrate from the filtrate chamber.
• an additional outlet is arranged in the concentration chamber to allow circulation of the sample.
• the membrane can be sealed in a variety of ways, for example by means of heat sealing, gluing with adhesive or solvent, ultrasonic welding or by means of a press fit.
• Material and wall thickness of the chamber, which is also sealing interconnected are chosen so that they withstand the operating pressure.
• the devices are sometimes additionally provided with separate pressure maintaining devices or membrane arrangements are arranged between external pressure plates, which are typically screwed together to create an additional holder.
• Another problem is to achieve a sufficiently tight seal between the chambers, especially with incompatible or non-sealing materials and with devices with a large area that have to withstand higher total pressures.
• centrifugal filtration device described in US-A-5,647,990, the teaching of this document incorporated herein is closed, has the disadvantage of damaging the relatively fragile membrane when the retaining housing is pushed onto the concentration chamber, since friction forces tend to push the membrane out of its required position.
• the pressure retention and the integrity of the seal is further due to the difficulty of forming a sufficiently thick membrane support plate and the incomplete support which is provided for the sealing surface of the membrane due to filtrate outlet channels which pass directly through the sealing surface in this prior art device , limited.
• the problem of frictional forces and incomplete seal support is further exacerbated if the membrane is not used sealingly in the concentration chamber first, but rather the sealing and the assembly in a single operation due to the pressure on the circumference of the membrane present during assembly the opening of the chamber is effected.
• GB-A-9819686.8 shows a so-called tangential current device.
• the economy of this device is limited by the need to machine the parts of the device due to the difficulty in forming the components with a thickness sufficient to withstand high pressure.
• screwing devices which are relatively expensive, are required in order to hold the assembled device together in a pressure-resistant manner.
• this feature offers a high degree of flexibility.
• Figure 1 shows a perspective view of a device According to the present invention, which is designed as a tangential current module.
• FIG. 2 shows a sectional view of the insert according to FIG. 1.
• FIG. 3 shows a side view of the embodiment according to FIG. 1.
• FIG. 4 shows a top view of the embodiment according to FIG. 1 in the assembled state.
• FIG. 5 shows a sectional view of the assembled device according to FIG. 4.
• FIG. 6 shows a top view of the upper transparent part of the insert according to FIG. 1.
• FIG. 7 shows a top view of the lower transparent part of the insert according to FIG. 1.
• FIG. 8 shows a top view of the upper transparent part of a further embodiment of the insert according to FIG. 1.
• FIG. 9 shows a perspective view of a further embodiment of the device according to the invention, which is designed as a centrifugal filtration device.
• FIG. 10 shows the assembly of the device according to FIG. 9.
• FIG. 11 shows an assembled device according to FIG. 9.
• FIG. 12a shows a sectional view of an assembled device according to FIG. 9.
• Figure 12b shows a sectional view of an assembled Device according to Figure 9, which is provided with a variant of the housing bushing or sleeve or sleeve.
• FIGS. 13a and b show two horizontal sectional views through the assembled device according to FIG. 12a.
• Figure 14 shows schematically a perspective view with an exploded view of the central part of an embodiment of the device according to the invention.
• Figure 15 shows a sectional view of an assembled device.
• FIG. 1 shows a perspective view of a device according to the present invention, which is designed as a tangential flow filtration module or cell, which can be used, for example, for concentrating or fractionating macromolecules in a solution.
• a filtration module of this type is connected to a pump, which typically draws liquid from a sample reservoir through the module or the cell and recirculates the sample liquid through a loop which encloses the cell.
• the module is integrated into this loop by means of an inlet 3 and an outlet 4 for the sample liquid.
• This inlet and this outlet are arranged on an insert 1 according to the invention.
• the required system pressure is formed by a throttle body or flow reducer, which is positioned at the outlet 4 of the cell.
• the insert 1 comprises a concentration chamber or spaces and a filtrate chamber or spaces which are separated by a membrane.
• FIG. 6 shows an example of a concentration chamber 10 in the form of a thin channel for the sample liquid, which is arranged in the upper part 12 of the insert, cf.
• Figure 2 which has an inlet 3 and an outlet 4, which are arranged at its end portions.
• This cam mer is separated from the cooperating filtrate chamber 11, which is arranged in the lower part 6 of the insert 1, by means of a membrane.
• An example of such a filtrate chamber is shown in FIG. 7.
• filtrate Due to the pressure difference between the inflow side and the filtrate side of the membrane, filtrate penetrates through the membrane into the filtrate chamber and is drawn off or discharged through outlet 5 and collected outside the cell.
• FIG. 2 shows a cross section through an example of an insert according to FIG. 1.
• the lower part 6 has a generally flat upper surface or surface 16, which is used as a membrane support or support. This surface is provided with a multiplicity of parallel grooves which form channels 9 for the filtrate, cf. also Figure 7. These channels are all, for example, by means of a collecting channel 8 and a transverse outlet channel 14, cf. FIG. 5, in connection with one another, which connects the end sections of the channels 9 on one side of the insert in order to feed all of the collected filtrate to a filtrate outlet 5 from the cell.
• the membrane 15, cf. FIG. 5 is arranged on the upper side of the surface 16 and extends along the edge of this surface to the vertical wall sections 13. Along the inside of the vertical wall sections on the surface 16 there is a generally flat sealing seat in this embodiment, cf. . Figure 2, 5, 7, arranged. This means that the membrane has a generally flat bearing surface or support over its entire circumference.
• a seal 7 in the form of an O-ring is arranged in this embodiment on the top of the membrane above the seal seat and the upper part 12, which closes the insert.
• a housing or sleeve 2, 2 ' preferably produced by molding a suitable plastic material, surrounds the insert.
• the housing is designed in two parts 2 and 2 ', which are pushed over the insert when assembled from two opposite sides in order to form the complete housing or sleeve. When assembled, this housing or sleeve presses the insert 1 onto the membrane without frictional forces, the concentration chamber and the filtrate chamber being formed simultaneously by sealing the edge or edge of the membrane.
• this module can be easily disassembled for inspection, for changing the membrane, for cleaning or for any other purpose without damaging one of the components.
• Figure 3 shows a side view of the embodiment according to Figure 1.
• the insertion of the insert in the two sleeves or. Housing parts is initially due to the wedge shape or tapered shape of the housing and the insert, cf. Figure 5, very light. A greater force is only required towards the end of the assembly while the seal is being compressed. It would also be possible to use a shrink technique to position the housing or sleeve.
• FIG. 4 shows a top view of the embodiment according to FIG. 1 in the assembled state.
• a dovetail edge or flange 17 is arranged on the lower part of the housing, which could cooperate with a corresponding slot or groove on the upper part of an adjacent module (not shown). In this way, filtration cells could be stacked on top of one another as required.
• FIG. 5 shows a cross section of the assembled device according to FIG. 4. As can be seen, the interior of the shaped housing was made wedge-shaped or tapered. This is of course practical for 'production purposes, but also creates a possibility of achieving the necessary compression forces for insert 1 if it also has a wedge shape.
• the upper and the lower surface of the insert could be made parallel and the wedge shape could be made by means of longitudinal wedge-shaped edges or flanges on the upper one and lower surface or at least one of the two can be realized.
• FIG. 8 shows the wedge-shaped edges or flanges 18.
• An additional advantage of the molded housing in two parts 2, 2 'according to the above embodiments is that a standard thread for the inlet 3 and the outlet 4 for the liquid sample could easily be made during the molding process.
• the chemical properties of the different components could also be chosen with greater flexibility.
• a material with higher solvent resistance could be chosen for the internal structure that is in contact with the liquid flow path.
• FIG. 9 shows a perspective view of a further embodiment of the device according to the invention, which is designed as a centrifugal filtration device.
• a concentration chamber 10 is provided to receive the sample to be processed.
• the sample is not recirculated into this chamber and therefore there is no outlet for the sample from this chamber, but only an inlet 3.
• a seal 7 is provided so that it is in a groove 19 or a rear jump is arranged around an opening in the wall of the chamber.
• a suitable membrane piece 15 is placed over the opening.
• FIG. 10 shows the assembled components 12, 7, 15 and 6 of the device according to FIG. 9.
• a one-piece housing 2 ′′ is pushed over the assembled components. Due to the wedge or cone shape of the component 6, that is to say the filtrate chamber, and the corresponding inner shape of the housing, the filtrate chamber is pressed against the membrane 15 and presses the sealing device against the concentration chamber. It should be noted that the membrane is only subjected to forces perpendicular to its surface when the housing is brought into position.
• Figure 11 shows the assembled device with the housing in position.
• FIG. 12a shows a cross section of an assembled device according to FIG. 9.
• a ventilation duct 20 in connection with the outside. This channel can evacuate air from the filtrate channels 9 at the start of the filtration process.
• three channels 5 ' are provided for the outlet of the filtrate, which is collected in a filtrate tube, not shown, into which the device is partially inserted during the process.
• the channels 5 ' as in the embodiment shown in Figure 5, are connected on the inside to a transverse outlet channel 14 which connects the end portions of the channels 9 on one side of the filtrate chamber in order to supply all the filtrate collected to the outlet channels 5'.
• the device lies with a flange 21 on the housing 2 on the edge or on the edge of the filtrate tube, which means Tet that the centrifugal forces acting on the device during the process hold the housing firmly in position with the flange 21 on the flange 22 of the upper part 12.
• FIG. 12b shows a cross section of an assembled device according to FIG. 9, which is provided with a variant of the housing.
• the housing or the sleeve was made less flexible in this area by adding a stabilizing ring 23 made of material around the opening in its lower part.
• the ring 23 may alternatively have a flatter configuration than that shown in cross section in FIG. 12b.
• FIG. 13a shows a horizontal cross section through the assembled device according to FIG. 12a in the upper part and FIG. 13b in the lower part.
• the wedge shape or tapering shape of the component 6, which forms the filtrate chamber, is clearly shown.
• devices according to the invention could initially be designed specifically for use in a centrifuge, such as the embodiment described with reference to FIGS. 9 to 13.
• gas or liquid pressure or vacuum could also be used to create the vector or gradient. to push or pull the solvent and small micromolecules through the membrane.
• the first embodiment according to the foregoing uses liquid pressure.
• the sealing device could have the shape of an O-ring, which is preferably positioned in a suitable groove around one of the two openings. Two O-rings are also conceivable, with one around each opening.
• the sealing of the membrane could be achieved by means of a sealing device which is integrated in one or both chambers. This embodiment is advantageous if a softer material has been used for the chambers or rooms or parts thereof. In general, the flexibility with regard to the choice of material for the various components (mechanical properties, chemical properties, etc.), which was discussed above with reference to the first embodiment, is available for all embodiments.
• the device according to the invention for the simultaneous filtration of a large number of liquid samples is composed of an insert 1 and a two-part housing 2, 2 ′ arranged around this insert 1.
• the insert consists of a component 6 designed as a support plate, a seal in the form of a sealing mat 7, flat filter media / membranes 15 and a plate 27 with a multiplicity of concentration chambers 10.
• the component 6 has a multiplicity of openings 24, which are preferably correspond in number and arrangement to the number and arrangement of the wells 25 of a microtiter plate 26.
• the openings 24 of the component 6 can additionally be equipped with a filter support, which is equipped by means of collecting channel 8 and channels for the outlet for filtrate 5 '.
• a preferably elastic sealing mat 7 is placed on the bag part 6 and is aligned with the openings 24.
• the passages 28 are surrounded by sleeves 30.
• the sleeves 30 have a larger inner width than the width of the passages 28 in such a way that a circumferential contact surface 31 made of the sealing material is formed on the base inside the sleeves 30.
• the flat filter media / membranes 15 are placed on the circumferential contact surfaces 31 of the sleeves 30 during assembly.
• the chambers 10 are inserted into the sleeves 30, for example in the form of tubes, which are open at both ends and which are connected to the plate 27.
• the chambers 10 have outer peripheral surfaces which are congruent to the inner peripheral surfaces of the sleeves 30.
• the chambers 10 serve on the one hand to hold the liquid samples and on the other hand in cooperation with the sealing device 4 of the liquid-tight edge seal of the flat filter means / membranes 15 between the circumferential contact surface 31 inside the sleeves 30 and the lower open end of the chambers 10, in which the Chambers 10 so far in the cuffs
• the two-part housing 2, 2 1 is provided on the upper side with inlets for the liquid samples 3 and on the underside with outlets 5 for filtrate, which are congruent with the openings 24 of the component 6.
• the two housing parts 2, 2 ' are pushed over the inserted insert 1 in such a way that the housing 2''is closed.
• Such compression forces are created and maintained that are sufficiently high to make the filter medium / membranes 15 liquid-tight against the Seal surfaces 31 of the cuffs 30.
• the insert 1 has a conical outer profile and the housing 2 '' has a conical inner profile, which in cooperation create the compression forces during assembly. As shown in FIG.
• the component 6 designed as a support plate and the plate 27 are equipped with lateral wedge-shaped flanges 18.
• the inlets 3 of the top of the housing 2 ′′, the ends of the chambers 10, the passages 10 of the sealing mat 28, the openings 24 of the support plate 6 and the outlets 5 of the underside of the housing 2 ′′ are aligned and lie on top a straight line.
• the outlets 5 on the underside of the housing 2 ′′ are equipped with filtrate outlet connections 32, via which the device is placed on a microtiter plate 26 as a filter attachment.
• a method for producing the device according to the invention comprises the following steps: a sealing device is first arranged around at least one of the openings in the concentration chamber or spaces or the filtrate chamber or spaces. One of the openings is then covered with a membrane, the inflow side facing the concentration chamber and the permeate side facing the filtrate chamber or opposite. The chambers are then assembled, with the openings one above the other, and a pressure-resistant housing or sleeve is then arranged on the outside and around the combination of the concentration chamber, the sealing device, the membrane and the filtrate chamber. The housing creates a pressure that is sufficiently high to seal the membrane liquid-tight against at least one of the chambers during the process and to maintain this pressure, while also increasing the strength or rigidity or load-bearing capacity of the structure of the entire arrangement.
• microtiter plate 25 wells of a microtiter plate 26 microtiter plate

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• Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Health & Medical Sciences (AREA)
• Water Supply & Treatment (AREA)
• Analytical Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Molecular Biology (AREA)
• Pathology (AREA)
• Hematology (AREA)
• Biomedical Technology (AREA)
• Manufacturing & Machinery (AREA)
• Physics & Mathematics (AREA)
• Biochemistry (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Clinical Laboratory Science (AREA)
• Separation Using Semi-Permeable Membranes (AREA)
• Centrifugal Separators (AREA)
• Physical Or Chemical Processes And Apparatus (AREA)
• Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
• Sampling And Sample Adjustment (AREA)
• External Artificial Organs (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)
• Investigating Or Analysing Biological Materials (AREA)

Priority Applications (5)

Applications Claiming Priority (2)

Publications (2)

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Family Applications (1)

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• 1999
  • 1999-02-15 SE SE9900530A patent/SE9900530D0/xx unknown
• 2000
  • 2000-02-08 DE DE50002721T patent/DE50002721D1/de not_active Expired - Lifetime
  • 2000-02-08 AT AT00906293T patent/ATE244053T1/de not_active IP Right Cessation
  • 2000-02-08 JP JP2000599492A patent/JP4394838B2/ja not_active Expired - Lifetime
  • 2000-02-08 EP EP00906293A patent/EP1144095B1/de not_active Expired - Lifetime
  • 2000-02-08 US US09/913,781 patent/US6837995B1/en not_active Expired - Lifetime
  • 2000-02-08 WO PCT/EP2000/000976 patent/WO2000048716A2/de not_active Ceased
  • 2000-02-08 DE DE10005427A patent/DE10005427A1/de not_active Withdrawn
  • 2000-02-08 DE DE20002188U patent/DE20002188U1/de not_active Expired - Lifetime

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