EP1268044A1 - Cross-flow filtration unit - Google Patents

Cross-flow filtration unit

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Publication number
EP1268044A1
EP1268044A1 EP00991619A EP00991619A EP1268044A1 EP 1268044 A1 EP1268044 A1 EP 1268044A1 EP 00991619 A EP00991619 A EP 00991619A EP 00991619 A EP00991619 A EP 00991619A EP 1268044 A1 EP1268044 A1 EP 1268044A1
Authority
EP
European Patent Office
Prior art keywords
gap
filtrate
filtration unit
substances
membrane
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00991619A
Other languages
German (de)
French (fr)
Inventor
Ina Pahl
Hans-Weddo Schmidt
Ulrich Grummert
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sartorius AG
Original Assignee
Sartorius AG
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Filing date
Publication date
Application filed by Sartorius AG filed Critical Sartorius AG
Publication of EP1268044A1 publication Critical patent/EP1268044A1/en
Withdrawn legal-status Critical Current

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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
    • B01D63/082—Flat membrane modules comprising a stack of flat membranes
    • B01D63/084—Flat membrane modules comprising a stack of flat membranes at least one flow duct intersecting the membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/12—Composite membranes; Ultra-thin membranes
    • B01D69/1218—Layers having the same chemical composition, but different properties, e.g. pore size, molecular weight or porosity
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2313/00—Details relating to membrane modules or apparatus
    • B01D2313/44—Cartridge types
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2315/00—Details relating to the membrane module operation
    • B01D2315/10—Cross-flow filtration
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A20/00—Water conservation; Efficient water supply; Efficient water use
    • Y02A20/124—Water desalination
    • Y02A20/131—Reverse-osmosis

Definitions

  • the invention relates to an improved crossflow filtration unit for separating substances by crossflow filtration of liquid media and obtaining the target substances in the filtrate and / or in the concentrate
  • fluids such as liquids, emulsions, suspensions, beverages such as beer, wine, juice, water and milk, whey, beer wort, industrial and waste water, solutions in pharmaceutical, medical, cosmetic , Chemical, biotechnology, genetic engineering, environmental protection and laboratory areas. They can be used to extract valuable materials, separate substances such as macromolecules and biomolecules, to depyrogenize and sterilize solutions, to separate pollutants from the fluids, to filter and concentrate biological solutions , for the separation of microorganisms such as bacteria, yeasts, viruses and cell components, for the desalination of protein solutions and other biological media
  • a feed liquid to be filtered flows tangentially over the surface of a filter material and is thereby split into a concentrate and a filtrate.
  • a microporous membrane in the ultrafiltration and microfiltration range is generally used as the filter material
  • the ultrafiltration membranes are characterized by medium pore sizes or exclusion limits which enable them to retain macromolecules, for example in the molar mass range between 500 and 1,000,000 Daltons, while the microfiltration membranes have medium pore sizes in the range between 0.01 and 10 ⁇ m.
  • medium pore size or exclusionlimit
  • EA Schezermann in chapter 4 3 3 "Membranes” in the manual of the industrial Fest Flussig-Filtration, published by H Gasper, Huthig Buch Verlag Heidelberg 1990, pages 250 to 262 used.
  • the concentrate is discharged from the overflowing surface of the membrane and can be recycled so that it can be recycled Repeated overflow of membrane surface
  • the filtrate flowing through the membrane perpendicular to the surface is discharged from the underside of the membrane.
  • Target substances to be obtained can be contained in the filtrate (filtrate substances) and / or in the concentrate (concentrate substances).
  • Crossflow filtration units are often used in the form of filter cassettes, such as They are described, for example, in DE-PS 34 41 249. They consist of a large number of adjacent filter cells, which generally consist of alternately arranged, flat blanks from a concentrate spacer to form an overcurrent gap for the feed liquid to be filtered, a first membrane system, a filtrate spacer to form a filtrate collection gap and a second membrane assembly.
  • Each overcurrent gap communicates with an inlet for the feed fluid to be filtered and with an outlet for the concentrate, and each filtrate collection gap communicates with an outlet for the filtrate
  • the concentrate substances which are excluded from passage through the pores of the membrane due to their size, should be rinsed away from the surface so that they do not clog the membrane pores for permeation of the filtrate and the filtrate substances
  • the membrane surface overflows in various ways with a cover layer, which usually affects the filtration performance, the yield of target substances and the service life of the crossflow filtration unit
  • the invention is therefore based on the object of proposing an improved crossflow filtration unit which is distinguished by improved filtration performance and a high product yield
  • the problem is solved by the features specified in the characterizing part of claim 1.
  • Advantageous developments of the invention are solved by the features of the subclaims
  • the improved crossflow filtration unit serves to separate substances of a feed liquid into filtrate substances of a filtrate and into concentrate substances of a concentrate.
  • a feed liquid into filtrate substances of a filtrate and into concentrate substances of a concentrate.
  • It consists of several sequences of a flat filter material, a filtrate collecting gap, a further flat filter material and an overcurrent gap in such a way that the filter materials with their back surface limit the filtrate collection gap and with its front surface the overflow gap and each filtrate collection gap is equipped with at least one outlet for filtrate and each overflow gap with an inlet for the feed liquid to be filtered and with an outlet for the concentrate.
  • the filter material consists of two superimposed microporous membrane layers i the membrane system facing the filtrate collecting gap has an average pore size in the range of an exclusion limit of 1000 daltons to 1.2 ⁇ m, which excludes the concentrate substances from passage through this membrane system and the membrane system facing the overcurrent gap is at least one larger by a factor of 1.3 has medium pore size, preferably by a factor in the range from 1.3 to 5 and particularly preferably by a factor in the range from 1.5 to 3.
  • the crossflow filtration unit is designed as a filter cassette, the membrane systems of which consist of microfiltration membranes.
  • a filter cassette is particularly preferred in which the membrane systems facing the filtrate collecting columns have an average pore size, which is selected from the range from 0.1 to 1.2 microns
  • the filtration unit has only a sequence of an overcurrent gap, a flat filter material from the two membrane layers with the different average pore sizes and a filtrate collecting gap in such a way that the filter material delimits the filtrate collecting gap with its rear surface and the overcurrent gap with its front surface
  • a yeast-containing cell suspension (Pichia) with a cell concentration of 6 ⁇ 10 6 yeast cells (concentrate substances) per ml, which contains a target protein with a molecular weight of 70,000 daltons ( Filtratstof ⁇ ) in a concentration of 127 mg / 1, filtered in the crossflow regime (circulation of the concentrate)
  • the pressure values were 0.9 bar at the inlet for feed liquid, 0.4 bar at the outlet for concentrate and 0.1 bar at the outlet for filtrate
  • Example 1 As a crossflow filtration unit according to the invention, a filter cassette with an overflowable membrane area of 0.4 m 2 is used, which has 13 overflow gaps and 12 filtrate collection gaps.
  • the membrane systems adjacent to the filtrate collection gaps consist of a cellulose acetate membrane with an average pore size of 0.2 ⁇ m and the membrane systems adjacent to the overcurrent gaps consist of a cellulose acetate membrane with an average pore size of 0.45 ⁇ m.
  • 7.3 l of the cell suspension were reduced to a final volume of concentrate of 1 1 concentrated
  • the average filtrate flow was 0.875 1 / min x 2
  • the filtration was ended after 18 minutes.
  • a concentration of target protein of 106.6 mg / 1 was found in the filtrate. 238 mg / 1 target protein was determined in the concentrate.
  • the yield of target protein in the filtrate was thus 72%
  • a filter cassette of the prior art (Sartocon * from Sarto ⁇ us AG) is used as the crossflow filtration unit with an overflowable membrane area of 0.7 m 2 , which has 17 overcurrent gaps and 16 filtrate collection gaps.
  • the membrane systems adjacent to the filtrate collection gaps consist of a single cellulose acetate membrane with an average pore size of 0.2 ⁇ m

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

The invention relates to an improved cross-flow filtration unit for separating substances by the cross-flow filtration of liquid media and recovering the desired substances in the filtrate and/or the concentrate. The unit is characterised by an improved filtration performance and product yield. The inventive cross-flow filtration unit has a filtration material consisting of two microporous membrane layers which lie on top of one another, whereby one membrane layer facing a filtrate collection gap has an average pore size that produces an exclusion limit of approximately 1000 dalton to 1.2 νm, preventing the concentrate substances from passing through this membrane layer and whereby the membrane layer facing the overflow gap has an average pore size which is greater than that of the first membrane by at least a factor of 1.3. The cross-flow filtration unit can be used in the pharmaceutical, medical, cosmetic, chemical, bio-technical, genetic engineering and environmental protection industries and the laboratory field to filter liquids, emulsions, suspensions, beverages, water and solutions for obtaining valuable materials, separating substances, for depyrogenisation or sterilisation, for separating harmful substances, micro-organisms or cellular components and for the desalination and concentration of protein solutions and other biological media.

Description

Crossflow-Filtrationseinheit Crossflow filtration unit
Die Erfindung betrifft eine verbesserte Crossflow-Filtrationseinheit zur Trennung von Stoffen durch Crossflow-Filtration flussiger Medien und Gewinnung der Zielsubstanzen im Filtrat und/oder im KonzentratThe invention relates to an improved crossflow filtration unit for separating substances by crossflow filtration of liquid media and obtaining the target substances in the filtrate and / or in the concentrate
Mit den erfindungsgemaßen, verbesserten Crossflow-Filtrationseinheiten können Fluide wie Flüssigkeiten, Emulsionen, Suspensionen, Getränke, wie Bier, Wein, Saft, Wasser, und Milch, Molke, Bierwürze, Brauch- und Abwasser, Losungen im Pharma-, Medizin-, Kosmetik-, Chemie-, Biotechnologie-, Gentechnik-, Umweltschutz- und Laborbereich filtriert werden Sie können zur Wertstoffgewinnung, Stofftrennung beispielweise von Makromolekülen und Biomolekulen, zur Entpyrogenisierung und Sterilisierung von Losungen, zur Abtrennung von Schadstoffen aus den Fluiden, für die Filtration und Aufkonzentrierung biologischer Losungen, für die Abtrennung von Mikroorganismen, wie Bakterien, Hefen, Viren und von Zellbestandteilen, für die Entsalzung von Proteinlosungen und anderen biologischen Medien verwendet werdenWith the improved crossflow filtration units according to the invention, fluids such as liquids, emulsions, suspensions, beverages such as beer, wine, juice, water and milk, whey, beer wort, industrial and waste water, solutions in pharmaceutical, medical, cosmetic , Chemical, biotechnology, genetic engineering, environmental protection and laboratory areas. They can be used to extract valuable materials, separate substances such as macromolecules and biomolecules, to depyrogenize and sterilize solutions, to separate pollutants from the fluids, to filter and concentrate biological solutions , for the separation of microorganisms such as bacteria, yeasts, viruses and cell components, for the desalination of protein solutions and other biological media
Bei der Crossflow-Filtration überströmt eine zu filtrierende Speiseflussigkeit tangential die Oberflache eines Filtermaterials und wird dabei in ein Konzentrat und ein Filtrat aufgespalten Als Filtermaterial wird in der Regel eine mikroporöse Membran im Ultrafiltrations- und Mikrofiltrationsbereich verwendetIn crossflow filtration, a feed liquid to be filtered flows tangentially over the surface of a filter material and is thereby split into a concentrate and a filtrate. A microporous membrane in the ultrafiltration and microfiltration range is generally used as the filter material
Die Ultrafiltrationsmembranen sind durch mittlere Porengroßen beziehungsweise Ausschlußgrenzen charakterisiert, die sie zur Ruckhaltung von Makromolekülen, etwa im Molmassenbereich zwischen 500 und 1 000 000 Dalton befähigen, wahrend die Mikrofiltrationsmembranen mittlere Porengroßen im Bereich zwischen 0,01 und 10 μm aufweisen Die Begriffe „mittlere Porengroße", „Ausschlußgrenze" und ihre Ermittlung wird in Übereinstimmung mit den Ausführungen von E A Schezermann im Kapitel 4 3 3 „Membranen" im Handbuch der industriellen Fest Flussig-Filtration, herausgegeben von H Gasper, Huthig Buch Verlag Heidelberg 1990, Seiten 250 bis 262 benutzt Das Konzentrat wird an der überströmten Oberflache der Membran abgeführt und kann im Kreislauf wieder zurückgeführt werden, so daß es die Membranoberflache wiederholt überströmt Das die Membran senkrecht zur Oberflache durchströmende Filtrat wird von der Unterseite der Membran abgeführt. Zu gewinnende Zielsubstanzen können im Filtrat (Filtratstoffe) und/oder im Konzentrat (Konzentratstoffe) enthalten sein Crossflow- Filtrationseinheiten werden häufig in Form von Filterkassetten eingesetzt, wie sie beispielsweise in der DE-PS 34 41 249 beschrieben sind Sie bestehen aus einer Vielzahl benachbarter Filterzellen, die in der Regel aus alternierend angeordneten, flachigen Zuschnitten von einem Konzentratabstandshalter zur Ausbildung eines Uberstromspalts für die zu filtrierende Speiseflussigkeit, einer ersten Membranlage, einem Filtratabstandshalter zur Ausbildung eines Filtratsammelspalts und einer zweiten Membranlage bestehen Jeder Uberstromspalt ist mit einem Einlaß für die zu filtrierende Speiseflussigkeit und mit einem Auslaß für das Konzentrat kommunizierend verbunden und jeder Filtratsammelspalt ist mit einem Auslaß für das Filtrat kommunizierend verbundenThe ultrafiltration membranes are characterized by medium pore sizes or exclusion limits which enable them to retain macromolecules, for example in the molar mass range between 500 and 1,000,000 Daltons, while the microfiltration membranes have medium pore sizes in the range between 0.01 and 10 μm. The terms "medium pore size""Exclusionlimit" and its determination is in accordance with the explanations of EA Schezermann in chapter 4 3 3 "Membranes" in the manual of the industrial Fest Flussig-Filtration, published by H Gasper, Huthig Buch Verlag Heidelberg 1990, pages 250 to 262 used. The concentrate is discharged from the overflowing surface of the membrane and can be recycled so that it can be recycled Repeated overflow of membrane surface The filtrate flowing through the membrane perpendicular to the surface is discharged from the underside of the membrane. Target substances to be obtained can be contained in the filtrate (filtrate substances) and / or in the concentrate (concentrate substances). Crossflow filtration units are often used in the form of filter cassettes, such as They are described, for example, in DE-PS 34 41 249. They consist of a large number of adjacent filter cells, which generally consist of alternately arranged, flat blanks from a concentrate spacer to form an overcurrent gap for the feed liquid to be filtered, a first membrane system, a filtrate spacer to form a filtrate collection gap and a second membrane assembly. Each overcurrent gap communicates with an inlet for the feed fluid to be filtered and with an outlet for the concentrate, and each filtrate collection gap communicates with an outlet for the filtrate
Bei der Uberstromung der Membranoberflache sollen die Konzentratstoffe, die auf Grund ihrer Große von der Passage durch die Poren der Membran hindurch ausgeschlossen werden, von der Oberflache fortgespult werden, damit sie die Membranporen für eine Permeierung des Filtrats und der Filtratstoffe nicht verstopfen Trotzdem bildet sich auf der überströmten Membranoberflache auf verschiedene Weise eine Deckschicht aus, durch die in der Regel die Filtrationsleistung, die Ausbeute an Zielsubstanzen und die Standzeit der Crossflow-Filtrationseinheit beeinträchtigt wirdWhen the membrane surface is overflowed, the concentrate substances, which are excluded from passage through the pores of the membrane due to their size, should be rinsed away from the surface so that they do not clog the membrane pores for permeation of the filtrate and the filtrate substances The membrane surface overflows in various ways with a cover layer, which usually affects the filtration performance, the yield of target substances and the service life of the crossflow filtration unit
Der Erfindung liegt daher die Aufgabe zu Grunde, eine verbeserte Crossflow- Filtrationseinheit vorzuschlagen, die sich durch eine verbesserte Filtrationsleistung und eine hohe Produktausbeute auszeichnet Die Aufgabe wird durch die im Kennzeichen des Anspruchs 1 angegebenen Merkmale gelost. Vorteilhafte Weiterbildungen der Erfindung sind durch die Merkmale der Unteranspruche gelostThe invention is therefore based on the object of proposing an improved crossflow filtration unit which is distinguished by improved filtration performance and a high product yield The problem is solved by the features specified in the characterizing part of claim 1. Advantageous developments of the invention are solved by the features of the subclaims
Die erfindungsgemäße verbessere Crossflow-Filtrationseinheit dient der Trennung von Stoffen einer Speiseflussigkeit in Filtratstoffe eines Filtrats und in Konzentratstoffe eines Konzentrats Sie besteht aus mehreren Abfolgen aus einem flachigen Filtermaterial, einem Filtratsammelspalt, einem weiteren flachigen Filtermaterial und einem Uberstromspalt derart, daß die Filtermaterialien mit ihrer Ruckflache den Filtratsammelspalt und mit ihrer Vorderflache den Uberstromspalt begrenzen und jeder Filtratsammelspalt mit mindestens einem Auslaß für Filtrat und jeder Uberstromspalt mit einem Einlaß für zu filtrierende Speiseflussigkeit und mit einem Auslaß für das Konzentrat ausgestattet ist Überraschenderweise wurde gefunden, daß mit der erfindungsgemäßen Crossflow- Filtrationseinheit bei der Crossflow-Filtration deutlich höhere Filtratflusse und höhere Produktausbeuten erzielt werden, wenn das Filtermaterial aus zwei aufeinander liegenden mikroporösen Membranlagen besteht, wobei die dem Filtratsammelspalt zugewandte Membranlage eine mittlere Porengroße im Bereich einer Ausschlußgrenze von 1000 Dalton bis 1,2 μm aufweist, welche die Konzentratstoffe von einer Passage durch diese Membranlage ausschließt und wobei die dem Uberstromspalt zugewandte Membranlage mindestens eine um den Faktor 1,3, aroßere mittlere Porengroße besitzt, vorzussweise um einen Faktor im Bereich von 1,3 bis 5 und besonders bevorzugt um einen Faktor im Bereich von 1,5 bis 3. Unterscheiden sich die Membranlagen durch einen geringeren unter 1,3 liegenden Faktor, sind wirtschaftlich nur noch unbedeutende oder überhaupt keine Effekte mehr festzustellen Unterscheiden sie sich im Mikrofiltrationsbereich durch einen über 5 liegenden Faktor nimmt die Verblockung der Membran mit dem größeren mittleren Porendurchmesser, insbesondere bei partikelhaltigen Speiseflussigkeiten rasch zu, sodaß die Filtration vorzeitig zum Erliegen kommt Die Uberstrom- und Filtratsammelspalte werden vorteilhafterweise durch Abstandshalter, die aus dem Stand der Technik bekannt sind, offen gehalten In einer bevorzugten Ausführungsform ist die Crossflow-Filtrationseinheit als Filterkassette ausgebildet, deren Membranlagen aus Mikrofiltrationsmembranen bestehen Besonders bevorzugt ist eine Filterkassette, bei der die den Filtratsammelspalten zugewandten Membranlagen eine mittlere Porengroße besitzen, die ausgewählt ist aus dem Bereich von 0, 1 bis 1,2 μmThe improved crossflow filtration unit according to the invention serves to separate substances of a feed liquid into filtrate substances of a filtrate and into concentrate substances of a concentrate.It consists of several sequences of a flat filter material, a filtrate collecting gap, a further flat filter material and an overcurrent gap in such a way that the filter materials with their back surface limit the filtrate collection gap and with its front surface the overflow gap and each filtrate collection gap is equipped with at least one outlet for filtrate and each overflow gap with an inlet for the feed liquid to be filtered and with an outlet for the concentrate. Surprisingly, it was found that with the crossflow filtration unit according to the invention Crossflow filtration significantly higher filtrate flows and higher product yields can be achieved if the filter material consists of two superimposed microporous membrane layers i the membrane system facing the filtrate collecting gap has an average pore size in the range of an exclusion limit of 1000 daltons to 1.2 μm, which excludes the concentrate substances from passage through this membrane system and the membrane system facing the overcurrent gap is at least one larger by a factor of 1.3 has medium pore size, preferably by a factor in the range from 1.3 to 5 and particularly preferably by a factor in the range from 1.5 to 3. If the membrane layers differ by a smaller factor below 1.3, they are economically insignificant or no effects at all any more If they differ in the microfiltration range by a factor above 5, the blocking of the membrane with the larger average pore diameter increases rapidly, particularly in the case of particle-containing feed liquids, so that the filtration comes to an early standstill.The overflow and filtrate collection gaps become advantageous usually kept open by spacers known from the prior art In a preferred embodiment, the crossflow filtration unit is designed as a filter cassette, the membrane systems of which consist of microfiltration membranes. A filter cassette is particularly preferred in which the membrane systems facing the filtrate collecting columns have an average pore size, which is selected from the range from 0.1 to 1.2 microns
In einer weiteren vorteilhaften Ausführungsform besitzt die Filtrationseinheit nur eine Abfolge aus einem Uberstromspalt, einem flachigen Filtermaterial aus den beiden Membranlagen mit den unterschiedlichen mittleren Porengroßen und einem Filtratsammelspalt derart, daß das Filtermaterial mit seiner Ruckflache den Filtratsammelspalt und mit seiner Vorderflache den Uberstromspalt begrenztIn a further advantageous embodiment, the filtration unit has only a sequence of an overcurrent gap, a flat filter material from the two membrane layers with the different average pore sizes and a filtrate collecting gap in such a way that the filter material delimits the filtrate collecting gap with its rear surface and the overcurrent gap with its front surface
Die Erfindung soll nun anhand der Ausführungsbeispiele naher erläutert werden Zur Aufzeigung der Leistungsfähigkeit der erfindungsgemäßen Crossflow- Filtrationseinheit wurde eine hefehaltige Zellsuspension (Pichia) mit einer Zellkonzentration von 6 x 106 Hefezellen (Konzentratstoffe) pro ml, die ein Zielprotein der Molmasse 70 000 Dalton (Filtratstofϊ) in einer Konzentration von 127 mg/1 enthält, im Crossflow-Regim (Kreislauf des Konzentrats) filtriert Wahrend der Filtration wurde die Filtrationseinheit bei einem konstanten Transmembrandruck von 0,64 bar betrieben (Transmembrandruck = (Eingangsdruck + Ausgangsdruck) 1 2 - Filtratdruck ) Die Druckwerte betrugen 0,9 bar am Eingang für Speiseflussigkeit, 0.4 bar am Ausgang für Konzentrat und 0, 1 bar am Ausgang für FiltratThe invention will now be explained in more detail with the aid of the exemplary embodiments. To demonstrate the performance of the crossflow filtration unit according to the invention, a yeast-containing cell suspension (Pichia) with a cell concentration of 6 × 10 6 yeast cells (concentrate substances) per ml, which contains a target protein with a molecular weight of 70,000 daltons ( Filtratstofϊ) in a concentration of 127 mg / 1, filtered in the crossflow regime (circulation of the concentrate) During the filtration, the filtration unit was operated at a constant transmembrane pressure of 0.64 bar (transmembrane pressure = (inlet pressure + outlet pressure) 1 2 - filtrate pressure ) The pressure values were 0.9 bar at the inlet for feed liquid, 0.4 bar at the outlet for concentrate and 0.1 bar at the outlet for filtrate
Für die Ausführungsbεispiele wurden Crossflow-Module mit unterschiedlich großen Filtrationsflachen gefertigt Um die Ergebnisse vergleichen und auf die Bauform zurück fuhren zu können, wurde die Flachenbelastung konstant gehalten Unter Flachenbelastung soll das vorgelegte zu filtrierende Volumen der Zellsuspension pro uberstromter Membranflache verstanden werdenFor the execution examples, crossflow modules with differently sized filtration surfaces were manufactured. In order to compare the results and to be able to trace them back to the design, the surface loading was kept constant. Surface loading is to be understood as the volume of the cell suspension to be filtered per overflowed membrane surface
Beispiel 1 Als erfmdungsgemaße Crossflow-Filtrationseinheit wird eine Filterkassette mit einer uberstrombaren Membranflache von 0,4 m2 verwendet, die 13 Uberstromspalte und 12 Filtratsammelspalte besitzt Die den Filtratsammelspalten benachbarten Membranlagen bestehen aus einer Celluloseacetat-Membran mit einer mittleren Porengroße von 0,2 μm und die den Uberstromspalten benachbarten Membranlagen bestehen aus einer Celluloseacetat-Membran mit einer mittleren Porengroße von 0,45 μm 7,3 1 der Zellsuspension wurden bis auf ein Endvolumen an Konzentrat von 1 1 aufkonzentriert Der durchschnittliche Filtratfluß betrug 0,875 1/mιn x m2 Die Filtration war nach 18 Minuten beendet Im Filtrat wurde eine Konzentration an Zielprotein von 106,6 mg / 1 gefunden Im Konzentrat wuden 238 mg / 1 Zielprotein ermittelt Die Ausbeute an Zielprotein im Filtrat betrug somit 72 %Example 1 As a crossflow filtration unit according to the invention, a filter cassette with an overflowable membrane area of 0.4 m 2 is used, which has 13 overflow gaps and 12 filtrate collection gaps. The membrane systems adjacent to the filtrate collection gaps consist of a cellulose acetate membrane with an average pore size of 0.2 μm and the membrane systems adjacent to the overcurrent gaps consist of a cellulose acetate membrane with an average pore size of 0.45 μm. 7.3 l of the cell suspension were reduced to a final volume of concentrate of 1 1 concentrated The average filtrate flow was 0.875 1 / min x 2 The filtration was ended after 18 minutes. A concentration of target protein of 106.6 mg / 1 was found in the filtrate. 238 mg / 1 target protein was determined in the concentrate. The yield of target protein in the filtrate was thus 72%
Beispiel 2 (Vergleichsversuch)Example 2
Als Crossflow-Filtrationseinheit wird eine Filterkassette des Standes der Technik (Sartocon*der Firma Sartoπus AG) verwendet mit einer uberstrombaren Membranflache von 0,7 m2, die 17 Uberstromspalte und 16 Filtratsammelspalte besitzt Die den Filtratsammelspalten benachbarten Membranlagen bestehen aus einer einzigen Celluloseacetat-Membran mit einer mittleren Porengroße von 0,2 μmA filter cassette of the prior art (Sartocon * from Sartoπus AG) is used as the crossflow filtration unit with an overflowable membrane area of 0.7 m 2 , which has 17 overcurrent gaps and 16 filtrate collection gaps. The membrane systems adjacent to the filtrate collection gaps consist of a single cellulose acetate membrane with an average pore size of 0.2 μm
12,7 1 der Zellsuspension wurden bis auf ein Endvolumen an Konzentrat von 1 1 aufkonzentriert Der durchschnittliche Filtratfluß betrug 0,328 1/mιn x m2 Die Filtration war nach 51 Minuten beendet Im Filtrat wurde eine Konzentration an Zielprotein von 81,3 mg / 1 gefunden Im Konzentrat wuden 621 mg / 1 Zielprotein ermittelt Die Ausbeute an Zielprotein im Filtrat betrug somit 59 %12.7 l of the cell suspension were concentrated to a final volume of concentrate of 1 l. The average filtrate flow was 0.328 l / min x m 2. The filtration was ended after 51 minutes. A concentration of target protein of 81.3 mg / l was found in the filtrate Concentrate was determined 621 mg / 1 target protein The yield of target protein in the filtrate was therefore 59%
Mit dem erfindungsgemaßen Modul erfolgt eine Erhöhung der Ausbeute an Zielprotein im Filtrat um 13 % und eine Erhöhung des Filtratflusses um den Faktor 2,7 Ein weiterer Vorteil besteht dann, daß beim Einsatz der erfindungsgemaß verbesserten Crossflow-Filtrationseinheit gleichzeitig eine Vor- und Endfiltration durchgeführt wird, wozu üblicherweise zwei Filtrationsschπtte durchgeführt werden Beim Emsaz der erfindungsgemaß verbesserten Crossflow-Filtrationsemheit sinken die Prozeßkosten der Filtration deutlich With the module according to the invention there is an increase in the yield of target protein in the filtrate by 13% and an increase in the filtrate flow by a factor of 2.7. Another advantage is that when using the improved crossflow filtration unit according to the invention, a preliminary and final filtration is carried out at the same time , for which purpose two filtration sections are usually carried out. In the Emsaz of the improved crossflow filtration unit according to the invention, the process costs of the filtration decrease significantly

Claims

Patentansprüche claims
1 Verbessere Crossflow-Filtrationseinheit zur Trennung von Stoffen einer1 Improve crossflow filtration unit to separate substances from one
Speiseflussigkeit in Filtratstoffe eines Filtrats und in Konzentratstoffe eines Konzentrats bestehend aus mehreren Abfolgen aus einem flachigen Filtermaterial, einem Filtratsammelspalt, einem weiteren flachigen Filtermaterial und einem Uberstromspalt derart, daß die Filtermaterialien mit ihrer Ruckflache den Filtratsammelspalt und mit ihrer Vorderfläche den Uberstromspalt begrenzen und der Filtratsammelspalt mit mindestens einem Auslaß für Filtrat und der Überströmspalt mit einem Einlaß für zu filtrierende Speiseflussigkeit und mit einem Auslaß für das Konzentrat ausgestattet sind, dadurch gekennzeichnet, daß das Filtermaterial aus zwei aufeinander liegenden porösen Membranlagen besteht, wobei die dem Filtratsammelspalt zugewandte Membranlage eine mittlere Porengroße im Bereich einer Ausschlußgrenze von 1000 Dalton bis 1,2 μm aufweist und welche die Konzentratstoffe von einer Passage durch diese Membranlage ausschließt und wobei die dem Uberstromspalt zugewandte Membranlage mindestens eine um den Faktor 1,3 größere mittlere Porengroße, vorzugsweise eine um den Faktor 1,3 bis 5 größere mittlere Porengroße, besitztFeed fluid in filtrate substances of a filtrate and in concentrate substances of a concentrate consisting of several sequences of a flat filter material, a filtrate collecting gap, a further flat filter material and an overflow gap in such a way that the filter materials with their back surface limit the filtrate collecting gap and with their front surface limit the overflow gap and the filtrate collecting gap At least one outlet for the filtrate and the overflow gap are equipped with an inlet for the feed liquid to be filtered and with an outlet for the concentrate, characterized in that the filter material consists of two porous membrane systems lying one on top of the other, the membrane system facing the filtrate collection gap having an average pore size in the region has an exclusion limit of 1000 Dalton to 1.2 μm and which excludes the concentrate substances from passage through this membrane system and the membrane facing the overcurrent gap was at least one medium pore size larger by a factor of 1.3, preferably a medium pore size larger by a factor of 1.3 to 5
2 Verbesserte Crossflow-Filtrationseinheit nach Anspruch 1, dadurch gekennzeichnet, daß die Crossflow-Filtrationseinheit als Filterkassette ausgebildet ist und die Membranlagen aus Mikrofiltrationsmembranen bestehen2 Improved crossflow filtration unit according to claim 1, characterized in that the crossflow filtration unit is designed as a filter cassette and the membrane systems consist of microfiltration membranes
3 Verbesserte Crossflow-Filtrationseinheit nach den Ansprüchen 1 und 2, dadurch gekennzeichnet, daß die den Filtratsammelspalten zugewandten Membranlagen eine mittlere Porengroße besitzen, die aus dem Bereich von 0, 1 bis 1,2 μm ausgewählt ist3 Improved crossflow filtration unit according to claims 1 and 2, characterized in that the membrane systems facing the filtrate collecting columns have an average pore size which is selected from the range from 0.1 to 1.2 μm
4 Verbesserte Crossflow-Filtrationseinheit nach den Ansprüchen 1 und 3, dadurch gekennzeichnet, daß die Filtrationseinheit aus einer Abfolge aus einem Uberstromspalt, einem flachigen Filtermaterial und einem Filtratsammelspalt besteht derart, daß das Filtermaterial mit seiner Ruckflache den Filtratsammelspalt und mit seiner Vorderflache den Uberstromspalt begrenzt 4 Improved crossflow filtration unit according to claims 1 and 3, characterized in that the filtration unit consists of a sequence of an overcurrent gap, a flat filter material and a filtrate collecting gap in such a way that the filter material delimits the filtrate collecting gap with its back surface and the overcurrent gap with its front surface
EP00991619A 2000-01-05 2000-12-21 Cross-flow filtration unit Withdrawn EP1268044A1 (en)

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Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005113578A1 (en) * 2004-05-14 2005-12-01 New Jersey Institute Of Technology Highly selective membrane systems and methods for protein ultrafiltration
DE102006026081B4 (en) * 2006-06-03 2014-11-27 Sartorius Stedim Biotech Gmbh Process for the preparation of ready-to-drink spirits
JP4899681B2 (en) * 2006-07-18 2012-03-21 富士ゼロックス株式会社 Microchannel device
JP5151204B2 (en) * 2007-03-27 2013-02-27 富士ゼロックス株式会社 Microchannel device and method of manufacturing microchannel device
JP5119848B2 (en) * 2007-10-12 2013-01-16 富士ゼロックス株式会社 Microreactor device
JP2010115624A (en) * 2008-11-14 2010-05-27 Fuji Xerox Co Ltd Microchannel device, separation device, and separation method
JP5003702B2 (en) 2009-03-16 2012-08-15 富士ゼロックス株式会社 Microfluidic device and microfluidic control method
US20100304953A1 (en) * 2009-05-21 2010-12-02 Battelle Memorial Institute Zeolite Membranes for Separation of Mixtures Containing Water, Alcohols, or Organics
US20110056126A1 (en) * 2009-08-13 2011-03-10 Harvey J T Process for producing high value products from biomass
CA2770439A1 (en) * 2009-08-13 2011-02-17 Geosynfuels, Llc Apparatus and process for fermentation of biomass hydrolysate
US8480978B2 (en) 2010-08-12 2013-07-09 University Of Southern California Microfluidic fluid separator and related methods
US9475709B2 (en) 2010-08-25 2016-10-25 Lockheed Martin Corporation Perforated graphene deionization or desalination
US20120208255A1 (en) * 2011-02-14 2012-08-16 Geosynfuels, Llc Apparatus and process for production of an encapsulated cell product
CA2859699C (en) * 2011-12-23 2020-04-28 Barokes Pty Ltd. Wine packaged in aluminium containers
US9463421B2 (en) 2012-03-29 2016-10-11 Lockheed Martin Corporation Planar filtration and selective isolation and recovery device
US10653824B2 (en) 2012-05-25 2020-05-19 Lockheed Martin Corporation Two-dimensional materials and uses thereof
US10376845B2 (en) 2016-04-14 2019-08-13 Lockheed Martin Corporation Membranes with tunable selectivity
US9744617B2 (en) 2014-01-31 2017-08-29 Lockheed Martin Corporation Methods for perforating multi-layer graphene through ion bombardment
US9834809B2 (en) 2014-02-28 2017-12-05 Lockheed Martin Corporation Syringe for obtaining nano-sized materials for selective assays and related methods of use
WO2014164621A1 (en) 2013-03-12 2014-10-09 Lockheed Martin Corporation Method for forming filter with uniform aperture size
US9572918B2 (en) 2013-06-21 2017-02-21 Lockheed Martin Corporation Graphene-based filter for isolating a substance from blood
CN105940479A (en) 2014-01-31 2016-09-14 洛克希德马丁公司 Methods for perforating two-dimensional materials using a broad ion field
CN106029596A (en) 2014-01-31 2016-10-12 洛克希德马丁公司 Processes for forming composite structures with a two-dimensional material using a porous, non-sacrificial supporting layer
CA2942496A1 (en) 2014-03-12 2015-09-17 Lockheed Martin Corporation Separation membranes formed from perforated graphene
WO2015148548A2 (en) * 2014-03-24 2015-10-01 Lockheed Martin Corporation Large area membrane evaluation apparatuses and methods for use thereof
CA2973472A1 (en) 2014-09-02 2016-03-10 Lockheed Martin Corporation Hemodialysis and hemofiltration membranes based upon a two-dimensional membrane material and methods employing same
AU2016303048A1 (en) 2015-08-05 2018-03-01 Lockheed Martin Corporation Perforatable sheets of graphene-based material
JP2018530499A (en) 2015-08-06 2018-10-18 ロッキード・マーチン・コーポレーション Nanoparticle modification and perforation of graphene
CA3020686A1 (en) 2016-04-14 2017-10-19 Lockheed Martin Corporation Method for treating graphene sheets for large-scale transfer using free-float method
KR20190018410A (en) 2016-04-14 2019-02-22 록히드 마틴 코포레이션 Two-dimensional membrane structures with flow passages
WO2017180134A1 (en) 2016-04-14 2017-10-19 Lockheed Martin Corporation Methods for in vivo and in vitro use of graphene and other two-dimensional materials
KR20180133430A (en) 2016-04-14 2018-12-14 록히드 마틴 코포레이션 Method for in situ monitoring and control of defect formation or healing
WO2017180141A1 (en) 2016-04-14 2017-10-19 Lockheed Martin Corporation Selective interfacial mitigation of graphene defects
RU2687921C1 (en) * 2018-05-03 2019-05-16 Закрытое Акционерное Общество "Владисарт" Filtering element for separation and concentration of liquid media
RU2687906C1 (en) * 2018-05-03 2019-05-16 Закрытое Акционерное Общество "Владисарт" Filtering element for separation and concentration of liquid media
KR20210134973A (en) * 2019-03-11 2021-11-11 젠자임 코포레이션 Tangential Flow Virus Filter
CN110551617B (en) * 2019-09-03 2022-11-01 中国科学院北京基因组研究所 Chip for separating body fluid bacteria and cells, manufacturing method and using method thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3341262A1 (en) * 1983-11-15 1985-05-23 Sartorius GmbH, 3400 Göttingen Stacked separation element made of layered sections for treating fluids
US4715955A (en) * 1986-12-22 1987-12-29 Filtron Technology Corp. Ultrafiltration apparatus
GB8823706D0 (en) * 1988-10-10 1988-11-16 Alcan Int Ltd Microfilter device
GB8918649D0 (en) * 1989-08-16 1989-09-27 Foseco Int Filtration
US5256294A (en) * 1990-09-17 1993-10-26 Genentech, Inc. Tangential flow filtration process and apparatus
DE4108055C1 (en) * 1991-03-13 1992-07-30 Thyssen Industrie Ag, 4300 Essen, De
IL121883A0 (en) * 1997-10-05 1998-03-10 Soda Club Holdings Nv Apparatus and method for the purification of water
US6099730A (en) * 1997-11-14 2000-08-08 Massachusetts Institute Of Technology Apparatus for treating whole blood comprising concentric cylinders defining an annulus therebetween

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0149401A1 *

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DE10000196A1 (en) 2001-07-12
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US20070062856A1 (en) 2007-03-22
US20050126980A1 (en) 2005-06-16

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