WO2023135046A1 - Microsoupape fonctionnelle - Google Patents

Microsoupape fonctionnelle Download PDF

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Publication number
WO2023135046A1
WO2023135046A1 PCT/EP2023/050147 EP2023050147W WO2023135046A1 WO 2023135046 A1 WO2023135046 A1 WO 2023135046A1 EP 2023050147 W EP2023050147 W EP 2023050147W WO 2023135046 A1 WO2023135046 A1 WO 2023135046A1
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WO
WIPO (PCT)
Prior art keywords
cavities
elements
cavity
connections
fluid
Prior art date
Application number
PCT/EP2023/050147
Other languages
German (de)
English (en)
Inventor
Juliane DIEHM
Rafaela MEUTELET
Matthias Franzreb
Original Assignee
Karlsruher Institut für Technologie
Priority date (The priority date 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 date listed.)
Filing date
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Application filed by Karlsruher Institut für Technologie filed Critical Karlsruher Institut für Technologie
Publication of WO2023135046A1 publication Critical patent/WO2023135046A1/fr

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0028—Valves having multiple inlets or outlets
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0082—Microvalves adapted for a particular use
    • F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/20—Injection using a sampling valve
    • G01N2030/202—Injection using a sampling valve rotary valves

Definitions

  • the present invention relates to slide valves comprising slidable elements with a plurality of cavities through which fluids can be selectively passed, and static elements against which the slidable elements are displaced, a kit comprising the elements and uses.
  • Valves can be used in many different ways and are relevant in many different areas.
  • the column is packed by first filling the permanently connected channel via the bead reservoir, then the valve on the second fritted channel is switched and the beads are transferred from one channel to the other. If a column is to be renewed, the beads can be removed from the column by increasing the flow rate and thus the pressure.This causes the beads to deform and can pass through the gap between the channel wall and the frit.
  • an "in-valve column” can also be used for sample preparation, which is like a capillary filled with chromatography resin that is connected to a 6-port valve.
  • SMB Simulated Moving Bed Chromatography
  • Multidimensional chromatography is a technique that combines different types of chromatography to separate a single sample.
  • On the one hand there is the possibility of linking the columns via an external connection of several valves, thereby enabling sample transfer.
  • the sample is guided through the various columns by switching the valves, whereby flow rates and buffer conditions can be adjusted for the individual columns.
  • Another option is to integrate the columns into a microfluidic chip.
  • the sample can be routed via integrated 2-way valves or via an external valve circuit, which regulates the flow rates in the various channels of the chip. In this case, the sample is transferred from one column to the other by a so-called "transfer cross".
  • the object of the present invention was to provide options for improving existing systems, in particular the systems should have increased flexibility and ease of maintenance.
  • fastening elements preferably, but not exclusively, means screws (with nuts), in particular self-locking nuts.
  • the present invention is based in particular, but not exclusively, on a simplified connection of a plurality of chromatography columns and a reduction in the dead volume between the columns.
  • the chromatography columns are integrated directly into the valve, so that the column bodies are part of the valve. This eliminates the connection capillaries and connectors between the valve and columns, which reduces dead volume and simplifies the wiring.
  • chromatography columns can be integrated into all components of a rotary valve system and the inflow and outflow of fluids between the columns can be implemented as desired.
  • the present invention therefore relates to slide valves, in particular SMB valves, comprising or consisting of, stacked one above the other, at least two displaceable elements (rotor) and at least one static element (stator), and optionally further elements.
  • slide valves in particular SMB valves, comprising or consisting of, stacked one above the other, at least two displaceable elements (rotor) and at least one static element (stator), and optionally further elements.
  • the slide valves are often referred to simply as valves in the following.
  • rotor for the displaceable element is used in particular when the displacement takes place about an axis of rotation. In the context of the present invention, however, the displacement does not have to be rotational, although this is preferred.
  • the first essential element I) of the slide valves according to the invention are at least two, or at least three, in particular two or three, displaceable, preferably rotatable, particularly preferably round, elements (rotor) each comprising a) at least one cavity with at least two connections per cavity, the Ports permit fluid flow through the at least one cavity, or b) at least one cavity without dedicated ports configured to receive inserts with at least two ports per insert, the ports permit fluid flow through the inserts, or c) at least one Cavity with at least two ports per cavity and at least one cavity without its own ports configured to receive inserts, preferably inserts with at least two ports per insert, wherein the ports allow fluids to flow through the inserts.
  • cavities mentioned represent cavities with a defined volume, which in principle can have any shape. However, it is often useful and therefore preferred if the individual cavities in the valve according to the invention have the same dimensions in order to enable the greatest possible interchangeability of cavity inserts and better comparability of flows or test results.
  • Cavity inserts are housings, in particular for accommodating (chromatography) columns, which are inserted into the corresponding cavities without their own connections to the displaceable elements I).
  • a displaceable element has in its center approximately square cavities without their own connections, which are therefore essentially indentations (approximately square means a deviation from the ideal square shape of at most 10%, preferably at most 5%, and in particular at most 2%.).
  • These cavities can directly adjoin one another, so that they do not have any directly visible borders to one another.
  • this can be implemented as a recess with approximately square corner edges.
  • Such a recess as an example for the cavities mentioned without their own connections is therefore the place at which, with the aid of inserts (housings), in particular (chromatography) columns, are inserted into the displaceable element. It can be in the context of present invention individual or all, preferably all, cavities are used.
  • Cavity inserts that can be used according to the invention are preferably adapted to the shape of the cavities and, in some preferred variants, can comprise or consist of single-column inserts and single-column housings.
  • the single-column inserts are inserted into the single-column housings in order to then form the assembled cavity inserts (in this example, single columns).
  • the assembled cavity inserts have connections which, in the simplest case, can be bores through which a fluid can flow.
  • cavity inserts can also be used, for example those that are designed as a (chromatography) column or those that merely represent an (empty) housing, depending on the exact purpose being pursued.
  • this one cavity is then particularly preferably subdivided or at least can be subdivided, for example by wall elements or the insertion of functional inserts, such as chromatography columns or the like.
  • chromatography column used in the present invention sometimes abbreviated simply as "column”, it should be pointed out that these columns are not in principle limited to a specific size, but only by the fact that they have to fit into the cavities to be used (Possibly with residual volume in the cavity), either in itself or using housings in which the columns are used.Such columns used in housing are particularly easy to handle, especially if the housing is adapted to the dimensions of the cavities, and can on Stock can be produced (also with different fillings/stationary phases or similar), so that columns can be easily exchanged (during operation).
  • this therefore preferably represents a polyfunctional unit within the scope of the present invention, in particular by use several columns, each preferably in housings, so that functionally ultimately a plurality of cavities results.
  • connections mentioned are sometimes also referred to as openings or inlets or outlets or connectors, which varies depending on the context.
  • Connectors are in particular those openings that already have a device/equipment by means of which a connection to other parts, such as hoses, is made possible.
  • this does not mean that the inlets/outlets or openings cannot (will) not be provided with appropriate devices/equipment.
  • the second essential element 11a) of the valves according to the present invention is at least one static, preferably round, element (stator) comprising at least one connection for fluid supply and at least one connection for fluid discharge.
  • This second element can additionally have one or more connections for fluid transmission.
  • the second essential element Ila) of the valves according to the present invention is at least one static, preferably round, element (stator) comprising at least one connection for fluid supply, at least one connection for fluid discharge, and one or more cavities for fluid transmission , preferably designed as (chromatography) column (s).
  • the second element can additionally have one or more connections for fluid transmission.
  • the static element is arranged one above the other with sliding elements, so that the static element covers cavities and connections of the sliding elements, with connections of static and displaceable elements are brought into congruence by moving and thus a fluid flow through the static element into at least one, but in variants also several, cavity(ies) of the displaceable elements, through this cavity(ies) and again through another connection or other connections of the static element.
  • the static and displaceable elements are pressed together in such a way, in particular by fastening means, that the fluid(s) cannot flow between the contact surfaces of the elements, but only along the respective connections.
  • the respective connections (openings, inlets or outlets, connectors) of the elements are provided with seals or sealing elements. Examples of preferred seals are, for example, O-rings.
  • connections of the static element which are used for the supply and discharge of fluids into the valve, are arranged on the side opposite a displaceable element. Additionally or alternatively, (the) connections of the static element, which are used to supply or discharge fluids into the valve, can be arranged on the peripheral sides of the static element.
  • the valve according to the invention can optionally include a preferably round, static cover plate III), which is arranged on the side of the uppermost of the at least two displaceable elements (rotors) opposite the stator.
  • the uppermost displaceable element (the rotor) is clamped between the static element and/or at least one further displaceable element and the static cover plate.
  • the cover plate is usually just a kind of "clamping aid" without its own connections or feed-throughs.
  • the cover plate can be replaced by a second static element.
  • a displaceable element can be used in special configurations, which has connections on the top and bottom, so that fluid streams can be routed through the valve and do not necessarily exit on the same side as they are introduced.
  • cover plates can also have connections or, for example, spacer elements (facing outwards, ie away from the valve) or feet.
  • the second essential element IIb) is a static, preferably round, element (stator) which has no connections for fluid (further) conduction.
  • the connections of the first element I) are arranged in such a way that they are accessible from the outside, ie from the sides of the stack of valve elements used.
  • the element IIb) largely corresponds to a cover plate or base plate, which, however, can still optionally be present in each case.
  • valves according to the invention are referred to as upper and lower sides (or similar), this refers to a structure comprising at least one sliding and static element, which are arranged one above the other, with the sliding element is considered “below” and the static element is considered “above”; the arrangements of the other elements, in particular of the second displaceable element, or plates then follow from this.
  • valve according to the invention can optionally also have a, preferably round, static base plate IV) on the II), in particular Ila) or optionally III) opposite side of the stack of at least one I), II), in particular Ila) and optionally III) is arranged include.
  • these base plates can have the same shape and structure as the cover plates, but they can also have connections or, for example (outwards, i.e. directed away from the valve) spacers or feet.
  • the bottom and top plates thus differ (essentially) only in that they are arranged on opposite sides of the valve.
  • valves according to the invention can also have devices or preparations V) for automatically driving the displacement of at least one, several or all of the elements I).
  • these are corresponding configurations of the outer peripheral surfaces of the respective rotatable element.
  • the facilities or devices V) are selected from the group consisting of: V) a) surfaces of the outer peripheral surface of the respective element I that are roughened or provided with a coating that increases grip (tackifyer);
  • V)c Lever or shaft attachment point(s), lever, handles on the outer
  • V)f Device for attaching driven components, preferably indentations into which such components can be inserted and/or provisions for the engagement of fastening means, preferably holes, in particular screw holes.
  • the drive is not part of the valve according to the invention per se, but a separate component that is made available separately.
  • This can be, for example, a conventional belt drive, gear drives, for example gears mounted directly on a motor, or sliding motors or the like.
  • motors can be permanently installed on or in the valve.
  • a displaceable element (rotor) I) (the top one) in a valve according to the invention should or must be driven from above the valve, for example via device or device V)d
  • the Static element II), in particular Ila) (in its middle), and also if present base plate IV), and the further (s) displaceable (s) element (s) (rotor (s)) each have a recess by which the drive can be brought into engagement with the facilities or devices V)d).
  • the several displaceable elements (rotors) in a valve according to the invention can have the same or different devices or devices V).
  • the respective devices or devices V) must be accessible, i.e. devices or devices V)d)/V)e)/V)f) that require a drive from above or below the valve should (must) not be inside.
  • valves according to the invention can be designed without such “drive pre-installations or devices”, so that the displacement is then carried out purely manually. This can be advantageous, for example, if there is no or too little space for automatic adjustment devices is.
  • the relative movement, i.e. the displacement, in particular rotation, of I) (only one, several or all) in relation to the other elements takes place either manually or with the aid of a drive.
  • the connections of the at least one static element are arranged in the valves according to the invention in such a way that they can be brought into alignment with all connections or selected connections of at least one displaceable element in order to selectively allow the transfer of Fluids between the elements to allow or prevent.
  • displaceable or rotatable refers to the respective assembled valve, i.e. the respective displaceable element is displaceable or rotatable, independently of other displaceable elements, relative to the static element or elements, as well as other displaceable elements.
  • rotatable preferably refers to an axis of rotation C m standing perpendicularly in the middle of the respective rotatable element, where m is the number of cavities in the element.
  • the rotatable element must have a round or m-cornered external (circumferential) shape, since the rotation is related to the cavities.
  • a uniform outer circumference of the rotatable element is preferred because this is simpler in terms of manufacturing technology and can be advantageous for a rotational drive via belts or gear wheels, for example, the outer shape can also be irregular (for example also trapezoidal). It is preferred in variants if, when the rotatable element rotates, no part of this element protrudes beyond the edges of the (largest built-in) static element or cover plate/base plate when the valve is viewed from above.
  • angular, displaceable, preferably rotatable, elements with round static elements or top/bottom plates or, conversely, round, displaceable, preferably rotatable, elements with square static elements or top/bottom plates (as well as independently of which round and/or angular shaped further sliding elements).
  • displaceable, in particular rotatable, elements are used in the present invention for each valve. In further variants of the present invention, these can each or partially be separated from one another by static elements.
  • 3RSRSRS; DRSRSRS; DRSRSRSB (alternating three times R and three times S)
  • these stacking sequences can of course also be further combined with one another, in which case preferably no cover plates or base plates are arranged on the combination surfaces.
  • valves according to the invention can therefore consist of only at least two displaceable elements and a static element, or several of these, in addition to parts such as seals, drive or the like, and optionally additionally comprise cover and/or base plates.
  • the components I), II), in particular IIa), III), IV) have a common axis of rotation which lies vertically in the center of the stack of the elements present, with the elements preferably all being round or approximately round , In particular round, are designed.
  • approximately round means a deviation from the ideally round shape of at most 20%, preferably at most 10%, more preferably at most 5% and in particular at most 2%.
  • Ila) is firmly connected to III) and/or IV) via appropriate fastening means. As already explained, this also applies if several displaceable and/or static elements are arranged.
  • the intervening displaceable, preferably rotatable elements I) can still be displaced, in particular can be rotated about the axis of rotation, but at the same time there is fluid-tightness between the elements and, if applicable, top/bottom plates, such that no Fluids flow between the contact surfaces, but only between connections provided in front of them.
  • the displaceable (rotatable) elements I) have at least two cavities; in some variants, this embodiment is preferred to that with a cavity (even if this is divided).
  • At least two of these at least two cavities are filled with the same or different materials or inserts containing such materials, with the materials being able to interact with the substances running in the fluid (dissolved and/or suspended in the fluid) (i.e. for Examples are in particular stationary phases in chromatography, the fluid would then be the eluent and the substances running in the fluid (dissolved and/or suspended in the fluid) are those that are to be (off) separated by chromatography).
  • a displaceable (rotatable) element I in the case of a round or uniformly polygonal element I) in particularly preferred configurations they have the same dimensions and are uniformly distributed around the center, so that the round or uniformly polygonal Element has an axis of rotation C n perpendicular to its center, where n is the number of cavities.
  • at least one flow path through at least two cavities is changed by the relative movement of the individual valve elements with one another.
  • the cavities are configured such that materials, preferably materials for performing a chromatographic separation, in particular for stationary phases for chromatography, can be introduced or inserts, preferably comprising chromatography columns, can be used.
  • optional frits/filters/nets/grids can be used to retain the materials, if necessary, in the cavities and/or at their inlets and/or outlets.
  • the cavities have a cylindrical shape or a geometry that deviates from the cylindrical shape.
  • the cavities can be adapted to the planned application within the scope of the present invention.
  • the cavities can be designed around, in order to then either only be filled with sample fluid or, in other preferred embodiments, used and designed as (chromatography) columns, for which they are then in particular filled with a stationary phase, for example in the form of small balls (beads/beadlets) can be filled.
  • the cavities as also described elsewhere in this description, can be designed and shaped in such a way that separately produced (chromatography) columns, if necessary with the aid of appropriately adapted and shaped housings.
  • particularly suitable 3D printing methods are those that work with resin-based starting material, preferably digital light processing (DLP), stereolithography (SL) or poly/multijetting.
  • DLP digital light processing
  • SL stereolithography
  • poly/multijetting liquid-tight components can be obtained, preferably with relatively (for 3D printing techniques) smooth surfaces.
  • the choice of material depends to a large extent on the respective application; acrylate-based plastics are preferred; these can be heavily fluorinated, e.g. to improve the sliding properties on the sealing surface and for increased chemical resistance.
  • the cavities have a volume of 10 nanoliters to 10 milliliters, preferably 1 microliter to 1000 microliters. This volume is the volume that can be used by the (chromatography) column, i.e. the (effective) column volume.
  • one or more cavities can be filled with structures of defined geometry, in particular produced by 3D printing, with different cavities preferably being filled with different materials for interaction with dissolved substances, or different cavities with the same materials for Interaction are filled with dissolved substances.
  • the cavities are preferably filled with materials for carrying out a chromatographic separation, it being possible for the filling to take place inside or outside the valve.
  • frits/filters/nets/grids are introduced to hold back the materials, if necessary, either in the cavity or between the individual valve elements.
  • Another subject of the present invention is also a kit for the production of slide valves, in particular for SMB processes, comprising i) various slide elements, preferably round, (rotors) comprising a) at least one, preferably at least two, cavity (s) with at least two ports per cavity, the ports allowing the flow of fluids through the at least one cavity, or b) at least one cavity without its own ports configured to receive at least two inserts with at least two ports per insert, the ports allowing the flow of fluids through which allow inserts, or c) at least one cavity with at least two connections per cavity and at least one cavity without its own connections configured to accommodate inserts, ii) static elements, preferably round, (stators) comprising at least one connection for fluid supply, and at least one Port for fluid removal, optional one or more cavities for
  • the kit according to the invention is based in particular on the fact that different slide elements and static elements are each of the same size or at least have coordinated dimensions, in particular with regard to Fastening elements, preferably screws (with nuts), in particular self-locking nuts, and axis of rotation C m ., are included.
  • the kit includes, on the one hand, different sets of elements i) in different sizes and with different configurations, in particular different numbers and dimensions of cavities.
  • the kit includes, on the one hand, different sets of elements ii) in different sizes and with different configurations, in particular connections (openings, inlets or outlets, connectors).
  • the kit includes different sets of top plates and base plates in different sizes and configurations.
  • the relative number of these can be lower because, for example, several provisions for fastening means can be arranged on a larger cover plate
  • kits according to the invention can also include motors v), with which the rotor or rotors can be moved.
  • kits according to the invention can also include housings vii), into which the valves can be inserted.
  • kits according to the invention can also include holders viii), which can hold the valves or individual parts.
  • kits according to the invention are also suitable for the variant of the present invention which uses the static element IIb) instead of the static element IIa).
  • the kit starting from the kit, it is possible and sufficient to select and install one (more) top or bottom plate.
  • the subject of the present invention is the use of the slide valves according to the invention or of slide valves produced by means of the kits according to the invention in the field of multi-column chromatography or in the coupling of chromatography methods with other processes.
  • the slide valves according to the invention or the slide valves produced using the kits according to the invention can also be used for (bio)chemical analyses, in particular those with small sample volumes, preferably for the analysis of environmental samples the food industry, in the (bio)pharmaceutical industry, in the chemical industry, in medical diagnostics.
  • the individual (chromatography) columns individually into the cavities of the displaceable element, in particular columns in housings into the cavities without their own connections, in order to be able to manufacture the columns individually and also to be able to replace them if necessary.
  • the columns are accordingly packed individually and only then integrated into the valve. This procedure makes it possible, among other things, to exchange the columns individually and to use them, for example, for further experiments / comparative experiments.
  • the cavities mentioned can be used as such if, for example, the cavities are/are filled with materials that can interact with the substances flowing into the fluid (substances dissolved and/or suspended in the fluid).
  • the interacting materials can be present in the cavities as a slurry or in powder form.
  • the cavities can also be used indirectly by using cavity inserts, which can then be designed, for example, as empty inserts or as (chromatography) columns.
  • the cavities are sometimes not referred to as such in the descriptions of the figures, but rather as column(s), which at the same time describes the respectively selected function of the relevant cavity.
  • the cavities with at least two connections per cavity of the displaceable elements I) are designed as (chromatography) columns and the cavities without their own connections of the displaceable elements I) are designed as cavities with inserted (chromatography) columns or cavity inserts ; in the latter case, the (chromatography) columns or cavity inserts used provide the necessary connections.
  • the present invention thus relates, in other words, to rotary valves consisting of a plurality of elements which are connected to one another so that they can be moved (rotated) relative to one another, the elements having fluidic channels and, in some cases, cavities. At least two cavities are preferably filled with materials that can interact with the substances flowing into the fluid (substances dissolved and/or suspended in the fluid). Different flow paths can be generated by the relative movement of the individual valve elements with one another.
  • the flow path through at least two cavities is changed by the relative movement of the individual valve elements with one another, and in preferred variants there is the possibility of supplying and/or removing fluid flows between the cavities.
  • a preferred variant of the present invention is a slide valve, in particular an SMB valve, comprising, arranged in a stack one above the other, I) at least two displaceable elements (rotors), each comprising a) at least one cavity or at least two cavities, preferably at least two cavities, for example two Cavities, with at least two connections per cavity, the connections allowing the flow of fluids through the at least one cavity, or b) at least one cavity or at least two cavities, preferably at least two cavities, for example two cavities, configured without their own connections for receiving at least two inserts with at least two connections per insert, the connections allowing fluids to flow through the inserts, or c) at least one cavity or at least two cavities, preferably at least two cavities, for example two cavities, with at least two connections per cavity and at least one cavity without its own connections configured to accommodate inserts,
  • At least one static element comprising at least one connection for fluid supply and at least one connection for fluid discharge, optionally one or more cavities for fluid transmission, optionally one or more connections for fluid transmission, III) optionally a static cover plate, which is arranged on the side opposite the static element (stator) of the displaceable element (rotor) furthest from the static element (stator),
  • a particularly preferred variant of the present invention is a slide valve, in particular an SMB valve, comprising, stacked one above the other,
  • two displaceable elements or three displaceable elements each comprising a) at least two cavities with at least two connections per cavity, the connections allowing the flow of fluids through the at least one cavity, or b) at least one cavity without its own connections configured to accommodate at least two inserts with at least two ports per insert, the ports allowing the flow of fluids through the inserts, or c) at least one cavity with at least two ports per cavity and at least one cavity without dedicated ports configured to receive inserts,
  • At least one static element comprising at least one connection for fluid supply and at least one connection for fluid discharge, optionally one or more cavities for fluid transmission, optionally one or more connections for fluid transmission,
  • III) optionally a static cover plate, which is arranged on the side opposite the static element (stator) of the displaceable element (rotor) furthest from the static element (stator), IV) optionally a static base plate which is arranged on the Ila) or optionally III) opposite side of the stack of I), Ila) and optionally III),
  • the slide valves according to the invention can be used wherever (bio)chemical analyzes are carried out with small sample volumes. In preferred variants, they are used for the analysis of environmental samples (drinking water, pollution, etc.) in the food industry, in the (bio) Pharmaceutical industry, in the chemical industry, used in medical diagnostics.
  • slide valves according to the invention are used in the field of multi-column chromatography or when chromatographic methods are coupled with other processes.
  • slide valves according to the invention are therefore advantageous for all manufacturers and users of (process) analytics in the areas mentioned above.
  • the present invention also relates to methods for carrying out chromatographic investigations, in particular SMB, using or using the slide valves according to the invention or valves produced from kits according to the invention.
  • the dead volume is reduced: As a logical consequence of the first two points, there is inevitably a lower dead volume in the overall system. This is advantageous for many analytical procedures as it minimizes dispersion effects.
  • multi-column chromatography methods are represented, for example, by simulated moving bed (SMB) chromatography or multidimensional chromatography. While SMB focuses on continuously solving a specific separation task, multidimensional chromatography focuses on combining different separation mechanisms.
  • a method can be used as multi-column chromatography MCC (multi-column chromatography), in which a sample is repeatedly passed through columns of the same construction (usually through two in alternation) in order to achieve the highest possible separation efficiency and limitations, which with a single long column, such as excessive pressure losses across the column, can occur.
  • MCC multi-column chromatography
  • the present invention offers increased flexibility and thus a larger area of application on a microfluidic scale.
  • FIG. 10 Another particularly preferred embodiment of the slide valve according to the invention is the variant shown in FIG. 10 with two displaceable elements.
  • FIG. 11 Another particularly preferred embodiment of the slide valve according to the invention is the variant shown in FIG. 11 with three displaceable elements.
  • FIG. 1 Another variant embodiment of the slide valve according to the invention that is preferred according to the invention is the variant shown in FIG.
  • a particular advantage of the present invention is that the dead volumes can be significantly reduced compared to the systems of the prior art.
  • the valves themselves have a certain dead volume, and on the other hand, in the systems of the prior art, the volume of the connecting capillaries is added.
  • a prior art system thus has a certain dead volume, to which is added the volume of the connecting capillaries, adding up to a total dead volume; this corresponds to the volume of all connecting channels between the columns (e.g. four) used for the SMB, regardless of whether these are in the form of channels in the valve or as connecting capillaries.
  • the more compact design through integration of the columns in the valve not only eliminates the dead volume of the capillaries, but the dead volume of the valve system can also be reduced and is then only a fraction of the dead volume of the systems of the prior art.
  • displaceable element not every displaceable element (every rotor) has to have cavities; it is also possible for one or more rotors to have only fluidic connections, for example; but preferably at least one displaceable element has cavities, preferably at least two displaceable elements have cavities.
  • the various elements, in particular the displaceable elements can have the same axis of rotation, but do not have to.
  • displaceable elements can be moved independently of one another in the same direction, or several or all can be moved in the same direction (with the same or different amounts).
  • either the fluidic connection at one pair of seals or at several seals can change at the same time during a movement.
  • the connection can be changed at the seal pairs during a process at different times per seal pair and the distance between the changes does not have to be uniform.
  • both displaceable elements (rotors) and stators can be made up of several disks (stacks). These stacks can (but don't have to) move as one piece and in that case can be considered as one element. Furthermore, it should be pointed out again that the complete system can also be integrated into other fluidic systems (for example "SMB on a chip").
  • the cavities of the valves according to the invention are not only filled with column inserts or direct absorber material, but also, for example, with capillaries (especially when manufacturing the valve with 3D printing techniques, in order to reduce contact with 3D printing material, or channel diameter to reduce) can be filled.
  • valves according to the invention always have at least two displaceable elements (rotors) that can be moved relative to one another, there are also the following advantages over the valves of the prior art, for example:
  • SMB not all ports need to be switched at once, it can also be switched asynchronously.
  • previous systems used either several decentralized valves (e.g. US Pat. No. 6,136,198) or at least two rotary valves (e.g. WO 2017/155664 A1).
  • the dead volume and the system costs can be further reduced by the present invention.
  • valves of the present invention make it possible that different functions are taken over in the valve itself by the different links, which is not possible with the valves of the prior art, which moreover do not relate to chromatography.
  • Miniaturized SMB systems are known from US Pat. No. 8,807,164 B2, with which processes such as the Varicol process can also be carried out—however, pneumatically controlled membrane valves are used instead of slide valves.
  • a simple SMB process does not require a valve as in the context of the present invention, but at least 8 valves, in the case described even 72. This makes the control much more complex and expensive, and the susceptibility to errors is significantly higher simply because of the high number of valves the dead volume of the system (even if the structure is kept comparatively compact) is still significantly larger than in the systems of the present invention.
  • the individual parts of the device/systems/valves according to the invention are functionally connected to one another in a manner known and customary in the art.
  • valves have a polygonal, for example rectangular or for example hexagonal, or for example octagonal or n-cornered basic shape. Furthermore, elliptical basic shapes are also suitable.
  • the special feature of this system according to the invention is that the columns are first manufactured individually and then inserted into the rotor ( Figure lb, lc). This allows the columns to be exchanged individually and it is possible to use the columns with the appropriate adapter ( Figure 5) as a single column (e.g. for characterization experiments) or columns with the same characteristics can be used for an SMB. These factors facilitate the design of the SMB and increase the predictability of the experimental results.
  • FIG. 1a shows a stator S of a valve V according to the invention in an oblique view (above) and in an oblique view from below (lower part of the figure).
  • the fluid connectors for external material flows S2 are also shown.
  • hoses can be connected to these connectors, through which fluids can then be conducted to the respective cavities 13 of the valve V, which are usually occupied by chromatography columns 13 .
  • On the sides (referenced only on the right-hand side) of the stator S, means S3 for aligning the rotor R and the stator S are shown.
  • this can be a bore.
  • Numeral S4 points to an O-ring groove which is arranged on the rotor-side ends of the fluid connectors and which serves to seal the contact points of rotor R and stator S.
  • these O-ring grooves S4 are essentially depressions in the stator S (or on/in the rotor-side ends of the fluid connectors and/or on/in the connecting channel openings S7), into which a seal is (or can be) inserted.
  • FIG. 1a this is indicated as round lines around the rotor-side openings of the fluid connectors or the openings of the connecting channels S7 (but only numbered once for the sake of clarity).
  • the area of the stator S that comes into contact with the rotor R is denoted by S5.
  • a device S6 can optionally be provided in the middle of the stator, which serves as a centering aid for rotor R and stator S.
  • This centering aid is preferably designed as a pin and/or annular centering groove (shown here as an annular centering groove).
  • S7 also indicates where a connecting channel can be located, with which two cavities 13, that is to say in particular chromatography columns 13, can be connected to one another.
  • This Connection channels can be simple bores or curved hollow tubes or the like.
  • FIG. This is denoted as well R9 and is the location where chromatography columns 13 are loaded into the rotor R.
  • well R9 is the location where chromatography columns 13 are loaded into the rotor R.
  • four places for chromatography columns 13 are therefore available.
  • individual or all depressions R9 can be used.
  • several (then thinner) chromatography columns 13 can be arranged per well R9.
  • other symmetries or shapes can be selected for the depressions R9 and consequently other numbers of depressions R9 can also be implemented; preferred numbers of depressions R9 per rotor R are three, four, five, six, seven and eight, in particular four.
  • these depressions R9 form cavities 13 together with the rotor R located above them or the stator located above them, which cavities 13 can be used per se or, preferably, by using chromatography columns 13 .
  • bores Ria are also illustrated, which are used to connect to a motor coupling (not shown) for rotating the rotor R (via appropriate fastening means).
  • these are arranged in the middle around a recess. Although this recess is illustrated as a circle, this does not necessarily have to be the case.
  • devices e.g.
  • stator for aligning rotor and stator (the stator, which is not shown here, then has corresponding counterparts, with bores in the rotor pins or similar would be arranged in the stator).
  • the circle segments outside of the depressions R9 shown represent the contact surfaces R5 of the rotor R to the stator S (not shown here) (or other rotors).
  • FIG. 1c shows examples of columns that can be used according to the invention.
  • RIO shows a single column insert RIO with an optional O-ring cord groove (for better pressure stability, shown by a double edge line) in the figure above.
  • Such single-column inserts RIO are then used in single-column housings Rll (third representation from above), which are preferably adapted to the shape of the cavities (this simplifies the exact positioning), and then used as assembled single columns R13 in the cavities or recesses R9 become.
  • the assembled individual columns R13 are shown in the bottom part of FIG. 1c, on the left in a top view and on the right in a view from below, with connections to the stator S, shown here as points R12, then being shown on the right. In the simplest case, these connections can be bores through which a fluid can flow.
  • Figure ld shows a cover plate D for the valves V according to the invention. This (if it is used) is attached to the side of a rotor R facing away from the stator S and then by attaching fastening elements, preferably screws (with nuts), in particular self-locking nuts , Pulled together and fixed through the holes Dl and tighten the fasteners, the valve according to the invention (where the rotor R between the stator S and / or further rotor R and cover plate D remains movable (rotatable)).
  • fastening elements preferably screws (with nuts), in particular self-locking nuts
  • the cover plate D is essentially a plate with bores D1 for receiving the fastening means, wherein the cover plate D can have a recess in the middle if the rotor R is to be driven from this side; if the rotor R is to be driven, for example, by toothed wheels or belts which act on its outer sides, such a recess is not necessary.
  • Figure le shows an assembled valve V according to the invention consisting of stator S, two rotors R and cover plate D (in the order given above one another).
  • a base plate B can of course also be arranged on the other side of the valve;
  • inlets or fluid connectors S2 remain accessible, which generally requires that these are arranged comparatively far in the middle—or on the outer peripheral edge of the stator S.
  • Figure 2 shows an example (simplified to one movable element for the drawing) the difference between the micro-SMB described in the prior art (indicated by a) in the upper part of the figure) and the corresponding interconnection according to the present invention (in the lower part of the Figure labeled b)).
  • a static element/stator S is shown at the top and a movable element/rotor R is shown at the bottom.
  • the inventive integration of the columns 13 in the valve V, more precisely in the rotor R eliminates the need for connecting channels (represented by cross-striped rectangles) in the valve and additional external capillaries (represented by arrows). This significantly reduces the dead volume.
  • frits Possible placement points for any frits are denoted by 14 (for the sake of clarity only on the right columns, which in turn are numbered only in the left part with 13 for the sake of clarity).
  • 14 By means of such frits it is possible to hold the stationary phase in the columns 13, even if this consists only of a bed;
  • a filter effect can be achieved so that only sufficiently small particles/substances reach the column itself (i.e. the stationary phase) and the remaining components are trapped.
  • sufficiently fine-meshed filters, nets or grids can also be used instead of the frits.
  • FIG. 3 shows a highly schematic example of a structure for a micro-SMB system using a valve according to the invention.
  • This exemplary structure includes four containers for each diluent, extract, sample and raffinate, as well as a container for waste, a multi-channel pressure control unit for microfluidics 15 with a pressure control probe PCR per channel, four flow sensors FCR, two UV sensors QR, two conductivity sensors LR and one (screwed together) valve V according to the invention with four integrated columns 13 (for example distributed over two rotors, each with two columns 13 or distributed over one column in the first rotor and three columns 13 in the second rotor).
  • Such a setup can (but is not mandatory) be used for investigations such as the example shown below.
  • FIG. 4 shows the results obtained in the example described below.
  • concentrations in the (inflow and outflow) streams of the system used are shown in FIG. A more detailed description can be found below in the example.
  • Figure 5 illustrates packing adapters for packing individual columns separately.
  • P9 designates a depression for inserting an individual column and PI bores for pressing the individual parts by means of appropriate connecting elements, preferably screws (in one example, these bores go through all parts and then the individual parts are pulled together or screwed together by tightening screws/nuts, for example).
  • screws in one example, these bores go through all parts and then the individual parts are pulled together or screwed together by tightening screws/nuts, for example.
  • the bores only go through one part and in other part a threaded groove is cut into which a screw can be screwed, or in still another example clamping rods are passed through the bores and then all parts of clamped together on the outside via the clamping rods. Other variants are possible).
  • P2 designates connectors for external fluid flows.
  • a single column is thus placed in the depression P9 of the lower part, then the cover is put on and the lower part and cover are fixed to one another by means of the connecting elements.
  • the column can then be connected and filled or operated via connectors P2.
  • the same pack adapter is shown again in a side view.
  • the third line shows the pack adapter on the left in a top view and on the right in a bottom view. You can see the holes PI and in the left part the Connectors P2 (not numbered for clarity).
  • the cuts through the adapter parts along the respective cutting lines AA and BB are then shown in the bottom line of FIG.
  • passage openings for fluids are then also shown, which are marked with arrows.
  • FIG. 6 exemplary embodiments according to the invention of rotor disks, in which chromatography columns are integrated ( Figures 6 to 8), base plates/cover plates ( Figure 9) and assembled valves from these rotors and base plates/cover plates ( Figures 10 and 11) illustrated.
  • Different designs of the rotor disks are shown as examples, which, for example, only have columns (FIG. 6), additional bypass channels that can also be used for direct sample injection (“sample loop") (FIG. 7) or additional microfluidic elements for flow control ( Figure 8). Numerous other configurations are conceivable.
  • the cover and base can be identical (Figure 9); in this case, fluid can be supplied and removed from both sides (top and bottom).
  • Figure 10 shows the assembled components of a valve according to the invention with two displaceable elements (rotors) and Figure 11 shows the assembled components of a valve according to the invention with three displaceable elements (rotors).
  • the rotor discs can be rotated, for example, via gear wheels or a belt drive.
  • the valves according to the invention allow the flexible connection of different chromatography columns or sample loops without any dead volume.
  • FIG. 6 shows a possible variant of the rotor R of the valves V according to the invention.
  • the teeth 24 of the outer circumference of the rotor R immediately catch the eye in this variant.
  • Such teeth make it possible to drive the rotor R via a toothed belt or toothed belt.
  • this possibility does not rule out the possibility of the rotor being driven from below by a motor that acts, for example, via the center hole.
  • FIG. 6 corresponds in principle to that shown in FIG. 1b, for example.
  • three chromatography columns 13 are illustrated here in FIG. 6, four or more (or fewer) are just as possible.
  • the columns 13 are only indicated here (dashed); the columns are designed here as an integral part of the rotor plate (accessible for example via additive manufacturing, in particular 3D printing), but the rotors shown in FIG. 1b can also be provided with teeth 24 in order to make the drive options more flexible.
  • the inlet 21 and outlet 22 of the cavity or column 13 are shown, which in this case show the possibility of the cavity/column 13 being supplied with fluid from one surface and drained from the other side.
  • both the inlet 21 and the outlet 22 on one (of the same) surface side.
  • number 20 illustrates an optional recess into which an (inlet) frit 14 can be inserted if desired (cf. also FIG. 2 and the description for possible positioning of frits or filters/nets/grids).
  • a centering bore 23 is also shown in the middle, by means of which (and other centering means, such as rods or the like) rotor R and stator S as well as cover plate D can be centered.
  • this centering bore 23 can also, alternatively or additionally, be used as an attachment point for a centrally arranged motor (or a means that transmits the rotation of a motor, such as a shaft).
  • FIG. 7 illustrates a similar exemplary embodiment of the present invention as FIG. 6.
  • additional passage channels (bypass channels) 25 are shown in FIG. Loop"
  • FIG. 6 which only illustrates cavities/columns 13
  • additional passage channels (bypass channels) 25 are shown in FIG. Loop"
  • FIG. 8 is another exemplary embodiment of the rotors according to the present invention, similar to FIGS. 6 and 7, but here additional microfluidic elements for flow guidance are illustrated.
  • a splitter 26 for dividing a fluid flow between two cavities/chromatography columns 13 is shown.
  • fluid can be fed into the splitter 26 from above, as a result of which the fluid then reaches both adjacent cavities/columns 13 (shown in a V-shape).
  • This can be used, for example, to use different columns (i.e. essentially different stationary phases) at the same time, which can be useful for example, but not only, for screening experiments.
  • a direct outlet is illustrated at 22a, which can be used to split a fluid flow; it is illustrated here that a fluid fed into the inlet 21 partly reaches the upper cavity/column 13 shown horizontally and partly directly to the outlet 22a—this is therefore also a variant of a splitter. It should be noted that these two illustrated microfluidic elements are not the only conceivable/usable ones.
  • splitters 26 illustrated here for dividing into two cavities/columns 13 instead of the splitters 26 illustrated here for dividing into two cavities/columns 13, splitters for dividing into three or four or more cavities/columns 13 are also possible; accordingly, the direct outlet 22a can also be connected to a splitter for splitting into two, three, four or more cavities/columns 13 (and not just one as illustrated).
  • the rotors R of the present invention In addition to being driven in rotation by a toothed belt or gear wheels, the rotors R of the present invention, as illustrated, for example, in FIGS 1 engaging elsewhere than the outer periphery of the rotors R, or rotated by hand, or by (non-toothed) belts, solely with sufficient friction between belt and rotor outer peripheral surface.
  • FIG. 9 shows a further variant according to the invention for a cover plate D, which of course can also be used as a base plate B on the other side of the valve can be arranged.
  • the cover plate/base plate D/B is additionally provided with connections S2 for external fluid connectors in addition to the bores D1 for the introduction of fastening means (as described above).
  • Flow channels 27 are also illustrated in this figure following these connectors S2. Such flow channels can of course also be present in the other embodiments when connectors S2 are placed on cover plate/base plate D/B or stator S (but for the sake of clarity they are not always shown in the figures).
  • connectors S2 and flow channels 27 are partially synonymous within the scope of the present invention (unless explicitly stated otherwise or defined in more detail).
  • two connectors S2 are shown here, this is not the only possibility according to the invention.
  • One, three, four or more connections S2 can just as easily be provided.
  • the exact number or the exact configuration of the cover/bottom plate will of course be selected depending on the rotors used/planned. In such a configuration, the cover D acts as a stator at the same time.
  • top plates/bottom plates D/B with connections S2 are arranged on both sides of a rotor R, in particular as shown in FIGS will be realized; With such an arrangement it is of course also possible to use one of the top plates/bottom plates D/B only as a cover and not to use the connections S2.
  • a valve that has a cover plate D and a base plate B according to FIG. 9 is very flexible in its application.
  • FIG. 10 illustrates the view of a fully assembled valve V according to the present invention, in which two rotors R, with teeth 24 on the outer peripheral edge, are arranged one above the other.
  • a cover D as also shown in FIG. 9, is illustrated at the top in this figure.
  • this can also be a stator S, which has corresponding connections, or the cover D has the function of a stator S in this illustrated, exemplary embodiment—or vice versa.
  • a cover plate D or base plate B is illustrated as the bottommost part in the figure; this can be a top/bottom plate as illustrated in FIG (then the valve of this embodiment would have two equal sides), but it can also be a cover plate as illustrated in Figure lc or a simple round disk with corresponding bores Dl, but care must then be taken that the lowest rotor R is designed in such a way that whose outlets either end in the area of the recess of the cover plate (according to FIG. 1c), or whose outlets are directed upwards and the fluids are then directed upwards again (through the other rotors).
  • this valve V there is also a centering axis Z, with the help of which the individual components can be centered precisely one above the other and which serves as the axis of rotation (of the rotors).
  • FIG. 11 illustrates the view of a fully assembled valve V according to the present invention, in which three rotors R, with teeth 24 on the outer peripheral edge, are arranged one above the other.
  • a cover D as also shown in FIG. 9, is illustrated at the top in this figure. However, this can also be a stator S, which has corresponding connections, or the cover D has the function of a stator S in this illustrated, exemplary embodiment—or vice versa.
  • a cover plate D or base plate B is illustrated as the bottommost part in the figure; this can be a top/bottom plate as illustrated in FIG. 9 (then the valve of this embodiment would have two equal sides), but it can also be a top plate as illustrated in FIG.
  • stator has one or more cavities for fluid transmission in addition to connections for fluid supply and discharge.
  • a zero dead volume injection valve is shown.
  • this valve only one cavity filled with separating material is used in the stator, whereas the rotor furthest away from the stator has cavities, these are (or are) only filled with sample, but do not contain any stationary phase; between these two one or more further rotors are arranged for connection.
  • FIGS. 12 to 15 represent a simplified version, since FIG. 15 in particular would otherwise be too confusing.
  • at least one further rotor belongs between the stator S-OV and the rotor R-OV, the cavities of which (or whose) are completely filled with sample and/or separating material, and which the cavities of the rotor R-OV and Stator connects S-OV with each other, for example outlet S0-0V with the inlet for 13-R-OV.
  • FIG. 12 shows the stator S-OV of the zero-dead-volume injection valve OV, viewed from above (upper part of the figure) and seen from below (lower part of the figure) with corresponding external (microfluidic) connectors (21-OV, 22- OV, 21-OVa, 22-OVa) and an integrated well 13-S-OV, which is preferably a chromatography column.
  • the corresponding further components correspond to those described above.
  • the inlet of the chromatography column is designated with 21-OV and the outlet with the number 22-OV.
  • 21-OVa and 22-OVa denote an inlet and an outlet, which, however, are not connected to the cavity/chromatography column 13-S-OV, but to the channels or channels adjoining them through the stator S-OV lead through to cavities in the rotor S-OV of the zero dead volume injection valve 0V. Also shown are bores S1-0V for fastening, preferably by means of screws, in particular with (self-locking) nuts, for axial compression (fastening/fixing) of the rotor and stator, which function as described above.
  • the lower part of the figure shows the contact surface S14- 0V to the additional rotor(s) R 2 -0V, which lies between S-OV and rotor R-OV, and at the outlet of the cavity/chromatography column 13-S-OV an optional recess 20-0V is again illustrated, in which, for example, a frit (or filter/mesh/grid) can be inserted if this is necessary or desired.
  • a frit or filter/mesh/grid
  • the cavity/chromatography column 13-S-OV can preferably be produced together with the entire stator S-OV using additive manufacturing processes, in particular 3D printing; the shape, depending on what you want, is particularly easy to achieve.
  • Figure 13 shows the rotor R-OV of the zero dead volume injection valve 0V which is furthest away from the stator S-OV, in which cavities 13-R-OV of different sizes, in particular designed as sample loops Ps-OV, are integrated (the additional rotors in between As mentioned, R2-OV are not shown for the sake of clarity).
  • These cavities 13-R-OV/Ps-OV can be curved as shown here, but they can also have any other shape, for example angled or serpentine; however, a curved shape is preferred.
  • These cavities 13-R-0V/Ps-0V preferably differ in terms of their diameter and possibly their curvature (if they are curved), the distance between their cavity ends remains (preferably) constant (the length of the cavity also depends on the radius of curvature and is therefore variable). In this way it is ensured that different quantities or volumes of the samples can be located in the respective cavities 13-R-0V/Ps-0V without the geometry or the construction of the stator S-OV with the respective connection positions being affected of inlets and outlets would have to be changed.
  • cutouts for the arrangement of frits can also optionally be provided here.
  • the cavities 13-R-0V/Ps-0V can preferably be produced together with the entire rotor R-OV using additive manufacturing methods, in particular 3D printing; the shape, depending on what you want, is particularly easy to achieve.
  • the rotor R-OV can have gears 24-R-OV (not shown) and can be rotated by them (e.g. by means of gears or toothed belts).
  • the rotor R-OV can of course also be driven by a motor, for example acting from below, which acts at a different point than the outer circumference of the rotor R-OV, or it can be turned by hand, or by (non-toothed) belts, solely via sufficient friction between the belt and the outer peripheral surface of the rotor.
  • a motor for example acting from below, which acts at a different point than the outer circumference of the rotor R-OV, or it can be turned by hand, or by (non-toothed) belts, solely via sufficient friction between the belt and the outer peripheral surface of the rotor.
  • the cover D-OV of the zero dead volume injection valve 0V shown in FIG. 14 is used for pressing rotor R-OV and stator S-OV (and intermediate rotors R 2 -0V, not shown) with fasteners, and this also has bores D1 accordingly -0V for fasteners, preferably screws, especially with (self-locking) nuts.
  • the cover plate D-OV is shown here as a continuous plate, without a cut-out in the middle.
  • a central recess can also be provided here, into which a motor (directly or indirectly via shafts or the like) can engage can.
  • FIG. 15 shows an oblique plan view of the arrangement of the parts S- 0V, R-OV and D-OV for one of the zero dead volume injection valve 0V - for the sake of clarity the part(s) belonging to the complete valve intermediate rotor(s) R2-OV are not shown for clarity.
  • the lower part shows a top view, with the stator S-OV being shown transparently, so that the position of the cavities/sample loops 13-R-0v/Ps-0V in the rotor R-OV in relation to the inlets and outlets of the stator S -OV, and in particular also in relation to the cavity/chromatography column 13-S-OV in the stator.
  • a sample loop referred to here as Ps-I-OV
  • Ps-I-OV is in the "inject” position, i.e. it is in contact with the cavity/chromatography column 13-S-OV in the stator S-OV.
  • a fluid from the sample loop Ps-I-OV can be introduced (injected) into the cavity/chromatography column 13-S-OV.
  • Another sample loop, referred to here as Ps-L-OV is located in the "Load"- position, meaning that it can be filled with fluid (or, alternatively, fluid can be removed therefrom) through the connectors of the stator; intermediate rotor(s) would be designed to make these precise connections.
  • samples were examined with a valve according to the invention comprising four columns and two rotors.
  • the columns were filled with Cytiva Sephadex G-25 F chromatography material.
  • the aim of the test experiment was to desalt bovine serum albumin (BSA) from ammonium sulfate (AS).
  • BSA bovine serum albumin
  • AS ammonium sulfate
  • a mixture with 2 g/L BSA and 200 mM AS was chosen as the feed solution (sample).
  • the BSA protein should be drawn off in the raffinate port of the system and the AS in the extract.
  • valve according to the invention was used as an SMB valve and an SMB process was carried out in a known manner at room temperature and ambient pressure.
  • the raffinate solution had an AS concentration of 32 mM and a BSA concentration of 1 g/L.
  • the BSA yield is thus 61% with a dilution factor of 50%.
  • 82% of the AS could be depleted.
  • Figure 4 shows the concentrations in all the influent and effluent streams of the system.
  • the concentrations are plotted on the ordinate and the application or withdrawal points of the respective fluid are plotted on the abscissa, with the respective columns and flow velocities specified under the coordinate system.
  • the direction of switching of the columns is indicated and the switching time tschait was 276 seconds.
  • valve of the present invention is very effective.
  • the applicability of the slide valves according to the invention for the operation of a micro-SMB could thus be successfully demonstrated.
  • R3 Device e.g. bore
  • fluid connectors for external material flows e.g. hose connections

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  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • Multiple-Way Valves (AREA)

Abstract

L'invention concerne des distributeurs à tiroir comprenant des éléments coulissants qui comportent plusieurs cavités par l'intermédiaire desquelles des fluides peuvent être acheminés de manière sélective, et des éléments statiques par rapport auxquels s'effectue le déplacement des éléments déplaçables, un kit comprenant lesdits éléments et des utilisations correspondantes.
PCT/EP2023/050147 2022-01-17 2023-01-05 Microsoupape fonctionnelle WO2023135046A1 (fr)

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