DE102022100987A1 - FUNCTIONAL MICROVALVE - Google Patents

Abstract

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.

Description

All documents cited in the present application are fully incorporated by reference into the present disclosure (=incorporated by reference in their entirety).

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.

State of the art

Valves can be used in many different ways and are relevant in many different areas.

There are solutions that use integration of chromatography columns into valves; sometimes called "lab-on-a-valve". In the lab-on-a-valve area, there are applications in which a chromatography column is integrated directly into a central distribution valve. For example, the selected channel, which is connected to a flow source, e.g. syringe pump, and another channel are closed with a frit. A bead reservoir is connected to another channel. The column is packed by first filling the permanently connected channel via the bead reservoir, then switching the valve to the second frited channel and transferring the beads 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. As a result, the beads are deformed and can pass through the gap between the channel wall and the frit. Alternatively, an "in-valve column" can also be used for sample preparation, which is basically a capillary filled with chromatography resin that is connected to a 6-port valve.

There are also solutions involving the integration of columns in microfluidic systems. There are already applications in the field of microfluidics in which chromatography columns are integrated directly into a microfluidic chip. However, these chips usually only contain passive elements. An exception are the lab-on-a-valve systems with integrated columns shown in the previous section. There are also approaches in which stationary chromatography phases or extraction materials are integrated directly into column housings, especially in the field of 3D printing by Housing and stationary phase are manufactured in one pressure. So far, however, these columns have not been further integrated into valves etc., but instead coupled with other components via connectors and capillaries.

There are also solutions within the framework of micro-simulated moving bed chromatography. Simulated Moving Bed Chromatography (SMB) is an established method for the continuous preparative separation of mixtures of substances.

Furthermore, multidimensional chromatography is known. Multidimensional chromatography is a technique that combines different types of chromatography to separate a single sample. There are already hardware variants that contain valves. 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”.

In all processes, the separation performance and peak capacity can theoretically be increased by using orthogonal separation methods compared to a single column. In order to successfully put this into practice, the coupling of the individual columns and the sample transfer from one column to the other is of particularly high relevance, since peak-broadening effects, which can destroy the separation performance of the previous column, must be minimized.

• Im Bereich der Mehrdimensionalen Chromatographie ist es zwar üblich mehrere Säulen in einen mikrofluidischen Chip zu integrieren, die Verbindungen zwischen den Säulen sind allerdings starr und diese können folglich nicht geändert werden. Gleichzeitig werden meistens zusätzliche externe Ventile für den Betrieb benötigt. Bei Lab-on-a-Valve Systemen wurden schon Säulen direkt in einen Ventilkanal integriert, wodurch der Feedstrom zur Säule direkt geändert werden kann. Da jenes System allerdings auf dem Einsatz eines zentralen Verteilventils basiert, können nicht mehrere Säulen im System miteinander verbunden werden. Dazu müsste der Fluidstrom immer zunächst aus dem Ventil heraus und erneut ins Ventil eingeleitet werden.

None of the prior art systems allow multiple columns to be flexibly connected within a microfluidic system:

• In the field of multidimensional chromatography, it is common to integrate several columns into one microfluidic chip, but the connections between the columns are rigid and consequently cannot be changed. At the same time, additional external valves are usually required for operation. With lab-on-a-valve systems, columns have already been integrated directly into a valve channel, which means that the feed flow to the column can be changed directly. However, since that system relies on the use of a central distribution valve, it is not possible to connect several columns in the system. To do this, the fluid flow would always first have to be fed out of the valve and back into the valve.

There is still a need for improvement here with regard to the systems of the prior art.

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.

Further tasks arise for the person skilled in the art from the following description.

These and other objects are solved within the scope of the present invention by the subject matter of the independent claims.
Preferred configurations emerge from the dependent claims and the following description.

In the context of the present invention, the term “comprise” also includes “consisting of”; This means that a corresponding list can contain (= include) other elements in addition to the elements explicitly mentioned, or it can contain exactly these elements (= consist of) (whereby insignificant elements such as screws, markings, etc. are not taken into account).
In the case of relative information such as up, down, left, right or the like, an observer standing upright on the ground in front of the object under discussion is assumed as the reference system within the scope of the present invention.

In the context of the present invention, the expression “and/or” means that both elements mentioned in the context are included individually as well as the combination of the elements mentioned in the context.
In the context of the present invention, the term “fastening elements” is preferably, but not exclusively, understood to mean screws (with nuts), in particular self-locking nuts.

The present invention is based on a simplified connection of several chromatography columns and a reduction in the dead volume between the columns. For this purpose, within the scope of the present invention, 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.
In contrast to the previous state of the art, within the scope of the present invention several 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 one displaceable element (rotor) and at least one static element (stator), as well as optionally further elements. For the sake of simplicity, within the scope of the present invention, the slide valves are often referred to simply as valves in the following.
The term 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 individual elements do not necessarily have to be arranged one above the other in the same order as the component designations I), IIa) ... may suggest, but can take on different sequences (as long as this makes sense from a technical point of view). See below for examples of sequences.

1. a) mindestens eine Kavität mit mindestens zwei Anschlüssen pro Kavität, wobei die Anschlüsse den Durchfluss von Fluiden durch die mindestens eine Kavität ermöglichen, oder
2. b) mindestens eine Kavität ohne eigene Anschlüsse konfiguriert zur Aufnahme von Einsätzen mit mindestens zwei Anschlüssen pro Einsatz, wobei die Anschlüsse den Durchfluss von Fluiden durch die Einsätze ermöglichen, oder
3. c) mindestens eine Kavität mit mindestens zwei Anschlüssen pro Kavität und mindestens eine Kavität ohne eigene Anschlüsse konfiguriert zur Aufnahme von Einsätzen, bevorzugt Einsätzen mit mindestens zwei Anschlüssen pro Einsatz, wobei die Anschlüsse den Durchfluss von Fluiden durch die Einsätze ermöglichen.

The first essential element I) of the slide valves according to the invention comprises at least one displaceable, preferably rotatable, particularly preferably round element (rotor).

1. a) at least one cavity with at least two connections per cavity, the connections allowing fluids to flow through the at least one cavity, or
2. b) at least one unported cavity configured to receive inserts with at least two ports per insert, which ports allow fluid to flow through the inserts, or
3. 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.

The cavities mentioned represent cavities with a defined volume, which in principle can have any shape. However, it often makes sense and is therefore preferred if the individual cavities in the valve according to the invention have the same dimensions in order to ensure the highest possible level of interchangeability of cavity inserts and to enable a 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).

In preferred variants of the present invention, the displaceable element has approximately square cavities in its center 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. For example, 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. Within the scope of the present invention, individual or all, preferably all, cavities can be used. In addition, several (then thinner) inserts (housings), in particular (chromatography) columns, can be arranged per cavity. Furthermore, other symmetries or shapes and also other numbers of cavities without their own connections can be realized; preferred numbers of cavities per displaceable element are three, four, five, six, seven and eight, in particular four. 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). By adapting the shape to the cavities, exact positioning is simplified. The assembled cavity inserts have connections which, in the simplest case, can be bores through which a fluid can flow.

However, other 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.

Although only one cavity can be present, 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.

In connection with the term chromatography column used in the present invention, sometimes abbreviated simply as “column”, it should be pointed out that these columns are not limited in principle to a specific size, but only because they have to fit into the cavities to be used (possibly with residual volume in the cavity), either by itself or using housings in which the columns are inserted. Such columns used in housings are particularly easy to handle, especially if the housings are adapted to the dimensions of the cavities, and can be produced in advance (also with different fillings/stationary phases or the like), so that columns can easily be exchanged (during operation). can become.

If there is only one cavity, this therefore preferably represents a multifunctional unit within the scope of the present invention, in particular by using a plurality of columns, preferably in housings, so that a plurality of cavities ultimately results functionally.

It is therefore particularly preferred within the scope of the present invention if a plurality of chromatography columns of the same or different type (in particular of the same or different stationary phases) are arranged in the valve in the displaceable element.

Within the scope of the present invention, the 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. However, this does not mean that the inlets/outlets or openings cannot (will) not be provided with appropriate devices/equipment.

• - mindestens einen Anschluss für Fluidzuführung, und
• - mindestens einen Anschluss für Fluidabführung.

The second essential element IIa) of the valves according to the present invention comprises at least one static, preferably round, element (stator).

• - 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.

• - mindestens einen Anschluss für Fluidzuführung,
• - mindestens einen Anschluss für Fluidabführung, und
• - ein oder mehrere Kavitäten zur Fluidweiterleitung, bevorzugt ausgestaltet als (Chromatographie-)Säule(n).

In another variant of the present invention, the second essential element IIa) of the valves according to the present invention comprises at least one static, preferably round, element (stator).

• - at least one connection for fluid supply,
• - at least one connection for fluid discharge, and
• - One or more cavities for fluid transfer, preferably designed as (chromatography) column (s).

In this other variant, too, the second element can additionally have one or more connections for fluid transmission.

In the context of the present invention, the static element is arranged one above the other with the displaceable element, so that the static element covers the cavities and connections of the displaceable element, connections of the static and displaceable element being brought into congruence by displacement and thus a fluid flow through the static element into at least one, but in variants also several, cavity(ies) of the displaceable element, through this cavity(ies) and again through another connection or other connections of the static element.

For this purpose, the static and displaceable element are pressed onto one another 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. For this purpose it is preferred if 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.

In variants of the present invention, the connections of the static element, which are used for supplying and removing fluids into the valve, are arranged on top of the static element, ie on the side opposite the 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 at least one displaceable element (rotor) opposite the stator. In this preferred variant, the displaceable element (the rotor) is clamped between the static element and the static cover plate. The cover plate is usually just a kind of "clamping aid" without its own connections or feed-throughs.

In variants, however, the cover plate can be replaced by a second static element. In these variants, 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.

These cover plates may also have ports or, for example, spacers (facing outwards, i.e. away from the valve) or feet.

In a further alternative of the present invention, the second essential element IIb) is a static, preferably round, element (stator) that has no connections for fluid (further) conduction. In this case, 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. In addition, in this case the element IIb) largely corresponds to a cover plate or base plate, which, however, can still optionally be present in each case.

For clarification, it should be pointed out once again that when the valves according to the invention are referred to as upper and lower sides (or similar), this refers to a structure comprising at least displaceable and static elements arranged one above the other, with the displaceable element is considered "below" and the static element as "above"; the arrangements of the remaining elements or plates then follow from this.

Furthermore, the valve according to the invention can optionally also have a, preferably round, static base plate IV), which is on the opposite side of II), in particular IIa) or optionally III) of the stack of I), II), in particular IIa) and optionally III) is arranged include.

According to the invention, these base plates can have the same shape and structure as the cover plates, but they can also have connections or, for example, spacer elements or feet (facing outwards, ie away from the valve). Floor and Cover plates thus (essentially) differ only in that they are arranged on opposite sides of the valve.

In preferred variants, the valves according to the invention can also have devices or preparations V) for automatically driving the displacement of the element I).

In some preferred variants, these are corresponding configurations of the outer peripheral surfaces of the respective rotatable element.

• V)a) aufgeraute oder mit einer die Griffigkeit erhöhenden Beschichtung (tackifyer) versehene Oberflächen der äußeren Umfangsoberfläche des jeweiligen Elements I);
• V)b) eine gezahnte Struktur der äußeren Umfangsoberfläche des jeweiligen Elements I) (Verzahnung),
• V)c) Hebel- bzw. Wellenansatzpunkt(e), Hebel, Griffe an der äußeren Umfangsoberfläche des jeweiligen Elements I);
• V)d) eine gezahnte Struktur der inneren Umfangsoberfläche einer (mittigen) Aussparung des jeweiligen Elements I) (innere Verzahnung),
• V)e) mindestens ein Zahnrad in
  • - der (mittigen) Aussparung des jeweiligen Elements I),
  • - einer Vertiefung in der Unterseite des jeweiligen Elements I), oder
  • - auf der Unterseite des jeweiligen Elements I), wobei dieses Element dann insbesondere das unterste des Ventils ist;
• V)f) Vorrichtung zum Ansatz von angetriebenen Bauteilen, bevorzugt Vertiefungen, in die solche Bauteile eingesetzt werden können und/oder Vorziehungen für den Eingriff von Befestigungsmitteln, bevorzugt Löcher, insbesondere Schraublöcher.

In preferred embodiments of the present invention, 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)b) a toothed structure of the outer peripheral surface of the respective element I) (toothing),
• V)c) lever or shaft attachment point(s), levers, handles on the outer peripheral surface of the respective element I);
• V)d) a toothed structure of the inner peripheral surface of a (central) recess of the respective element I) (internal toothing),
• V)e) at least one gear wheel in
  • - the (central) recess of the respective element I),
  • - a recess in the underside of the respective element I), or
  • - on the underside of the respective element I), this element then being in particular the lowest of the valve;
• 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.

In variants V)a), V)b) and V)c), 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.

In the case of variant V)c), it must be taken into account that the displaceable element can then usually only be displaced by a certain amount; a complete displacement in the sense of a rotation can be implemented, but is often too complex; this variant is accordingly less preferred.

In variants V)d), V)e) and V)f), motors can be permanently installed on or in the valve.

In the event that 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 means or device V)d), it is preferred that the static element II), in particular IIa) (in its middle), and also if present base plate IV), has a recess through which the drive can be brought into engagement with the facilities or devices V)d).

If several displaceable elements (rotors) are combined in a valve according to the invention, these can have the same or different devices or devices V). Of course, it must be taken into account that 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.

Within the scope of the present invention, all displaceable elements can be shifted (rotated) manually, even if they have a facility or device V). It is therefore not absolutely necessary to provide an additional drive. Variant V)c) in particular is well suited for manual shifting.

In further preferred variants, the 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 an advantage, for example, if there is no or too little space for automatic adjustment devices.

In preferred embodiments of the present invention, the relative movement, i.e. the displacement, in particular rotation, of I) in relation to the other elements takes place either manually or with the aid of a drive.

Due to the possibility that the displacement can take place very precisely when using a drive, in particular with electronic control, it is particularly preferred in some embodiments of the present invention to undertake the displacement (rotation) by a drive, in particular an electronically controlled drive.

• - des mindestens einen verschiebbaren Elements

oder, falls mehrere verschiebbaren Elemente vorhanden sind,

• - von mindestens einem verschiebbaren Element

in Deckung gebracht werden können, um selektiv die Überleitung von Fluiden zwischen den Elementen, zu ermöglichen oder zu unterbinden.As also stated/indicated elsewhere in this description, the connections of the at least one static element are arranged in the valves according to the invention in such a way that they are connected to all connections or selected connections

• - The at least one movable element

or, if there are several movable elements,

• - by at least one movable element

can be brought into register to selectively allow or prevent the transfer of fluids between the elements.

In the context of the present invention, displaceable or rotatable refers to the respectively assembled valve, i.e. the respective displaceable element, is displaceable or .rotatable.

In this case, 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. This means that preferably the relative position of the whole element with respect to the valve is not changed, in particular the element is not rotated out of the valve (if the valve itself is not rotationally symmetrical (e.g. oval or rectangular), the composite valve has possibly no such axis of rotation, but a different symmetry group).

However, this does not necessarily mean that the rotatable element must have a round or m-cornered external (circumferential) shape, since the rotation is related to the cavities. Although 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 particularly preferred if, during a rotation of the rotatable element, 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. In this sense, it is also possible according to the invention, for example, to combine 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 indicated, it is possible in preferred variants of the present invention to use a plurality of displaceable, in particular rotatable, elements per valve. In further variants of the present invention, these can each or partially be separated from one another by static elements.

In this way, a wide variety of sequences of (displaceable and static) elements can be implemented, resulting in a flexible valve (system) that can be adapted to a wide variety of requirements.

1

RS; DRS; DRSB (einmal R, einmal S)

2

RRRS; DRRRS; DRRRSB (dreimal R, einmal S)

3

RSRS; DRSRS; DRSRSB (alternierend zweimal R und zweimal S; 1 verdoppelt)

4

RSRSRS; DRSRSRS; DRSRSRSB (alternierend dreimal R und dreimal S)

5

RSRRRS; DRSRRRS; DRSRRRSB (1 und 2 kombiniert)

6

RRRSRRRS; DRRRSRRRS; DRRRSRRRSB (2 verdoppelt)

7

RRS; DRRS; DRRSB (zweimal R, einmal S)

8

RRRRS; DRRRRS; DRRRRSB (viermal R, einmal S)

9

RSSRS

10

RSSD; BRSSD

Some examples of sequences included according to the invention, but by no means even approximately all possible ones, are (R=displaceable, in particular rotatable, element, S=static element; D=cover plate; B=base plate; in each case from bottom to top):

1

RS; DRS; DRSB (once R, once S)

2

RRRS; DRRRS; DRRRSB (three times R, once S)

3

RSRS; DRSRS; DRSRSB (alternating twice R and twice S; 1 doubled)

4

RSRSRS; DRSRSRS; DRSRSRSB (alternating three times R and three times S)

5

RSRRRS; DRSRRRS; DRSRRRSB (1 and 2 combined)

6

RRRSRRRS; DRRRSRRRS; DRRRSRRRSB (2 doubled)

7

RRS; DRRS; DRRSB (twice R, once S)

8th

RRRRS; DRRRRS; DRRRRSB (four times R, once S)

9

RSSRS

10

RSSD; BRSSD

According to the invention, 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.

As already mentioned, the valves according to the invention can therefore, in addition to parts such as seals, drive or the like, consist of only a displaceable and static element, or several of these, and optionally additionally comprise a cover and/or base plate.

In preferred variants of the present invention, the components I), II), in particular IIa), III), IV) have a common axis of rotation which lies vertically in the middle of the stack of the elements present, the elements preferably all being round or approximately round , In particular round, are designed. In this context, 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%.

As already described, it is preferred in some variants according to the invention that, in addition to I), IIa) and III) or IV), or I), III) and IV) are also present.

In some variants according to the invention, it is preferred that IIa) 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.

As already explained, it is essential for these fixed connections that 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.

In preferred embodiments of the present invention, 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).

It is particularly preferred if 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.

If two or more cavities are present in the 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 point, 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.

In preferred embodiments of the present invention, different flow paths are generated by the relative movement of the individual elements in relation to one another. In further preferred embodiments of the present invention, at least one flow path through at least two cavities is changed by the relative movement of the individual valve elements with one another.

In preferred embodiments of the present invention, there is also the possibility of supplying and/or removing fluid streams between the cavities.

In preferred embodiments of the present invention, 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.

In addition, in further preferred embodiments of the present invention, 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.

Furthermore, the cavities in preferred embodiments of the present invention have a cylindrical shape or a geometry that deviates from the cylindrical shape. This means that the cavities can be adapted to the planned application within the scope of the present invention. For example, it is possible to incorporate the cavities directly during production and to determine their shape accordingly, which works particularly well when production is carried out using additive manufacturing techniques, in particular 3D printing. For example, 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. In other embodiments, the cavities, as also described elsewhere in this description, can be designed and shaped in such a way that separately produced (chromatography) columns can be used, optionally with the aid of appropriately adapted and shaped housings.

Accordingly, it is preferred in various embodiments of the invention that individual or all elements I), II), in particular IIa), III), IV), optionally V), are manufactured using additive manufacturing processes, in particular 3D printing.

In the context of the present invention, particularly suitable 3D printing methods are those that work with resin-based starting material, preferably digital light processing (DLP), stereolithography (SL) or poly/multijetting. With these methods, 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.

In preferred embodiments of the present invention, 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 column volume.

In the context of the present invention, in particularly preferred configurations, 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.

In variants of the present invention, 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.

Furthermore, in preferred variants of the present invention, frits/filters/nets/grids, preferably frits, are introduced to hold back the materials, if necessary, either in the cavity or between the individual valve elements.

• i) Schieber-Elemente, bevorzugt rund, (Rotoren) umfassend
• a) mindestens eine, bevorzugt mindestens zwei, Kavität(en) mit mindestens zwei Anschlüssen pro Kavität, wobei die Anschlüsse den Durchfluss von Fluiden durch die mindestens eine Kavität ermöglichen, oder
• b) mindestens eine Kavität ohne eigene Anschlüsse konfiguriert zur Aufnahme von mindestens zwei Einsätzen mit mindestens zwei Anschlüssen pro Einsatz, wobei die Anschlüsse den Durchfluss von Fluiden durch die Einsätze ermöglichen, oder
• c) mindestens eine Kavität mit mindestens zwei Anschlüssen pro Kavität und mindestens eine Kavität ohne eigene Anschlüsse konfiguriert zur Aufnahme von Einsätzen,
• ii) statische Elemente, bevorzugt rund, (Statoren) umfassend
  • - mindestens einen Anschluss für Fluidzuführung, und
  • - mindestens einen Anschluss für Fluidabführung,
  • - optional ein oder mehrere Kavitäten zur Fluidweiterleitung,
  • - optional ein oder mehrere Anschlüsse zur Fluidweiterleitung,
• iii) statische Deckplatten, bevorzugt rund,
• iv) statische Bodenplatten, bevorzugt rund,
• vi) Einsätze, die konfiguriert sind, in die Kavitäten von i)b) eingesetzt zu werden, bevorzugt ausgestaltet als chromatographische Säulen,

wobei die einzelnen Elemente des Kits konfiguriert sind, miteinander zu einem Schieberventil verbunden werden zu können,
die Anschlüsse der statischen Elemente ii) so angeordnet sind, dass sie mit den Anschlüssen oder ausgewählten Anschlüssen der verschiebbaren Elemente i) in Deckung gebracht werden können.A further subject matter of the present invention is also a kit for the production of slide valves, in particular for SMB processes

• i) slide elements, preferably round, (rotors) comprising
• a) at least one, preferably at least two, cavity(ies) with at least two connections per cavity, the connections allowing fluids to flow through the at least one cavity, or
• b) at least one unported cavity configured to receive at least two inserts with at least two ports per insert, the ports allowing fluid to flow through the 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 connection for fluid drainage,
  • - optionally one or more cavities for fluid transfer,
  • - optionally one or more connections for fluid transmission,
• iii) static deck plates, preferably round,
• iv) static floor panels, preferably round,
• vi) inserts configured to be inserted into the wells of i)b), preferably designed as chromatographic columns,

wherein the individual elements of the kit are configured to be able to be connected to one another to form a spool valve,
the connections of the static elements ii) are arranged in such a way that they can be brought into alignment with the connections or selected connections of the displaceable elements i).

The individual elements correspond to the above-described elements of the valve according to the invention as follows: i)=I); ii) = IIa), iii) = III), iv) = IV).

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 with coordinated dimensions, in particular with regard to fastening elements, preferably screws (with nuts), in particular self-locking nuts, and axis of rotation C _m . For this purpose, 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.

Accordingly, 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).
Likewise, the kit includes different sets of top plates and base plates in different sizes and configurations. In variants, the relative number of these can be lower because, for example, several provisions for fastening means can be arranged on a larger cover plate

In preferred configurations, the kits according to the invention can also include motors v), with which the rotor or rotors can be moved. In preferred configurations, the kits according to the invention can also include housings vii), into which the valves can be inserted. In preferred configurations, the kits according to the invention can also include holders viii), which can hold the valves or individual parts.

It should be noted that the 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). In this case, starting from the kit, it is possible and sufficient to select and install one (more) top or bottom plate.

Furthermore, 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, in the food industry, in the (bio)pharmaceutical industry, in the chemical industry, in used in medical diagnostics.

In variants of the present invention, it may be preferable to insert 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.

In preferred embodiments of the present invention, 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.

This variability and ease of maintenance is one of the great advantages of the present invention.

Within the scope of the present invention, 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 in the fluid. In such a case, the interacting materials can be present in the cavities as a slurry or in powder form. Alternatively, however, 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.
For the sake of simplicity, 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.

In particularly preferred configurations of the present invention, 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. In this case, at least two cavities are preferably filled with materials that can interact with the substances flowing into 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 discharging fluid flows between the cavities.

• I) mindestens ein verschiebbares Element umfassend
• a) mindestens zwei Kavitäten mit mindestens zwei Anschlüssen pro Kavität, wobei die Anschlüsse den Durchfluss von Fluiden durch die mindestens eine Kavität ermöglichen, oder
• b) mindestens eine Kavität ohne eigene Anschlüsse konfiguriert zur Aufnahme von mindestens zwei Einsätzen mit mindestens zwei Anschlüssen pro Einsatz, wobei die Anschlüsse den Durchfluss von Fluiden durch die Einsätze ermöglichen, oder
• c) mindestens eine Kavität mit mindestens zwei Anschlüssen pro Kavität und mindestens eine Kavität ohne eigene Anschlüsse konfiguriert zur Aufnahme von Einsätzen,
• IIa) mindestens ein statisches, Element umfassend
  • - mindestens einen Anschluss für Fluidzuführung, und
  • - mindestens einen Anschluss für Fluidabführung,
  • - optional ein oder mehrere Kavitäten zur Fluidweiterleitung,
  • - optional ein oder mehrere Anschlüsse zur Fluidweiterleitung,
• III) optional eine statische Deckplatte, die auf der dem Stator gegenüberliegenden Seite des mindestens einen Rotors angeordnet ist,
• IV) optional eine statische Bodenplatte, die auf der IIa) bzw. gegebenenfalls III) gegenüberliegenden Seite des Stapels aus I), IIa) und gegebenenfalls III) angeordnet ist,
• V) optional Einrichtungen oder Vorbereitungen zum automatischen Antrieb der Verschiebung des Elements I),

wobei die Anschlüsse des mindestens einen statischen Elements so angeordnet sind, dass sie mit allen Anschlüssen oder ausgewählten Anschlüssen des mindestens einen verschiebbaren Elements oder, falls mehrere verschiebbaren Elemente vorhanden sind, von mindestens einem verschiebbaren Element in Deckung gebracht werden können, um selektiv die Überleitung von Fluiden zwischen den Elementen, zu ermöglichen oder zu unterbinden.A preferred variant of the present invention is a slide valve, in particular SMB valve, comprehensive, stacked one above the other,

• I) comprising at least one displaceable element
• a) at least two cavities with at least two connections per cavity, the connections allowing fluids to flow through the at least one cavity, or
• b) at least one unported cavity configured to receive at least two inserts with at least two ports per insert, the ports allowing fluid to flow through the 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,
• IIa) comprising at least one static element
  • - at least one connection for fluid supply, and
  • - at least one connection for fluid drainage,
  • - optionally one or more cavities for fluid transfer,
  • - optionally one or more connections for fluid transmission,
• III) optionally a static cover plate which is arranged on the side of the at least one rotor opposite the stator,
• IV) optionally a static base plate, which is arranged on the IIa) or optionally III) opposite side of the stack of I), IIa) and optionally III),
• V) optional devices or preparations for automatically driving the displacement of the element I),

wherein the terminals of the at least one static element are arranged such that they can be brought into register with all terminals or selected terminals of the at least one displaceable element or, if there are multiple displaceable elements, at least one displaceable element in order to selectively effect the transition of Fluids between the elements to allow or prevent.

In principle, 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.

In further variants, the slide valves according to the invention are used in the field of multi-column chromatography or when chromatographic methods are coupled with other processes.
The slide valves according to the invention are therefore advantageous for all manufacturers and users of (process) analytics in the areas mentioned above.

Last but not least, 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.
Of course, these methods also have the advantages described, which result from the valves and/or kits according to the invention. All or some of the various described embodiments of the valves of the present invention may be used in these methods.

• - Komplexe Schaltungen können einfacher realisiert werden, da Verbindungen zwischen den Säulen ohne eine externe Verschaltung geändert werden können.
• - Kompaktere Bauweise: gerade in Anwendungen, bei denen viele verschiedene Strömungspfade benötigt werden, kann die Anzahl und Größe von Fluidkonnektoren der limitierende Faktor in Bezug auf den System-Footprint darstellen. Durch die Integration mehrerer Komponenten in ein Bauteil entfällt die Notwenigkeit für diese Konnektoren.
• - Das Totvolumen wird verringert: Als logische Konsequenz der ersten beiden Punkte ergibt sich zwangsläufig ein geringeres Totvolumen des Gesamtsystems. Das ist für zahlreiche analytische Verfahren vorteilhaft, da dadurch Dispersionseffekte minimiert werden.
• - Verschiedene Mehrsäulenchromatographiemethoden stellen zum Beispiel die Simulated Moving Bed (SMB) Chromatographie oder die mehrdimensionale Chromatographie dar. Während der Schwerpunkt bei der SMB darauf liegt, eine bestimmte Trennaufgabe kontinuierlich zu lösen, liegt der Fokus bei der mehrdimensionalen Chromatographie darauf, verschiedene Trennmechanismen miteinander zu kombinieren. Außerdem kann als Mehrsäulenchromatographie MCC (multi column chromatography) eine Methodik angewandt werden, bei der eine Probe immer wieder durch baugleiche Säulen (meistens abwechselnd durch zwei) geführt wird, um eine möglichst hohe Trennleistung zu erzielen und Limitierungen, die bei einer einzelnen langen Säule, wie z.B. zu hohe Druckverluste über die Säule, auftreten können, zu umgehen. Für alle diese Verfahren bietet die vorliegende Erfindung eine erhöhte Flexibilität und damit einen größeren Anwendungsbereich im mikrofluidischen Maßstab.

The direct integration of columns and valve into a single assembly within the scope of the present invention results in the following advantages, among others:

• - Complex circuits can be realized more easily because connections between the columns can be changed without external wiring.
• - More compact design: Especially in applications where many different flow paths are required, the number and size of fluid connectors can be the limiting factor in terms of the system footprint. The integration of several components into one component eliminates the need for these connectors.
• - 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.
• - Different multi-column chromatography methods represent, for example, simulated moving bed (SMB) chromatography or multi-dimensional chromatography. While the focus of SMB is on continuously solving a specific separation task, the focus of multi-dimensional chromatography is on combining different separation mechanisms with each other In addition, 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 alternately) in order to achieve the highest possible separation efficiency and limitations that are associated with a single long Column, such as excessive pressure losses across the column, can occur. For all of these methods, the present invention offers increased flexibility and thus a larger area of application on a microfluidic scale.

If, in the description of the slide valves or kits according to the invention, parts or the entirety are marked as “consisting of”, this is to be understood to mean that this refers to the essential components mentioned. This does not exclude self-evident or inherent parts such as piping, valves, screws, housings, gauges, raw material/product reservoirs, etc. that would not substantially change the spool valves or kits.

A particularly preferred embodiment of the slide valves according to the invention is in 1e shown variant.

Another embodiment of the slide valves according to the invention that is particularly preferred according to the invention is that in 10 shown variant.

Another variant embodiment of the slide valves according to the invention that is preferred according to the invention is in 14 shown variant.

A particular advantage of the present invention is that the dead volumes can be significantly reduced compared to the systems of the prior art. In the valve systems of the prior art, on the one hand, 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.

According to the invention, for example, reductions in the dead volume of more than 80% are possible.

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.

The various configurations of the present invention, e.g. - but not exclusively - those of the various dependent claims or individual configurations described in the figures can be combined with one another in any way, provided such combinations do not contradict one another.

The embodiments of the present invention explained in more detail below with reference to the figures represent various preferred embodiments. Many of the features or embodiments shown below in individual figures can be combined with features and embodiments shown in other figures or the rest of the description, in particular where the Features are described accordingly. For example, different rotor configurations shown in the figures can be combined in a valve according to the invention. Moreover, the figures are not to be interpreted as limiting and are not true to scale. Furthermore, the figures do not contain all the features that have the usual devices/plants, but are reduced to the features that are essential for the present invention and its understanding, for example screws, brackets, etc. are not shown or not shown in detail.

The same reference symbols/numbers mean the same or equivalent device parts; for better understanding and clarity, some reference numbers are provided with letters which indicate the location shown (e.g. R for rotor, this feature is then found in the rotor = the displaceable element of the present invention) - however, the numbered elements in each case are the same or equivalent, for example bores D1, R1a, S1, S1-0V.

It should be noted that although the figures show preferred round embodiments of the valves according to the invention, the invention is in no way limited to these round examples. It is of the present invention as well includes that the valves have a polygonal, for example rectangular or for example hexagonal, or for example octagonal, or n-sided basic shape. Furthermore, elliptical basic shapes are also suitable.

The following are in the 1a until 1e exemplary embodiments according to the invention for individual components of a slide valve according to the invention, in particular for SMB, shown with integrated columns. The special feature of this system according to the invention is that the columns are first manufactured individually and then inserted into the rotor ( 1b , 1c ). This allows the columns to be exchanged individually and it is possible to use the columns with the appropriate adapter ( 5 ) can be used 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.

1a shows a stator S of a valve V according to the invention in an oblique top view (above) and in an oblique view from below (lower part of the figure). You can see the bores S1 for pressing the rotor R and stator S by means of suitable fastening elements, preferably screws (with nuts), in particular self-locking nuts. The fluid connectors for external material flows S2 are also shown. For example, 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. In the simplest case, this can be a bore. With the help of this device and the corresponding counterpart (R3) on the rotor R, the two parts can be reliably aligned in relation to each other. 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. In this way, when moving (rotating) the rotor R, fluid is prevented from escaping unintentionally. Accordingly, 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. In this respect, the present invention is not limited to this specific embodiment; rather, another form of seal can also be used. In 1a however, 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. Similar to device S3, 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). Furthermore, 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. These connection channels can be simple bores or curved hollow tubes or the like.

1b shows in the upper part an oblique view from above of a rotor R of a valve V according to the invention. This is denoted as well R9 and is the location where chromatography columns 13 are loaded into the rotor R. In the example shown and its quasi-square design, four places for chromatography columns 13 are therefore available. In this case, individual or all depressions R9 can be used. In addition, several (then thinner) chromatography columns 13 can be arranged per well R9. Furthermore, 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. In the assembled state of the valves V according to the invention, these depressions R9 form cavities 13 together with the rotor R located above them (if several rotors are arranged) or the stator located above them, which cavities 13 can be used per se or, preferably, by using chromatography columns 13 . In this rotor R, bores R1a are also illustrated, which are used to connect to a motor coupling (not shown) for rotating the rotor R (via appropriate fastening means). In the example shown, 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. Also illustrated here are devices (eg bore) for aligning rotor and stator (the stator, not shown here, then has corresponding counterparts; with bores in the rotor, pins or something 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).

In the lower part of 1b is the one above in 1b shown rotor R with (four) individual columns R13 arranged therein, where connection channels R12 to the stator S can be seen. The circle segments outside of the columns R13 shown represent the contact surfaces R5 of the rotor R to the stator S. Finally, a device R3 for aligning the rotor R and the stator S is also labeled R3.

In 1c Examples of columns that can be used according to the invention are shown. R10 shows a single column insert R10 with an optional O-ring cord groove (shown by a double edge line for better pressure stability) at the top of the figure. Such single-column inserts R10 are then inserted into single-column housings R11 (third view from the top), which are preferably adapted to the shape of the cavities (this simplifies exact positioning), and then inserted into the cavities or depressions R9 as assembled single columns R13 become. The assembled individual columns R13 are in the lowest part of the 1c shown, on the left in top view and on the right in bottom view, 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. Finally, as the second view from above, a sectional view through the individual column housing R11 with inserted columns R13 is shown (sectional view along the line CC in the third view from the top). One can clearly see how the connections R12 lead out downwards from the housing R11 and on the other hand are connected to the columns R13 used.

1d shows a cover plate D for the valves V according to the invention. This is attached to the side of the rotor R facing away from the stator S and then by attaching fastening elements, preferably screws (with nuts), in particular self-locking nuts, through the bores D1 and tightening the Fastening elements pulled together and fixed the valve according to the invention (where the rotor R between the stator S and cover plate D remains movable (rotatable)). In this respect, the cover plate D is essentially a plate with bores D1 for receiving the fastening means, it being possible for the cover plate D to 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.

1e shows an assembled valve V according to the invention consisting of stator S, rotor R and cover plate D (in the given order one above the other).

It's in the 1a until 1e not illustrated, but of course a bottom plate B can be placed on the other side of the valve; However, it should be noted here that 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.

In the configurations according to the invention 1a until 1e however, it is generally preferred not to arrange a base plate opposite the cover over the stator.

2 shows an example of the difference between the micro-SMB described in the prior art (designated a) in the top part of the figure) and the corresponding interconnection according to the present invention (designated b) in the bottom part of the figure). In both parts, a static element/stator R is shown at the top and a movable element/rotor R is shown at the bottom. The inventive integration of the columns 13 into the valve V, more precisely into 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. 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). 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; In addition, 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. In further variants of the present invention, sufficiently fine-meshed filters, nets or grids can also be used instead of the frits. In addition, the frits/filters/nets/grids can be exchanged, for example in the event that they become clogged, so that the entire column does not always have to be replaced (which means cost advantages and material savings).

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 sensors QR, two conductivity sensors LR and a valve V according to the invention (screwed together) with four integrated columns 13. Such a structure can (but is not mandatory) be used for investigations such as the example shown below.

4 shows the results obtained in the example described below. In 8th the concentrations in the (inflow and outflow) streams of the system used are shown for this. A more detailed description can be found below in the example.

5 illustrates packing adapters for packing single columns separately. At the top is a plan view showing the pack adapter lid on the left and the main body (or base) on the right. P9 denotes a depression for inserting an individual column and P1 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). pressed, or in another 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. In the second line, 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 P1 and the connectors P2 on the left (not numbered for the sake of clarity). The cuts through the adapter parts along the respective cutting lines AA and BB are then in the bottom row of 4 shown. In the section along AA of the cover, passage openings for fluids are then also shown, which are marked with arrows.

With these adapters it is possible to use the columns independently of the valve according to the invention, whereby a single column can be packed with the adapter or used as a column independent of the valve, depending on whether a frit is used in the feed stream of the adapter.

The following are in the 6 until 10 exemplary embodiments according to the invention of rotor disks in which chromatography columns are integrated ( 6 until 8th ), bottom plates/top plates ( 9 ) and a composite valve illustrated from these rotors and bottom/top plates ( 10 ). Different versions of the rotor disks are shown as examples, which, for example, only have columns ( 6 ), additional bypass channels, which can also be used for direct sample injection (“sample loop”) ( 7 ) or additional microfluidic elements for flow control ( 8th ) contain. Numerous other configurations are conceivable. To compress the rotor discs, for example, the cover and base can be identical ( 9 ); in this case, fluid can be supplied and discharged from both sides (above and below). 10 finally showing the assembled components. The rotor disks can be rotated, for example, via gear wheels or a belt drive. The valves according to the invention enable the flexible connection of different chromatography columns or sample loops without any dead volume.

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. However, 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. In this respect, it is entirely possible and included within the scope of the present invention to produce rotors R with toothing 24 and, if necessary, other devices for motor contacting and then to drive them (e.g. depending on local possibilities) either by gearwheels/belts or by motors acting at a different point . Otherwise, the basic functionality of the rotor R in 6 in principle the ones as they also appear, for example, in 1b is shown. Although here in 6 only three chromatography columns 13 are illustrated, but four or more (or less) are also possible. Furthermore, the columns 13 are only indicated here (dashed); the pillars are designed here as an integral part of the rotor plate (accessible for example via additive manufacturing, in particular 3D printing), but the in 1b rotors shown are provided with a toothing 24 in order to make the drive options more flexible. coming back on 6 , 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 being discharged from the other side. According to the invention, however, it is just as possible to arrange both the inlet 21 and the outlet 22 on one (of the same) surface side. In addition, number 20 illustrates an optional recess into which, if desired, an (inlet) frit 14 can be inserted (cf. also possible positions of frits or filters/nets/grids 2 and description). Finally, 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. However, 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).

7 illustrates an exemplary embodiment of the present invention similar to FIG 6 . In contrast to 6 , which only illustrates cavities/columns 13, are shown in 7 additional passage channels (bypass channels) 25, which can also be used for direct sample injection (“sample loop”), illustrated. With these it is possible, if the rotor R is positioned with them via corresponding fluid receptacles (e.g. sample container, additional columns, eluent collection container etc.), to dose fluids bypassing the cavities/columns 13, for example into the eluent or additional columns. In this way, for example, specific, individual eluted fractions could be provided with an indicator or the like.

8th 12 is another exemplary embodiment of the rotors of the present invention, similar to FIG 6 and 7 , but additional microfluidic elements for flow guidance are illustrated here. On the one hand, a splitter 26 for dividing a fluid flow between two cavities/chromatography columns 13 is shown. As in the lower part of the 8th As can be seen, 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 helpful for example, but not only, for screening experiments. Likewise, 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. For example, it is also possible within the scope of the present invention, 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).

In addition to a rotation drive by toothed belt or gears, the rotors R of the present invention, as for example in the 1b or 6 until 8th are illustrated, can of course also be driven by a motor, for example acting from below, as is the case in example in 1 illustrated, which engages elsewhere than the outer circumference of the rotors R, or rotated by hand, or by (non-toothed) belt, solely by sufficient friction between belt and rotor outer peripheral surface.

In 9 a further variant according to the invention for a cover plate D is shown, which of course can also be arranged as a base plate B on the other side of the valve. In this figure, the cover plate/bottom 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). Depending on the exact design of connectors S2 and flow channels 27, an exact distinction is not always possible, or they can merge continuously - in this respect, as already mentioned in the description, connectors S2 and inlet 21 are partially synonymous within the scope of the present invention (unless explicitly stated otherwise or defined in more detail). Although 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. Moreover, if top plates/bottom plates D/B with connections S2, on both sides of a rotor R, in particular as in FIGS 6 until 8th shown, are arranged, with the valves according to the invention variable flow rates (in terms of amounts, materials, etc.) can be easily implemented; with such an arrangement it is natural It is also possible to use one of the cover plates/base plates D/B only as a cover and not to use the connections S2. In this respect, a valve that has a cover plate D and a base plate B according to 9 exhibits very flexible in its application.

10 12 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 is illustrated as the uppermost part in this figure, as is also shown in 9 is shown. 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. Furthermore, 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 shown in 9 is illustrated (then the valve of this embodiment would have two equal sides), but can also have a cover plate as in 1c illustrated or a simple round disc with corresponding bores D1, but then it must be ensured that the lowest rotor R is designed in such a way that its outlets are either in the area of the recess of the cover plate (according to 1c ) end, or its outlets are directed upwards and the fluids then are directed upwards again (through the other rotors). In the middle of 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).

The following are in the 11 until 14 exemplary embodiments shown for a further, different variant of the invention; In this variant, the stator has one or more cavities for fluid transmission in addition to connections for fluid supply and discharge.

In this variant, a zero dead volume injection valve is shown. In this valve, only one cavity filled with separating material is used in the stator, whereas the rotor has cavities, but these are (or are) only filled with sample, but do not contain any stationary phase. In the field of chromatography, it is of great interest to keep the dead volume between the injection and the column as small as possible so that the sample is injected in a liquid volume that is as compact as possible.

11 shows the stator S-OV of the zero-dead-volume injection valve 0V, seen from above (upper part of the figure) and from below (lower part of the figure) with corresponding external (microfluidic) connectors (21-0V, 22-0V, 21-0Va, 22-0Va) and an integrated cavity 13-S-0V, which is preferably a chromatography column. The corresponding further components correspond to those described above. The inlet of the chromatography column is labeled 21-0V and the outlet is labeled 22-0V. Similarly, 21-0Va and 22-0Va denote an inlet and an outlet, which, however, are not connected to the cavity/chromatography column 13-S-0V, but to the channels or channels adjoining them through the stator S-OV pass 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. In the lower part of the figure, the contact surface S14-0V to the rotor R-OV is shown and at the outlet of the cavity/chromatography column 13-S-0V an optional depression 20-0V is again illustrated, in which, for example, a frit (or filter/ mesh/grid) can be used if necessary or desired. The cavity/chromatography column 13-S-0V can preferably be produced together with the entire stator S-0V using additive manufacturing processes, in particular 3D printing; the shape, depending on what you want, is particularly easy to achieve.

12 shows the rotor R-OV of the zero-dead-volume injection valve OV, in which cavities 13-R-OV of different sizes, designed in particular as sample loops Ps-OV, are integrated. 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. At the respective ends/exit points from the rotor R-OV of the respective cavities 13-R-0V/Ps-0V, cutouts for the arrangement of frits (or filters/nets/grids) can also optionally but preferably be provided again. 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 is depending on your wishes, particularly easy to reach. The rotor R-OV can have teeth 24-R-0V (not shown) and can be rotated by them (e.g. by means of gears or toothed belts). Instead of being driven in rotation by a toothed belt or gear wheels, 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.

the inside 13 The shown cover D-OV of the zero dead volume injection valve 0V is used to press rotor R-OV and stator S-OV with fasteners, correspondingly this also has bores D1-0V for fasteners, preferably screws, in particular with (self-locking) nuts , on. The cover plate D-OV is shown here as a continuous plate, without a cut-out in the middle. Depending on the exact way in which the rotor 0V is to be turned, a central recess can also be provided here, into which a motor can engage (directly or indirectly via shafts or the like). However, if the R-OV rotor has 24-R-0V teeth and this is to be used to rotate, no recess needs to be provided, just as not if the rotor is to be rotated using belts, for example, but only with sufficient friction (or even by hand).

14 shows in the upper part an oblique plan view of the arrangement of all parts S-0V, R-OV and D-OV to one of the zero dead volume injection valve 0V. 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-0V in the stator. You can see that a sample loop, referred to here as Ps-I-0V, is in the "inject" position, i.e. it is in contact with the cavity/chromatography column 13-S-OV in the stator S-OV. This means that a fluid from the sample loop Ps-I-OV can be introduced (injected) into the cavity/chromatography column 13-S-OV. Another sample loop, here designated Ps-L-0V, is in the “Load” position, meaning that it can be filled with fluid (or, alternatively, fluid can be removed from it) through the connectors of the stator.

Example:

The invention will now be further elucidated with reference to the following non-limiting example.
Using an experimental setup with a flow source and process sensors, as also shown in 3 is illustrated, samples were tested with a valve according to the invention comprising four columns. 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). 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.
To carry out the test, the 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.

At the end of the experiment, 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%. At the same time, 82% of the AS could be depleted.

In summary shows 4 the concentrations in all 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 switching direction of the columns is indicated and the switching time t _switch was 276 seconds.

It can be seen from the data that the 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.

Reference List

13

(chromatography) column

14

frit

15

Multi-channel pressure control unit for microfluidics (with pressure control sensors PCR)

16

conductometer

FCR

flow sensors

QR

UV sensors

LR

conductivity sensors

20

(optional) recess for inserting a frit

21

Inlet (of the chromatography column)

22

outlet (of the chromatography column)

22a

direct outlet to split the flow stream

23

center hole

24

Toothing for (belt) drive

25

Through channel for column bypass or sample injection

26

Device (splitter) for splitting a flow stream between (two) chromatography columns

27

flow channel

D

cover plate

D1

Hole for pressing the rotor and stator using fasteners (e.g. screws) / for inserting screws or other fasteners for external pressing

P

pack adapter

P1

Drilling (of the pack adapter) for pressing the individual parts

p2

Connector (of the pack adapter) for external fluid flows

P9

Indentation (of the pack adapter) for inserting a single column

R

rotor

R1a

Connection holes for the motor coupling to turn the rotor

R3

Device (e.g. bore) for aligning rotor and stator

R5

Contact area of assembled rotor (with (four) single columns inserted) to stator

R9

Cavity (of the rotor) for inserting the columns

R10

Use of the single column with optional O-ring (string) groove for better pressure stability

R12

Connection channel to the stator

R13

composite single column

S

stator

S1

Hole (in the stator) for pressing rotor and stator

S2

Fluid connectors for external material flows (e.g. hose connections)

S3

Device (e.g. bore) for aligning rotor and stator

S4

O-ring groove for sealing the contact points of rotor and stator

S5

contact surface to the rotor

S6

(optional) centering aid for rotor and stator

S7

(optional) connecting channel between two columns

V

(composite) valve (with integrated columns)

Z

center axis

0V

Zero Dead Volume Injection Valve

13-0V

cavity (of rotor or stator)

20-0V

Deepening (for fries or similar)

21-0V

Inlet of the 13-0V chromatography column in the S-OV stator

21-0Va

Inlet for sample loop Ps-0V

22-0V

Outlet of the chromatography column 13-0V in the stator S-OV

22-0Va

Outlet for sample loop Ps-0V

D-OV

Cover plate of the zero dead volume injection valve

D1-0V

Holes for fasteners

Ps-0V

Sample loop of the R-OV rotor of the zero dead volume injection valve

Ps-I-0V

Sample loop on the "Inject" position

Ps-L-0V

Sample loop on the "Load" position

R-OV

Zero dead volume injection valve rotor

SO V

Zero dead volume injection valve stator

S1-0V

Holes for fasteners

S14-0V

Contact area to the rotor R-OV of the zero dead volume injection valve

Claims (15)

Slider valve, in particular SMB valve, comprising, stacked one above the other, I) comprising at least one displaceable element a) at least one cavity with at least two connections per cavity, the connections allowing fluids to flow through the at least one cavity, or b) at least one unported cavity configured to receive inserts with at least two ports per insert, which ports allow fluid to flow through the 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, in particular inserts with at least two connections per insert, the connections allowing fluids to flow through the inserts, IIa) comprising at least one static element - at least one connection for fluid supply, and - at least one connection for fluid drainage, - optionally one or more cavities for fluid transfer, - optionally one or more connections for fluid transfer, or IIb) a static element that has no connections for fluid (further) conduction, III) optionally a static cover plate, which is arranged on the side of the at least one displaceable element opposite the static element, IV) optionally a static base plate, which is arranged on the IIa) or optionally III) opposite side of the stack of I), IIa) and optionally III), V) optional devices or preparations for automatically driving the displacement of the element I), wherein the ports of the at least one static element are arranged to interface with all ports or selected ports - The at least one movable element or, if there are several movable elements, - by at least one movable element can be brought under cover to selectively allow or prevent the transfer of fluids between the elements. slide valve after claim 1 , characterized in that - the components I), IIa), III), IV) have a common axis of rotation, which lies vertically in the middle of the stack of the existing elements, with the elements in particular all being round or approximately round in shape, - that , in addition to I) IIa) and III) or IV), or I), III) and IV) are present, and - that IIa) is firmly connected to III) and/or IV) via appropriate fastening means, but intervening( s) I) is still rotatable about the axis of rotation. Gate valve according to one of Claims 1 or 2 , characterized in that the displaceable (rotatable) element I) has at least two cavities, of these at least two cavities, at least two cavities are preferably filled with the same or different materials or inserts containing such materials, the materials being filled with the substances running in the fluid can interact. Gate valve according to one of Claims 1 until 3 , characterized in that different flow paths are generated by the relative movement of the individual elements with one another and preferably at least one flow path is changed by at least two cavities by the relative movement of the individual valve elements with one another. Gate valve according to one of Claims 1 until 4 , characterized in that between the cavities there is the possibility of supplying and/or removing fluid streams. Gate valve according to one of Claims 1 until 5 , characterized in that the cavities are configured in such a way 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 inserted and optionally, - frits for retention of the materials, if necessary, can be used in the cavities and/or at their inlets and/or outlets. Gate valve according to one of Claims 1 until 6 , characterized in that the cavities have a cylindrical shape or the cavities have a geometry deviating from the cylindrical shape. Gate valve according to one of Claims 1 until 7 , characterized in that the cavities have a volume of 10 nL to 10 mL, preferably 1 µL to 1000 µL. Gate valve according to one of Claims 1 until 8th , characterized in that individual or all elements I), IIa), III), IV), optionally V) are manufactured using additive manufacturing processes, in particular 3D printing. Gate valve according to one of Claims 1 until 9 , characterized in that the relative movement, preferably displacement, of I) in relation to the other elements takes place either manually or with the aid of a drive. Kit for manufacturing slide valves, in particular for SMB processes, comprising i) comprising slider elements a) at least one cavity with at least two connections per cavity, the connections allowing fluids to flow through the at least one cavity, or b) at least one unported cavity configured to receive inserts with at least two ports per insert, which ports allow fluid to flow through the 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) comprising static elements - at least one connection for fluid supply, and - at least one connection for fluid drainage, - optionally one or more cavities for fluid transfer, - optionally one or more connections for fluid transmission, iii) static deck plates, iv) static floor panels, vi) inserts configured to be inserted into the wells of i)b), preferably configured as chromatographic columns, wherein the individual elements of the kit are configured to be able to be connected to one another to form a spool valve, the connections of the static elements ii) are arranged in such a way that they can be brought into alignment with the connections or selected connections of the displaceable elements i). kit after claim 11 additionally comprising one or more of the following elements v) motors with which the rotor or rotors can be moved, vii) housings into which the valves can be inserted. viii) include brackets which can hold the valves or individual parts. Use of a slide valve according to one of Claims 1 until 10 or one with a kit according to claim 11 or 12 manufactured slide valve in the field of multi-column chromatography or in the coupling of chromatography methods with other processes. use after Claim 13 , for (bio)chemical analyses, especially those with small sample volumes, preferably for the analysis of environmental samples, in the food industry, in the (bio)pharmaceutical industry, in the chemical industry, in medical diagnostics. Method for carrying out chromatographic investigations, in particular SMB, using or by means of a slide valve according to one of Claims 1 until 10 or with a kit according to any one of Claims 11 or 12 manufactured slide valve.

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