DE102006049347A1 - Formulation station for dosing and mixing of substances, comprises a platform having a module with a supply container for different substances and another module with a sample container for reception of substances, and a dosing station - Google Patents

Abstract

The formulation station (1) for dosing and mixing of substances, comprises a platform having a module with a supply container (11) for different substances and another module with a sample container for reception of substances, a station (01) for dosing of substances into the sample container, a device (04) for mixing of substances in the sample container, a process control unit for controlling and/or regulating of the platform, a coating unit and analysis unit. The mixing device comprises a mixer, a gripping device (02) and a coupling rod. The formulation station (1) for dosing and mixing of substances, comprises a platform having a module with a supply container (11) for different substances and another module with a sample container for reception of substances, a station (01) for dosing of substances into the sample container, a device (04) for mixing of substances in the sample container, a process control unit for controlling and/or regulating of the platform, a coating unit and analysis unit. The mixing device comprises a mixer for contact-free mixing of two substances without the use of stirring tools, a gripping device (02) for inserting and/or exchange of the sample container in and/or from the mixing device and a coupling rod, on which a holder is present and detachably takes up the sample container. The sample container in the mixing device rotates around two rotation axes that are different from one another. The coupling rod is implemented as rotating arm/turnstile or as rotating plate and is arranged, so that the holder is lockable with the sample container. The surface of the free-flowing mixture in the sample container reaches an angle of 0-60[deg] opposite to horizontal plane. The coupling rod and the holder are arranged, so that the sample container with the substances rotates around the rotation axis of the rod and around its own rotation axis. A first drive for a rotation around the axle of the sample container and second drive for a rotation around the axle of the coupling rod are independently adjustable via a process monitoring unit. An independent claim is included for a method for production of substance formulation of two substances.

Description

The The present invention relates to a formulation station for production of substance formulations. The formulation station according to the invention preferably comprises at least one dosing station and at least one mixing device. The mixing device serves in a preferred embodiment for contactless mixing of at least two substances, wherein at least one of these at least two substances has an increased viscosity or is fixed.

The The present invention also relates to a method of formulation of at least two substances, at least one of which is at least two Substances an increased viscosity or solid, and the step of mixing is contactless, i. without the use of stirring tools, carried out becomes.

The Producing new materials, in particular of substance formulations, and the optimization of already known substance formulations, the are composed of a variety of different substances, is great in many areas economic importance. In many applications, for example in the manufacture and cosmetics, pharmaceuticals, plastics, Color mixtures, adhesives, food, etc., it is necessary that a desired Substance formulation by means of suitable metering and mixing methods from a big one Number of different liquid and optionally also solid starting components with high precision within produced, mixed and optionally analyzed can be. Especially when using a variety of substances and / or the production / analysis of a variety of substance formulations It is particularly advantageous if one or all units of the used for this purpose can be automated.

The different liquid and optionally at least partially also solid substances which to dose for the preparation of a (complex) substance formulation and possibly to be mixed, often have different Properties, in particular with regard to their miscibility, density and viscosity. Thus, conventional devices and methods of dosing and for mixing liquids with low viscosity, in particular with the viscosity of water or aqueous Solutions, not for adapted the preparation of such substance formulations, the at least one liquid with elevated viscosity and / or at least one solid component.

In In practice, formulations of low viscosity liquids, especially when these are well miscible with each other, no separate mixing process at all but already "blended" when dosing. Thus, in particular conventional Pipetting machines not for dosing and especially not for mixing liquids increased Viscosity or of substances solid or pasty Consistency.

Formulation platforms for preparing substance formulations are known, for example, from US Pat WO 2004/030819 known. This document describes a work station for handling chemicals and vessels which comprises a combination of a solids dosing device with a dosing device for liquids. The WO 2004/030819 However, it does not show how a formulation station can be designed in which also and precisely substances with increased viscosity can be processed in an automated workflow and, in particular, mixed.

A formulation platform is also from the DE 10 2006 006 288 known. The platform described therein comprises a dosing station which allows to dose liquids with increased viscosity, in particular liquids with a viscosity which is more than one hundred times the viscosity of water. In this case, the metering station according to DE 10 2006 006 288 a high flexibility in terms of the amount and / or type of substances to be dosed and in particular allows combinatorial produce a variety of different substance formulations at a high throughput. However, this document does not teach how a mixing device for formulating substances having an increased viscosity can be integrated into an (automated) workflow.

With regard to mixing means for formulating liquids of increased viscosity, the representative prior art is US Pat DE 11 2004 001 671 T5 called. There is described a stirring / venting device containing a container and a kneaded object, wherein the container simultaneously circulates in an orbit about a center and rotates about its own axis. However, the device mentioned there can not be integrated into an automated workflow, since, for example, the replacement of the mixing container can only be done mechanically by hand and is not involved in a formulation process at all. However, automated loading and unloading of samples is essential for combinatorial formulation of a variety of different samples.

The The present invention avoids or minimizes the shortcomings of the above-mentioned prior art.

A the tasks of the invention is to provide a formulation station that partially or completely can be operated automatically or automatically. simultaneously the formulation station should have a high degree of flexibility with regard to the have to be formulated substances.

The Invention should also make it possible at least two different substances, possibly in different Proportions so in two or more different sample containers to dose and / or to mix that at least two or more different substances or substance formulations prepared in parallel or processed can be. In particular, dosing and mixing should be possible in parallel.

There a variety of tasks of substance formulations are to be produced as possible few cleaning steps will be necessary, as well as possible fast and automatically controllable replacement of components, in particular of sample vessels, be possible.

The or Formulation according to the invention the inventive method should for the high-throughput formulation of liquids with increased viscosity, i.e. one possible enable fast dosing and mixing of liquids with increased viscosity, wherein the mixtures produced should be as homogeneous as possible.

• (i) zumindest eine Plattform, welche zumindest umfaßt: (a) zumindest ein Modul mit zumindest zwei Vorratsgefäßen für zumindest zwei verschiedene Substanzen, sowie (b) zumindest ein Modul mit zumindest einem Probengefäß zur Aufnahme von zumindest zwei Substanzen,
• (ii) eine Dosierstation zum Dosieren von zumindest zwei Substanzen in zumindest ein Probengefäß,
• (iii) eine Mischeinrichtung zum Mischen der zumindest zwei Substanzen in zumindest einem Probengefäß.

The objects mentioned here and further on which the invention is based are achieved by providing a formulation station for dosing and mixing at least two substances, which is preferably of modular construction and comprises at least the following units:

• (i) at least one platform which comprises at least: (a) at least one module with at least two storage vessels for at least two different substances, and (b) at least one module with at least one sample vessel for receiving at least two substances,
• (ii) a dosing station for dosing at least two substances into at least one sample vessel,
• (iii) a mixing device for mixing the at least two substances in at least one sample vessel.

• (iv) zumindest eine Prozesskontrolleinheit zum Steuern und/oder Kontrollieren von zumindest einer der Einheiten (i)–(iii) oder (v), (vi) der Formulierungsstation,
• (v) zumindest eine Beschichtungseinheit (2),
• (vi) zumindest eine Analyseneinheit (3).

According to a preferred embodiment of the present invention, the formulation station according to the invention further comprises at least one of the following further units:

• (iv) at least one process control unit for controlling and / or controlling at least one of the units (i) - (iii) or (v), (vi) of the formulation station,
• (v) at least one coating unit ( 2 )
• (vi) at least one analysis unit ( 3 ).

The The present invention also relates to a method of preparation of substance formulations of at least two substances, wherein preferably the formulation station according to the invention is used. The process preferably comprises (i) a Design step, in which a virtual arrangement ("library") of the substance formulations to be formulated is created, which then, preferably under the control of a process control unit, in a (ii) synthesis step comprising at least one step dosing and at least one step of mixing physically is produced. The Verfabren invention is characterized in that the step of mixing in the synthesis step contactless, i. without the use of stirring tools. Preferably, this step is subject to control and / or control through a process control unit that automates the exchange of sample vessels. The term stirring tool, as used in the sense of the present invention relates on physical Means in a vessel or container, in particular in a sample vessel, are introduced and in direct contact with the formulation to be mixed are located. Here, the mixing effect is achieved by the fact that kinetic energy over physical Means is transferred to the formulation to be mixed. Examples of such physical Means are magnetic stirring fish, powered by a magnetic stirring motor be, stirring spindles or rotors with a mechanical or electric drive motor are provided.

According to one preferred embodiment of Procedures are initially determined by the user in the design step Specify parameters that preferably the type and / or quantity of Concern substances contained in the substance formulations could be or should, or the number of substance formulations to be prepared in total. These parameters are preferably stored in a file of the process control unit stored.

In a preferred embodiment The process control unit can refer to substances for information access that in this or one provided by the user File are stored and preferably information about the respective physical or chemical properties of the selected substances.

Such a virtual design in advance of the actual physical formulation is advantageous Because the process control unit thereby automatically predetermines boundary conditions for the actual formulation step and can preclude impractical designs, for example those formulation designs that would result in a viscosity or amount of substance formulation for which the device is not designed.

• (a) einen Designschritt, in welchem eine virtuelle Anordnung der zu formulierenden Substanzformulierungen erstellt wird sowie hieran anschließend
• (b) einem Syntheseschritt umfassend zumindest einen Schritt des Dosierens in einer Dosierstation und zumindest einen Schritt des Mischens in einer Mischeinrichtung, gemäß welchem die Substanzformulierungen physikalisch erzeugt werden,

wobei der Schritt des Mischens der zumindest zwei Substanzen kontaktlos, d.h. ohne Verwendung von Rührwerkzeugen, durchgeführt wird.The following embodiments of the method according to the invention are preferred:
Preferred is a method for producing at least one substance formulation from at least two substances, comprising at least the two following steps:

• (A) a design step in which a virtual arrangement of the substance formulations to be formulated is created and then thereafter
• (b) a synthesis step comprising at least one step of dosing in a dosing station and at least one step of mixing in a mixing device according to which the substance formulations are physically generated,

wherein the step of mixing the at least two substances is carried out without contact, ie without the use of stirring tools.

there it is preferred that steps (a) and (b) are under control or Triggered by a process control unit, which the Information from step (a) in step (b) to a dosing station and passes a mixing device.

Further it is preferred that the viscosity of at least one of the dosing and substance to be mixed higher is than 5 mPa · s, preferably higher as 50 mPa · s.

The inventive formulation station and the inventive method are preferably used to make a variety of different Substance formulations used and are preferably used the optimization of substance formulations and the discovery of new substance formulations with desired target properties or with new properties. The formulation station may be in communication operated with appropriate software both as a research platform as well as a serial synthesis platform.

According to the present Invention should be at least a substance formulation of at least two Substances are obtained. A substance formulation will too referred to as a "sample", a substance also as a "component" (the sample). Regarding the Nature of the substances are not limited as long as the sample vessel is chosen that it can absorb and hold the substances.

Brief description of the figures:

1 shows a formulation station ( 1 ) with a dosing station ( 01 ) with eight dosing modules ( 11 ), a balance ( 13 ) and with a mixing device ( 04 ) Is provided. In addition, the unit has a module ( 05 ) for sample vessels and a device for closing (sample) vessels ( 03 ). The sample containers are placed in position by means of a positioning unit ( 02 ) automatically transported to the individual points of the station.

2 shows a coating unit ( 2 ) with a device ( 06 ) for the transfer of liquid from sample vessels and a substrate coating device ( 75 ) and a coating knife ( 71 ) coating arm ( 07 ). In addition, a storage warehouse with substrates ( 72 ) and with exchange blades ( 73 ) as well as a cleaning station ( 74 ) intended.

3a shows a schematic representation of a double rotary mixer ( 3A ) with pendulum tilting device, consisting of tilting bracket ( 44 ) and pendulum weight ( 46 ). In a preferred embodiment, the rotation about the vessel axis by means of a compressed air driven rotor ( 45 ) reached.

3b Schematic representation of a double rotary mixer ( 3B ) at rest or during rotation of the sample vessel about its own axis. Also shown are rotary feedthroughs ( 48 ), Compressed air line ( 49 ) and bottom plate ( 50 ).

3c shows a schematic representation of the double rotary mixer ( 3C ) during the rotation of the turntable about the axis of rotation of the turntable. The drive for the rotation of the sample vessel can be switched on or off about its own axis. Also shown are the drive shaft ( 51 ) for the turntable and the associated toothed belt ( 52 ).

4 Schematic representation of the program flow from the library design to the preparation of a substance formulation in connection with an integrated software system.

With respect to the platform of the dosing station there are no restrictions, except that at least one module with at least two storage vessels must be present on or in this and at least one module with at least one sample vessel, preferably with at least two sample vessels. Preferably, the platform also comprises a closure device ( 03 ) for closing vessels, preferably of sample vessels.

According to a preferred embodiment, the dosing station ( 01 ) at least one metering module ( 4 ).

In a preferred embodiment of the present invention, the dosing station ( 01 ) for metering of liquids and pasty substances, a pressure metering device, as described for example in the application DE 10 2006 006 288.4 (with filing date of 10.02.2006) is described. The relevant passages of said application is explicitly referred to in this context.

According to a preferred embodiment, the dosing station ( 01 ) at least one metering module comprising at least one storage container ( 11 ) with substance to be metered to which a dosing head ( 4 ) connected. The dosing head preferably has a closure tip provided with a closure valve, which can be opened and closed by the process control unit in a controlled manner. The closure valve on the dosing head is preferably a valve which is pneumatically controlled. In an alternative embodiment of the invention, the closure valve is a piezoelectrically actuated valve.

In a preferred embodiment, the dosing station ( 01 ) modular and comprises at least two metering modules, preferably at least two Druckdosiermodule, and at least one scale ( 13 ), preferably a precision balance. The balance is preferably decoupled from the mixing device such that the function of the balance is not impaired by possible vibrations of the mixing device.

Preferably there are means by which the metering modules or the contents of the storage container can be heated and / or stirred. These heating and / or stirring means ( 12 ) are used when the viscosity of the substances to be dosed at room temperature is too high to transfer the substances by means of pressure dosing in sample vessels. By stirring the reservoir, it is furthermore possible to prevent parts of the substances to be metered from settling in the storage vessel, which is possible, for example, in the case of suspensions or emulsions. The stirring thus leads to a homogenization of the substances to be metered or ensures that they remain in a homogeneous state. It is also conceivable to cool the metering modules if the substances to be metered should be unstable at room temperature.

In a further preferred embodiment has the dosing station according to the invention via a Sensor device by means of which the position and / or positioning the dosing heads or metering tips absolute and / or relative to the sample vessel and / or can be determined to the scale and / or a cover housing. Preferably communicates the sensor device with the central process control unit, i.e. is controlled by this and / or driven.

In a preferred embodiment, it is possible by means of the device according to the invention to also meter in solids into the sample vessels. In this regard, the appropriate disclosure of the WO 2004/030819 directed.

According to one preferred embodiment the dosing station also and especially for the dosage of substances increased Viscosity. The viscosities the substances to be dosed are in a range of 0.5 to 10,000 Pa · s. It is not excluded to dose substances whose Viskoität above 10,000 Pa · s lies. It is preferred that at least one of the dosed substances a liquid with elevated Viscosity is. "Liquids with elevated Viscosity "within the meaning of the present Invention have a viscosity, the higher is the viscosity of water (at the respective processing temperature), preferably higher than 5 mPa.s, more preferably higher than 50 mPa.s, more preferably higher as 100 mPa · s, continue preferably higher than 500 mPa.s, more preferably higher as 1 Pa · s. Non-Newtonian fluids, Dispersions, suspensions, oils, Lubricants and pastes are also "liquids" in the context of the present invention.

According to one preferred embodiment of present invention is the dosing also and straight to the Dosing of small amounts of substance suitable. As "small amounts of substance" are quantities below 1 g, preferably less than 0.5 g, more preferably less than 0.1 g, more preferably less than 0.01 g, more preferably less than 1 mg.

According to a preferred embodiment, the mixing device ( 04 ) at least one of the following components, which are preferably of modular design and are thus exchangeable or replaceable independently of one another: (i) at least one mixer for non-contact mixing of at least two substances and / or (ii) at least one gripping device ( 02 ) for insertion and / or replacement of at least one sample vessel, which is located in the mixer.

In a preferred embodiment, the mixing device ( 04 ) of the formulation station according to the invention no stirring tools ("contactless mixing"). This is particularly relevant for the processing of liquids of increased viscosity and / or solids of technical relevance, as a result, the cleaning step and / or the step of exchanging stirrers is superfluous, or a mutual contamination of substance formulations is avoided. Another disadvantage with the use of agitators is that when removing the stirring tool often comes to an uncontrolled substance discharge from the respective sample vessel. This can lead to inaccuracies, in particular in the handling of very small amounts of sample, which are usually compensated by the fact that the substance quantities are increased. Furthermore, when removing the agitating tool, it is possible that individual components of the substance formulation, which may better adhere to the agitating tool than others, are unintentionally removed from the substance formulation, thereby changing the composition of the mixture. However, the use of larger amounts of sample is not preferred from an economic point of view. Stirring tools have the further disadvantage that the abrasion of the same, ie their impurities, can get into the substance formulation.

The Possibility, without stirring tools is of particular importance in the present case since it allows that a largely automated workflow is achieved can, as he particularly in connection with the combinatorial formulation a variety of substances is sought.

Corresponding is the Verfabren invention in particular, characterized in that the process of mixing of at least two substances in a sample vessel without contact, i. without use of stirring tools, he follows.

in the Meaning of the present formulation platform and within the meaning of the present Method, it is preferred that by at least one rotational movement centrifugal forces on the located in the sample container be applied to mixing substances, so that these substances are mixed, preferably towards Homogeneity. Accordingly, it is with respect to the formulation station according to the invention preferred that the sample vessel in the Mixing device rotates at least about a rotation axis.

Farther it is preferred that for this purpose two overlapping rotational movements be performed around two different rotation centers.

Further it is preferred that the surface of the fluid, viscous or liquid Substance mixture in the sample vessel during the Mixing process is not arranged parallel to the horizontal, but at an angle between 0 ° and 90 ° thereto, i. that the sample vessel is tilted is. The angle is preferably from 20 ° to 60 °, more preferably from 30 ° to 50 °.

Further It is preferred that this angle is stepless and automated adjusted and / or controlled, preferably by a process control unit. It is particularly preferred that this angle at the time dosing the substances into the sample vessel and / or at the time of Insertion and / or removal of the sample vessel into / out the mixing device is 0 ° or as close to 0 °, that automated dosing, inserting or removing possible or promoted becomes.

According to one preferred embodiment of Mixing device without stirring tools ("contactless mixer") includes these a Ausstellglied, on which there is a holder which at least one sample vessel detachable and can record automatically controllable. It is preferred that the Ausstellglied can rotate about a rotation axis. Regarding the Design of the Ausstellgliedes are no restrictions, as long as this the rotation of the sample vessel about an axis of rotation allows. Preferably, the Ausstellglied is as Dreharm / turnstile or as Turntable realized.

Further, it is preferred that the Ausstellglied is set up so that it can tilt the holder with sample vessel so that the surface of the flowable mixture in the sample vessel at an angle of 0 ° and 90 °, preferably from 20 ° -60 °, more preferably from 30 ° -50 ° towards the horizontal. This angle is preferably controlled, adjusted and optionally controlled by the process control unit. By variably setting this "mixing angle", a multiplicity of different substance formulations can be homogeneously mixed as effectively as possible in the shortest possible time using the same formulation station. In this case, higher-viscous, poorly homogenizable mixtures are preferably mixed at relatively large angles (ie with the occurrence of stronger centrifugal forces) than low-viscosity, readily miscible mixtures. It is preferred that the sample vessel has a tilted position during the rotation about the large axis of rotation, as this, inter alia, also prevents the substance formulation or constituents of the substance formulation from escaping or adhering in the region of the vessel closure. The selection of the tilt angle depends essentially on the respectively selected rotational speed for the large axis of rotation. In a preferred embodiment, the tilt angle at the respectively selected rotational speed, which is given in revolutions per minute, automa specified by the process control unit.

In this regard is it is preferred that the axis of rotation of the Ausstellgliedes, ie the axis about which the Ausstellglied rotates, during the tilting process unchanged remains. In one embodiment the Ausstellglied is an at least two-part rotary arm, which with a joint-like device, preferably a joint, is over which of these angles can be adjusted.

Further Preferably, the sample vessel (with the at least two to mixing substances) in addition for rotation of the Ausstellgliedes about its own axis of rotation. The own rotation axis is preferably the axis of symmetry the sample vessel, for example in a cylindrical Sample vessel the cylinder axis. This means preferably that the substances to be mixed containing sample vessel during the mixing process simultaneously rotated both about the central axis of the sample vessel as well, preferably on a circular path or an ellipsoid, around the center or contact point, ie the axis of rotation of the Ausstellgliedes ("double rotation"). Such a mixer is in the context of the present invention as a double rotary mixer designated. The two directions of rotation can be the same or opposite be.

there it is preferable that the area, which is larger than the Ausstellglied in a 360 ° rotation as the corresponding area, which the rotating sample vessel during the same rotation passes over. In this case, the axis of rotation of the Ausstellgliedes is preferably except for Vessel axis or Symmetry axis of the sample vessel.

To the It is also possible to mix that the sample vessel at the same time before or after undergoing a shaking movement, thus subject to a force acting in all three spatial effects force vector.

It is according to the invention preferred that the rotational speeds of the two rotations independently can be adjusted as well automatically and centrally via the process control unit is detected and / or controlled. Thus, you can with the same formulation station a variety of different Substance formulations in as possible as soon as possible effectively mixed homogeneously. This contributes to a particularly variable Use of the mixer contributes, because of a very wide range of components to be mixed in be flexibly mixed with the same mixer. Especially can also very difficult to mix components by choosing suitable ones Mixing conditions mixed into homogeneous pastes within short mixing times or be kneaded.

In a preferred embodiment, the sample container is rotated ( "minor" axis of rotation) at a speed of up to 5000 min ^-1, preferably of up to 3000 min ^-1, more preferably of up to 1000 min ^-1. For the "large" rotation axis (Ausstellglied) are up to 10,000 min ^-1 preferred, more preferably to 5,000 min ^-1 , more preferably to 2,000 min ^-1 . The number of revolutions of the major axis is preferably greater than the number of revolutions of the small one.

Farther advantageous in the use of a non-contact double rotary mixer It is also that small amounts of components to be mixed extremely effective can be mixed with each other.

The Arrangement Ausstellglied - holder - sample vessel corresponds preferably an arrangement such as that in a centrifuge place. Accordingly, it is further preferred that means provide which during the the rotation of a sample vessel, if appropriate reduce or prevent the unbalance on the actuator. For this purpose, a second sample vessel may be provided symmetrically on the opposite side to the sample vessel be. It is preferred that the imbalance with the help of a on the Process control unit to be controlled or adjustable counterweight is balanced or that the opposite sample vessel exactly so filled is that no imbalance occurs, or that this is minimized. The adjustment of the counterweight may preferably via a Servomotor or a stepper motor are made, these directly or via Sensors in connection with the process control unit stand.

It is further preferred that the mixer at least two Ausstellglieder (preferably rotating arms), which independently rotate next to each other about the same axis of rotation and in each case at least one sample vessel with holder include.

In a preferred embodiment, in the 3a - 3c is illustrated, the Ausstellglied is a turntable ( 41 ), wherein preferably in the center of the turntable, the rotation axis (rotation axis) is located. It is preferred that the sample vessel ( 63 ' ) in a holder ( 43 ) with a pendulum weight ( 46 ) and at a tilting bracket ( 44 ) is tiltably mounted.

This causes that when the turntable (see 3b ) the sample vessel perpendicular to the horizontal and easy, preferably with the aid of a gripper, from the holder ( 43 ) can be removed or used in this. In this position, the surface of the liquid in the sample vessel has an angle of 0 ° (± tolerances) to the horizontal, that is, is substantially parallel to the horizontal. On rotation of the turntable on the other hand (see 3a and 3c ) drives the centrifugal force of the pendulum weight ( 46 ) to the outside and causes a tilting of the sample vessel. The tilt angle can be adjusted by the rotational speed of the turntable. Preferably, the drive of the turntable ( 41 ) via the drive shaft ( 51 ) and the toothed belt ( 52 ).

In a preferred embodiment, the sample vessel ( 63 ' ) in the holder ( 43 ) simultaneously with the rotation of the turntable by a rotor operated by compressed air ( 45 ) rotated around its own vessel axis. In a further preferred embodiment, one through the unit ( 46 ) - ( 45 ) - ( 44 ) - ( 43 ) - ( 63 ' ) possibly caused imbalance of the turntable by an adjustable balance weight ( 42 ) balanced. For adjustment is preferably a rail ( 42 ' ) and a controllable by the process control unit motor.

The following embodiments of the mixing device ( 04 ) are within the meaning of the formulation station according to the invention ( 1 A formulation station is preferred in which the sample vessel ( 63 ) in the mixing device ( 04 ) is rotated about at least one axis of rotation, preferably about two axes of rotation which are different from each other.

A formulation station is preferred, in which the mixing device has at least one release member ( 41 ), on which a holder ( 43 ), which at least one sample vessel ( 63 ) can absorb releasably. The Ausstellglied is preferably realized as a rotary arm or as a turntable.

Further preferably, the Ausstellglied ( 41 ) so that the holder ( 43 ) with sample vessel ( 63 ) is tiltable, preferably so that the surface of the flowable mixture in the sample vessel reaches an angle of 0 ° to 60 ° from the horizontal.

Further preferably, the Ausstellglied ( 41 ) and the bracket ( 43 ) is designed so that the sample vessel ( 63 ) can rotate with the at least two substances to be mixed both about the axis of rotation of the Ausstellgliedes and about its own axis of rotation.

Further, it is preferred that the drive for a rotation about the axis of the sample vessel ( 63 ) and the drive for a rotation about the axis of the Ausstellglieds are independent of each other, and the two rotations are independently adjustable, preferably automatically via the process control unit.

To the Driving the rotor of the centrifuge, the tilting device or the Gripper can preferably the following means are used: pneumatic motor, the Depending on the design, it is equipped with and without a toothed belt; Servomotors, wherein the servomotor can be designed with a toothed belt or driven directly can be, i. can represent a torque motor.

In a further preferred embodiment is the formulation station or is single functional Assembly units of the formulation station equipped with sensors that a precise position detection of the turntable or the Enable exhibitor to the one possible Detect imbalance of the counterweight to the holder on the turntable, which is then automatically corrected by the process control and / or the monitor the individual grippers.

In a preferred embodiment the present invention, the transport of each object, but in particular the transport of sample vessels and / or sample arrays caused by a unit for positioning. A unit for positioning is preferably adapted to an object from a point in space to move to another point in the room. The unit for positioning may also be suitable for two or more positioning steps simultaneously or in succession.

A Unit for positioning can for Displacements in two ("x-y positioning unit") or in three ("x-y-z positioning unit") spatial directions be suitable. The movements of the unit for positioning can be linear or circular be composed of sequences of such movements.

A preferred unit for positioning is a gripping device ("gripper"), preferably a positioning robot with gripper arm ( 21 ). It is further preferred if the unit for positioning comprises a Knickarm- or a Scara robot with gripper. The gripper can preferably be controlled electrically or pneumatically.

With the help of the gripping device, the same but also different sample vessels can be moved from their stands, for example a balance or a module with at least one sample vessel. The gripping device is also suitable in a preferred embodiment, sample containers in the holder of the mixing device introduce or use there.

In a preferred embodiment the gripping device is designed so that this both in terms of their Form as well as re different in size Objects, in particular different dosing modules and / or different Sample containers, handle can. If necessary, it may be necessary and / or useful to Gripper of a gripping device to exchange between two operations, for example, during the transition from the operation "insert a particularly large one Dosing module "on a predetermined place to "exchange a particularly small sample vessel in the mixing device ".

According to one preferred embodiment, the gripper has a Position detection to determine where a particular object, which is to be gripped, for example, where is the sample vessel to be replaced is located.

In a further preferred embodiment The present invention is a gripping device (gripper) also as a holder for the sample vessel in the Mixing device. In this case, this gripper is preferably on the outer end, i.e. the end remote from the axis of rotation, the Ausstellgliedes (Rotary arm or turntable) attached and serves to the sample vessel during the mixing process so fix it around its axis and / or around the axis of rotation of the Ausstellgliedes can rotate, as well as can be tilted, optionally at angles of 90 ° -45 ° to the horizontal (corresponding to an angle of 0 ° -45 ° of the liquid surface against the horizontal). This gripper (holder) is preferably firmly connected to the Ausstellglied and serves to hold sample containers and preferably does not serve to sample containers (or other objects) through the Room to move.

In a preferred embodiment becomes the basic functionality a gripper (regardless of whether it is used to move objects through the gripper) Space or for holding a sample vessel) by at least two, preferably at least three or four vertically positioned holding means determined, preferably by pneumatic force Clamp object. As "holding means" can be any means be used, which exerts or transmits a force on the object, so that the object is grasped so firmly that it is in all three spatial directions be moved or held firmly in a predetermined position can. In a preferred embodiment the holding means is designed as a pin or jaw. Farther it is preferred that the gripper device has four holding means, wherein two holding means are diametrically opposed and the holding means are concentric with each other and / or away from each other.

The Holding means are preferably over two linearly aligned slide rail pairs concentrically guided and by means of two adjusting spindles and threaded bushes over one adjusted electrical or pneumatic drive. Here are the two pairs of slides preferably at right angles to each other arranged. By adjusting the spindles, the gripper radius the pins are arbitrarily adjusted in a preferred embodiment. This makes it possible also different sample vessels, too while one and the same workflow to integrate into the system. This will become the parent Demand for the greatest possible flexibility enough done.

In a preferred embodiment a pneumatic clamping is chosen, whereby vessel size tolerances and / or asymmetries compensated and a non-positive connection between Object and the holding means is produced. For the (preferred) case that the holding means are realized as pins or jaws, are the Pins or jaws provided with single or with several grooves, a form-fitting Support connection.

In a preferred embodiment The holding means are arranged so that they form a complementary clamping with the geometry of the object to be clamped, in particular the Sample jar, allow.

The Holding means are preferably at least in the area which at least partially with an object, in particular the sample vessel in contact can, coated with a material that increases the static friction, to thereby strengthen the holding power.

In a preferred embodiment has the gripper device over a sensor which monitors the clamping process. As such a sensor For example, a proximity switch be used. The task of the sensors is, when approaching an object to a specific, predefined value, a signal to send out, which makes it possible abort, slow down or reverse the movement process. mechanical, electrical, magnetic, acoustic, ultrasound-based, optical, IR-optical and other sensors are for detection an approach possible.

The fact that the mixing device according to the present invention due to their modular design largely or completely auto can be integrated and integrated into a computer-controlled formulation station, it is also possible to prepare substance formulations according to complex recipe specifications. These complex formulations contain, for example, intermediate mixing steps, which are followed by further dosing steps and mixing steps. In particular, it is also possible to carry out dosing and mixing operations in parallel.

During the Production of successive substance formulations, it is possible that the type of sample treatment including the choice of mixing parameters between successive samples in a flexible manner within a big one Variation width changed can be, with the individual treatment steps of the process control unit recorded and stored in a structured form or get saved. It is preferred that the structured Form stored information stored as records in a database or saved.

• • Modul (62) zur Aufnahme von Probengefäßen (63)
• • Vorrichtung zum Transfer von Flüssigkeiten (06)
• • Beschichtungsarm (07) mit Halterung für eine Beschichtungsrakel (71)
• • Modul mit unbehandelten Substraten (72)
• • Austauschstation (73) und Reinigungsstation (74) für Rakeln
• • Substratbeschichtungsvorrichtung (75)
• • Ablageplätze für beschichtete Substrate (76).

According to a preferred embodiment, the formulation station comprises a coating unit ( 2 ) with at least one of the following components, which preferably have a modular structure and thus can be replaced or replaced independently of each other:

• • module ( 62 ) for receiving sample containers ( 63 )
• • Device for transferring liquids ( 06 )
• • coating arm ( 07 ) with a holder for a coating blade ( 71 )
• Module with untreated substrates ( 72 )
• • exchange station ( 73 ) and cleaning station ( 74 ) for doctoring
• Substrate coating device ( 75 )
• • Storage spaces for coated substrates ( 76 ).

• • (Farb-)Messanalysator
• • Robotervorrichtung
• • Einrichtung zur Zufuhr von beschichteten Substraten.

According to a further preferred embodiment, the formulation station comprises an analysis unit ( 3 ), preferably a color analysis unit, with at least one of the following components, which preferably have a modular structure and thus can be exchanged or replaced independently of one another:

• • (color) measurement analyzer
• • robot device
• • Device for feeding coated substrates.

According to one preferred embodiment of present invention is the central process control unit, superior to the modular units and includes at least one means of data management, data analysis and for the visualization of measured data.

According to one preferred embodiment of inventive method Creates the process control unit as specified by the user a library of substance formulations of different composition, which are to be made from predetermined components / substances. The Compilation of the library can be done on the random selection consist of components and quantities or on the application of systematic Selection methods are based. The application of systematic selection methods for the definition of the substance formulations to be prepared is in As a rule, this is the experimental parameter space be better represented for a given number of samples to be produced can be considered by accident selected Rehearse.

In a preferred embodiment of the method according to the invention, a virtual library of the desired substance formulations is generated in a design step prior to the actual formulation. These are preferably arranged in a (virtual) array, which in the realization phase corresponds to a substrate, for example a plate, on which the various substance formulations are arranged (sample array). In 4 This virtual library is called an "order library".

The obtained in the context of the design step of the inventive method virtual Library design is in a preferred embodiment following the Design phase taken from the process control unit and the physical Preparation of a template with sample arrays to the formulation station forwarded. The template with sample array represents the physical objectively Illustration of virtual library design. The formulation platform is able to partially or fully automatically select the given sample array manufacture, preferably controlled by the process control unit.

A sample vessel according to the present invention is adapted to receive at least one of the dosed liquids. The sample vessel is also suitable for receiving an optionally metered solid. With regard to the material and the design of the sample vessel, there are no restrictions. In particular, for the purposes of the present invention, the sample vessels need not all be of the same shape, but rather differently shaped or differently sized sample vessels may be used. With respect to the material from which the sample vessel is made, there are no limitations, as long as the material is chemically and physically compatible with both the dosed substances and, in particular, for the mixing of two if necessary or more substances occurring chemical reactions or temperature changes due to released enthalpy of mixing is suitable.

Prefers are the sample containers on a module a platform arranged. The module preferably comprises two or more sample containers. Lies a variety of sample vessels, so these are preferably in an array, more preferably in one Matrix, arranged. Such an array can be used, for example, as a bundle vessel or bundle insert be realized.

individual Sample containers - or also Sample arrays - become preferably over an identification means - for example by barcode or chip marking - by the process control unit captured, and can thus be identified at any time of the procedure. Also the Position of the Ausstellgliedes and / or the sample vessel thereon is preferred identifiable, for example via a predetermined stop position.

In a preferred embodiment of the method according to the invention, it is possible for individual or all sample vessels to be closed with closures in order to preclude changes in the composition of the mixture, as may occur, for example, by evaporation of volatile substances or by the absorption of water in the case of hygroscopic substances. This is preferably done in a device belonging to the formulation device for closing vessels ( 03 ) ("capping unit").

at the design of the vascular occlusions for removal of substances or substance formulations consisting of closed vessels - depending on Type of application - the possibility a use of resealable vascular occlusions. In an alternative Embodiment, the Vessels too with closures be provided, each containing or include a septum, which pierced with suitable hollow needles for sampling or sample dosing can be. Suitable septa can For example, made of silicone, rubber or other elastomers.

In a preferred embodiment has the formulation station over Means of monitoring the manufacturing process of each individual substance formulation. By this with respect to each individual substance formulation related monitoring For example, it is in a preferred step of the method according to the invention possible, mixing times to change, if the substance formulation does not work after passing through a mixing process should have the required minimum homogeneity. These funds for monitoring are preferably integrated into the process control unit or with this connected. As a means of monitoring, for example to serve a video camera.

According to one preferred embodiment of present invention the substances and / or the substance formulations during storage and / or during are tempered after or after the mixing operation, i. there are Means for temperature control (heating or cooling) of Sample vessels and / or the storage vessels available.

In a preferred embodiment the method according to the invention the temperature or the heating / cooling capacity is a parameter that taken by the process control unit and stored in a file in Connection with the treated sample can be stored.

through the device according to the invention and the method according to the invention is it possible in particular Produce substance formulations that a small amount of sample exhibit. In general, the total amount for a single produced Substance formulation, below 250 g. Prefers. is it, if the single substance formulation is prepared in an amount the smaller than 100 g and - continue preferred - smaller than 50g. About that In addition, it is preferred that each individual substance formulation has a total amount smaller than 10 g. The production this only small amounts of samples comprehensive substance formulations is at the same time well reproducible, so that the individual Substance formulations as representative for the given composition are to be considered. Consequently, the number the repetition experiments are kept to a minimum. one the significant advantages of using the device according to the invention and the apparatus of the invention is the high reproducibility with which the samples are produced can. At the same time, the manufacturing process is different Substance formulations save time.

In a further preferred embodiment of the present invention, the substance formulations which are metered and mixed by means of the method according to the invention are subjected to an analysis after the formulation. The analysis may be, for example, that the substance formulation is first prepared for analytical characterization and then subjected to a characterization. Preferably, the preparation of the analytical characterization in the case of color mixtures is that a substrate is coated with the sample or a part of the sample and this coated sample in the coating unit ( 2 ) a colora analysis in the analysis unit ( 3 ). The sample preparation and sample characterization are preferably carried out by the program control and the characterization data are stored in the same file in which the other information on the sample (substance formulation) are stored.

In a further preferred embodiment of the present invention, the sample containers are automatically conveyed by a gripper arm for positioning to the respective manipulation points of the respective unit. In the case that the formulation station consists of several units - for example dosing and mixing unit ( 1 ), Coating unit ( 2 ) and analysis unit ( 3 ) - the different units (physically) can be connected together in a single device. However, it is also conceivable that the individual units are not directly in communication with each other, yet they are connected to the same process control unit and are controlled by this. The design of the transfer mechanism and gripping devices depends in particular on the spatial arrangement of the individual units to each other. It is therefore preferred that a single robot arm handles the transfer tasks of multiple units of the formulation platform, or that each individual unit has a separate transfer device.

In In a preferred embodiment, the formulation station can in particular also for that can be used, the substance formulations at high speed to produce a particularly high throughput of samples achieve, which is also a significant advantage for the implementation of combinatorial material research represents.

If the formulation station equipped with an analysis unit is, then the measured data obtained in the analysis in connection preferably stored in a file with the respective sample. The stored measurement data are usually further analysis and evaluation steps, wherein the results of the measured data as well as the results of the analysis and evaluation steps preferably be graphically visualized on a monitor. If it is the performed Relates analysis to target properties of the substance formulations, then the program looks for the relative and / or absolute values, which show the improved properties. This is the program able to get the information over improved properties in conjunction with specific formulation parameters and / or process parameters into the design phase in the design of subsequent ones To take over library generation, so that the entire formulation process in an iterative optimization process can be made. In the file, the obtained measured values and properties of the samples filed, the process control unit is able to provide such sample information for the design phase of new (especially from optimized) libraries.

In Bonding with any real sample is preferably one File exists, on the basis of which the real sample prepared in full can be. Possible repetitions of measurements already previously prepared samples can in connection with a characterization of the service life the samples are used.

example

in the the following becomes a possible Workflow chosen for the preparation of substance formulations described in more detail. The example presented here relates to finding a substance formulation for coating surfaces. The substance formulation is intended to have eight different individual components containing that formulation, which has certain properties, among others, the optical properties represent a target parameter that determines certain should have preferred properties. The method of finding can also be performed iteratively be, first a run takes place during which a particular series of substance formulations produced and examined. Based on the examination result is then followed by a second series of substance formulations designed and produced to study those formulation areas is used, in which improved properties in the first pass were found.

The total number of substance formulations that are to be produced in a process run can be specified by the user, but also in the program control choices are given, is supported by the selection or is completely taken by the program. The number of samples to be prepared depends on the number of components that the substance formulation is to contain. In a preferred embodiment of the method, a particular experimental design is specified by the user or by the program, which is then translated into a recipe file, which in turn is routed as a job library - converted into jobs - to the individual system components of the formulation platform. A scheme of the procedure is in 4 shown.

The Processing of the order is carried out by the individual system components - preferably fully automatic. i.e. without intervention from outside. The individual sample vessels are from the storage rack subject to registration and then to Balance is transferred where this by means of the respective recipe file provided amounts of substance components are filled. That with the substance components filled sample vessel filling is closed with a lock and by the gripping device in used the holder of the centrifuge. In a preferred embodiment is the holder of the centrifuge, which is the receptacle of the Sample vessel serves, always in the same position.

Subsequently, the sample vessel fixed in the holder of the centrifuge is subjected to a mixing process which is predetermined by the program control. In the case of the present example, the mixing process is that the sample vessel with numbers of revolutions of 2000 min ^-1 with respect to the major axis of rotation and with respect to 1000 min ^-1, the small axis of revolution for a period of 90 seconds rotated. The time period for reaching the rotational speed or number of revolutions of 2000 min ^-1 and for braking is 30 seconds for the major axis. The total duration of the mixing process used is therefore 150 seconds.

While a single sample vessel in the centrifuge is subjected to a mixing process, at the same time other sample vessels at other Make the workstation subject to registration or with Substance formulations filled, causing it possible is, several sample vessels at the same time to handle.

In In the present example, the formulation station is with a Double rotary mixer equipped with a holder for each has a sample vessel, so that within the operating time of 12.5 hours a total of 256 dosed, blended and different substance formulations could be subjected to an optical characterization test.

1

formulation station

2

coating unit

3

analysis unit

4

dosing

01

dosing

11

Storage vessel of the dosing module

12

Beheizungs- and / or stirring means

13

Libra

02

unit for positioning

21

claw arm

03

contraption to close of vessels

31

sample slide with vessels

04

mixing device

05

module with at least one sample receiving vessel

06

contraption for the transfer of liquids

41

turntable

42

adjustable counterweight

42 '

rail

43

bracket for the sample vessel

44

tilt bracket

45

Compressed air rotor (for rotation around the vessel axis)

46

bob

48

Rotary union

49

Compressed air line

50

baseplate

51

drive shaft for turntable

52

toothed belt

61

aspirate for the transfer of liquids

62

module for holding sample containers

63

Sample containers (resp. 63 ' : single sample vessel)

07

coating arm

71

coating knife

72

(Untreated) substrates

73

exchange station

74

cleaning station

75

Substrate coating device

76

storage box for coated substrates

81

Compressed air inlet

82

outlet for too dosing substance

83

Rule- or actuator for setting the cable cross-section

84

closure piston

85

inlet for too dosing substance component

86

Compressed air operated piston

3A

Double rotary mixer

3B

Double rotary mixer

3C

Double rotary mixer

Claims (13)

Formulation station ( 1 ) for dosing and mixing at least two substances, wherein the formulation station comprises at least the following units: (i) at least one platform comprising at least: (a) at least one module with at least two storage vessels for at least two different substances, and (b) at least one module ( 05 ) with at least one sample vessel ( 63 ) for receiving at least two substances, (ii) a dosing station ( 01 ) for dosing at least two substances into at least one sample vessel ( 63 ) (iii) a mixing device ( 04 ) for mixing the at least two substances in at least one sample vessel ( 63 ), characterized in that the mixing device ( 04 ) comprises at least one mixer for non-contact mixing of at least two substances, ie for mixing without the use of stirring tools. Formulation station according to claim 1, characterized in that the mixing device ( 04 ) additionally at least one gripping device ( 02 ) for insertion and / or replacement of at least one sample vessel in and / or from the mixing device. Formulation station according to claim 1 or 2, characterized in that the sample vessel ( 63 ) in the mixing device ( 04 ) is rotated at least about one axis of rotation, preferably about two axes of rotation that are different from each other. Formulation station according to claim 3, characterized in that the mixing device at least one Ausstellglied ( 41 ) on which there is a holder ( 43 ), which at least one sample vessel ( 63 ) can absorb releasably. Formulation station according to claim 4, characterized in that that the Ausstellglied as Dreharm / turnstile or as a turntable is realized. Formulation station according to claim 4 or 5, characterized in that the Ausstellglied ( 41 ) is set up so that the holder ( 43 ) with sample vessel ( 63 ) is tiltable, preferably so that the surface of the flowable mixture in the sample vessel reaches an angle of 0 ° to 60 ° from the horizontal. Formulation station according to one of claims 3 to 6, characterized in that the Ausstellglied ( 41 ) and the bracket ( 43 ) are designed so that the sample vessel ( 63 ) can rotate with the at least two substances to be mixed both about the axis of rotation of the Ausstellgliedes and about its own axis of rotation. Formulation station according to claim 7, characterized in that the drive for rotation about the axis of the sample vessel ( 63 ) and the drive about the axis for rotation about the Ausstellglied are independent of each other and both rotations are independently adjustable, preferably automatically via the process control unit. Formulation station according to one of the preceding claims, characterized in that it comprises at least one of the following additional units: (iv) at least one process control unit for controlling and / or controlling at least one of the units (i) - (iii) or (v), ( vi) the formulation station, (v) at least one coating unit ( 2 ), (vi) at least one analysis unit ( 3 ). Method for producing at least two substance formulations of at least two substances comprising at least the following two Steps: (a) a design step in which a virtual Arrangement of the formulated substance formulations created and then on (B) a synthesis step comprising at least one dosing step in a dosing station and at least one step of mixing in a mixing device, according to which the substance formulations are physically generated, thereby characterized in that the step of mixing the at least two Substances are contactless, i. without the use of stirring tools, carried out becomes. A method according to claim 10, characterized that steps (a) and (b) are under control or control by a process control unit carried out, which contains the information from step (a) transfers in step (b) to a dosing station and a mixing device. Method according to claim 10 or 11, characterized that the viscosity at least one to the dosing and to be mixed substance is higher than 5 mPa.s, preferably higher as 50 mPa · s. Method according to one of Claims 10-12, characterized that centrifugal forces due to at least one rotational movement located in the sample vessel to be mixed substances so that these substances are mixed.