DE102007009806A1 - Arrangement for handling of fluid useful in biochemical and biomedical industry, comprises two micro reactor plates, which possess same spacing and same and/or different obvious allocatable number of storage and/or absorption elements - Google Patents

Abstract

The arrangement for handling of fluid in pl-to mu l scale useful in chemical, biochemical, pharmaceutical and& biomedical industry, comprises micro array plates (1a, 1b), which possess same spacing and same and/or different obvious allocatable number of storage and/or absorption elements. One of the microarray plates possesses monolithic fluid storage element (2a, 2b) that is based on temperature sensitive and/or physical networking thermo reversible hydrogel. The microarray plate is joined with upper and lower part by a joining device. The arrangement for handling of fluid in pl-to mu l scale useful in chemical, biochemical, pharmaceutical and biomedical industry, comprises micro array plates (1a, 1b), which possess same spacing and same and/or different obvious allocatable number of storage and/or absorption elements. One of the microarray plates possesses monolithic fluid storage element (2a, 2b) that is based on temperature sensitive and/or physical networking thermo reversible hydrogel. The microarray plate is joined with upper and lower part by a joining device after loading of the storage element and/or absorption element with the process media in precise and medium-tight manner so that isolated reaction chambers form together in medium tight manner. In the reaction chamber, the storage elements are vivified through homogeneous influencing of temperature functioning as control parameter for releasing the temperature until the media is stored. The storage elements and/or the absorption elements are loaded with the process media through loading device over channel or other structures. The joining device controls a mechanism, with which the accurate and exact condition of the microarray plate can be retained. Two microarray plates are paired together sequentially in corresponding sequence as stack for mixing and processing several process media in a process step. Both sides of the enclosed microarray plate have openings of single cell, in which storage elements find to its connection partner. A foil is present between the microarray plates and its connection partners and destroyed mechanically or by influencing of certain temperature. The storage elements remain in the single cell through removing of the microarray plate. The storage volume of the hydrogel based storage element is adjusted over its networking characteristics or through variation of its dimensions. The chemical networking temperature sensitive hydrogel possesses a lower critical solution temperature behavior on the basis of N-isopropylacrylamide and poly(methylvinylether) and an upper critical solution temperature behavior on the basis of hydroxyethyl methacrylat and acetoacetoxyethyl-methacrylat. Substances with low melt temperature e.g. soft paraffin are used for fixing and/or storage particle like substance. The temperature functioning as control parameter distinctively influences on part areas of the microarray plates in temporary and quantitative manner.

Description

Technical area

The The invention relates to devices for handling or processing of liquid-based array arrangements.

In chemical, biochemical, pharmaceutical and biomedical Industry and science find most of the synthesis and analysis processes in the liquid phase or on surfaces instead. By the miniaturization of the reactors one tries on the one hand drastically reduce the demand for chemicals and samples, on the other hand shrinking causes shorter process times with improved Automation options. Some processes are also only possible in very small volumes. The miniaturization trend corresponds to the microarray concept. Microarrays consist of many small reactors or substrates in or on which different Samples are stored. Because of this collection character they are also called libraries (eg DNA Library). Microarrays for Biochemical or biological investigations become frequent also called biochips. Leaving some environmental parameters act on the entire microarray, so in one fell swoop hundreds or thousands of samples depending on the array size examined in one step.

to Production and processing of arrays with surface adsorbing Samples is an extensive range of mostly lithographic methods, especially photographic and increasingly also soft lithographic processes, to disposal. Unlike surface-based Processes can not be small volumes of liquid to handle with such simple methods.

State of the art

In general, the often multi-step liquid-based procedures are performed manually on microtiter plates consisting of ml large reactors or microwells by introducing the liquids into the reactors with a special device, the pipette. The repetition of a manual activity one hundred thousand times or more is burdened with the risk of pipetting errors, which often leads to only limited reproducible results. Therefore, robotic systems have been developed which realize the metering of liquids with high precision and with significantly higher throughput [ PS Dittrich, A. Manz, Nature Rev. Drug Discov. 5, 210 (2006) ]. Pipette robotic systems with 96 parallel channels are known. But robotic systems are in principle very expensive and therefore not available in many laboratories. Another high-throughput approach is based on the microfluidic in-a-droplet technology [ AJ deMello, Nature 442, 394 (2006) ]. In this case, small droplets are used in a non-water-miscible carrier medium, which serve as microreactors and can be processed sequentially in the microfluidic channel structure. However, developments are still at an early stage.

Presentation of the invention

task The invention is to provide a device which a simple, versatile and cost-effective liquid-phase microarray technology and even for single-use applications suitable is.

According to the invention the object is achieved by the features specified in claim 1. advantageous Embodiments are specified in claims 2 to 15.

Of the The basic idea of the invention consists in high-grade discretization liquid process media through switchable hydrogel-based Memory elements on a microarray plate, combining two or several different microarray plates with each other, the associated forms of isolated individual reactors and the subsequent mixing of the discrete subsets in the individual Reactors, which can then react accordingly separated and subsequently examined (discrete isolation, mixing and investigation DIXI). These processes are running exactly parallelized at the same time, about the same Period and under the same conditions.

The Function as a switchable liquid storage is through the special ability of stimuli-sensitive hydrogels, fluids to record, store and submit in a controlled manner. The Microarray can be used simultaneously with uniform media, but also with a variety of different media are processed.

When Environment size that controls the storage elements or switches, the temperature is preferred. She lets Master well globally and locally. As well as a whole range well-controllable temperature-sensitive hydrogels exist, form especially temperature-sensitive hydrogels the material Basis for the invention.

Most temperature-sensitive hydrogels have a lower critical solution temperature (LCST) characteristic, ie, they are swollen at low temperatures and escape when a phase transition temperature is exceeded. The best-known LCST characteristic hydrogel, poly (N-isopropylacrylamide) (PNIPAAm), has one Volume phase transition temperature of approx. 34 ° C. The position of the phase transition or switching temperature of NIPAAm-based hydrogels can be adjusted by copolymerization and variation of the synthesis parameters in a range of + 5 ° C and approx. + 60 ° C. Possible synthesis and structuring methods of PNIPAAm-based hydrogels are e.g. In [ A. Richter et al., J. Microelectromech. Syst. 12 (2003) 5, pp. 748-753 ]. Other representatives with LCST characteristic are based z. On poly (methyl vinyl ether) (PMVE) [ K.-F. Arndt et al., Macromol. Symp. 164 (2001), pp. 313-322 ] or hydroxypropylcellulose [ Kabra et al., Macromolecules 31 (1998), pp. 2166-2173 ]. Temperature-sensitive hydrogels with an Upper Critical Solution Temperature (UCST) characteristic swell when the phase transition temperature is exceeded and are swollen at low temperatures. A hydrogel with UCST behavior is the copolymer of hydroxyethyl methacrylate (HEMA) and acetoacetoxyethyl methacrylate (AAEM) [ Boyko et al., Macromol. Chem. Phys. 204 (2003), pp. 2031-2039 ].

Physically crosslinked hydrogels can also be temperature-sensitive. Such "thermoreversible" gels have a sol-gel transition behavior, ie they gel (crosslink) on reaching critical temperatures or dissolve by dewetting Typical temperature-switchable physically crosslinkable hydrogels are, for example, gelatin, pectin, carrageenan and agar [ K. te Nijenhuis, Thermoreversible Networks, Adv. Polym. Sci. 130, Springer-Verlag Berlin, Heidelberg, New York 1997 ]. Temperature-sensitive hydrogels can also be sensitized to light. For this purpose one can synthesize color pigments in the hydrogels or make the carrier substrate colored. For light with a broad spectrum of wavelengths, a black coloration is particularly suitable. The colors convert the light energy by absorption into heat energy, so that the hydrogel is heated above its phase transition temperature.

Ways to carry out the invention

The Invention is intended to be based on exemplary embodiments are explained, wherein the reference numerals used are the same lasting importance. In the accompanying drawings demonstrate:

1 the basic structure of the microarray system with hydrogel-based storage elements,

2 a device for accurately fitting and fixing the microarray components to each other,

3a and 3b the discharge process of chemically crosslinked, deswelling temperature-sensitive hydrogel storage,

4a to 4d the discharge process physically networked, dissolving temperature-sensitive hydrogel storage,

5a and 5b the processing of substances that are applied to a microarray on the surface,

6a and 6b Possibilities for handling more than two process media simultaneously, wherein
6a the sandwich-like combination of three microarray plates and
6b illustrate the introduction of monolithic storage elements in reaction chambers,

7a . 7b and 7c Means for loading the microarray components with different media,

8th a microarray component with storage elements of different volumes, and

9 a microarray plate with six subarrays.

Based on 1 to 3 the principle of operation of the liquid handling system is explained.

The basic element of the liquid handling system is the microarray. As 1 shows, this consists of a microarray plate 1 and carries storage elements 2 , The storage elements can be used as freestanding monoliths ( 2a ) on a smooth microarray plate 1a be executed or in individual chambers, which are separated by walls (memory element 2 B on plate 1b ), are located. During a loading process to be described later take the memory elements 2 according to their predetermined by synthesis and geometry storage volume, a defined amount of a process fluid by swelling. This process divides the liquid into many discrete subsets. With a second microarray plate 1 is handled in a similar manner with another process medium. Then the two microarrays are to be combined. To do this with the necessary spatial precision, the use of an auxiliary device is recommended. One possible embodiment in the form of a microarray cassette is in 2 outlined. In the cassette parts 11a and 11b be in corresponding recesses 12a . 12b the microarray plates 1a and 1b placed. By suitable structural design of these recesses 12 can the microarray plates 1 which in terms of their Speicherele Mente have the same pitch, accurately aligned with each other and then placed on each other. Can do this 11a and 11b For example, have a hinge connection. As 3a illustrated form after pressing the microarray plates together 1a and 1b and locking the cassette parts 11a and 11b Pairs of memory elements 2a and 2 B isolated from each other and tightly closed reaction chambers 13 , The microarray cassette is now ready for processing. The process starts with the simultaneous in all reaction chambers 13 ongoing mixing of the media, which is triggered for example by homogeneous heating of the entire cassette on the switching temperature of the memory elements. In the case of thermally induced reactions, such. As polymerase chain reactions, the necessary heating can be carried out with the Thermozykliergerät.

The Reaction result is by subsequent mating with another Microarray further processable. This reaction chain can be continued as desired be, d. that is, multi-step reactions can be performed become.

The discharge process of the storage elements varies depending on the storage materials used and the substances to be processed. Essential possibilities are in the 3 to 5 shown.

The 3a and 3b illustrate the functioning of storage elements based on temperature-sensitive chemically cross-linked hydrogels such as PNIPAAm or PMVE. The memory elements 2d and 2e the microarray plates 1a and 1b absorb the respective process media by swelling and fix them at the same time. When swelling mainly liquids can be absorbed. Due to their porosity, the hydrogels are also able to absorb dissolved substances and particles up to a certain maximum size. The porosity of the hydrogels can be adjusted by varying the synthesis conditions. For unloading the whole construction is in 3a but at least the hydrogel elements 2d . 2e over its volume phase transition temperature, at PNIPAAm, ie above 34 ° C, heated. As 3b shows then the storage elements ( 2f and 2g ) with delivery of the process medium 14 which does not come from the tightly closed single reaction chambers 13 can escape.

The unloading process of thermo-reversible physically cross-linked hydrogels such as agar show the 4a and 4b , While the plate 1a with chemically networked storage elements 2d is provided has the plate 1b thermoreversible hydrogel storage elements 2h on. These can also be loaded by swelling in the process medium. After exceeding the critical temperature, with standard agar this is 95 ° C, the gel dissolves by dewetting and releases the process medium. Now the medium can be 16 with the medium 14 mix.

Physically crosslinked hydrogels can furthermore be used for immobilizing or storing particulate substances which, because of their size, can not be handled with chemically cross-linked hydrogels ( 4c and 4d ). For loading, the gelable liquid is added to the corresponding substance. For dissolved agar, this can be done, for example, at temperatures above 45 ° C. Below 45 ° C, the agar solidifies to a solid matrix 17 which are the solid substances 19 contains as inclusions. To release or discharge these substances, the critical temperature above which the thermo-reversible gel dissolves, must be exceeded. Agar goes from 95 ° C in the dissolved state 18 over and puts the substances 20 free. For fixing or storing particulate substances can also substances with low melting temperature, such. B. soft paraffins (Vaseline has melting temperatures between 35 ° C and 60 ° C) and fats use.

The 5a and 5b illustrate the functionality of the fluid handling system for substances or subjects that adsorb to surfaces. Into the individual chambers of the microarray plate 1b becomes an adsorbent 21 introduced, which itself may be a hydrogel or commercially available materials (eg., Aldehyde, amino, epoxy-modified surface coatings). After the substance-containing solution has been flushed in, a certain number of particles are adsorbed on the adsorbent, depending on the adsorption rate and the free adsorbate sites 21 , After mating the plate 1b with the plate 2a , which loaded chemically crosslinked hydrogel storage 2d carries, sets this by the already described discharge process, the process medium 14 free, which now on the adsorbate 22 can act.

As 6a illustrated, more than two microarray plates can be combined simultaneously. While the plates 1a and 1b already in the 3 to 5 may have shown construction, the microarray plate 1c has openings of the individual chambers up and down. The memory element located therein 2i However, it has the same functionality as the other memory elements 2 , In a figurative sense, the other storage media 17 and 21 For 1c be used. As a special measure, the use of a film is recommended on certain occasions 23 which essentially serves a sealing function as protection against media loss or leakage. It must be after joining the microarray plates 1a to 1c destroyed or at least media-permeable. Destruction can be done mechanically when joining the plates 1a to 1c done or if the film 23 fusible, dissolvable or otherwise variable in their properties, by the action of a certain environmental parameter, in particular the temperature, take place. The single cells of the three microarray plates 1a to 1c now form the reaction chamber 13 , which contains three process media. The combination of microarray plates can be continued in the manner described.

The combination of several process media in one process step can also be realized by using microarray plates with monolithic memory elements ( 6b ). To that in the element 2e the plate 1b stored medium can be successively elements 2a to 2c Add by the microarray plates 1a on 1b be placed and then by pulling away from 1a the memory elements 2a and by repeating this process 2 B and 2c be stripped off, leaving these in the reaction chamber 13 remain. Again, all of these types of storage can be used.

• – gleichförmig
• – mit einem Medien unterschiedlicher Konzentration
• – mit verschiedenen Medien

sowie entsprechenden Kombinationen beladen sein. Die gleichförmige Beladung lässt sich beispielsweise durch Eintauchen in das Medium realisieren.Of particular importance is the loading of the microarrays. A microarray can:

• - uniform
• - with a media of different concentration
• - with different media

as well as corresponding combinations. The uniform loading can be realized for example by immersion in the medium.

The 7a to 7c illustrate ways to load a microarray with different media. Microarray plates 1 with monolithic storage elements 2 can be with a special device 3 loaded ( 7a ). This is the plate 1 so on 3 positioned that the memory elements 2 in channel structures 4 penetration. About different connections 5 can then be in the respective channel 4 located memory elements 2 loaded with the provided medium by swelling. Depending on the channel structure geometry, rows, columns or other segments of the microarray can be loaded similarly.

A loading device for microarray plates with storage elements located in separate individual chambers show the 7b and 7c , After precise and media-tight joining of the microarray plate 1 with the device 3 be over the connections 5a to 5f those storage elements 2 equipped with the same medium, which via the respective supply lines 6a to 6f , if necessary via individual connections 7 are connected accordingly. For venting or for the purpose of discharging superfluous medium each memory cell is also with the discharge 8th connected.

After loading, the device 3 removed and the prepared microarray plates combined.

• – 8 min bei 95°C Initialisierung
• – Zyklusstart (insgesamt 40 Zyklen) mit • 15 s 95°C Denaturierung • 60 s 60°C Anlagerung und Elongation.

Based on 7c is to represent many other procedures a quantitative polymerase chain reaction (quantitative polymerase chain reaction Q-PCR), which as a special case of the polymerase chain reaction (PCR) not only amplify nucleic acids, but also quantify them. The biochip system after 7c is able to combine 10 DNA-containing samples with 10 different assay reagents (assays), ie perform 100 different reactions. Practically used biochip systems will certainly have a significantly higher number of sample and assay channels, e.g. 48x48 (2304 different reactions) or 96x96 (9216 reactions) channels. A first microarray plate 1a is using the loading device 3 over the connections 5a to 5y with a solution containing the DNA samples and a master mix (eg TaqMan Universal PCR Master Mix, ratio 1: 1)). Supply way ( 6a to 6y ) are ever ten memory elements 2 loaded with the same sample medium by absorbing the medium by swelling. In the same way, a second microarray plate 1b loaded with the assay solution containing the primers and the TaqMan probe. After tightly fitting the loaded microarray plates 1a and 1b in the cassette, this is spent in a Thermozykliergerät and driven a suitable PCR temperature program, which z. B. can look like this:

• - 8 min at 95 ° C initialization
• - cycle start (40 cycles in total) with • 15 s 95 ° C denaturation • 60 s 60 ° C annealing and elongation.

After that or even during the cycles (real-time Q-PCR) can be quantitatively examine the results with fluorescence measurements.

The typical storage capacity of the storage elements 2 is between about 100 pl and a few hundred nl. For example, with structural dimensions in the range of 50 μm and 500 μm, this volume is between 1 nl and 125 nl.

The volume ratios of the liquids to be mixed can be initially determined by their concentrations. To vary the mixing ratios on the microarrays, as z. B. for enzyme kinetic studies and other methods with the need for concentration gradients is necessary, simply the memory capacity of the memory elements preset who the. This is possible by synthetically adjusting the maximum degree of swelling of the hydrogel (net chain molecular weight, crosslink density). It is easier to calculate the dimensions of the storage elements 2 to adjust. As 8th Illustrated, a microarray plate 1b with a plate 1a combined, their monolithic storage elements 2a . 2 B . 2c each have a different size or volume and thus have different storage capacities for the same hydrogel material. In a comparable way, the size of separated individual chambers can be varied.

Especially for studies with high statistical certainty, but also for the targeted examination of highly diluted media for specific target substances, microarrays are needed, which break down the sample into a particularly large number of small discrete subsets. Such a system is in 9 shown. The microarray plate 1 is in six subarrays 15 divided. Each sub-array can accommodate a particular sample-assay mixture. If dilution series of the sample material are examined with this system, it is possible, for example, to realize an absolute quantification of a target substance.

The Components of the microarray system exist almost completely made of plastic. They can therefore be with the usual Processes of plastics processing such as injection molding, hot deformation and hot stamping. As plastics can for example polycarbonate (PC), polymethyl methacrylate (PMMA), Polyamide (PA), polystyrene (PS), cyclo-olefin copolymers (COC) as well as Polyester (PES) find use. For smaller series and Unique products are particularly suitable polydimethylsiloxane PDMS. With this Material can with a simple master impression technology Even complicated microstructures can be realized in a short time. The channel and other structures are called photostructured Resist on conventional PCB material in negative realized and then by molding and then Curing by the PDMS imitated in the positive.

Hydrogels can also be structured in a variety of forms. This can be z. By photocrosslinking, photopolymerizing or molding [ A. Richter, in CT Leondes: MEMS / NEMS HANDBOOK: Techniques and Applications. Springer New York 2006, vol. 2, chap. 5, pp. 141-171 ].

One great advantage of the microarray technology according to the invention is its cost efficiency. The required basic elements technology, such as the microarray plates, the loading devices and also cassettes, have an extremely simple, im Usually planar construction and can therefore be very inexpensive produce. The handling of the components is not special Equipment and skills are tied and practical be used in every laboratory.

One particular advantage of the handling system is the possibility carrying out multi-step reactions by adding several Microarrays combined and processed in sequential order become. The technology has the potential, the conventional one To replace the microtiter plate technique.

The Fluid handling system is due to the high grade Parallelization of processes for high-throughput investigations with a large number of individual reactions or handling steps particularly suitable.

Liquid phase chips, which combine x media of one chip plate with y media of another chip plate (see also 7c ), are particularly suitable for screening processes (wide-ranging testing for specific properties, substances, behavior, etc.). The technology is equally suitable for chemical, biochemical and biological systems.

For combinatorial chemistry is interesting the way execute each of the (x · y) combinations in one stage in parallel, and then later the reactions in new stages by new ones To be able to continue microarray pairings.

In Molecular biology and biochemistry benefit nucleic acid-related Methods such as PCR, enzymatic and immunoassays (eg enzymes Linked Immunosorbent Assay ELISA) of the invention, however only representative of a variety of liquid phase coupled biochemical methods.

in the medical and biological field can be the effect from environmental factors, growth factors, pollutants, etc. to living Examine organisms or biomolecules. Furthermore, can a drug or drug screening very easy realized become. In addition, the technology of disease diagnostics opens completely new possibilities.

Main applications of arrays after 9 , which break down a sample into a particularly large number of small discrete subsets, are studies in which a high statistical certainty is required. It can also be used to perform high to absolute quantitative studies on dilution series. In biological systems, for example, the mutation tendency of certain organisms can be examined.

The Liquid handling system is a matter of course not only for manual use, but also for automated and semi-automated systems suitable.

1, 1a-1c

Microarray plate

2, 2a-2c

Fluid storage element

2d, 2e, 2i

swollen chemically cross-linked hydrogel storage element

2f, 2g

unloaded or swelled chemically cross-linked hydrogel storage element

2h

loaded or swelled physically crosslinked hydrogel storage element

3

contraption for loading

4

channel structure the loading device

5, 5a-5j

connection

6 6a-6j

supply

7

individual connection for a storage element

8th

ventilation, removal

9

Single transfer for a storage element

10

connection the exhaustion

11 11a, 11b

cassette part

12 12a, 12b

recess for a microarray plate

13

reaction chamber

14

process medium

15

subarray

16

process medium with dissolved polymer chains

17

solid matrix material

18

dissolved or liquefied matrix material

19

Amber inclusion, enclosed substance

20

released substance

21

adsorbent, adsorbing surface

22

adsorbate adsorbed substance

23

foil

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited non-patent literature

• - PS Dittrich, A. Manz, Nature Rev. Drug Discov. 5, 210 (2006) [0004]
• - AJ deMello, Nature 442, 394 (2006) [0004]
• A. Richter et al., J. Microelectromech. Syst. 12 (2003) 5, pp. 748-753 [0010]
• - K.-F. Arndt et al., Macromol. Symp. 164 (2001), pp. 313-322 [0010]
• B. Kabra et al., Macromolecules 31 (1998), pp. 2166-2173 [0010]
• Boyko et al., Macromol. Chem. Phys. 204 (2003), pp. 2031-2039 [0010]
• K. te Nijenhuis, Thermoreversible Networks, Adv. Polym. Sci. 130, Springer-Verlag Berlin, Heidelberg, New York 1997 [0011]
• - A. Richter, in CT Leondes: MEMS / NEMS HANDBOOK: Techniques and Applications. Springer New York 2006, vol. 2, chap. 5, pp. 141-171 [0042]

Claims (15)

Device for handling liquids in the pl to μl scale, characterized in that it consists of at least two microreactor plates ( 1a ) and ( 1b ) which has the same pitch and the same or a different uniquely assignable number of storage or adsorbent elements ( 2 . 2a - 2i . 17 . 18 . 21 ), at least one microarray plate ( 1 . 1a . 1b ) Liquid storage elements ( 2 . 2a - 2i ), which are based on stimuli-sensitive, in particular temperature-sensitive and / or thermoreversible hydrogels, the microarray plates ( 1 . 1a - 1c ) after loading the storage or adsorbent elements ( 2 . 2a - 21 . 17 . 18 . 21 ) with process media ( 14 . 19 . 22 ) are fitted accurately and media-tight, so that mutually isolated reaction chambers ( 13 ) in which the memory elements ( 2 . 2a - 2i . 17 . 18 ) by homogeneously acting on an environment variable acting as a control variable, in particular the temperature, simultaneously releasing the previously stored media ( 14 . 16 . 20 ). Device according to claim 1, characterized in that the memory elements ( 2 . 2a - 2h . 17 . 18 ) or adsorbent elements ( 21 ) of the microarray plates ( 1 . 1a . 1b . 1c ) by loading devices ( 3 ) via channel ( 4 . 6a - 6y ) or other structures with process media ( 14 . 19 . 22 ). Device according to claim 1, characterized in that the microarray plates ( 1 . 1a . 1b . 1c ) by a special device, in particular a cassette with upper and lower part ( 11 . 11a . 11b ), are fitted accurately, so that the resulting reaction chambers ( 13 ) are isolated from each other and are media-tight. Device according to claim 3, characterized that the joining device has a mechanism has, with the tailor-made and media-dense state the microarray plates can be maintained. Device according to Claim 1, characterized in that, to carry out multi-stage processes, a plurality of microarray plates ( 1 . 1a . 1b ) are sequentially paired in appropriate order with each other. Device according to claim 1, characterized in that for mixing and processing of a plurality of process media in a single operation more than two microarray plates ( 1 ) are paired as a stack, with the enclosed on both sides microarray plates 1c two-sided openings of the individual cells in which the memory elements 2i to have their connection partners. Device according to claim 6, characterized in that between the microarray plates 2i and its affiliates a slide 23 is present, which is destroyed mechanically or by the action of certain environmental variables, in particular the temperature. Device according to claim 1, characterized that for mixing and processing multiple process media in one Step in sequential order several microarray plates, which have monolithic storage elements, with single cell-containing Microarray plates are paired, whereby by pulling away the one Microarray plate the monolithic storage elements in the single cell remain. Device according to claim 1, characterized in that the storage volume of the hydrogel-based storage elements ( 2 . 2a - 2h . 17 . 18 ) is adjusted via their networking properties. Device according to claim 1, characterized in that the storage volume of the hydrogel-based storage elements ( 2 . 2a - 2h . 17 . 18 ) is adjusted by varying their dimensions. Device according to claim 1, characterized that the chemically crosslinked temperature-sensitive hydrogels a Lower Critical Solution Temperature characteristics, in particular Hydrogels based on N-isopropylacrylamide and poly (methyl vinyl ether). Device according to claim 1, characterized that the chemically crosslinked temperature-sensitive hydrogels a Upper Critical Solution Temperature characteristics, in particular Hydrogels based on hydroxyethyl methacrylate and acetoacetoxyethyl Methacrylate. Device according to claim 1, characterized that the physically crosslinked thermo-reversible hydrogels gelatins or polysaccharides such as carrageenan, pectins and agar. Device according to claim 1, characterized in that for fixing or storing particulate substances ( 19 ) Substances ( 17 ) with a low melting temperature, such. As soft paraffins, are used. Device according to Claim 1, characterized in that the environmental variable acting as a control variable is based on subregions of a combination of process-ready microarrays ( 1 . 1a - 1c ) acts temporally and / or quantitatively different.