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OwnerRonald Frank, Stefan Matysiak +3inventors
InventorsRonald Frank, Stefan Matysiak, Olaf Schreuer, Heinrich Gausepohl, Andre Rosenthal
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The disclosed synthesis system is based on the idea of designing a synthesis and treatment procedure, substrates and anchor groups which enable biomolecules to be simultaneously produced in an entirely automatic manner. By using a pipetting robot to dispense the reagents, the reaction column can be arranged in a format suitable for subsequent treatment. For a pipetting robot to carry out even water-sensitive or air-sensitive synthesis protocols, certain structural measures must be taken. The operation principle of the automaton and the synthesis sequence are described below as an example of a possible solution. The automaton can work with conventional substrates and reagents. Handling, however, is simplified by new, specially adapted substrates and anchor groups. A special, simultaneous purification and aliquot portioning process improves product quality and makes the device easier to use.
Apparatus for automated simultaneous chemical synthesis and optional purification of a large number of products on solid phase, which apparatus has a large number, especially from 10 to 100, preferably 48 or a multiple thereof, and preferably 400, of separate reaction vessels/reactors, which are open at the top and at the bottom, in the form of channels/reaction channels or columns/reaction columns, especially small columns, which are arranged in parallel in a block/reactor block (FIG. 6) and which are removable either together or separately;
Apparatus according to any one of the preceding claims, characterised by vessels which are sealed by means of septa and provided in a reagent block separate from the reaction block for a large number, especially from 2 to 100 and preferably 24, of chemical building blocks and reagents.
Apparatus according to any one of the preceding claims, characterised by a control computer, by means of which it is possible, using a list of ASCII words of software wherein the chemical building blocks/monomers used for building up the products are coded as ASCII characters and the products are therefore described as a sequence of build-up reactions/monomer incorporation reactions by means of ASCII words, for the totality of all products for a synthesis program to be converted into valve-switching operations, dispensing-syringe movement operations and robot arm movement operations, it being possible for each monomer incorporation to consist of a succession of several reaction steps and switching operations.
Reactor according to any one of the preceding claims, characterised by an arrangement of affinity columns (FIG. 9) which is complementary to the reactor/reactor arrangement and/or an arrangement of collection vessels which is complementary to the reactor arrangement.
Method especially using an apparatus according to any one of the preceding claims, characterised in that, linking building blocks/linkers suitable for covalently linking the products to support material are provided, which allow final removal of the products to take place selectively under mild conditions, there being provided, especially, for the synthesis of oligomeric compounds, especially oligonucleotides or peptides, a universal linker, to which there can also be linked the building blocks of the first build-up reaction of the same chemical reaction type as that used for the further build-up reactions, as a result of which only one type of building block is needed for the entire synthesis of a class of compounds, especially only one nucleoside-3′-phosphoramidite for the synthesis of 3′-OH-oligonucleotides.
Dependencies are inferred from the claim text.