Methods and devices for synthesizing molecules

Abstract

The present invention relates to a computer-implemented method performed by a device (600) configured to synthesize a molecule, the synthesis comprising performing cycles of a plurality of process steps (PS1-PS4), the synthesis being controlled by blocks of parameters, the method comprising receiving instructions for a target molecule, generating a synthesis process description (300) by generating a plurality of blocks of parameters (310), each block (310) controlling a process step of a respective cycle, receiving user input indicating modification of the generated plurality of blocks of parameters, modifying the generated plurality of blocks of parameters using the user input, and controlling the synthesis of the target molecule by applying the modified plurality of blocks of parameters to control the respective cycles.

Description

[Technical field]

[0001] The present invention relates to a method for synthesizing molecules.The present invention further relates to a device configured to synthesize molecules. [Background technology]

[0002] Synthesis of molecules is commonly used, for example, in the production of diagnostic kits, clustered regularly interspaced short palindromic repeats (CRISPR) therapeutics, and oligonucleotide therapeutics. An example of a diagnostic kit is a kit for testing for COVID-19. An example of an oligonucleotide therapeutic is Spinraza® (Nusinersen), for example, for treating infants diagnosed with spinal muscular atrophy. Another exemplary oligonucleotide therapeutic is Leqvio® (Inclisiran), a treatment for high cholesterol.

[0003] Examples of synthetic molecules are oligonucleotides and oligopeptides.

[0004] An example of a conventional method for synthesizing the molecule is described in US20200032250A1.

[0005] However, the drawback of such conventional methods is that they lack flexibility in terms of synthesis method, synthesis chemistry, and synthesis scale. Another drawback is that they are not as efficient as one would expect in the use of reagents.

[0006] Thus, there is a need for improved methods for synthesizing molecules. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] US Patent Application Publication No. 2020 / 0032250 [Patent Document 2] European Patent No. 0844910 [Patent Document 3] GB 2118139 [Patent Document 4] U.S. Pat. No. 4,589,049 Summary of the Invention [Problem to be solved by the invention]

[0008] It is an object of embodiments of the present invention to provide a solution that mitigates or eliminates the above-mentioned drawbacks and problems. [Means for solving the problem]

[0009] The above and further objects are achieved by the subject matter described herein.Further advantageous implementations of the invention are also further defined herein.

[0010] According to a first aspect of the present invention, the above and other objects are achieved by a computer-implemented method performed by a device configured to synthesize a molecule, the synthesis comprising performing cycles of a plurality of process steps, the synthesis being controlled by blocks of parameters, the method comprising receiving instructions for a target molecule, generating a synthesis process description by generating a plurality of blocks of parameters, each block controlling a process step of a respective cycle, receiving user input indicating modification of the generated plurality of blocks of parameters, modifying the generated plurality of blocks of parameters using the user input, and controlling the synthesis of the target molecule by applying the modified plurality of blocks of parameters to control the respective cycles.

[0011] At least one advantage of the disclosure according to the first aspect is that an improved process for synthesizing molecules is achieved by optimizing cycles and even process steps in a highly flexible manner.

[0012] In one embodiment according to the first aspect, each cycle includes a plurality of process steps, each respective block including a corresponding number of sub-blocks of parameters as that number of process steps in the plurality of process steps, the received user input further indicating modification of one or more of the sub-blocks, and controlling the synthesis further includes applying the modified sub-blocks to control the process steps of the respective cycle.

[0013] In one embodiment according to the first aspect, modifying the generated plurality of blocks comprises globally applying user input to all cycles by modifying the respective blocks of parameters.

[0014] In one embodiment according to the first aspect, modifying the generated plurality of blocks comprises applying user input to all cycles of the same type by modifying a respective block of parameters.

[0015] In one embodiment according to the first aspect, the user input further indicates a selected cycle of the process description, and modifying the generated plurality of blocks includes applying the user input to the selected cycle.

[0016] In one embodiment according to the first aspect, the target molecule is an oligonucleotide and the multiple process steps comprise at least detritylation, coupling, oxidation, and capping.

[0017] In one embodiment according to the first aspect, each subblock for the detritylation process step includes parameter values ​​for start level, end level, linear flow, efficiency limit, wash CV, each subblock for the coupling process step includes parameter values ​​for base identity, Eq, amidite concentration, coupling CT, activator percentage, extrusion flow rate, recycle time, and wash CV, each subblock for the oxidation process step includes parameter values ​​for ox CT DNA, ox Eq ​​DNA, ox CT RNA, ox Eq ​​RNA, chase CV ox, wash CV ox, and each subblock for the capping process step includes parameter values ​​for cap CT, cap CV, chase CV ox, and wash CV ox.

[0018] In one embodiment according to the first aspect, the target molecule is an oligopeptide and the multiple process steps comprise at least detritylation, coupling and optionally capping.

[0019] In one embodiment of the first aspect, receiving user input includes rendering a representation of the synthesis process description, the representation including representations of blocks and / or sub-blocks and / or parameter values, displaying the representation to a user, and receiving user input indicating interaction with the representation, thereby receiving user input indicating modification of parameters of the generated plurality of blocks.

[0020] In one embodiment according to the first aspect, the interaction at least indicates modified parameter values ​​and indicates that the modified parameter values ​​should be applied globally to all cycles by modifying respective blocks of parameters.

[0021] In one embodiment according to the first aspect, the interaction at least indicates modified parameter values ​​and indicates that the modified parameter values ​​should be applied to all cycles of the same type by modifying the respective blocks of parameters.

[0022] In one embodiment according to the first aspect, the interaction at least indicates a selected cycle of the process description, indicates a modified parameter value, and indicates that the modified parameter value should be applied to the selected cycle.

[0023] According to a second aspect of the present invention, the above mentioned and other objects are achieved by a device configured to synthesize a molecule, the synthesis comprising performing a cycle of a plurality of process steps, the synthesis being controlled by blocks of parameters, the device comprising a controllable fluidic network, an input device, a display and a control unit comprising circuitry, the circuitry comprising a processing circuit and a memory, the memory comprising instructions executable by the processing circuit, the control unit being communicatively coupled to the controllable units of the fluidic network, whereby the device is configured to perform the method according to the first aspect when the instructions are executed by the processing circuit.

[0024] According to a third aspect of the present invention, the above and other objects are achieved by a computer program comprising computer executable instructions which, when executed on processing circuitry contained within the control unit, cause the control unit to perform a method according to the first aspect.

[0025] According to a fourth aspect of the present invention, the above and other objects are achieved by a computer program product comprising a computer readable storage medium, the computer readable storage medium having a computer program as set forth in the third aspect embodied herein.

[0026] A more complete understanding of embodiments of the present invention may be obtained, as well as a realization of additional advantages, by those skilled in the art through a consideration of the following detailed description of one or more embodiments. It will be understood that like reference numerals are used to identify like elements illustrated in one or more of the figures. [Brief description of the drawings]

[0027] [Figure 1] FIG. 1 illustrates a process cycle for synthesizing a molecule, including multiple process steps according to one or more embodiments of the present disclosure. [Diagram 2] FIG. 1 illustrates a process cycle for synthesizing oligonucleotides according to one or more embodiments of the present disclosure. [Diagram 3] FIG. 1 illustrates an example of a process description configured to synthesize a molecule according to one or more embodiments of the present disclosure. [Figure 4] FIG. 2 illustrates a selected block of parameters in accordance with one or more embodiments of the present disclosure. [Diagram 5] FIG. 1 illustrates a computer-implemented method performed by a device configured to synthesize molecules according to one or more embodiments of the present disclosure. [Figure 6] FIG. 1 illustrates a device configured to synthesize molecules according to one or more embodiments of the present disclosure. [Figure 7] FIG. 1 illustrates an example of a device configured to synthesize oligonucleotides according to one or more embodiments of the present disclosure. [Figure 8] FIG. 1 illustrates an example of a device configured to synthesize oligonucleotides according to the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] A more complete understanding of embodiments of the present invention may be obtained, as well as a realization of additional advantages, by those skilled in the art through a consideration of the following detailed description of one or more embodiments. It will be understood that like reference numerals are used to identify like elements illustrated in one or more of the figures.

[0029] The related patents / applications EP0844910B1, GB 2 118 139 and US 4,589,049 are hereby incorporated by reference.

[0030] "Or" in this specification and the corresponding claims should be understood as a mathematical OR, including "and" and "or," and not as an XOR (exclusive OR). The indefinite article "a" in this disclosure and claims in the English original is not limited to "one," but may also be understood as "one or more," i.e., plural.

[0031] In this disclosure, references to processing circuitry and processing means are made interchangeably.

[0032] In this disclosure, the term "fluid source" refers to a unit or arrangement capable of supplying a fluid, such as a fluid container, a fluid tank, or a fluid reservoir. In the following description, the fluid source is described as a container, although any suitable fluid source may be used.

[0033] In this disclosure, the phrase "block of parameters" refers to a set of parameters, each parameter being assigned a parameter value. The set of parameters controls the behavior or characteristics of a device configured to synthesize molecules in a particular process cycle, the process cycle including multiple process steps. The block of parameters may include or be divided into sub-blocks of parameters, each sub-block controls the behavior or characteristics of the device when performing a particular process step. It is understood that multiple subsequent blocks can control multiple subsequent cycles, each of the multiple subsequent cycles including multiple process steps.

[0034] In this disclosure, the phrase "synthesizing a molecule" refers to performing multiple cycles of process steps to add molecular building blocks to a chain of molecular building blocks to form a target molecule. One example of synthesizing a molecule is producing an oligonucleotide chain from support-bound nucleosides. Another example of synthesizing a molecule is producing an oligopeptide chain from amide-linked amino acids.

[0035] In this disclosure, the term "target molecule" refers to a desired molecule formed / produced by performing cycles of process steps, adding building blocks until a chain of the desired building blocks forms the target molecule. Exemplary molecules are oligonucleotides or oligopeptides.

[0036] In this disclosure, the phrase "controlling synthesis" refers to controlling a device configured to synthesize a molecule.

[0037] In this disclosure, the term "fluidic network" refers to fluidically coupled device components configured to hold, direct, and control fluid flow. Examples of device components included in a fluidic network are conduits / pipes, fluid containers / receptacles, sensors, valves, fluid columns, etc. Some device components may be controllable and communicatively coupled to a control unit, react to control signals received from the control unit, and / or transmit data, e.g., device component properties and / or measurement data, as control signals to the control unit. Examples of such controllable device components include sensors and valves.

[0038] The present disclosure relates to improved methods and devices for synthesizing molecules, typically oligonucleotides and oligopeptides.

[0039] An oligonucleotide is a polymer that contains a sequence of nucleosides, each of which contains a sugar and a base. Each nucleoside is separated from the adjacent nucleoside by an internucleotide bond, which effectively binds the nucleosides together. The sugar is generally a pentose sugar, most commonly deoxyribose, ribose, or 2'-0-substituted ribose. Many different bases can be used, the four most common being adenine, cytosine, guanine, and thymine (abbreviated as A, C, G, and T, respectively). The internucleoside bond is most commonly a phosphate, which can be substituted at the non-bridging oxygen atom by a variety of substituents, most commonly sulfur, alkyl groups, ester groups, and amide groups.

[0040] Different methods are used to synthesize oligonucleotides, including phosphoramidite, phosphotriester, and H-phosphonate methods, each of which is commonly known in the field of molecular biology.The phosphoramidite method is described here as an exemplary method.To produce a large number of oligonucleotide molecules by this method, a solid support is provided in a reaction vessel, and a large number of DMT-protected nucleosides are fixed to the support.

[0041] In the removal or detritylation process step, a deprotecting agent, e.g., acting through a detritylation mechanism, is added to remove DMT from the nucleoside, thereby "deprotecting" its one hydroxyl group, so that the last nucleoside in the sequence has one hydroxyl group ready to accept the next amidite.

[0042] In the coupling process step, a nucleoside phosphoramidite (hereinafter "amidite") dissolved in a solvent such as acetonitrile (ACN) is introduced into the vessel. An activator, such as tetrazole, is also introduced into the vessel along with the amidite. The phosphorus in the amidite combines with the oxygen in the hydroxyl group, thereby providing a support-bound nucleotide. After the support-bound nucleotide is formed, the excess amidite is poured out of the vessel along with ACN.

[0043] In the oxidation process step, an oxidizing agent is added to convert the trivalent phosphorus to pentavalent phosphorus.

[0044] In the capping process step, a capping agent is added to prevent any unprotected hydroxyl groups from reacting with the amidite introduced at a later stage, and ACN is again introduced to flush out the capping agent.

[0045] These process steps can be repeated / cycled any number of times to produce oligonucleotide chains growing from the support-bound nucleosides, each of which should have an identical repeating sequence of nucleosides.

[0046] The above processes for producing oligonucleotides are time consuming and the materials used, particularly the amidites, are expensive and require special handling and disposal after use.

[0047] At least one advantage of the present disclosure is that cycles and even process steps can be modified to optimize the process and the use of fluids such as amidites. This modification can be performed at different levels, for example globally, for specific types of cycles, and for individual selected cycles.

[0048] In the laboratory, oligonucleotides are typically synthesized on the scale of about 1 micromole. One group of devices / machines used to synthesize molecules are produced under the name OligoPilot (a trademark of the assignee of the present invention) and have improved the process to produce molecules on the order of 3-4 millimoles. It would be desirable to increase the number of molecules that can be produced at one time and to produce them efficiently using the minimum amount of reagents required.

[0049] An oligopeptide is a macromolecule that contains a sequence of amino acids linked through amide bonds. A cycle for forming a target molecule or a target oligopeptide may include the following process steps:

[0050] In the removal or Fmoc removal process step, a deprotecting agent, which acts through the removal mechanism, is added to "deprotect" the molecule so that the last amino acid in the sequence is ready to receive the next amino acid.

[0051] In the coupling process step, the amino acid chain forms an amide bond with the next amino acid.

[0052] In an optional capping process step, a capping agent is added to prevent reaction with the amidites introduced at a later stage.

[0053] FIG. 1 illustrates a process cycle C for synthesizing a molecule, which includes multiple process steps PS1-PS4 according to one or more embodiments of the present disclosure. The process steps are performed sequentially from a first process step PS1 to a last process step PS4. Cycle C may be repeated any number of times by repeating the multiple process steps PS1-PS4. It is understood that any number of process steps may be used without departing from the present disclosure. Although four process steps are illustrated in FIG. 1, a cycle may include two, three, five, or more process steps.

[0054] Additional cycles C' (not shown) can be generated by modifying multiple process steps PS1 to PS4, each cycle typically adding to a chain that ultimately forms the target molecule.

[0055] The process cycle is typically controlled by a block of parameters as they are supplied or sent to a device configured to synthesize molecules, which are further described with respect to Figures 6 to 8. The block of parameters may be divided into or include sub-blocks, each sub-block controlling a respective process step PS1 to PS4.

[0056] 2 illustrates a process cycle 200 for synthesizing oligonucleotides according to one or more embodiments of the present disclosure. The process cycle 200 includes multiple process steps including at least detritylation 211, coupling 212, oxidation 213, and capping 214. The process steps are further described above in the first part of the detailed description.

[0057] In the detritylation process step 211, the "deprotecting agent" DMT is added to "deprotect" one hydroxyl group from the nucleoside, i.e., the last nucleoside in the sequence has one hydroxyl group ready to receive the next amidite.

[0058] In the coupling process step 212, an amidite is introduced along with an activator, thereby providing a support-bound nucleotide.

[0059] In the oxidation process step 213, an oxidizing agent is added to convert the trivalent phosphorus to pentavalent phosphorus.

[0060] In the capping process step 214, a capping agent is added to prevent any unprotected hydroxyl groups from reacting with the amidites introduced in a later stage.

[0061] FIG. 3 illustrates an example of a process description 300 configured to synthesize a molecule according to one or more embodiments of the present disclosure. A process description configured to synthesize a molecule is also commonly referred to in the art as a "method." The process description 300 illustrates multiple cycles C and parameters controlling the respective process steps PS1-PS4. In the example illustrated in FIG. 3, the process description 300 is rendered as a tree-like or hierarchical graphical representation. Other suitable graphical representations are contemplated, for example, simple lists, other hierarchical or relational diagrams such as mind maps, etc. In other words, a graphical representation that can illustrate the order of cycles and the hierarchical relationships cycle → process steps → parameters.

[0062] The process description may have a top level (Main) that represents the highest level of the tree / hierarchical structure. Just below the top level, the process description 300 includes a block level, where the blocks of parameters 310 that control each cycle are arranged in a particular order. In FIG. 3, the blocks for each cycle are shown as "Add DNA T", "Add DNA A", "Add DNA G", etc. Just below the block level, the process description 300 includes a sub-block level, where the sub-blocks of parameters 310 that each control each process step are arranged in a particular order, for example, the order shown with respect to FIG. 2. In FIG. 3, the sub-blocks for each cycle are shown as "Block: Detritylation", "Block: Coupling DNA T", "Block: Oxidation DNA#", "Block: Capping", etc.

[0063] Each block of parameters may be associated with a particular type, for example "A", "C", "G", or "T".

[0064] In one example, each of the blocks includes a "coupling" process step. The parameters of this process step can be edited and set globally for all cycles "A", "C", "G" or "T" by modifying the respective sub-blocks of parameters related to the "coupling" process step. This is referred to herein as global modification of parameters. Examples of globally modified parameters are "flow rate", "volume", "chase volume", "wash volume", and in fact are modified to achieve optimal or maximum coupling efficiency without excess reagents as much as possible.

[0065] In one example, all blocks of parameters of type "A" are modified. The parameters of this process step may be edited and set for all cycles of type "A" by modifying the respective parameters and / or sub-blocks of parameters. This is referred to herein as modifying parameters for cycles of the same type. A first and second block of parameters 330, 340 are shown in FIG. 3. The first and second blocks of parameters 330, 340 are both block / cycle type "A". Examples of parameters for cycles of the same type are "base", "amidite equivalent", "amidite concentration", "coupling change time", "% activator", "recirculation time", "coupling wash" and are in fact modified to achieve optimal or maximum coupling efficiency without excess reagents as much as possible.

[0066] In one example, only a selected block of parameters is modified. The parameters of the block of parameters indicated by the user input are modified by modifying the respective parameters and / or sub-blocks of parameters. This is referred to herein as modifying the selected cycle / block of parameters of the process description 300. Examples of parameters for the selected cycle are "index", "base", "amidite equivalent", "amidite concentration", "charge time", "activator mix", "recirculation time", "wash volume" and are in fact modified to achieve optimal or maximum coupling efficiency without excess reagents as much as possible.

[0067] Selected blocks of parameters are illustrated with respect to FIG.

[0068] 4 illustrates a selected block of parameters 410 according to one or more embodiments of the present disclosure. Parameters 440 for the sub-block / process step "Coupling" are shown to the right of the figure. Examples of parameters for a selected cycle are "Index", "Base", "Amidite Equivalent", "Amidite Concentration", "Charge Time", "Activator Mix", "Recirculation Time", and "Wash Volume".

[0069] A check box 410 to the left of each cycle / block is shown either checked 430 or unchecked 420, thereby indicating a selection; that is, the check box indicates a selected cycle / block. In the example shown in Figure 4, the first cycle / block 420 of type "T" is not selected, while the second cycle / block 430 of type "T" is selected and is modified using user input.

[0070] 5 illustrates a computer-implemented method performed by a device configured to synthesize a molecule according to one or more embodiments of the present disclosure. The synthesis includes performing a cycle of multiple process steps PS1 to PS4, the synthesis being controlled by blocks of parameters. The method includes:

[0071] Step 510: An indication of a target molecule is received.

[0072] In one example, a text entry field is rendered and displayed to the user. The user then provides user input by entering a text string indicating the target molecule, for example, "ACG GTA AAT T." This instruction is then received by the device.

[0073] Step 520: Generate the composite process description 300 by generating multiple blocks 310 of parameters, each block 310 controlling a process step for a respective cycle.

[0074] In one example, a block of parameters is generated by using a text string to perform a search in a memory or database to find a block of known combinations of cycles that when subsequently executed produce the target molecule.

[0075] Step 530: Receive user input indicating modification of the generated blocks of parameters.

[0076] In one example, the generated process description 300 is rendered and displayed in a manner similar to that shown in connection with Figure 3. A user may then interactively manipulate the rendered and displayed representation of the generated process description 300, for example, by adding blocks or sub-blocks, deleting blocks and / or sub-blocks, or modifying parameter values ​​of parameters included in the blocks and / or sub-blocks.

[0077] Step 540: Modify the generated blocks of parameters using user input.

[0078] In one example, blocks and / or sub-blocks are added and / or deleted as indicated by the user input, hi a further example, parameters are updated to new values ​​using the user input.

[0079] Step 550: Controlling synthesis of the target molecule by applying the modified blocks of parameters to control each cycle.

[0080] In one example, the modified blocks of parameters are provided or loaded into a device configured to synthesize a molecule, and then execute the cycles and process steps indicated by the modified blocks of parameters.

[0081] In one embodiment, each cycle 110 includes a plurality of process steps PS1-PS4, and each respective block 310 includes a corresponding number of sub-blocks 320 of parameters for that number of process steps in the plurality of process steps PS1-PS4. The received user input further indicates modification of one or more of the sub-blocks. Controlling the synthesis further includes applying the modified sub-blocks to control the process steps PS1-PS4 of the respective cycle.

[0082] In one non-limiting example, every cycle includes a process step of "coupling". Then, sub-blocks of parameters related to the "coupling" step for some blocks may be modified. If the sub-blocks of parameters related to the "coupling" step for all blocks are modified in the same way, this is referred to as a global modification. If the sub-blocks of parameters related to the "coupling" step for blocks of the same type are modified in the same way, this is referred to as a modification of all cycles of the same type, e.g., using base "A". If only selected sub-blocks of parameters related to the "coupling" step are modified, this is referred to as a modification of a selected cycle.

[0083] In one embodiment, modifying the generated blocks includes globally applying user input to all cycles by modifying the respective blocks of parameters.

[0084] In one embodiment, modifying the generated blocks includes applying user input to all cycles of the same type by modifying the respective blocks of parameters.

[0085] In one embodiment, the user input further indicates a selected cycle of the process description 300, and modifying the generated blocks includes applying the user input to the selected cycle.

[0086] In one embodiment, the target molecule is an oligonucleotide and the multiple process steps PS1-PS4 include at least detritylation 211, coupling 212, oxidation 213, and capping 214.

[0087] Additionally or alternatively, each subblock for process step detritylation 211 includes parameter values ​​for start level, end level, linear flow, efficiency limit, wash CV; each subblock for process step coupling 212 includes parameter values ​​for base identity, Eq, amidite concentration, coupling CT, activator percentage, extrusion flow rate, recycle time, and wash CV; each subblock for process step oxidation 213 includes parameter values ​​for ox CT DNA, ox Eq ​​DNA, ox CT RNA, ox Eq ​​RNA, chase CV ox, wash CV ox; and each subblock for process step capping 214 includes parameter values ​​for cap CT, cap CV, chase CV ox, and wash CV ox.

[0088] In one embodiment, the target molecule is an oligopeptide and the multiple process steps include at least detritylation, coupling, and optionally capping.

[0089] In one embodiment, the method step 530 of receiving user input includes rendering a representation of the synthesis process description 300, the representation including representations of the blocks 310 and / or sub-blocks 320 and / or parameter values ​​220, 440. The step 530 further includes displaying the representation to a user. The step 530 further includes receiving user input indicating an interaction with the representation, thereby indicating modification of the generated plurality of blocks of parameters.

[0090] Additionally or alternatively, the interaction may at least indicate modified parameter values ​​and indicate that the modified parameter values ​​should be applied globally to all cycles by modifying the respective blocks of parameters.

[0091] Additionally or alternatively, the interaction may at least indicate modified parameter values ​​and indicate that the modified parameter values ​​should be applied to all cycles of the same type by modifying the respective blocks of parameters.

[0092] Additionally or alternatively, the interaction may at least indicate a selected cycle of the process description 300, indicate modified parameter values, and indicate that the modified parameter values ​​should be applied to the selected cycle.

[0093] 6 illustrates a device 600 configured to synthesize molecules according to one or more embodiments of the present disclosure. Device 600 comprises a fluidic network, for example comprising fluidically coupled pipes, fluidically coupled valves, and fluidically coupled pumps.

[0094] The fluid network may be configured / controlled to receive fluid from fluid sources F1-F3 via solvent valve VH9-IB. The fluid network may be further configured / controlled to direct the received fluid to recirculation valve V9H-RC. The fluid network may be further configured to direct fluid to a waste port via recirculation valve V9H-RC, and optionally via waste valve V9H-O1. The fluid network may be further configured to direct fluid to column valve V9H-O1 via recirculation valve V9H-RC. The column valve V9H-C is configured to direct fluid to one or more columns 640 and / or receive fluid from one or more columns 640. The fluid network may be further configured to direct fluid to a second solvent valve V9H-IA1 via column valve V9H-C. The fluid network may be further configured to direct fluid to a fluid receptacle, e.g., a vessel, via second solvent valve V9H-IA1. The fluid network may further be configured to direct fluid through the second solvent valve V9H-IA1 to the first amidite valve V9H-IA2 and / or the second amidite valve V9H-IA3, which may distribute amidites A21-A23 and the second amidite valve V9H-IA3 may distribute amidites A31-A33, for example, to containers.

[0095] Additionally or alternatively, the device may further comprise a display 618 .

[0096] Additionally or alternatively, the device may further comprise an input device 617 .

[0097] Additionally or alternatively, the device further comprises a control unit 610 including circuitry, the circuitry including a processing circuit and a memory, the memory including instructions executable by the processing circuit, the control unit 610 being communicatively coupled to each controllable portion of the fluid network, e.g., pumps and valves. The device 600 including the control unit 610 is configured to perform any method steps described herein.

[0098] Selected ones of the device components of the fluid network are communicatively coupled to a control unit 610 (illustrated in dashed lines), e.g., sensors and valves. Information about properties of the fluid network or properties of fluids carried by the fluid network may be measured by the sensors and transmitted as control signals to the control unit 610. The control unit 610 may respond to the blocks of parameters and / or information about the properties of the fluid network and control valves in the fluid network by transmitting control signals.

[0099] In one embodiment, the device further comprises one or more sensors configured to measure properties of the fluid network. The control unit 610 is further communicatively coupled to each of the sensors. The sensors may be configured to measure pressure and / or measure the pH and / or conductivity of the generated buffer solution. Any suitable sensor for performing fluid measurements may be used.

[0100] In one example, the device is the OligoPilot II (also a trademark of the assignee of the present invention), which uses a flow-through design in which the various conduits, pumps, and valves are constantly filled with liquid / fluids. Liquid introduced into a vessel (called a "column" in a flow-through device) displaces the liquid previously introduced. This flow-through system is distinct from a "batch" system in which liquid is introduced into a reaction vessel, the introduced liquid is washed out, and the steps of introducing and washing out liquid are repeated. In such batch devices, liquid is fed into the vessel by gas pressure rather than by a pump. This approach can be used since batch processes have gaps in the liquid flow.

[0101] In the OligoPilot II device, first and second 8-way valves, each having eight individually selectable inlet ports, have an output port coupled to an inlet port of a first 3-port valve of a type in which only one of the inlet ports must remain open. Each of the two 8-way valves has four inlet ports coupled to receive one of four different types of amidites and four inlet ports coupled to receive ACN (a flushing agent).

[0102] The outlet port of the first three-port valve is coupled to the first inlet port of a second three-port valve of the same type as the first. The second inlet port to this second three-port valve is coupled to a third eight-way valve having various inputs including ACN, oxidant, capping agent, and activator. The outlet port of the second three-way valve is provided with a valve coupled to the inlet side of a reagent pump for pumping liquid into the column through the valve on the outlet side of the reagent pump. This last valve is also coupled to two pumps dedicated to the task of pumping deprotectant and ACN at a higher flow rate than the reagent pump.

[0103] The liquid output from the column is fed through a valve on the inlet side of the pump to a monitor that detects the absorption of light to sense the displaced trityl groups, and then to a waste valve that receives one input and has multiple separate outputs for waste. By selecting several ports on the inlet and outlet valves of the reagent pump, the liquid can be circulated through the column for a desired period of time.

[0104] In the OligoPilot II machine, to introduce the next amidite into the column, one of the 8-way valves is set to receive the next amidite and the other of the 8-way valves is set to receive the activator. The 8-way valves receiving the activator and the amidite are pulsed back and forth to introduce alternating amounts of each.

[0105] Each of the pumps is initially calibrated to regulate the amount of liquid delivered to the column. During operation, the pumps are run for a period of time to deliver the desired amount of liquid. Periodically, the pumps must be rechecked and recalibrated to avoid problems that may result from pump drift. For the scale of synthesis involved, such flow rate calibration is accurate enough to control the amount of reagent delivered to the column. However, for larger scale synthesis, more sophisticated means of controlling the delivery of liquid are required.

[0106] In one embodiment, a device 600 is provided and configured to synthesize molecules. The synthesis comprises performing a cycle of a number of process steps PS1 to PS4, the synthesis being controlled by a block of parameters. The device includes: A controllable fluid network; An input device 617; an optional display 618; and A control unit 610 comprising a circuit, A processing circuit; and a memory including instructions executable by the processing circuitry, the control unit 610 being communicatively coupled to the controllable units of the fluid network, whereby the device is configured to perform the methods described herein when the instructions are executed by the processing circuitry.

[0107] In one embodiment, a computer program is provided that includes computer-executable instructions that, when executed on processing circuitry included within the control unit 610, cause the control unit 610 to perform the method steps described herein.

[0108] The control unit 610 may take the form of, for example, an electronic control unit, a server, an on-board computer, a fixed computing device, a laptop computer, a tablet computer, a handheld computer, a wrist-worn computer, a smart watch, a smartphone, or a smart TV. The control unit 610 may comprise a processing circuit communicatively coupled to a transceiver configured for wired or wireless communication. The control unit may further comprise at least one optional antenna (not shown). The antenna may be coupled to the transceiver and configured to transmit and / or radiate and / or receive wired or wireless signals within a communication network, such as Wi-Fi, Bluetooth, 3G, 4G, 5G, etc. In one example, the processing circuit may be any of a selection of a processing circuit and / or a central processing unit and / or a processor module and / or a plurality of processors configured to cooperate with each other. Additionally, the control unit 610 may further comprise a memory. The memory may include, for example, a selection of hard RAM, a disk drive, a floppy disk drive, a flash drive or other removable or fixed media drive, or other suitable memory known in the art. The memory may contain instructions executable by the processing circuit to perform any of the steps or methods described herein. The processing circuit may optionally be communicatively coupled to a transceiver, memory, one or more sensors such as pH sensors, conductivity sensors, and pressure sensors, or any selection of any suitable type of sensor capable of measuring properties of the device and / or the fluid processed by the device. The control unit 610 may be configured to send / receive control signals directly to / from any of the above-mentioned units or external nodes, or to send / receive control signals via a wired and / or wireless communication network.

[0109] The wired / wireless transceiver and / or wired / wireless communication network adapter may be configured to transmit and / or receive data values ​​or parameters as signals from the processing circuit to or from the external node, for example the measured pH or conductivity of a buffer solution or the volume produced.

[0110] In one embodiment, the transceiver communicates with an external node directly or via a wireless communication network.

[0111] In one or more embodiments, the control unit 610 may further comprise an input device 617 configured to receive input or instructions from a user and transmit a user input signal indicative of the user input or instructions to the processing circuit.

[0112] In one or more embodiments, the control unit 610 may further include a display 618 configured to receive display signals from the processing circuit indicating rendered objects, such as text or graphical user input objects, and to display the received signals as objects, such as text or graphical user input objects.

[0113] In one embodiment, display 618 is integrated with user input device 617 and is configured to receive display signals from the processing circuitry indicating rendered objects, such as text or graphical user input objects, and display the received signals as objects, such as text or graphical user input objects, and / or to receive input or instructions from a user and transmit user input signals indicative of the user input or instructions to the processing circuitry.

[0114] In further embodiments, the control unit 610 may further comprise and / or be coupled to one or more additional sensors (not shown) configured to receive and / or acquire and / or measure physical properties related to the device and / or the air surrounding the device and transmit one or more sensor signals indicative of the physical properties of the device to the processing circuitry, for example a temperature sensor measuring the ambient air temperature.

[0115] In one or more embodiments, the processing circuitry is further communicatively coupled to an input device and / or a display and / or additional sensors and / or any of the units described herein.

[0116] In an embodiment, the communication network is a Local Area Network (LAN), a Metropolitan Area Network (MAN), Global System for Mobile Networks (GSM), Enhanced Data GSM Environment (EDGE), Universal Mobile Telecommunications System, Long Term Evolution, High Speed ​​Downlink Packet Access (HSDPA), Wideband Code Division Multiple Access (W-CDMA), Code Division Multiple Access (CDMA), Time Division Multiple Access (TDMA), Bluetooth, Zigbee, Wi-Fi, Voice over Internet Protocol (VoIP), LTE Advanced, IEEE 802.16m, WirelessMAN-Advanced, Evolved High-Speed ​​Packet Access (HSPA+), 3GPP Long Term Evolution (LTE), Mobile WiMAX (IEEE 802.16e), Ultra Mobile Broadband (UMB) (formerly Evolution-Data Optimized (EV-DO) Rev. C), Fast Low-latency Access with Seamless Handoff The communication may be performed using wired or wireless communication technologies, which may include, but are not limited to, at least one of Orthogonal Frequency Division Multiplexing (Flash-OFDM), High Capacity Spatial Division Multiple Access (iBurst®), and Broadband Mobile Radio Access (MBWA) (IEEE 802.20) systems, High Performance Wireless Metropolitan Area Network (HIPERMAN), Beam Division Multiple Access (BDMA), World Interoperability for Microwave Access (Wi-MAX), and ultrasonic communications.

[0117] Further, it will be appreciated by those skilled in the art that the control unit 610 may comprise necessary communication functionality, e.g. in the form of functions, means, units, elements, etc. Examples of other such means, units, elements and functions are processors, memories, buffers, control logic circuits, encoders, decoders, rate matchers, de-rate matchers, mapping units, multipliers, decision units, selection units, switches, interleavers, deinterleavers, modulators, demodulators, inputs, outputs, antennas, amplifiers, receiver units, transmitter units, DSPs, MSDs, TCM encoders, TCM decoders, power supply units, power feeds, communication interfaces, communication protocols, etc., suitably arranged and assembled to perform the solutions of the present invention.

[0118] In particular, the processing circuit and / or processing means of the present disclosure may include one or more instances of processing circuits, processor modules, and multiple processors, central processing units (CPUs), processing units, processing circuits, processors, application specific integrated circuits (ASICs), microprocessors, field programmable gate arrays (FPGAs), or other processing logic that may interpret and execute instructions, configured to cooperate with one another. Thus, the phrases "processing circuit" and / or "processing means" may refer to a processing circuit that includes multiple processing circuits, such as, for example, any, some, or all of those mentioned above. The processing means may further perform data processing functions for input, output, and processing of data, including data buffering, and device control functions such as user interface control, and the like.

[0119] FIG. 7 illustrates an example of a device configured to synthesize oligonucleotides according to one or more embodiments of the present disclosure. The device is described with reference to FIG. 6. The device of FIG. 7 is fluidically coupled in a manner similar to that described in FIG. 6. Optionally, an ultraviolet sensor, UV sensor, U9 is fluidically coupled between the recirculation valve V9HRC and the column valve V9H-C. In addition, a conductance sensor C9n is further fluidically coupled between the recirculation valve V9HRC and the column valve V9H-C. Optionally, a first pressure sensor R9_1 is further fluidically coupled between the recirculation valve V9HRC and the column valve V9H-C. The UV sensor U9, the conductance sensor C9n, and the first pressure sensor R9_1 are typically fluidically coupled in series in any order suitable or practically selected.

[0120] Optionally, a second pressure sensor R9_2 is further fluidly coupled between the column valve V9H-C and the second solvent valve V9H-IA1. In addition, a third pressure sensor R9_3 is further optionally fluidly coupled between the second pressure sensor R9_2 and the second solvent valve V9H-IA1.

[0121] Optionally, a pressure sensor P90(A) is fluidly coupled between the second or third pressure sensor R9_2, R9_3 and the second solvent valve V9H-IA1.

[0122] The second solvent valve V9H-IA1 in this example includes fluid outlet ports, e.g., for thiolation, Cap A, Extra 1, Detrit, CAN A7, and oxidation. The second solvent valve V9H-IA1 is further fluidly coupled to the first amidite valve V9H-IA2 and / or the second amidite valve V9H-IA3.

[0123] The first amidite valve V9H-IA2 in this example provides fluid outlet ports for, for example, A, C, G, T, Q, X, Y, Z amidites, or any acetonitrile bonds therebetween.

[0124] The second amidite valve V9H-IA3, in this example, provides fluid outlet ports for, for example, a, c, g, u, w, x, y, z amidites, or any acetonitrile bonds therebetween.

[0125] 8 illustrates one example of a device configured to synthesize oligonucleotides according to one or more embodiments of the present disclosure. In FIG. 8, device 8 for synthesizing oligonucleotides has inlet ports for fluidly receiving liquids from multiple fluid sources / containers holding different types of liquids, and outlet ports for delivering selected liquids to columns. Although described here with respect to the phosphoramidite method for synthesizing oligonucleotides, device 8 can be readily used with other methods for synthesizing oligonucleotides.

[0126] The four most commonly used amidites, which are the monomers used in the phosphoramidite method, are stored separately in containers 10, 12, 14, and 16, respectively. These amidites have a deoxyribose sugar, and thus the amidites are deoxyadenosine, deoxycytidine, deoxyguanosine, and deoxythymidine, known as dA, dC, dG, and dT, respectively. Other amidites that may be used, referred to here as dX and dY, are stored in containers 18 and 20. All of the amidites are dissolved in ACN.

[0127] Other agents are also stored in separate containers. The capping agents, designated Cap A and Cap B, are stored in containers 22 and 24, the activating agent, preferably tetrazole, is stored in container 26, the oxidizing agent is stored in container 28, and the deprotecting agent, preferably a detritylation agent, is stored in container 124. In the case of the oxidizing agents, two additional valves and pumps can be used to select between two different types of oxidizing agents, one used to form phosphodiester bonds and the other used to form phosphorothioate bonds.

[0128] Each container 10-28 is fluidly coupled through a respective conduit 40-49 to a first optional inlet port of one of the optional valves 30-39 (not in any particular order). The valves 30-39 are preferably three-port / three-way valves, i.e. each has three ports, typically one outlet port and two inlet ports, where one, both or neither of the inlet ports can be left open. The second inlet port of each optional valve 30-39 is fluidly coupled through a respective conduit 70-79 to a conduit 80 carrying ACN from a flushing agent container 82. Each of the valves 30-39 is fluidly coupled at its outlet port to a respective pump 50-59 through a conduit 60-69. Each of the introduced liquids is thus associated with a separate pump module comprising a pump and a valve.

[0129] These modules are coupled downstream through a valve arrangement that is controlled to select liquids for introduction into the column. The outlet ports of pumps 50 and 51, which receive Cap A and Cap B, are fluidly coupled to the inlet port of valve 90, whose output port is fluidly coupled to a first inlet port of valve 92. When capping agent is introduced, both inlet ports of valve 90 are typically left open simultaneously to dispense equal amounts of capping agent. The second inlet port of valve 92 receives oxidant from the output of pump 52. Thus, valve 92 can selectively deliver one of a combination of Cap A and Cap B, oxidant, and ACN.

[0130] Pumps 53-58, fluidly coupled to receive dA, dC, dG, dT, dX, and dY, respectively, are paired and the outlets of these pumps are fluidly coupled to part of a valving arrangement for selecting one of the amidites (or ACN) for introduction into the column. The outlet ports of pumps 53 and 54 are fluidly coupled to the inlet port of valve 94, and the outlet ports of pumps 55 and 56 are fluidly coupled to the inlet port of valve 96. The outlet ports of valves 94 and 96 are fluidly coupled to the inlet port of valve 98, which in turn supplies ACN or one of the amidites dA, dC, dG, and dT to a first inlet port of valve 102. Pumps 57 and 58, which selectively pump dX and dY, are fluidly coupled to valve 100, which supplies liquid at its outlet port to a second inlet port of valve 102. The outlet port of valve 102 therefore supplies one of the six amidites or ACN. Since one amidite is supplied at a time, valves 94-102 generally only have one inlet port open at a time.

[0131] Pump 59 for pumping the activator, preferably tetrazole, from container 26 is not paired with any other pump.

[0132] Fluid output from valve 92, valve 102, and pump 59 is provided to respective flow sensors 110, 112, and 114. These sensors are preferably turbine flow meters, such as the model FTO-3 produced by EG&G / Amtele AB, which have a rotating turbine for carefully metering the amount of fluid flow. The flow meters provide signals to a controller, which uses the signals to regulate pumps 50-59.

[0133] The amidite or ACN flowing through sensor 112 and the activator or ACN flowing through sensor 114 are fed to inlet ports of valve 116. Valve 116 is a three-way valve and can receive liquid at two inlet ports simultaneously so that when the amidite is fed from valve 102 and the activator is fed from sensor 114, the liquids can be mixed together in valve 116. The liquid flowing through sensor 110 is coupled to a first inlet port of valve 118, which receives liquid from an outlet port of valve 116 at a second inlet port. The inlet ports to valve 118 are typically only open one at a time, if at all.

[0134] An outlet port of valve 118 is fluidly coupled to a first inlet port of valve 120. A second inlet port of valve 120 receives ACN from container 82 or deprotection agent from container 124. The ACN and deprotection agent are each provided to a pump module that includes valve 126 and pump 128. An outlet port of pump 128 is fluidly coupled to a second inlet port of valve 120. Pump 128 is of a generally similar design to pumps 50-59, but has a flow rate ten times greater than any of pumps 50-59.

[0135] Fluid from the outlet port of valve 120 is fed to a piezoelectric pressure transmitter 140, which senses the pressure of the fluid and provides an electrical signal to a controller indicative of the pressure of the flowing fluid.

[0136] The liquid is then fed to an ultrasonic air sensor 142 having a sensor unit disposed in the conduit carrying the liquid and a control unit coupled to the sensor unit. The air sensor continuously monitors the liquid and senses air bubbles or gaps in the liquid within the conduit. Such air bubbles or gaps should not occur in a flow-through system; rather, the various conduits should always have liquid in them. If an air bubble is detected, the flow of liquid may be interrupted to prevent air from entering the downstream columns, and an alarm may sound.

[0137] The liquid is then provided to a UV monitor and transmitter 144. The monitor is preferably a model UV-M / 1 and the UV-transmitter is preferably a model UV-P. Each of these models are distributed by the assignee of the present invention. The monitor has a light source for providing light, a filter for providing light of a first selected wavelength, and a photodetector for sensing the amount of UV absorption. The wavelength is selected such that the UV absorption is indicative of the amount of nucleosides in the liquid. The monitor provides an analog signal to the transmitter, which has a high resolution analog to digital converter that converts the analog signal to digital information for use by the controller.

[0138] The liquid from the UV monitor and transmitter 144 is then fed to a valve 146 having a first outlet port 147 for coupling to a flow-through column 151 where the oligonucleotides are produced, and a second outlet port 148 that can be used to bypass the column 151 during testing or at start-up when all liquid conduits are primed.

[0139] As shown above, there are many steps where liquid must be flushed (or at least sufficiently diluted) from column 151. Therefore, provisions are provided to receive and monitor the liquid feed from these flushing processes. Column 151 is coupled to an inlet port of valve 150 which receives liquid displaced from column 151 as new liquid is introduced into the column. A second inlet port of valve 150 is coupled to outlet port 148 of valve 146 to bypass column 151 when desired.

[0140] The displaced liquid is provided at the outlet port of valve 150 to first and second UV monitors and transmitters 152, 154, two of the same general type as UV monitor and transmitter 144. Monitor and transmitter 152 detects the nucleosides displaced from column 151 using the same wavelengths as monitor and transmitter 144. By receiving signals from UV monitor and transmitters 144 and 152, the controller can determine the amount of nucleosides introduced into and displaced from column 151, and therefore the difference left in the column due to reaction with the nascent oligonucleotide.

[0141] The UV monitor and transmitter 154 uses a second selected wavelength (which may be visible rather than ultraviolet) different from the first wavelength to sense the amount of DMT removed by the deprotectant. The deprotectant is introduced and indicates the start of a deprotectant cycle when the amount of DMT sensed by the monitor and transmitter 154 exceeds a first threshold. The controller then determines that the deprotectant cycle is finished when the sensed amount of DMT falls below a second threshold. This process leaves a certain amount of deprotectant in the line between the column and the valve 120 (FIG. 1), but this amount is insignificant with respect to the volume of the column. The sensing performed by the monitor and transmitter 154 can also be performed using a conductivity sensor.

[0142] After the UV monitor and transmitter, the liquid passes through a flow sensor 156. In addition to generally sensing the flow of liquid being expelled, sensor 156 is also used to regulate the flow rate of pump 128. Sensor 156 is generally similar to sensors 110, 112, 114, but is preferably a model FT4-8 which accommodates larger volumes of liquid flow.

[0143] From the flow sensor 156, the liquid is fed to a back pressure valve and then to a first waste valve 160. Valve 160 has one inlet port and two outlet ports, the first of which is provided as a waste output and the second of which is provided to a second waste valve 162. Valve 162 also has two outlet ports. The combination of valves 160 and 162 therefore provides three separate outputs for waste resulting from column flushing. This separation is useful as different waste liquids have different requirements for handling and disposal.

[0144] Each of the valves described above is preferably a pneumatically actuated, 3 port / 3 way diaphragm valve, a model produced by Robolux AB, Lidingö, Sweden. An air valve is controlled by a solenoid valve coupled to a controller to provide a pneumatic drive to control the valve. Each of the pumps is preferably a vane pump with a magnetic coupling drive produced by Castor, Italy. Most of the pumps are model MPA114AP, with capacities ranging from 3 to 48 liters per hour, and pump 128 is model MPA116AP, with capacities ranging from 30 to 480 liters per hour.

[0145] Finally, it is to be understood that the present invention is not limited to the embodiments described above, but also relates to and incorporates all embodiments falling within the scope of the appended independent claims. [Explanation of symbols]

[0146] A21, A22, A23 Amidite A31, A32, A33 Amidite C. Process Cycle C9n Conductance Sensor F1,F2,F3 Fluid source P90(A) Pressure Sensor PS1, PS2, PS3, PS4 process steps R9_1 1st pressure sensor R9_2 Second pressure sensor R9_3 3rd pressure sensor U9 UV Sensor V9H-C Column valve V9H-O1 Waste valve V9H-O1 Column valve V9H-RC Recirculation Valve V9HRC Recirculation Valve V9H-IA1 Second Solvent Valve V9H-IA2 First Amidite Valve V9H-IA3 Second Amidite Valve VH9-IB Solvent Valve 10,12,14,16,18,20,22,24,26,28 container 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 Valves 40,41,42,43,44,45,46,47,48,49 Conduit 50,51,52,53,54,55,56,57,58,59 Pump 60,61,62,63,64,65,66,67,68,69 Conduit 70,71,72,73,74,75,76,77,78,79,80 Conduit 82 Flushing agent container 90,92,94,96,98,100,102 Valves 110 cycles 110,112,114 Flow Sensor 116,118,120 Valve 124 Container 126 Valve 128 Pump 140 Piezoelectric Pressure Transmitter 142 Ultrasonic Air Sensor 144 UV Monitor and Transmitter 146 Valve 147 First Exit Port 148 Second Exit Port 150 valves 151 Flow-Through Column 152 First UV Monitor and Transmitter 154 Second UV Monitor and Transmitter 156 Flow Sensor 160 First drain valve 162 Second drain valve 200 process cycles 211 Detritylation 212 Coupling 213 Oxidation 214 Capping 300 Process Description 310 Parameter 320 Subblocks 330 First block of parameters 340 Second block of parameters 410 Parameters 410 Checkbox 430 Checked 420 No check mark 440 Parameters 600 devices 610 Control Unit 617 Input Devices 618 Display 640 Column

Claims

1. 1. A computer-implemented method executed by a device configured to synthesize a molecule, said synthesis comprising performing a cycle of a plurality of process steps (PS1-PS4), said synthesis being controlled by blocks of parameters, said method comprising: receiving an indication of a target molecule; generating a composite process description (300) by generating a number of blocks (310) of parameters, each block 310 controlling a process step of a respective cycle; receiving user input indicating modification of said generated blocks of parameters; modifying the generated blocks of parameters using the user input; controlling synthesis of the target molecule by applying the modified blocks of parameters to control each of the cycles; A method comprising:

2. Each cycle (110) includes a number of process steps (PS1-PS4), each block (310) including a corresponding number of sub-blocks (320) of parameters for said number of process steps in said number of process steps (PS1-PS4); the received user input further indicates one or more modifications of the sub-block; The method of claim 1, wherein controlling the synthesis further comprises applying the modified sub-blocks to control the process steps (PS1 to PS4) of the respective cycles.

3. The method of claim 1 or 2, wherein modifying the generated blocks comprises globally applying the user input to all cycles by modifying respective blocks of parameters.

4. 4. The method according to claim 1, wherein modifying the generated blocks comprises applying the user input to all cycles of the same type by modifying a respective block of parameters.

5. 5. The method of claim 1, wherein the user input further indicates a selected cycle of the process description (300), and modifying the generated plurality of blocks comprises applying the user input to the selected cycle.

6. 6. The method according to claim 1, wherein the target molecule is an oligonucleotide and the plurality of process steps (PS1 to PS4) comprises at least detritylation (211), coupling (212), oxidation (213), and capping (214).

7. Each sub-block for the process step detritylation (211) includes parameter values ​​for start level, end level, linear flow, efficiency limit, wash CV; the respective subblocks for the coupling (212) process step include parameter values ​​for base identity, Eq, amidite concentration, coupling CT, activator ratio, extrusion flow rate, recycle time, and wash CV; The respective sub-blocks for the process step Oxidation (213) include parameter values ​​for ox CT DNA, ox Eq ​​DNA, ox CT RNA, ox Eq ​​RNA, Chase CV ox, Wash CV ox; 7. The method of claim 6, wherein the respective sub-blocks for the process step capping (214) include parameter values ​​for CAP CT, CAP CV, chase CV ox, and wash CV ox.

8. 8. The method of claim 1, wherein the target molecule is an oligopeptide and the process steps include at least detritylation, coupling, and optionally capping.

9. The step of receiving a user input includes: - rendering a representation of said synthesis process description (300), said representation including representations of blocks (310) and / or sub-blocks (320) and / or parameter values; displaying said representation to a user; receiving user input indicating a modification of the generated plurality of blocks of parameters by receiving user input indicating an interaction with the representation; 9. The method of any one of claims 1 to 8, comprising:

10. 10. The method of claim 9, wherein the interaction at least indicates modified parameter values ​​and indicates that the modified parameter values ​​should be applied globally to all cycles by modifying respective blocks of parameters.

11. 11. The method according to claim 9 or 10, wherein the interaction at least indicates modified parameter values ​​and indicates that the modified parameter values ​​should be applied to all cycles of the same type by modifying respective blocks of parameters.

12. 12. The method of claim 9, wherein the interaction at least indicates a selected cycle of the process description (300), indicates modified parameter values, and indicates that the modified parameter values ​​should be applied to the selected cycle.

13. A device (600) configured to synthesize a molecule, said synthesis comprising a cycle of a plurality of process steps (PS1 to PS4), said synthesis being controlled by blocks of parameters, said device comprising: A controllable fluid network; An input device (617); Display (618) and A control unit (610) having a circuit; The circuit comprises: A processing circuit; a memory containing instructions executable by said processing circuitry; 13. A device (600) comprising: a control unit (610) communicatively coupled to a controllable unit of the fluid network, whereby the device is configured to perform the method of any one of claims 1 to 12 when the instructions are executed by the processing circuitry.

14. 13. A computer program comprising computer-executable instructions which, when executed on processing circuitry contained within a control unit (610), cause the control unit (610) to perform a method according to any one of claims 1 to 12.

15. A computer readable storage medium storing the computer program of claim 14.

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