Parallel synthesis apparatus for combinatorial chemistry

Abstract

A parallel synthesis device for combinatorial chemistry is provided. [Solution] The parallel synthesis apparatus 100 includes a plurality of reaction vessels 102, each including a sealed chamber with a controlled gas inlet 102(a) and outlet system 102(b) for regulating the reaction environment, a reaction control module 104 connected to the reaction vessels and configured to monitor and regulate parameters including temperature, pressure, and reagent flow rates within each vessel, a reagent distribution unit 106 consisting of a plurality of precisely controlled pumps for delivering various chemical reagents to the reaction vessels, a parallel heating unit 108 integrated with each reaction vessel, a mixing device 110 installed within each reaction vessel, an automatic sampling mechanism 112 consisting of a robotic arm, and a processing unit 114 communicatively coupled to the reaction control module, the reagent distribution unit, the parallel heating unit, and the automatic sampling mechanism.

Description

[Technical field]

[0001] The present invention relates to a parallel synthesis device for combinatorial chemistry that simultaneously synthesizes multiple chemical compounds using an automated process. [Background technology]

[0002] Modern chemical and pharmaceutical research faces the problem of generating vast libraries of compounds for screening and testing. Chemical synthesis has traditionally involved sequential reactions (time- and resource-intensive) to produce small molecules. Parallel synthesis systems, which perform multiple reactions simultaneously, offer one answer by allowing libraries to be created much more quickly. However, while parallel synthesis systems exist, many of them suffer from scalability issues, poor control of reaction conditions, and lack of reproducibility across multiple vessels. Treating each reaction condition equally requires complex control of reaction temperature, pressure, and reagent delivery. Moreover, even available systems are often too rigid to be scaled or configured to accommodate new experimental demands.

[0003] The invention disclosed herein addresses these challenges by providing a parallel synthesis device for independently directing multiple reaction vessels with precise control of temperature, pressure, and reagent delivery and mixing. This system enables scalable parallel synthesis with well-defined control, providing an effective route to high-throughput chemical synthesis.

[0004] Combinatorial chemistry for the parallel synthesis of compounds is becoming more important due to its possible applications in drug discovery, materials science, and innovative chemicals. High-throughput screening has led to an increased interest in parallel synthesis systems for creating large compound libraries. By running reactions in parallel, many compounds can be prepared at once. However, even with improvements in automation and parallel processing, older systems struggle to work faster than necessary or are limited in scale due to scalability limitations.

[0005] Traditional approaches to chemical synthesis are a typical methodology, where reactions are usually performed in parallel or serial fashion. This is a labor-intensive process, consuming large amounts of manpower, reagents, and equipment. While this system is suitable for small-scale research, it becomes inefficient when trying to synthesize hundreds or thousands of compounds (combinatorial chemistry). To overcome these limitations, parallel synthesis systems have been developed, which allow many reactions to be performed simultaneously. Parallel synthesis systems dramatically outperform these systems in terms of throughput, saving valuable time and resources in synthesis. However, parallel synthesis systems also have their weaknesses.

[0006] The use of multi-well reaction plates, where each well acts as an individual mini-reaction vessel, was one of the earliest solutions for parallel synthesis. Multiple compounds can be synthesized simultaneously by adding reagents to each well and activating the reaction under common conditions. Although multi-well synthesis offers a simple solution for parallel synthesis, many multi-well plate formats do not allow for precise metering of reaction conditions to each well. Temperature, pressure, and mixing of reagents in a particular well can cause inconsistent results. Furthermore, multi-well plates are inherently poorly scalable, and simply increasing the number of wells does not improve reaction control or reproducibility. As a result, variability in yields from such reactions can reduce the quality of compound synthesis and undermine the high-throughput precision required for pharmaceutical research.

[0007] Some have further automated the process, removing the limitations of multi-well plates. These devices are equipped with robotic arms and automated pipetting stations, responsible for precise dispensing of reagents into reaction vessels. They also incorporate temperature-controlled environments and automated mixing, allowing for better control of reaction conditions. Finally, while these systems are a step ahead of manual synthesis in many ways, they tend to be expensive ($200,000-$1 million), finicky, and not user-friendly. The cost of acquiring and maintaining such systems can be prohibitive, especially for small laboratories and start-ups. Although automated, these systems continue to fail to provide effort-independent control of each reaction vessel. As a result, most, if not all, reactions within the system are run at the same temperature and pressure, which may not be ideal for the individual reactions.

[0008] Continuous flow chemistry systems have long been employed as a complementary solution in parallel synthesis; that is, reagents are pumped continuously through a series of reaction chambers where they undergo chemical reactions. Continuous flow systems, which offer precise control over reaction time, reagent flow rates, and many other reaction conditions, have emerged as a promising technology for the parallel synthesis of molecules. They also provide an avenue for monitoring reaction progress and product formation in real time. However, continuous flow systems have several drawbacks. First, flow rates and reaction times need to be thoroughly optimized for each reaction. Moreover, continuous flow systems generally cannot be used for a wide range of reactions, as they are not all completed within typical reaction times and environmental conditions that are convenient for operation. Moreover, when scaling up continuous flow systems for industrial use, larger volumes of reagents and solvents must be precisely controlled while maintaining reaction efficiency.

[0009] Another common system in parallel synthesis is the use of batch reactors. These are essentially small-scale vessels in which multiple reactions can be run at once. Chemists can tweak the reactor to get unique control over temperature, pressure, mixing, etc., making them ideal for a wide variety of chemical reactions. However, batch reactors have limitations. While batch reactions are a popular start, scaling up a batch reaction can lead to poor mixing and cold / hot spots that can occur in larger vessels. Batch reactors also generally require operator interaction (setting, loading and unloading the reaction vessel), reducing overall efficiency and throughput. In addition to this, batch reactors and associated equipment are expensive investments, and expanding their scope of use can be cost-prohibitive, especially in low-budget research environments.

[0010] The lack of individual control in parallel synthesis systems is one of the most challenging problems. Most current platforms, utilizing multi-well plates, automated pipetting, and sophisticated flow conditions in batch reactors, treat each reaction vessel the same. Treating all reactions simultaneously as if they would proceed optimally under the same conditions is a dangerous one-size-fits-all approach to providing clean deoxyribonucleic acid from multiple samples. In reality, different reactions may require different temperatures, pressures, or mixing rates to proceed most effectively. The lack of individual control of these parameters for each reaction vessel can adversely affect the quality and reproducibility of the synthesis. This is paramount in industries such as pharmaceuticals, where small deviations from reaction conditions can lead to artifacts in compound identity, purity, and ultimately bioactivity.

[0011] A further constraint is the scalability of available parallelization systems. Typically, throughput-specific systems are deployed to scale up these processes to allow for more reactions, but this scale often involves a trade-off between quantity and quality. For example, scaling up the number of wells in a multiwell plate or reaction vessels from 1 to n (where n is an integer) can overcome the challenges of reagent supply, mixing, and temperature control. However, as the number of reactions increases, issues of scalability and resource consumption costs of system management emerge. For researchers and industry who need to synthesize large quantities of staggering libraries, rather than just a few dozen compounds, without sacrificing precision and quality, this system can become cumbersome.

[0012] Waste management is an area where the already available parallel synthesis solutions fall short. Most parallel synthesis systems lack a means of waste disposal, forcing end users to rely on manual procedures to safely collect, treat, and dispose of chemically contaminated by-products. This is not only time-consuming but also dangerous, especially when dealing with toxic and reactive chemicals. While some automated systems have waste collection units, they are simple equipment and may not include the proper features to properly inactivate or treat hazardous waste. This requires additional safety procedures during waste disposal, creating a second complication for the synthesis.

[0013] Currently available parallel synthesis systems show progress towards better throughput and automation, but some developing limitations can be found in them. Such systems often suffer from poor control of each reaction condition, limited scalability, and cost and waste due to contamination of reagents that are discarded in landfills. The growing demand for robots to complete high-throughput chemical synthesis is evident, and the need for new systems that can address these challenges should be considered. When the reaction is performed, the properties of each vessel must be individually controlled to adjust the reaction parameters that result in the optimal synthesis. Furthermore, it is fundamental that it is scalable, inexpensive, or able to handle waste in the most economically safe sense. This would be a major leap in the field of combinatorial chemistry to enable researchers and industry to develop complex libraries more precisely and on a larger scale. Summary of the Invention [Problem to be solved by the invention]

[0014] The discovery concerns a uniquely modular parallel synthesis device that is used for the simultaneous multiple synthesis of one or more chemicals under controlled conditions. The system consists of an array of reaction modules, each with its own independent control of temperature and pressure and reagent supply. A dedicated central processing unit controls the process, tightly regulating all modules in perfect harmony and making online adjustments to maintain favorable reaction conditions.

[0015] Each reaction module is equipped with a high-pressure, high-temperature resistant reaction vessel. The vessel containing the sample is plumbed to a network of reagent reservoirs, pumps, and valves that dispense predetermined amounts of chemicals according to pre-set protocols. The system also provides built-in sensors that control the temperature, pressure, pH, and progress of the reaction. Real-time feedback from the sensors to a central processing unit allows for a high degree of control, allowing on-the-fly adjustments if reaction conditions are not as desired.

[0016] A key attribute of the system is the fact that it is scalable. The design is modular, allowing reaction modules to be added or removed depending on each user's specific use case. The synthesizer can be used at both lab and industrial scale, Brain adds. Furthermore, the system consists of a waste management module, which not only processes and removes by-products generated during chemical reactions in a safe way.

[0017] Therefore, the main objective of this invention is to provide a parallel synthesis device that can synthesize multiple compounds separately in a controlled and automated environment in combinatorial chemistry. Although several systems for parallel synthesis have already been reported, the new system is unique in that it allows independent control of the reaction conditions (temperature, pressure, reagent supply and mixing) for any number of reactions performed simultaneously. This ensures that each reaction is performed under exactly the right conditions and that each step of this scaled-up synthesis can be controlled. This system can be scaled up from small laboratory to large industrial applications depending on the needs of the researcher.

[0018] Another objective of the invention is to make the chemical synthesis process more efficient by automating the most critical functions such as dispensing reagents at different temperature ranges and investigating reaction partners. This means that the system requires less human intervention and increases throughput by integrating real-time monitoring sensors along with a central processor that adapts the reaction conditions. Automating this step speeds up the synthesis and improves consistency across all reaction vessels by reducing potential human errors.

[0019] A further objective of the present invention is to provide an economical, simple and user-friendly parallel synthesizer. The system includes a simple graphical user interface with powerful protocol programming and reaction monitoring capabilities. The system is modular, allowing the addition or removal of multiple reaction modules, reagent reservoirs and pumps themselves without interrupting the overall functionality of the setup. However, this scalability opens the door for use by academic researchers and industrial chemists.

[0020] The invention is also directed towards minimizing waste in chemical synthesis. LBC's waste prevention-compatible parallel synthesis equipment features an integrated system for both discreet reception of waste and neutralization of by-products resulting from the reaction. This system reduces the handling of hazardous chemicals and significantly reduces the time and manpower required for waste management, making the entire synthesis procedure safer and limiting the associated health risks.

[0021] Finally, the present invention provides a relatively versatile platform suitable for many chemical transformations. The system provides a simple way to perform reactions that require high temperatures, pressures, or specific reagent delivery systems. The parallel synthesizer will be a useful tool in fields such as medicine, materials science, and biochemistry, where there is a need to more rapidly synthesize new compounds and test them for biological activity. [Means for solving the problem]

[0022] The present invention is directed to solving the above problems, and provides a parallel synthesis apparatus for combinatorial chemistry, comprising: a plurality of reaction vessels, each reaction vessel configured to hold chemical reactants, each reaction vessel including an enclosed chamber having a controlled gas inlet and outlet system to regulate a reaction environment; a reaction control module connected to each reaction vessel and configured to monitor and adjust parameters including temperature, pressure, and reagent flow rates in each reaction vessel; a reagent dispensing unit consisting of a plurality of precisely controlled pumps for supplying various chemical reagents to said reaction vessels, the supply of reagents being controlled by individual flow controllers to ensure accurate volumetric delivery for combinatorial synthesis; parallel heating units integrated with each reaction vessel, configured to independently adjust a heating profile based on real-time reaction data monitored by a thermal sensor in each reaction vessel; a mixing device located within each reaction vessel, the mixing device including a rotating magnetic stirrer that can be varied in speed to ensure homogenous mixing of the reactants; an automated sampling mechanism consisting of robotic arms, each configured to access an individual reaction vessel and remove samples for real-time analysis, the samples being sent to an in-line analysis unit equipped with a spectroscopic sensor for immediate data feedback on reaction progress; and a processing unit communicatively coupled to the reaction control module, the reagent dispensing unit, the parallel heating unit, and the automated sampling mechanism, the processing unit configured to execute a control algorithm that synchronizes the operation of all modules to facilitate parallel reactions under various conditions for high throughput chemical synthesis, the reagent dispensing unit comprising: a multi-channel microvalve assembly, each valve corresponding to a specific reagent line, the assembly operatively connected to a reagent reservoir system, the microvalves being actuated by piezoelectric elements to precisely control reagent flow rates;wherein the controlled gas inlet and outlet system includes a gas purity monitoring sensor integrated in each inlet line, the sensor being capable of detecting impurities down to the parts per billion level, and a gas flow regulating subunit consisting of an electronically controlled valve for adjusting the gas mixture composition in real time based on the detected reaction conditions in each vessel, wherein the mixing device in each reaction vessel further includes an adjustable magnetic field generator operatively connected to a magnetically levitated stirrer that can vary the vertical and horizontal position of the stirrer within the vessel, thereby optimizing reactant mixing efficiency in different reaction zones of the vessel; [Brief description of the drawings]

[0023] These and other features, aspects and advantages of the present invention will become better understood from the following detailed description taken in conjunction with the accompanying drawings.

[0024] FIG. 1 is a block diagram of a parallel synthesis apparatus for combinatorial chemistry.

[0025] Further, those skilled in the art will appreciate that elements in the figures are illustrated for simplicity and may not necessarily be drawn to scale. For example, a flow chart illustrates a system in terms of the most prominent steps involved to help improve understanding of aspects of the present disclosure. Furthermore, with respect to the structure of the device, one or more components of the device may be represented in the drawings by conventional symbols, and the drawings may show only certain details appropriate to understanding the embodiments of the present disclosure, so as not to obscure the drawings with details that will be readily apparent to those skilled in the art having the benefit of the description herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe them. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, and that such changes and further modifications in the illustrated system, and such further applications of the principles of the invention as illustrated therein, are contemplated as would normally occur to one skilled in the art to which the invention pertains.

[0027] It will be understood by those skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention but are not intended to be restrictive.

[0028] References throughout this specification to "one aspect," "another aspect," or similar language mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of "in one embodiment," "in another embodiment," and similar language throughout this specification do not necessarily all refer to the same embodiment.

[0029] "Comprises," "comprising," or other variations thereof are intended to be non-exclusive inclusive, and a process or system comprised of a list of steps does not include only those steps, but may include other steps not expressly listed or inherent to such process or system. Similarly, one or more apparatus or subsystems or elements or structures or components preceded by "comprises..." does not, without more constraints, preclude the presence of other apparatuses or other subsystems or elements or structures or components or additional apparatuses or additional subsystems or additional elements or additional structures or additional components.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. The systems, systems, and examples provided herein are illustrative only and are not intended to be limiting.

[0031] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the accompanying drawings.

[0032] Referring to Figure 1, a block diagram of a parallel synthesizer for combinatorial chemistry is shown. System 100 comprises: A parallel synthesizer for combinatorial chemistry comprising: a plurality of reaction vessels 102 configured to hold chemical reactants, each reaction vessel comprising an enclosed chamber having a controlled gas inlet 102(a) and outlet system 102(b) for regulating the reaction environment; a reaction control module 104 connected to each reaction vessel, configured to monitor and regulate parameters including temperature, pressure, and reagent flow rates within each vessel; a reagent dispensing unit 106 consisting of a plurality of precisely controlled pumps for delivering various chemical reagents to the reaction vessels, the reagent delivery being controlled by individual flow controllers to ensure precise volumetric delivery for combinatorial synthesis; a parallel heating unit 108 integrated with each reaction vessel, configured to independently adjust heating profiles based on real-time reaction data monitored by thermal sensors within each vessel; a mixing device 110 located within each reaction vessel, the mixing device including a rotating magnetic stirrer that can be varied in speed to ensure homogenous mixing of the reactants; an automated sampling mechanism 112 consisting of robotic arms, each configured to access an individual reaction vessel and remove a sample for real-time analysis, said samples being sent to an in-line analysis unit equipped with a spectroscopic sensor for immediate data feedback on the progress of the reaction; and a processing unit 114 communicatively coupled to the reaction control module, the reagent dispensing unit, the parallel heating unit, and the automated sampling mechanism, the processing unit configured to execute a control algorithm that synchronizes the operation of all the modules to facilitate parallel reactions under various conditions for high throughput chemical synthesis.

[0033] In one embodiment, the reagent dispensing unit 106 further includes: a multi-channel microvalve assembly, each valve corresponding to a specific reagent line, said assembly being operably connected to a reagent reservoir system, and the microvalves being actuated by piezoelectric elements for precise control of reagent flow rate.

[0034] In one embodiment, the controlled gas inlet 102(a) and outlet system 102(b) includes gas purity monitoring sensors integrated within each inlet line, said sensors capable of detecting impurities down to parts per billion levels, and a gas flow regulating subunit consisting of electronically controlled valves for adjusting the gas mixture composition in real time based on the detected reaction conditions within each vessel.

[0035] In one embodiment, the reaction control module 104 is further configured with an adaptive feedback loop mechanism, where the thermal sensor is integrated with a response system that dynamically adjusts the heating profile of individual containers by sending control signals to the heating units based on pre-set thermal thresholds and the progression of the reaction kinetics.

[0036] In one embodiment, the mixing device 110 in each reaction vessel further includes an adjustable magnetic field generator operably connected to a magnetically levitated stirrer that can vary the vertical and horizontal position of the stirrer within the vessel, thereby optimizing the mixing efficiency of the reactants in different reaction zones of the vessel.

[0037] In one embodiment, the automated sampling mechanism 112 further includes a sterile sampling system utilizing vacuum-sealed sampling needles, with each needle being independently sterilized between sampling operations via an integrated UV-C sterilization chamber located adjacent to the robotic arm, ensuring prevention of cross-contamination during multiple sample extractions.

[0038] In one embodiment, the processing unit 114 is further configured to execute real-time data analysis algorithms that process spectroscopic data from the in-line analytical unit, generate predictive models of reaction completion times, and suggest optimized reaction parameters based on historical data from previous reaction batches, thereby enabling autonomous synthesis cycle adjustments.

[0039] In one embodiment, the reagent dispensing unit 106 further comprises: a chemically resistant flow path and a solvent compatibility detection system consisting of dedicated sensors that monitor the pH, viscosity, and chemical composition of the reagents to prevent degradation and corrosion of internal components during synthesis.

[0040] In one embodiment, the reaction vessel 102 further includes an integrated pressure relief valve system connected to a safety override unit, which activates when the internal pressure exceeds a pre-set safety limit and automatically stops all reagent delivery and heating processes to prevent system malfunction.

[0041] The present invention is directed to a parallel synthesis device for combinatorial chemistry adapted for parallel or simultaneous synthetic chemical synthesis by a high-throughput efficient system with multiple reactors in various embodiments. The integrated system is composed of a series of specialized modules running in an interconnected manner to provide automated and efficient solutions for various stages of chemical reactions carried out across multiple reaction vessels. It provides a route synthesis device centered on combinatorial synthesis of reaction conditions with excellent reaction and reagent regulation, and is friendly to human environment monitoring.

[0042] The system consists of several reaction vessels, each with a sealed chamber to receive one or more chemical reactants. The reaction vessels are equipped with a gas inlet and outlet system that allows them to be used as reactors to provide a controlled atmosphere for optimal reaction conditions. Each gas inlet has a built-in gas purity monitor sensor that can detect impurities as low as one part per billion. The quality, make-up and composition of the gases are controlled by sensors in this system to avoid any influence on the chemical reactions. An automated system connected to the gas inlets controls electronically controlled valves that change the actual mixture at any time based on the measurements detected in each vessel, so that these conditions are reproduced exactly in this series of synthesis steps.

[0043] Each reaction vessel is fitted with a reaction control module that continuously monitors and adjusts critical parameters such as temperature, pressure and reagent flow rates in a feedback loop. It is further made to communicate with a parallel heating unit equipped with each reaction vessel. This same adaptive feedback control is employed within the unit by thermal sensors that read temperature data and send it to a central location for evaluation with the real-time information of the individual heaters. Using the registered temperature data, the heating profile is continuously optimized on the fly to achieve and maintain ideal reaction conditions. This real-time feedback ensures precise management of reaction kinetics that can have a variable impact on efficiency and results.

[0044] Another important part of the system is the reagent dispensing unit, which precisely delivers chemical reagents to the reaction vessels using pipettes. This unit contains several individually controlled precision pumps incorporating flow controllers to ensure that the reagents are delivered with precise volumetric accuracy. The dispensing unit also incorporates a microvalve assembly, which can be actuated in multiple dimensions by piezoelectric elements to precisely control the flow rate of the reagents. The reagent lines are connected to a solvent compatibility check system, which monitors the ph, viscosity, and chemical composition of the reagents and prevents them from destroying the internal components.

[0045] The reaction vessel scheme includes an integrated stirring system that uses magnetic levitation stirrers for internal stirring. Paddle stirrers: These are adjustable in speed and position to provide near uniform mixing in all zones of the vessel across the various volumes. The stirrers are actuated by adjustable magnetic field generators, allowing the stir bar position to be independently adjusted between horizontal and vertical within the well.

[0046] The system is also designed with an automated sampling system, including two robotic arms that continuously sample from each reaction vessel without interrupting the continuous process flow. The robotic arms, located under the capper assembly, are equipped with sterile sampling needles that feature separate sterilization between cycles, performed through an integrated Ultraviolet-C sterilization chamber. This design allows us to prevent cross-contamination in the extraction of multiple samples. We transfer the samples to an in-line dropper, where they are analyzed using a spectroscopic sensor, providing direct data feedback on the progress of the reaction. This processing unit is set up to work with a real-time analytical algorithm, which processes the spectroscopic data obtained during sampling. Such information is interpreted by this algorithm and used to create a predictive model of how long the reaction will take. Taking into account the historical data of past reaction batches, the algorithm is used to recommend optimized reaction parameters for future synthesis runs, allowing the synthesis cycle to be autonomously fine-tuned cycle by cycle in order to improve productivity.

[0047] It combines a reaction control module, a reagent distribution unit, and a parallel heating unit with automated sampling. It uses a control algorithm that coordinates the (parallel) operation of all modules, so there should be no race starts leading to parallel reactions. The system works by adjusting environmental and process parameters for each reaction vessel based on real-time feedback from thermal sensors, gas purity monitors, and reagent distribution controllers, and uses algorithms that can integrate these adjustments. Data analysis algorithms developed within the processing unit use machine learning to learn from past reactions over time and fine-tune the control parameters. This real-time optimization maintains the system's high throughput and accuracy in combinatorial processes.

[0048] If the reaction is triggered with even greater force than is expected from a safety point of view, i.e. if the pressure rises above a certain limit, all reactors are under a pressure valve system. These are fitted with safety override units that automatically activate if the pressure in the vessel becomes dangerously high. The safety override units stop the supply of reagents and heating, preventing further processes from starting until the problem is resolved.

[0049] The parallel synthesis device described here provides a versatile, precise, and highly automated tool for combinatorial chemistry experiments. Using real-time monitoring and adaptive control strategies, as well as data-driven machine learning algorithms, the system adjusts conditions to achieve optimal, high-throughput synthesis with virtually no human intervention. This patented technology addresses the growing need for systems that can run multiple chemical reactions in parallel with tight control over the reaction environment, speeding up chemical discovery and development.

[0050] The Parallel Synthesizer consists of multiple reaction modules, each of which can be individually controlled for pressure, temperature and reagent input. This is because they are made from chemically inert materials, most commonly glass or Teflon-lined stainless steel, making them compatible with many reagents and solvents. Each compartment comes with a pressure-resistant heating and cooling jacket that is used to determine the reaction temperature, along with a temperature sensor built into the module for real-time live monitoring. The system produces controlled temperatures from sub-ambient to high temperatures, making it suitable for many types of chemical reactions.

[0051] Multiple chemical reagent reservoirs, each connected to a bank of precision pumps and control valves, store the required chemicals. A separate central processor directs the timing and amount of reagent delivery to maintain the proper stoichiometry for each reaction. The system is also useful for on-demand delivery of microliter to milliliter volumes, depending on the scale of the synthesis. This allows for fine-tuning of the flow of reagents through each reaction module, thus allowing multiple conditions to be used to perform different reactions simultaneously.

[0052] The synthesizer also provides a mechanism for uniformly mixing the contents of each reaction vessel. Depending on the reaction type, mechanical or magnetic stirrers can be used in the system. These stirring devices can be independently controlled to vary the stirring speed and time for each vessel. This is particularly useful for fast or multi-phase reactions that rely on rapid mixing of the reactants.

[0053] Heating, cooling, reagent delivery and mixing are coordinated in real time by a central processor across all modules to ensure reactions follow pre-programmed protocols. The other is the operating room itself, which receives real-time data from built-in sensors such as temperature measurement points, pressure gauges and pH analyzers. The central processor can detect when reactions are not occurring within specified reaction parameters and automatically adjust to ensure reactions are occurring as intended by the protocol.

[0054] A particular feature of this system is that it allows real-time monitoring and feedback. Sensors built into each reaction module are able to continuously sense important reaction parameters such as temperature, pressure, pH and optical clarity. Information from these sensors is sent back to the central processing unit, which allows the reaction conditions to be controlled in real-time. So, for example, if the temperature of a reaction vessel rises but is still within a safe range at its set point (set by you), the central processing unit U can turn on the jacket of the reactor to cool it down. This feedback mechanism thus allows all reactions to proceed at the optimal point possible, avoiding uncontrollable variations and greatly improving reproducible results.

[0055] All synthesizer processes and user control parameters are programmed using an easy to use graphical user interface, allowing users to monitor ongoing reactions and program reaction protocols with as many steps as required. Reaction Modules: Users can monitor in real time how each reaction module is graphically represented, as well as see live data for temperature, pressure and reagent flow rates. Users can set alerts if any of the parameters go out of tolerance.

[0056] The modular design of the system makes it scalable, so more levels can be conveniently added in the future. Reaction modules, reagent reservoirs, and pumps can be added without changing the core functionality of the system. As a result, the Parallel Synthesizer can be used for a wide range of applications, from small-scale laboratory-scale research to industrial synthesis.

[0057] The present invention is a flexible system for the combinatorial synthesis of compounds, with the following advantages: (1) modularized system design, (2) precise control of reaction parameters, (3) in situ monitoring of coupling events, and finally, scalability. By keeping the reaction conditions the same for each module, this parallel synthesizer represents a major advance over existing systems that, when used for combinatorial chemistry, lead to batch-to-batch variability and overall poor efficiency.

[0058] This invention belongs to the field of combinatorial chemistry, specifically aimed at parallel chemical synthesis. The technology is designed for well-plate-based high-throughput synthesis systems that require precise control of reaction conditions, reagent delivery, and real-time monitoring. The technology is typically employed in situations where a large number of chemical reactions are performed simultaneously, such as drug discovery research and industrial materials synthesis. The hardware part is combined with sophisticated computational algorithms to optimize reaction parameters and obtain significant synthesis efficiency.

[0059] The drawings and the above description illustrate examples of embodiments. Those skilled in the art will appreciate that one or more of the described elements may well be combined into one functional element. Alternatively, certain elements may be divided into multiple functional elements. Elements of one embodiment may be added to another embodiment. For example, the order of steps described herein may be changed and is not limited to the aspects described herein. Furthermore, the acts of any flow diagram need not be performed in the order shown, and not all acts necessarily need to be performed. Also, acts that are not dependent on other acts may be performed in parallel with other acts. The scope of the embodiments is in no way limited by these specific examples. Numerous variations are possible, such as differences in structure, dimensions, and use of materials, whether or not explicitly shown in this specification. The scope of the embodiments is broad, at least as provided by the following claims.

[0060] Although advantages, other benefits, and solutions to problems have been described above with respect to particular embodiments, the advantages, benefits, solutions to problems, and elements that may cause or make the advantages, benefits, or solutions more noticeable are not to be construed as critical, essential, or required features or elements of any or all of the claims.

Claims

[Claim 1] 1. A parallel synthesis apparatus for combinatorial chemistry, comprising: a plurality of reaction vessels, each configured to hold a chemical reactant, each reaction vessel including an enclosed chamber having a controlled gas inlet and outlet system for regulating the reaction environment; a reaction control module coupled to each reaction vessel and configured to monitor and regulate parameters including temperature, pressure, and reagent flow rates within each reaction vessel; a reagent dispensing unit consisting of multiple precisely controlled pumps for delivering various chemical reagents to said reaction vessels, the delivery of reagents being controlled by individual flow controllers to ensure precise volumetric delivery for combinatorial synthesis; Parallel heating units integrated with each reaction vessel, the parallel heating units configured to independently adjust a heating profile based on real-time reaction data monitored by a thermal sensor in each reaction vessel; a mixing device located within each reaction vessel, the mixing device including a rotating magnetic stirrer whose speed can be varied to ensure homogeneous mixing of the reactants; an automated sampling mechanism consisting of robotic arms, each configured to access individual reaction vessels and remove samples for real-time analysis, said samples being delivered to an in-line analytical unit equipped with a spectroscopic sensor for immediate data feedback on the progress of the reaction; and a processing unit communicatively coupled to the reaction control module, the reagent dispensing unit, the parallel heating unit, and the auto-sampling mechanism, the processing unit configured to execute a control algorithm that synchronizes the operation of all modules to facilitate parallel reactions under a variety of conditions for high throughput chemical synthesis; The reagent dispensing unit comprises: a multi-channel microvalve assembly, each valve corresponding to a specific reagent line, the assembly being operatively connected to a reagent reservoir system, the microvalves being actuated by piezoelectric elements to precisely control reagent flow rates; wherein the controlled gas inlet and outlet system includes a gas purity monitoring sensor integrated within each inlet line, the sensor capable of detecting impurities down to parts per billion levels, and a gas flow regulating subunit consisting of an electronically controlled valve for adjusting the gas mixture composition in real time based on detected reaction conditions within each vessel; Here, the mixing device in each reaction vessel further includes an adjustable magnetic field generator operably connected to the magnetically levitated stirrer that can vary the vertical and horizontal position of the stirrer within the vessel, thereby optimizing reactant mixing efficiency in different reaction zones of the vessel.

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