Method and system for planning, performing, and assessing high-throughput screening of multicomponent chemical compositions and solid forms of compounds

A method for determining one or more solid forms of a compound, comprising the steps of:

• selecting a combination of experimental parameters that may be varied by a high-throughput automated experimentation apparatus;
• determining a first plurality of distinct combinations of values of the experimental parameters, each combination corresponding to a distinct experiment;
• causing the automated experimentation apparatus to conduct a first set of experiments for each of at least a portion of the first plurality of distinct combinations of values of the experimental parameters;
• determining a first collection of experimental results of the first set of experiments, the first collection comprising a plurality of individual result sets, each individual result set corresponding to a distinct experiment;
• based on the first collection of experimental results, determining a second plurality of distinct combinations of values of the experimental parameters, each combination corresponding to a distinct experiment;
• causing the automated experimentation apparatus to conduct a second set of experiments for each of at least a portion of the second plurality of distinct combinations of values of the experimental parameters;
• determining a second collection of experimental results of the second set of experiments, the second collection comprising a plurality of individual result sets, each individual result set corresponding to a distinct experiment;
• selecting one or more solid forms based on the first collection of experimental results and the second collection of experimental results.

A method of estimating a property of a multicomponent chemical composition comprising the steps of:

• receiving signals representing a simulation result set for each of a plurality of simulations of a compound;
• for at least a portion of the simulations, generating a predictive model based on signals characterizing each simulation result set according to the property to be estimated and signals characterizing the simulation results sets with respect to a set of molecular descriptors;
• receiving signals representing experimental result sets for a plurality of experiments conducted by a high-throughput automated experimentation apparatus;
• estimating the property for the multicomponent chemical composition by providing signals characterizing the multicomponent chemical composition with respect to the set of molecular descriptors as input to the predictive model.

A method of estimating a property of a solid form of a compound comprising the steps of:

• receiving signals representing simulation result sets for a plurality of simulations of a compound;
• for at least a portion of the simulations, generating a predictive model based on signals characterizing the simulation result sets according to the property to be estimated and signals characterizing the simulation result sets with respect to a set of molecular descriptors;
• receiving signals representing experimental result sets for a plurality of experiments conducted by a high-throughput automated experimentation apparatus;
• estimating the property for the solid form of the compound by providing signals characterizing the solid form of the compound with respect to the set of molecular descriptors as input to the predictive model.

A method of determining one or more multicomponent chemical compositions comprising:

• conducting a plurality of experiments using a high-throughput automated experimentation apparatus;
• for each experiment, electronically storing:
• a set of experimental parameters;
• a set of experimental results;
• a set of molecular descriptors characterizing an aspect of the experiment;
• associating data representing each experiment with previously stored data by querying a database comprising information not derived from the plurality of experiments;
• processing at least a portion of the experiment data and the associated previously stored data with a processor programmed to apply a discriminator algorithm to associate at east one experiment with at least one classification;
• determining one or more multicomponent chemical compositions based on the at east one classification.

A method of determining one or more solid forms of a compound comprising:

• conducting a plurality of experiments using a high-throughput automated experimentation apparatus;
• for each experiment, electronically storing:
• a set of experimental parameters;
• a set of experimental results;
• a set of molecular descriptors characterizing an aspect of the experiment;
• associating data representing each experiment with previously stored data by querying a database comprising information not derived from the plurality of experiments;
• processing at least a portion of the experiment data and the associated previously stored data with a processor programmed to apply a discriminator algorithm to associate at least one experiment with at least one classification;
• determining one or more solid forms based on the at least one classification.

A system for determining a multicomponent chemical composition comprising:

• a database comprising at least one table, the at least one table further comprising:
• a plurality of molecular descriptors;
• a plurality of compound identifiers;
• a plurality of compound/descriptor relations associating at least a portion of the compound identifiers with molecular descriptors;
• a plurality of empirically determined physical, chemical and biological parameters;
• a plurality of compound/parameter relations associating one or more compound identifiers with one or more of the empirically determined physical, chemical and biological parameters;
• data representing results from a plurality of experiments performed with a
• high-throughput automated experimentation apparatus;
• a query system for selecting subsets of related information from the at least one table;
• a multidimensional representation generation module capable of generating visual representations of data sets having at least four dimensions;
• a plurality of modeling modules, each module capable of receiving information selected by the query system and estimating at least one property of a formulation.

A system for determining a solid form of a compound comprising:

• a database comprising at least one table, the at least one table further comprising:
• a plurality of molecular descriptors;
• a plurality of compound identifiers;
• a plurality of compound/descriptor relations associating compound identifiers with molecular descriptors;
• a plurality of empirically determined physical, chemical and biological parameters;
• a plurality of compound/parameter relations associating one or more compound identifiers with one or more of the empirically determined physical, chemical and biological parameters;
• data representing results from a plurality of experiments performed with a
• high-throughput automated experimentation apparatus;
• a query system for selecting subsets of related information from the at least one table;
• a multidimensional representation generation module capable of generating visual representations of data sets having at least four dimensions;
• a plurality of modeling modules, each module capable of receiving information selected by the query system and estimating at least one property of a formulation.

A method for producing crystals comprising:

• (a) electronically calculating a set of predicted crystal polymorphs of a target compound;
• (b) electronically calculating expected experimental results for at least a portion of the predicted polymorphs;
• (c) conducting a first plurality of crystallization experiments using a high-throughput automated experimentation apparatus;
• (d) electronically comparing at least a portion of the expected experimental results with the actual experimental results to determine which of the at least a portion of the predicted polymorphs were produced.

A method for determining a solid form of a compound comprising:

• (a) predicting a crystal structure of a target chemical species;
• (b) selecting a first range of conditions for crystal generation;
• (c) conducting a first plurality of experiments within the first range of conditions using a high-throughput automated experimentation apparatus;
• (d) testing at least a portion of the experimental results for the presence of crystals;
• (e) classifying at least a portion of the experiments based on predicted crystal forms;
• (f) selecting a second range of conditions for crystal generation based on one or more of the classifications;
• (g) conducting a second plurality of experiments within the second range of conditions using the high-throughput automated experimentation apparatus.

A method for preparing a crystal comprising:

• (a) performing simulated hydrogen-bond-biased simulated annealing to predict a plurality of polymorphs of a target compound;
• (b) calculating expected properties of at least a portion of the predicted polymorphs;
• (c) conducting a plurality of crystallization experiments using a high-throughput automated experimentation apparatus;
• (e) comparing measured properties of crystals produced by the plurality of crystallization experiments with the expected properties of at least a portion of the predicted polymorphs to determine which of the at least a portion of the predicted polymorphs were produced by the experiments;
• (f) generating a predictive model of the relationship between experimental parameters and polymorphs produced;
• (g) calculating a set of experimental parameters for a second set of crystallization experiments from the predictive model.