The goal of a mixture design is to generate a set of components and compositions whose physical properties satisfy a set of constraints. Thus, to design mixtures, Synapse requires:

1. Components: one or more sets of chemicals from which our mixture's components will be selected.
2. Compositions: ranges of compositions which will be used to generate compositions for each combination of components.
3. Constraints: once components have been selected and their compositions assigned, we can estimate the mixture's physical properties. These properties are then used to evaluate constraints.

Dimethyl sulfoxide, DMSO, is a good solvent for many applications. Unfortunately, DMSO's high melting point of 18.52 °C can sometimes result in the freezing of stored material. Adding an appropriate cosolvent can often significantly lower the freezing point.

The following examples detail the steps needed to design DMSO + cosolvent mixtures that have acceptable freezing points.

Synapse generates candidate mixtures from lists of chemicals and then estimates those physical properties of each candidate mixture needed to evaluate the design constraints. Thus, every mixture design has an associated knowledge base which is used as the source of chemicals and estimation techniques.

Thus, the first step in a mixture design is develop a knowledge base that contains the all the desired chemical components and whose estimation techniques can accuractely predict the properties needed to evaluate design constraints. Often the MKS Core Knowledge Base will be sufficient for a design. However, it is very likely that it will need to be expanded by adding new chemicals, new physical property data and new estimation techniques.

At a minimum, you should evaluate your design's constraints on existing mixtures to determine the accuracy of the knowledge base's estimation techniques.

1. Open the MKS Core Knowledge Base document. (Create a copy of the document (see here) to use for these examples.)
2. Change to the Mixtures Chapter and navigate to the Dimethyl sulfoxide + Water mixture. (See the Navigation Overview documentation for details on navigating chapters and pages.)
3. Scroll down to the Phase Equilibrium Section and click on the section's Property control. Select the property "SLE, Liquidus Point - f(T,P,X)" and the values type "Temperature Estimates". Finally, press the dialog's OK button. The application will display solid-liquid equilibrium data for the dmso + water mixture.
4. Click the left mouse button in the Phase Equilibria Section's table control. The application will activate the field's data edit dialog.
5. Click and hold down the left mouse button in the dialog table's first row. Drag the mouse downward, selecting several table rows.
6. Press the dialog's Series button and select Composition Series from the displayed submenu. The application will activate the Composition Series Dialog.
7. Specify the Variable and Remainder compositions, the Fixed Pressure value and the Starting and Ending Composition values. Finally, press the dialog's OK button. The application will used the entered values to generate a series of state variables.
8. Press the dialog's Save button. The application will save the state variables series into the current document.
9. Select the Compute Estimates command from the Commands menu. The application will activate the Property Estimation Dialog.
10. Press the dialog's Start button. The application will begin estimating all properties of the current mixture.
11. Once all estimations have been performed, press the dialog's Save button to store the estimated values into the current document. The agreement between estimated values and data, especially at higher concentrations of DMSO, is good.

Once we have verified that we can adequately estimate the physical properties we plan to use in our design, we can develop the design functions that use these estimated physical properties.

1. Select the New command from the File menu. The application will activate the Create a New Document dialog. Select the Mixture Design Document document type and press the dialog's OK button.
2. The application will activate the File Dialog prompting you for the filename of the new document. Enter a name and press the dialog's Save button. The application will create and open the new design document.
3. Enter values for the document's title, subtitle and descriptions. See documentation on the Document Titles Section and Document Information Section for details.
4. Using the tabs at the top of the document, change to the Functions Chapter by clicking the left mouse button on Functions tab. (See the Navigation Overview documentation for details on navigating chapters and pages.)
5. Create a new design function entity by pressing the "+" button in the menubar or executing the "Add New Page" command found on the Edit menu. A new, blank Function page will be added to the current document.
6. Click the left mouse button on the Identifier Pane's edit control. The application will activate the edit dialog. Enter the name "Freezing Point [°C]" and press the dialog's Save button.
7. Now click the left mouse button on the Function Section's large edit control. The application will activate the Function Code dialog. Enter the following code:
   // Default declarations double xwtpct[25]; string candidate; int ncomps; // Default assignments ncomps = XWtPercents(xwtpct); candidate = Mixture(); // Variable declarations double tm, pres; string prop; int err; // Initialize values prop = "SLE, Liquidus Temperature - f(P,X)"; pres = 101325.0; // Pa - std units // Estimate liquidus temperature tm = XProp(candidate, prop, 0.0, pres, xwtpct, err); if( err != 0 ) return FALSE; tm = tm - 273.15; // Assign result SetResult(tm); // Successful return TRUE;
8. Finally, press the Code dialog's Save button.

Before performing a mixture design, it is important to ensure the constraints and design functions have been entered correctly. Synapse provides a testing mechanism in which you can run a design function on an existing mixture entity using one or more of the mixture's default compositions.

1. Activate the copy of the knowledge base document we created in the first example.
2. Change to the Mixtures Chapter and navigate to the Dimethyl sulfoxide + Water mixture. (See the Navigation Overview documentation for details on navigating chapters and pages.)
3. Scroll down to the Default Compositions Section and click on the section's table control.The application will activate the Default Compositions Dialog.
4. Click on the first row and enter a default composition of 95 wt% DMSO and 5 wt% water. See documentation on the Default Compositions Dialog for editing details.
5. Add the remaining default compositions shown in the image below and then press the dialog's Save button. Synapse will store the default compositions into the current knowledge base document.
6. Now navigate to the "Freezing Point [°C]" design function in the Functions Chapter of our newly created mixture design document.
7. Select the Test Mixture Function command from the Commands menu.
   The application will activate the Test Mixture Function Dialog.
8. Select Dimethyl sulfoxide + Water as the mixture candidate and 90, 10 wt% as the default composition and then press the dialog's Calculate button. Synapse will execute the design function using the selected mixture candidate and display the results in the dialog. In this example, the design function successfully calculated a mixture freezing point of -2.0378 °C.

1. Activate the mixture design document we created in a previous example.
2. Using the tabs at the top of the document, change to the Combinatorials Chapter by clicking the left mouse button on Combinatorials tab.
3. Create a new Combinatorial design by pressing the "+" button in the menubar or executing the "Add New Page" command found on the Edit menu. A new, blank page will be added to the current document.
4. Click the left mouse button in the Identifier Pane, the large white box at the top of the page. The application will activate the pane's datum edit dialog.
5. Enter a name for the new design. Optionally enter a reference and comment.
6. Finally, press the dialog's Save button. The application will save the new design's identifier into the current document and display the new name you just entered.

A combinatorial mixture design will assemble ingredient chemicals in all possible combinations to generate candidates, use estimation techniques to obtain physical properties for each candidate mixture and then use these physical property values to evaluate each design constraint. The ingredient chemicals and estimation techniques used in this process are retrieved from the design's associated knowledge base.

1. Ensure the copy of the knowledge base document we created in the first example is open.
2. Navigate to the new combinatorial mixture design we created in the previous example.
3. Click the left mouse button on the Source Knowledge Base Section's edit control. The application will activate the Knowledge Base selection dialog.
4. Select the knowledge base we have been using in these examples and press the dialog's OK button. The application will store this selection into the current document.

Synapse generates candidate mixtures by assembling a given set of ingredient chemicals in all possible combinations. Ingredient chemicals are grouped into categories for generalization. For example, suppose we wanted Synapse to generate all mixtures using the following ingredient categories:

Category	Ingredient Chemicals
Solvent 1	Water
Solvent 2	Ethanol; 1-Propanol; 2-Propanol
Thickener	T-940; T-941
Humectant	1,2-Propylene glycol; Gylcerol

Generating all possible mixtures from these ingredient chemicals results in twelve possible mixtures:

1	Water + Ethanol + T-940 + 1,2-Propylene glycol
2	Water + Ethanol + T-941 + 1,2-Propylene glycol
3	Water + 1-Propanol + T-940 + 1,2-Propylene glycol
4	Water + 1-Propanol + T-941 + 1,2-Propylene glycol
5	Water + 2-Propanol + T-940 + 1,2-Propylene glycol
6	Water + 2-Propanol + T-941 + 1,2-Propylene glycol

7	Water + Ethanol + T-940 + Gylcerol
8	Water + Ethanol + T-941 + Gylcerol
9	Water + 1-Propanol + T-940 + Gylcerol
10	Water + 1-Propanol + T-941 + Gylcerol
11	Water + 2-Propanol + T-940 + Gylcerol
12	Water + 2-Propanol + T-941 + Gylcerol

For our DMSO Cosolvent design, we will have only two categories: 1) a category containing the single chemical dimethyl sulfoxide; 2) a category containing a list of possible cosolvents.

1. Navigate to the new combinatorial mixture design we created in a previous example.
2. Click the left mouse button on the Design Categories Section's large table control. The application will activate the Component Categories dialog.
3. Select the dialog table's first row and press the Edit button. The application activates the Component Category dialog.
4. Enter values for the name and description, and optionally for the reference and comment, of the DMSO category. Then press the dialog's OK button.
5. Select the Component Categories dialog table's second row and press the Edit button. The application again activates the Component Category dialog.
6. Enter values for the name and description, and optionally for the reference and comment, of the Cosolvent category. Then press the dialog's OK button.
7. Finally, press the Categories dialog's Save button. The application stores the two design categories into the current document.
8. Now scroll down to the Category Chemicals Section and click the left mouse button on the section's large edit control. The application activates the Category Chemicals dialog.
9. Select the "DMSO" Category from the upper left Category control, click the left mouse button on the Category Chemicals table's first row, and press the dialog's Add button. The application activates the Add Chemicals Dialog listing all the chemicals in the design's associated knowledge base.
10. Select dimethyl sulfoxide from the dialog's Chemicals list and press the Add button.
11. Now select the "Cosolvent" Category from the upper left Category control, click the left mouse button on the Category Chemicals table's first row, and press the dialog's Add button. The application again activates the Add Chemicals Dialog listing all the chemicals in the design's associated knowledge base.
12. This time, select the following chemicals from the dialog's Chemicals list and press the Add button.

    1-Butanol	1-Propanol	2-Aminoethanol
    2-Butanone	2-Methoxyethanol	2-Propanol
    Acetone	Diethanolamine	Diethyl ether
    Ethanol	Ethyl acetate	Methyl acetate
13. Finally, press the Category Chemicals Dialog's Save button. The application will store the selected category chemicals into the current design document. The document shows the chemicals in each category in a separate column in the Category Chemicals Section.

Synapse generates candidate mixtures by assembling a given set of ingredient chemicals in all possible combinations. For each of these candidate mixtures, Synapse must also generate a set of compositions. These compositions are generated using the values entered into the Category Concentration Limits Section.

In the Category Concentration Limits Section you enter a minimum concentration, maximum concentration and concentration increment for each category. The concentration increment for one of the categories must be quantum sufficit (qs) which is calculated as the concentration needed to bring the total to 100 wt%.

For example, suppose we are designing a three component mixture with the following ingredient categories and concentration limits.

Category	Minimum	Maximum	Increment
Solvent	70	95	10
Additive	5	30	QS
Thickener	1	2	1

Using the above limits, six possible compositions can be generated.

1	70% Solvent + 29% Additive + 1% Thickener
2	70% Solvent + 28% Additive + 2% Thickener
3	80% Solvent + 19% Additive + 1% Thickener

4	80% Solvent + 18% Additive + 2% Thickener
5	90% Solvent + 9% Additive + 1% Thickener
6	90% Solvent + 8% Additive + 2% Thickener

For our DMSO Cosolvent design, we need to specify concentration limits on two categories.

1. Navigate to the new combinatorial mixture design we created in a previous example.
2. Scroll down the datapane and click the left mouse button on the Design Category Concentration Limits Section's large table control. The application activates the Category Limits dialog.
3. Click the left mouse button on the dialog table's first row, i.e., the row labeled with the DMSO category. Then press the dialog's Edit button. The application activates the Category Limit dialog.
4. Enter a minimum value of 70, a maximum value of 95 and an increment of 5. Optionally, enter values into the Reference and Comment fields. Finally, press the dialog's OK button.
5. Now click the left mouse button on the Category Limits dialog table's second row, i.e., the row labeled with the Cosolvent category. Then press the dialog's Edit button. The application activates the Category Limit dialog.
6. Enter a minimum value of 0, a maximum value of 40 and select "quantum sufficit" from the Increment control's drop down list. Optionally, enter values into the Reference and Comment fields. Finally, press the dialog's OK button.
7. Once concentration limits have been entered for both categories, press the dialog's Save button. The application will store the entered limits into the current design document.

Each mixture design contains one or more constraints which viable candidates must satisfy. Design constraints can be imposed on a single physical property, such as density or viscosity, or on a complex function of physical properties such as a heat transfer coefficient calculated by a Nusselt number correlation.

Each constraint contains a function name, a minimum value, a goal value and a maximum value. Some example constraints are shown in the following table.

Function	Minimum	Goal	Maximum
Freezing Point [°C]	-40	-10	0
Liquid Density at 20°C [kg/m3]	850	1000	1150
Heat Transfer Coefficient at 20°C [W/m2 K]	1000	1200	2000

The goal of our example DMSO Cosolvent design is to identify cosolvents that could lower the freezing point of DMSO. We will thus enter a constraint on the melting point.

1. Navigate to the new combinatorial mixture design we created in a previous example.
2. Scroll the datapane and click the left mouse button on the Constraints Section's large table control. The application activates the Edit Constraints dialog.
3. Click the left mouse button on the dialog table's first row. Then press the dialog's Edit button. The application activates the Edit Constraint dialog.
4. Enter the name of the function we created in a previous example. Press the dialog's List button for a list of all functions present in the current document. Enter a minimum value of -40, a goal value of -10 and a maximum value of 0. Optionally, enter values into the Reference and Comment controls. Finally, press the dialog's OK button.
5. Press the Constraints Dialog to save the entered constraint into the current document.

1. Navigate to the new combinatorial mixture design we created in a previous example.
2. Select the Design Candidates command from the Commands menu. Synapse activates the Combinatorial Mixture Design dialog.
3. Press the dialog's Start button. Synapse will:
   • Generate all mixtures by combining all category chemicals in all possible ways.
   • Generate all compositions that satisfy the concentration limits.
   • Estimate the freezing point of each mixture + composition pairing.
   • Check if the estimated freezing point of any mixture + composition pair satisfies the entered constraint.

   The Design dialog shows that Synapse generated 72 candidates, nine of which satified our freezing point constraint.

4. Finally, press the dialog's Save button to store the design results into the current document.

In the previous example, Synapse designed nine candidate mixtures that had freezing points below 0 °C. This example shows how it is often useful to transfer candidates to a knowledge base for further analysis.

1. Ensure that the copy of the knowlege base created in our first example is still open.
2. Activate the Mixture Design document we created and navigate to the combinatorial mixture design we just ran in the previous example.
3. Select the Transfer Candidates command from the Commands menu. Synapse activates the Transfer Mixture Candidates dialog.
4. In the Destination Knowledge Base control, select the name of the copied template knowledge base. Then press the dialog's Select All button. All candidates will be selected for transfer. Finally, press the dialog's Transfer button. Synapse will create a new mixture entity in the knowledge base for each mixture candidate. Press the Transfer Candidates Dialog's Done button.
5. Activate the knowledge base, change to the Mixtures chapter and navigate to any one of the newly transferred candidates.
6. Scroll to the Phase Equilibria Section and select "SLE, Liquidus Point - f(T,P,X)" and "Temperature Estimates" from the section's Property control.
7. Click the left mouse button on the Phase Equilibria Section's table control. The application activates the edit dialog. Select several rows in the dialog's table control by clicking and holding down the left mouse button on the first row and then dragging the mouse downward.
8. Press the dialog's Series button and select Composition Series from the displayed submenu. The application activates the Composition Series dialog. Enter the values shown in the image below.
9. Finally, press the Series dialog's OK button and then the Edit dialog's Save button. The application stores the generated state variables in the current document.
10. Select the Compute Estimates command from the Commands menu. Press the Start button in the Property Estimation Dialog and then Save button once all properties have been estimated. The application will estimate the SLE Liquidus Point, i.e., the mixture's freezing point, for each set of state variables.

Topic	Description
Estimating Chemical Properties	a short video demonstrating how to estimate the physical properties of pure chemical using either Synapse or Cranium.
Estimating Mixture Properties	a short video demonstrating how to estimate the physical properties of mixtures using either Synapse or Cranium.
Getting Started using Cranium	provides a quick tour of Cranium's capabilities including physical property estimation and a discussion of structure editing.
Getting Started using Synapse	provides a quick tour of Synapse's capabilities including examples of chemical product design.