Analysis of Interacting Solutes

Step 1: 2DSA refinement

#. Follow steps 1-6 in the 2DSA Flowchart to perform a 2DSA analysis and fit the boundary conditions and the associated time- and radially-invariant noises using iterative refinements.

Step 2: Define the model

  1. Open the Discrete Model Genetic Algorithm (DMGA) function from the velocity menu.

  2. Select Define Base Model to create a new model to be fitted.

  3. The Model Editor window will open an existing model, or allow the user to create a new model.

  4. To create a new model, select Create New Model and change the name in the Model Description text box.

  5. Select Manage Components to open the Component window and to define the analytes in the model.

  6. Click on New Analyte to select a previously entered analyte from the analyte management window and Accept.

  7. For non-interacting models - Update the signal concentration to the partial concentration of each solute from a GA statistical report.

  8. For interacting models - Update the signal concentration of the reactants to the total concentration from the 2DSA-IT results. The product concentration should remain 0 and allow the DMGA fit to simulate the concentration based on the kD and Ka ranges to be provided.

Note

During DMGA fitting, the concentration of each analyte is simulated based on the user-defined ranges of kD and Ka. For best results, initial fitting should be performed using broad log-scale ranges for both parameters, enabling the algorithm to approximate the correct values efficiently. These ranges should then be progressively refined through iterative fitting until the optimal kD and Ka values are determined.

  1. Review the parameters carefully and once satisfied, click Accept.

  2. The Component dialog will close. Click Manage Associations to define the models.

  3. The analytes will be listed in the Association Text box. Drag each analyte into the Analyte and Product positions.

  4. For each reaction, add the approximate K_dissociation (kD) and K_off Rate (Ka).

  5. Multiple model reactions can be made. Models can also be deleted by clicking the D button next to the row number.

  6. Review the reactions carefully and once satisfied, click Accept.

  7. Once both Components and Associations have been defined, click Accept in the Model Editor window.

  8. Click Save Base Model in the DMGA main window and edit the name of the model and save.

Step 3: Define the constraints

  1. If a constraints has previously been defined, click Load DMGA constraints and select the model from the Load Distribution Model window and click Accept.

  2. Click Define Constraints in the DMGA main window and the DMGA Constraints Editor will open.

Note

For interacting models, only for reactant analyte parameters can be floated.

  1. Select three Parameters that will be floated by check the Float? checkbox next to each parameter.

  2. Enter the Low and High limits for each selected parameter.

  3. Review the constraints carefully and once satisfied, click Accept and Save Constraints in the DMGA main window and edit the name of the constraints model and save.

Step 4: Perform DMGA Monte Carlo Analysis

  1. Log in and select the run and triples in USLIMS.

  2. Locate the dataset and select Setup Discrete Model GA Control.

  3. Select 8-10 Monte Carlo iterations and submit data to DMGA analysis, but do not refit time or radially invariant noise.

Step 5: Review parameter results

  1. Visualize results by using the Velocity: FE Model Viewer.

  2. Review the statistical results by clicking Advanced DMGA-MC Controls.

Step 6: Refine constraints

  1. Edit the Constraints parameters to improve simulation fit and repeat steps 4-5.