User Guide

Step 1: Pick a buffer species (single, dual, etc) using the
autocomplete input

As soon as you pick the buffer species the tool will populate
the input for you in the correct format

Step 2: Format the Natural Language Input

Your input should be in the following format:

• • Buffer concentration: This should be a
    number followed by “mM”. For example, “50mM”.
  • Buffer species: This should be the name of
    the buffering species. For example, “Phosphate”.
  • Salt concentration (optional): If you want
    to include a salt, this should be a number followed by “M”.
    For example, “0.1M”.
  • Salt name (optional): If you include a salt
    concentration, you should also include the name of the salt.
    For example, “Sodium Chloride”.
  • pH: This should be the keyword “pH”
    followed by the target pH. For example, “pH 7.0”.

So a complete input might look like this: “50mM Phosphate,
0.1M Sodium Chloride, pH 7.0″.

Step 3: Generate Your Buffer Recipe

Click on the Get Recipe button to generate
your buffer recipe. This action will trigger several events:

• Status Message: A status message will
  appear. If the buffer design and calculation are successful,
  this message will simply read “Done”. If there are any
  issues with the design or calculation, the status message
  will provide detailed feedback.
• Solution List: The resulting buffer
  solution will be added to your solution list.
• Buffer Recipe: A detailed recipe for your
  buffer will be provided.
• Buffer Analysis: A comprehensive analysis
  of your buffer will be displayed, including:
  • Compound Concentrations
  • Ion Concentrations
  • Ion-Species Concentrations
  • A Heatmap: This visual representation shows the impact
    of variability in compound concentrations.

Please note that the buffer design process has certain
constraints and limitations, which are outlined in the
following sections.

Step 1: Select Acidic and Basic Compounds

Begin by selecting your desired acidic compound from the first
drop-down list. This list contains both buffering and
non-buffering compounds. If you choose a non-buffering compound,
ensure you select a buffering compound from the basic compound
list.

Next, select your desired basic compound from the second
drop-down list. This list also contains both buffering and
non-buffering compounds. If the selected basic compound does not
contain the same buffering species as the acidic compound, its
concentration will be adjusted to achieve the target pH.

Step 2: Specify the Target Buffer Species Concentration

Enter the target concentration for the buffering species in
molar units. This will be the concentration of the buffering
species in the final buffer. If both compounds contain the same
buffering species, their concentrations will be adjusted to
achieve this target concentration.

If the basic compound is non-buffering or contains a different
buffering species, the entered concentration will be the target
for the acidic compound’s buffering species. If a non-buffering
compound was selected from the acidic compound list, a buffering
compound must be selected from the basic compound list.

Step 3: Choose a Salt Compound (Optional) and Its Concentration

Optionally, select a salt compound from the provided list, which
currently includes Sodium Chloride, Sodium Sulfate, and Ammonium
Sulfate. Enter the desired concentration for the salt compound
in molar units.

Step 4: Input the Target pH

Enter your desired target pH. The concentrations of the acidic
and basic compounds will be adjusted as necessary to achieve
this pH.

Step 5: Generate Your Buffer Recipe

Click the Get Recipe button to send your
request to the server. The calculated recipe and detailed
analysis will be displayed.

Additional Considerations

• pH Range Limitations: Certain compound and
  concentration combinations may limit the achievable pH range
  due to inherent chemical properties. If this occurs, an error
  message will display the achievable pH range. This range
  varies based on the selected compounds and target
  concentrations.
• Concentration and pH Constraints: The
  Designer has built-in constraints on the choice of
  concentrations for the buffer and salt compounds to produce
  meaningful buffers commonly used in practice. Please note that
  ionic strength corrections are not accurate beyond 0.4M. While
  the GenAI Designer does not have this limitation, choosing a
  broad range of concentrations may result in impractical
  recipes.

Step 1: Pick Acidic and Basic Compounds

From the first drop-down list, which is a list of acidic
compounds, pick the one that contains the buffering species
that you want. Alternatively, you can pick a non-buffering
compound from this list. However, you have to make sure you
pick a buffering compound from the basic compound list below.

From the second drop-down list, which is a list of basic
compounds, pick the one that contains the buffering species
that you want to target. Alternatively, you can pick a
non-buffer containing compound, or a compound that provides a
different buffering species.

Step 2: Enter Acidic and Basic Compound Concentrations

Enter the concentration for the acidic compound in the input
provided. Similarly, enter the concentration for the basic
compound in the input provided. This number is entered as
molar concentration. Enter only the number.

Step 3: Pick a Salt Compound Name (Optional) and Concentration

You can pick a salt compound name from the Salt Compound list.
Currently, the list is restricted to Sodium Chloride, Sodium
Sulfate, and Ammonium Sulfate. Enter a concentration for the
salt compound. This will be in Molar.

Step 4: Click the Calculate pH Button

The request will be sent to the server to calculate the recipe
and the details will be populated.

Step 1: Pick Acidic and Basic Compounds

From the first drop-down list, you can pick any acid or basic
compound

From the second drop-down list, you can pick any acid or basic
compound

From the third drop-down list, you can pick any acid or basic
compound

Step 2: Enter Compound Concentrations

In the corresponding concentration inputs you can enter the
concentration of the compounds in Molar

Step 3: Pick a Salt Compound Name (Optional) and Concentration

You can pick a salt compound name from the Salt Compound list.
Currently, the list is restricted to Sodium Chloride, Sodium
Sulfate, and Ammonium Sulfate. Enter a concentration for the
salt compound. This will be in Molar.

Step 4: Check the “Adjust pH” box (optional)

You can check this box, which will enable you to enter the
target pH for the solution. The tool will automatically pick
Sodium Hydroxide or Hydrochloric Acid to adjust the pH to the
target pH.

Step 5: Enter the target pH (optional)

You can check this box, which will enable you to enter the
target pH for the solution. The tool will automatically pick
Sodium Hydroxide or Hydrochloric Acid to adjust the pH to the
target pH.

Step 6: Click the Calculate pH Button

The request will be sent to the server to calculate the recipe
and the details will be populated.

• Buffers are a fundamental concept in chemistry, particularly
  in the field of biochemistry. Buffers are solutions that
  resist changes in pH when small amounts of acid or base are
  added to them. They are essential in maintaining the pH of
  biological systems, as well as in many laboratory
  applications.
• Buffers are generally composed of a buffering species (such as
  Phosphate) and a counter-ion (Sodium), and optionally a fully
  ionized salt, such as Sodium Chloride. The buffering species
  provides the specific characteristic of the buffer, due to its
  dissociation properties. Buffering species can have multiple
  dissociation steps, with each step having a specific
  dissociation constant (referred to as pKa). For a detailed
  explanation of the dissociation constants jump to the section
  below.
• Counter-ions are ions that are present in a buffering solution
  that provide the appropriate charge balance to achieve a
  specific pH. See the charge balance equations below in the
  next section for details. The counter-ions should produce ions
  of the opposite charge to be able to modify the pH.
• In order to prepare buffered solutions, we typically use
  compounds containing the buffering species, either in a “pure”
  form, (e.g., Phosphoric Acid) or “salt form” where the
  buffering species is present in combination with the counter
  ion (e.g., Sodium Phosphate Monobasic).
• If a pure form is chosen as one of the compounds, then the
  counter-ion is supplied separately as a “strong acid” (e.g.,
  Hydrochloric Acid) or “strong base” (e.g., Sodium Hydroxide),
  depending on the counter-ion desired. We can call this pairing
  as “Weak Acid/Base” – “Strong Base/Acid”.
• If a salt form is chosen as one of the compounds, and if the
  compound in solution is “acidic”, then the secondary compound
  is chosen to be one that will be “basic” essentially to
  provide the charge balance to achieve the target pH. There are
  several scenarios with this pairing, which are described, and
  the way to achieve the target pH and concentration in the app
  are included below.

Both Compounds Containing Same Buffering Species

• • Single buffering species, with each compound containing both
    the counter-ion and the buffering species – Example: Sodium
    Phosphate Monobasic, Sodium Phosphate Dibasic. Here both
    compounds contain Phosphate as the buffering species, which
    is a negatively charged buffering species. The counter-ion
    is Sodium (positively charged) and is supplied by both
    compounds.

Classic Buffer Designer

In specifying this buffer in the app with the “Classic Buffer
Designer”, you can pick an acidic compound from the first
list, and a basic compound from the second list, such that
both contain the same buffering species and the same
counter-ion. Then you can specify the target buffer
concentration, which specifies the total buffering species
concentration in the final buffer and the target pH. The
Design calculation engine will then determine the right
proportion of each compound to achieve the target pH, while
maintaining the target buffering species concentration.

One Compound Only Containing Buffering Species

• Single buffering species, with one compound containing the
  buffering species – counter-ion combination, and the other
  compound containing the counter-ion only. Example: Sodium
  Phosphate Monobasic and Sodium Hydroxide. Here the Sodium
  Phosphate Monobasic provides both Phosphate and Sodium,
  while the Sodium Hydroxide provides the counter-ion only.
  Again, the Sodium Phosphate Monobasic is “acidic” in
  solution and the Sodium Hydroxide is “basic” in solution,
  forming a pair. Notice that the “strong base” (Sodium
  Hydroxide) has the same ion as the ion in the first
  compound. While this is desirable to keep the solution
  simple, it is necessary to choose the same counter-ion. For
  example, you can choose Potassium Hydroxide, to achieve the
  target pH.

  Classic Buffer Designer

  In specifying this buffer in the app with the “Classic
  Buffer Designer”, you can pick a compound in either of the
  lists containing the buffering species counter-ion salt, and
  then choose the other compound which contains only the
  counter-ion Again, you will specify the target buffering
  species concentration in the final solution, and the target
  pH. The Design calculation engine will determine the right
  concentration of the two compounds to achieve the target pH,
  while achieving the target buffering species concentration.

Two buffering species, achieved with two compounds one of each
containing only the “pure form” of the buffering species. One
will choose the buffering species such that one contributes the
positive (or basic) ions and the other the negative (or acidic)
ions. A popular example of this, is Acetate-Tris buffer, where
Acetic Acid and Tris Base combined to produce the buffer. In
designing this buffer, you will first choose Acetic Acid from
the first list and Tris Base from the second list. It is
important to note that the target concentration refers to the
buffering species in the acidic component and not the basic
component (the flexibility of choosing either will be a future
improvement in the app). With a target pH, the Design
calculation engine will find the concentration of the second
compound that will achieve the target pH.

Classic Designer

You can easily achieve this with the Classic Designer. First you
choose the buffering species pair using the autocomplete input.
As soon as you choose the pair, the drop downs corresponding to
the compounds will auto populate. All you need to do is specify
the buffer concentration (of the first species) and the target
pH. If you want to choose a pair that is not in the
autocomplete, you can choose the appropriate secondary buffer
compound. The primary buffer species concentration will be set
and the secondary compound will be used to adjust the pH, if
possible.