PCR master mix calculator

Master mix volumes for a batch of PCR reactions, with overage.

Reactions

Master mix

Component1 rxnMix
ComponentStockFinal

Template and additives

How to calculate a PCR master mix

Everything that is the same in every tube goes into one mix, which is then split between the tubes; only the template is pipetted separately. Each component is diluted from its stock to its final concentration in the reaction, so its volume follows the dilution rule:

volume per reaction = reaction volume × (final concentration ÷ stock concentration)
master mix per reaction = reaction volume − template volume
total mix = master mix per reaction × reactions × (1 + extra ÷ 100)

Water makes up whatever is left of the reaction volume once the other components and the template are accounted for. The extra percentage covers what stays behind in the tip and on the walls of the tube; without it the last reaction is always short.

Worked example

Taq, 25 µL reactions, 12 reactions, 10 % extra, 1 µL of template, which is the built-in example. Each reaction takes 2.50 µL of 10× Standard Taq Buffer, 0.50 µL of 10 mM dNTPs, 0.50 µL of each 10 µM primer, 0.13 µL of Taq at 5 U/µL and 19.88 µL of water, which is 24.00 µL of mix plus 1 µL of template. The mix is made for 12 × 1.10 = 13.2 reactions, so the buffer becomes 33.00 µL, the dNTPs 6.60 µL, each primer 6.60 µL, the Taq 1.65 µL and the water 262.35 µL: 316.80 µL of master mix. Aliquot 24.00 µL per tube and add the template.

What is in each preset

PresetBufferPrimersEnzyme
Taq10× Standard Taq0.2 µM0.025 U/µL
OneTaq5× OneTaq Standard0.2 µM0.025 U/µL
Phusion5× Phusion HF0.5 µM0.02 U/µL
Q55× Q5 Reaction0.5 µM0.02 U/µL
Pfu10× Pfu with MgSO₄0.2 µM0.05 U/µL
2× master mix2× ready mix0.2 µMin the mix

All of them assume 10 mM dNTPs and 10 µM primer stocks and give 200 µM dNTPs in the reaction. The buffers carry their own magnesium, so no separate MgCl₂ row appears; if your Taq buffer does not, add 1.5 mM Mg²⁺ from a 25 mM stock, which is 1.5 µL in a 25 µL reaction.

Practical points

  • Count the controls. A no-template control and a positive control are two more reactions. Add them to the number of reactions rather than relying on the overage.
  • Watch volumes under 1 µL. A 0.13 µL pipetting step is not reproducible, which is exactly why it belongs in a mix. If a total in the mix column is still under 1 µL, make a bigger batch or dilute that stock.
  • Keep the mix cold and add the polymerase last, or use a hot-start enzyme. Mix by flicking or gentle pipetting, not vortexing.
  • Check the cycling conditions too. Theextension time and annealing calculator sets the program, and the Tm calculator gives the primer melting temperatures it needs.

Frequently asked questions

How much extra master mix should I make?

Ten percent is the usual allowance for eight to twenty-four reactions, and it is what this calculator starts with. For fewer than eight reactions use fifteen or twenty percent, because the fixed loss in the tip and the tube is a larger share of a small mix. For a whole 96-well plate five percent is normally enough. Count the no-template control and any positive control as reactions of their own.

Why is the template not in the master mix?

Because each reaction gets a different template, and because a common mix contaminated with template ruins every tube including the no-template control. The mix holds buffer, dNTPs, both primers, the polymerase and water; the template goes into each tube separately, which is why the calculator asks how much of it you add and subtracts that volume.

What final primer concentration should I use?

The polymerase supplier decides. NEB specifies 0.2 microMolar for Taq and OneTaq and 0.5 microMolar for Phusion and Q5, and those are the values used here. Raising the primer concentration rarely helps a weak reaction and does make primer dimer more likely, so change the annealing temperature or the template amount first.

Can I use a 2x ready-mix instead?

Yes, pick the 2x master mix preset. It contains the buffer, dNTPs, magnesium and the polymerase, so the only things you add are primers, template and water. Half the reaction volume is ready mix; the calculator works out the rest.

Do I need DMSO?

Only for templates with strong secondary structure or high GC content. Three percent final is a common starting point with Phusion and Q5, and it lowers the effective annealing temperature by roughly a degree for each percent, so drop the annealing temperature when you add it. Enter the final percentage under the result and it appears in the table as neat DMSO.