Home Cell Biology Polymerase Chain Reaction (PCR) Protocol
Steps
  1. 1 Understand PCR principles and requirements --:--
  2. 2 Design primers and gather materials 01:36
  3. 3 Prepare PCR reaction mix on ice 02:33
  4. 4 Program PCR machine with thermal cycles 03:24
  5. 5 Run final extension cycle 04:49
  6. 6 Prepare agarose gel for analysis 05:01
  7. 7 Verify PCR product by gel electrophoresis 05:18
  8. 8 Troubleshoot and optimize if needed 05:31
Cell Biology Addgene

Polymerase Chain Reaction (PCR) Protocol

Protocol
Difficulty
intermediate

Steps

1
Understand PCR principles and requirements

Learn what polymerase chain reaction is, how it amplifies DNA through repeated heating and cooling cycles, and review the key reagents needed: primers, dNTPs, Taq polymerase, buffer, and template DNA.

▶ --:--
2
Design primers and gather materials

Design forward and reverse primers with similar melting temperatures that are complementary to the DNA region you want to amplify, and gather all necessary lab materials including PCR tubes, ice bucket, and the PCR machine.

▶ 01:36
3
Prepare PCR reaction mix on ice

Place thin-walled PCR tubes on ice and prepare a 50 microliter reaction mix containing all reagents. Optionally create a master mix with common reagents like water, Taq polymerase, and dNTPs to save time on multiple reactions.

▶ 02:33
4
Program PCR machine with thermal cycles

Set up the PCR machine with the initial denaturation step (2 minutes at 94°C) followed by 25-30 cycles of denaturation (30 seconds at 94°C), annealing (30 seconds at 5°C below primer melting temperature), and extension (1-2 minutes per kilobase at 72°C).

▶ 03:24
5
Run final extension cycle

Set the PCR machine to perform a final extension for 5 minutes at 72°C to fill in any protruding ends of the newly synthesized DNA strands.

▶ 04:49
6
Prepare agarose gel for analysis

While the PCR cycles are running, prepare an agarose gel for later use in verifying the PCR product.

▶ 05:01
7
Verify PCR product by gel electrophoresis

After the final cycle completes, run 2 microliters of the PCR product on the agarose gel to check the size and concentration of the amplified DNA.

▶ 05:18
8
Troubleshoot and optimize if needed

If the PCR reaction did not work, try adding magnesium chloride and/or DMSO to each reaction, or adjust the annealing temperature to improve specificity and product yield.

▶ 05:31

🚨 Failure Case Library (15) + Submit your own case

critical
No Band Due to Incorrect Component Concentrations
No visible band or very faint band on gel despite proper thermal cycling parameters. The reaction components may be at suboptimal or inhibitory concentrations.
💡 5 · ✓ 5
critical
No Band or Faint Band Due to Incorrect Component Concentrations
PCR amplification fails or produces very weak bands. Thermal cycling parameters appear correct, but reaction components may be improperly balanced or missing.
💡 6 · ✓ 6
critical
No Band Due to Omitted Critical Components
Complete absence of PCR product on gel due to missing essential reaction components, representing a critical setup error.
💡 5 · ✓ 5
critical
No PCR Product Detected
Gel electrophoresis shows no visible band at the expected product size after PCR amplification, indicating complete reaction failure.
💡 8 · ✓ 8
critical
False Positive Amplification from Contamination
PCR products appear in negative control reactions without template. Products may appear in samples expected to be negative.
💡 4 · ✓ 5
critical
False Positive PCR Results from DNA Contamination
No-template controls (NTC) or negative controls show unexpected amplification. Particularly problematic in sensitive applications like human identification qPCR where trace DNA contamination produces false positives.
💡 3 · ✓ 3
severe
No Band or Faint Band Due to Suboptimal Thermal Cycling Parameters
No visible PCR product band appears on the gel, or only a very faint band is detected. This occurs despite using appropriate template and primers, suggesting insufficient amplification.
💡 6 · ✓ 6
severe
Incorrect PCR Product Size
Gel electrophoresis shows PCR product band(s) at unexpected molecular weight, either larger or smaller than the predicted amplicon size.
💡 3 · ✓ 4
severe
Insufficient Amplification from Polymerase Issues
Weak or absent PCR product. Primers are degraded or show primer-dimer formation at the bottom of gel.
💡 4 · ✓ 5
severe
No or Low PCR Amplification Due to Plastic Consumable Issues
PCR reaction fails to produce expected amplification or yields significantly reduced product, despite optimized reagents and cycling parameters. The issue traces to suboptimal thermal transfer or contamination from the plastic vessel itself.
💡 4 · ✓ 4
severe
Plate or Tube Melting and Adhering to Block
After PCR program completion, plates or tubes are found melted or stuck to the thermal cycler block, making removal difficult and potentially damaging samples. Plastic shows signs of thermal degradation.
💡 3 · ✓ 3
severe
PCR Inhibition from Contaminated Template
No or weak PCR amplification despite correct reaction setup, with template DNA containing residual contaminants from extraction or purification that inhibit polymerase activity.
💡 4 · ✓ 6
moderate
No Band or Faint Band Due to Template Quality Problems
PCR fails or produces weak products despite correct reagent concentrations and cycling parameters, due to compromised template DNA quality or presence of inhibitors.
💡 4 · ✓ 4
moderate
Nonspecific Amplification and Smearing on Gel
Gel shows multiple bands, smears, or high background instead of single clean product band. May include primer-dimers at bottom of gel.
💡 6 · ✓ 6
moderate
PCR Tube Crushing or Deformation Under Lid Pressure
PCR tubes become crushed, collapsed, or deformed after thermal cycling, potentially causing sample loss or compromised seal integrity. Tubes may show visible damage especially when using tube strips.
💡 3 · ✓ 3
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