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 (46) + 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
Complete Absence of PCR Product
No bands visible on agarose gel after PCR amplification, indicating complete reaction failure.
💡 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 Thermal Cycling Errors
No visible band or very faint band appears on the gel after PCR amplification. This indicates insufficient or failed amplification of the target sequence.
💡 6 · ✓ 6
severe
No Band Due to Template or Reagent Quality Issues
PCR fails to produce visible band despite correct concentrations and cycling parameters. Template degradation, contamination, or impure reagents may be inhibiting the reaction.
💡 5 · ✓ 5
severe
No Band Due to Primer Design or Synthesis Errors
No amplification observed even with optimized reaction conditions. Primers may have incorrect sequences, poor design, or target sequence may be too long for current protocol.
💡 4 · ✓ 5
severe
No Band or Faint Band Due to Thermal Cycling Issues
After PCR amplification and gel electrophoresis, no visible band appears at the expected product size, or only a very faint band is observed, indicating insufficient or failed amplification.
💡 6 · ✓ 6
severe
No Band or Faint Band Due to Reagent Concentration Issues
Gel shows no amplification product or very weak bands despite correct thermal cycling parameters, indicating problems with reaction component concentrations.
💡 6 · ✓ 6
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
No Band Due to Primer Design or Quality Issues
No PCR product is obtained despite correct thermal cycling and component concentrations. Investigation reveals potential primer-related issues including design flaws or contamination.
💡 5 · ✓ 5
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
Multiple or Non-Specific PCR Products
Gel electrophoresis reveals multiple bands, smearing, or bands at incorrect sizes in addition to or instead of the expected product, indicating lack of amplification specificity.
💡 7 · ✓ 7
severe
Amplification Failure with Complex Templates
No or weak PCR product when amplifying GC-rich sequences (>65% GC content), long amplicons (>10 kb), or high-complexity genomic DNA despite optimization of standard parameters.
💡 4 · ✓ 6
severe
Low or No Amplification Due to Template Issues
PCR yields little to no product visible on gel electrophoresis. Expected band is absent or extremely faint despite using standard reaction conditions.
💡 6 · ✓ 6
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 Sample Evaporation and Loss During Cycling
Visible reduction in reaction volume after thermal cycling, with condensation on tube caps or film. May result in concentrated reagents, failed reactions, or inability to recover product.
💡 3 · ✓ 3
severe
Sample Fails to Amplify Despite Positive Control Success
Positive control amplifies successfully but test sample known to contain target shows no amplification; undiluted template fails while dilutions may show improved amplification
💡 3 · ✓ 5
severe
Assay Failure When Switching Master Mix Products
Previously working assay fails completely when switching to different master mix brand; positive controls fail; original master mix works but new one does not despite similar specifications
💡 4 · ✓ 5
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
severe
No Band or Faint Band with GC-Rich Templates
PCR fails or produces very weak amplification specifically with high GC content templates (>65%). Standard protocols work with other templates but not GC-rich sequences.
💡 3 · ✓ 4
severe
Sequence Errors in PCR Product
Sequencing of the PCR product reveals mutations, insertions, deletions, or other sequence variations compared to the original template DNA.
💡 6 · ✓ 6
severe
No Product Due to Suboptimal Cycling Parameters
No amplification product visible despite proper template and reagents, suggesting thermal cycling conditions are inappropriate.
💡 4 · ✓ 4
severe
Amplification Failure from Primer Problems
No visible PCR product despite good template quality. Control reactions with different primers may work normally.
💡 4 · ✓ 4
severe
Sequence Errors Within PCR Product Body
Sequencing reveals point mutations, insertions, or deletions within the amplified fragment that are not present in original template.
💡 5 · ✓ 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
Smeared Bands on Gel
PCR products appear as continuous smears rather than discrete bands on gel, indicating template degradation, excessive cycling, or nonspecific amplification throughout a size range.
💡 5 · ✓ 5
moderate
Nonspecific Bands or Primer-Dimers Due to Component Imbalance
Multiple bands or primer-dimers appear on gel despite optimized thermal cycling. Component concentrations may be promoting nonspecific primer interactions or amplification.
💡 5 · ✓ 5
moderate
Smeared Bands Due to Template Quality or Concentration Issues
Gel displays smeared bands suggesting degraded products or heterogeneous amplification. Template-related issues such as degradation, contamination, or excessive concentration are suspected.
💡 6 · ✓ 6
moderate
PCR污染和携带污染
Unexpected products appear in negative controls or multiple samples show identical non-specific bands, indicating contamination from previous amplifications or environmental sources.
💡 4 · ✓ 7
moderate
Primer Dimer Formation
Small molecular weight band (typically 50-100 bp) visible at bottom of gel, representing primer self-amplification artifacts that compete with target amplification.
💡 3 · ✓ 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
moderate
PCR Tube Caps Popping Off During Cycling
Individual tube caps become dislodged during thermal cycling, exposing samples to evaporation and potential contamination. Caps are found loose or completely separated from tubes after run completion.
💡 3 · ✓ 3
moderate
Nonspecific Bands or Primer-Dimers
Multiple bands appear on gel in addition to or instead of the expected target band. Primer-dimer artifacts or nonspecific amplification products are visible, indicating lack of reaction specificity.
💡 7 · ✓ 7
moderate
Nonspecific Bands or Primer-Dimers Due to Reagent Issues
Multiple unwanted PCR products appear on gel alongside or instead of target band, caused by reagent concentration imbalances or primer design problems.
💡 4 · ✓ 4
moderate
Smeared Bands Due to Excessive Thermal Cycling
Gel shows smeared or diffuse bands rather than discrete sharp bands. The smearing pattern suggests heterogeneous product populations from excessive amplification or nonspecific priming.
💡 6 · ✓ 6
moderate
Nonspecific Bands or Primer-Dimers Due to Thermal Cycle Issues
Gel shows multiple bands instead of single target band, or primer-dimers appear as small molecular weight products. The desired product may be present but accompanied by unwanted amplification artifacts.
💡 6 · ✓ 6
moderate
Excessive DNA Smearing on Gel
Amplified DNA appears as broad smear rather than discrete bands, indicating degradation or over-amplification artifacts.
💡 8 · ✓ 8
moderate
Amplification Failure from Suboptimal Cycling Parameters
No product or very weak bands despite proper template and primer quality. Reaction components appear functional in other assays.
💡 4 · ✓ 4
moderate
JumpStart Taq ReadyMix Underperforming Due to Incorrect Hot Start Protocol
JumpStart Taq ReadyMix does not work as well as similar products from different suppliers; amplification is weak or absent despite correct assay design
💡 3 · ✓ 3
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