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PCR (Sigma Guide) severe

Sample Fails to Amplify Despite Positive Control Success

Symptom
Positive control amplifies successfully but test sample known to contain target shows no amplification; undiluted template fails while dilutions may show improved amplification
Common Causes
  1. 1 Sample concentration is inappropriate (too high or too low)
  2. 2 Inhibition present in the test sample
  3. 3 Sample contains PCR inhibitors that are diluted out in lower concentrations
Solutions
  1. 1 Test amplification with a diluted sample (1:5 or 1:10 dilution)
  2. 2 Add up to 0.3% BSA to the PCR reaction
  3. 3 Purify the input nucleic acid to remove inhibitors
  4. 4 Spike the reaction with a low level of exogenous target and test for amplification (SPUD Protocol)
  5. 5 Perform SPUD assay to confirm inhibition
Related Video (3)
Addgene ★ 80
Polymerase Chain Reaction (PCR) Protocol
"Addgene's step-by-step PCR protocol demonstration shows correct setup including template handling, useful for understanding how template concentration affects amplification."
Bilibili (China-Accessible Mirrors) ★ 75
PCR protocol fundamentals—hands-on operation guide
"Structured hands-on PCR protocol demonstration covers operational steps where template concentration/troubleshooting decisions arise."
Thermo Fisher Scientific ★ 65
How to Optimize qPCR using SYBR Green Assays - Ask TaqMan #38
"qPCR optimization guidance discusses troubleshooting poor amplification and template/assay optimization, moderately relevant to failed amplification despite positive controls."
Source: sigmaaldrich.com ↗
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