Failure Case Library

Real lab failures, root causes, and fixes — curated and bilingually annotated by our team.

All Techniques (12) PCR (Sigma Guide) (12) End-point PCR Primers (9) Western Blot (9) Wound Healing Assay (5) Cell Culture (Contamination) (7) Lipid Transfection (8) CCK-8 Cell Viability Assay (5) Colony Formation Assay (10) Transfection (8) Nucleic Acid Quantification (9) Transfection (Co-transfection) (1) Protein Extraction (4) Plasmid Construction (Double Digest) (1) Sanger Sequencing (2) Plasmid Construction (1) qPCR (RT-qPCR) (5) Transwell Migration / Invasion Assay (5) Immunohistochemistry (IHC) (6) PCR (Polymerase Chain Reaction) (26) Restriction Enzyme Digest (13) DNA Cleanup & Plasmid Purification (7) RNA Cleanup (4) NGS Library Preparation (NEBNext Ultra II) (7) HMW DNA Extraction (Monarch) (7) LAMP (Loop-mediated Isothermal Amplification) (7) RNA Depletion for RNA-seq (7) Bacterial rRNA Depletion (4) Cell-free DNA Extraction (8) ELISA (Competitive) (18) ELISA (Signal Problems) (11) ELISA (High Background) (8) ELISA (Inconsistent Results / High CV) (6) ELISA (Standard Curve Fit Problems) (6) Western Blot (Weak / No Signal) (6) Western Blot (Detection Problems) (7) Western Blot (Bands at Wrong MW) (5) Western Blot (Misshapen / Uneven Bands) (5) Western Blot (Unexpected Multiple Bands) (7) Western Blot (Unusual Gel Band Appearance) (3) ChIP (High Background) (1) ChIP (Low Resolution with High Background) (6) ChIP (Low Signal) (8) ChIP (PCR Amplification Problems) (4) Immunohistochemistry (High Background) (9) Immunohistochemistry (No Staining) (9) Immunoprecipitation (High Antibody Elution) (1) Immunoprecipitation (High Background) (8) Immunoprecipitation (No Protein Detected) (5) Immunoprecipitation (Protein Obstruction) (1) ELISPOT (8) Tissue Imaging (Autofluorescence) (9) Flow Cytometry (Troubleshooting) (8) ELISA Development (9) Flow Cytometry (Autofluorescence) (7) Flow Cytometry (Compensation) (7) Flow Cytometry (Fc Blocking) (7) Flow Cytometry (Fixation & Permeabilization) (9) Flow Cytometry (Isotype Controls) (7) Flow Cytometry (Fixation Buffers) (7) Western Blot (CST Guide) (8) ChIP (CST Guide) (8) Immunoprecipitation (CST Guide) (14) Immunohistochemistry (CST Guide) (14) Flow Cytometry (CST Guide) (8) ELISA (R&D Guide) (10) ELISA (Sigma Guide) (6) Western Blot Immunodetection (19) IP-Western Blot (6) Flow Cytometry (Sample Considerations) (14) Flow Cytometry (Paraformaldehyde Fixation) (14) Western Blot (Sigma Protocol) (8) PCR / RT-PCR Amplification Problems (5) Cell Culture (Cell Death) (8) Cell Culture (Precipitates) (6) PCR (Invitrogen Guide) (8) PCR / qPCR Plastics (9) Flow Cytometry (Controls) (8) Plasmid Mini-prep (1) Transfection (siRNA Knockdown) (1) Western Blot (Blue Background) (1)
PCR (Sigma Guide) 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 causes ✓ 5 fixes
PCR (Sigma Guide) moderate

Incorrect Reaction Efficiency Due to Oligo Binding to Non-Molecular Biology Tubes

Variable and incorrect standard curve efficiency when using serial dilutions; effect more pronounced when same dilution series stored at 4°C and reused; inconsistent differences between amplification plots; problem resolves when different operator uses different tubes

💡 4 causes ✓ 5 fixes
PCR (Sigma Guide) severe

PCR Efficiency Greater Than 120% with Inconsistent ΔCq

PCR efficiency calculated from standard curve is greater than 120%; ΔCq between 10-fold dilutions is much less than expected 3.3 cycles (e.g., 1.5 cycles); standard curve gradient indicates abnormally high efficiency

💡 4 causes ✓ 6 fixes
PCR (Sigma Guide) moderate

Primer Dimer Formation at Low Template Concentrations

Low concentration data points do not fit linear standard curve profile; NTC shows amplification with lower Tm and broader melt peak than positive samples; primer dimers visible on gel, inversely proportional to template concentration

💡 4 causes ✓ 5 fixes
PCR (Sigma Guide) severe

Low Fluorescence Due to Inadequate Probe Labeling or Quenching

Low or absent fluorescence in both test sample and positive control; correct PCR product is visible on gel; one probe in multiplex shows consistently high background with no amplification signal; background fluorescence equivalent to water control

💡 5 causes ✓ 6 fixes
PCR (Sigma Guide) 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 causes ✓ 5 fixes
PCR (Sigma Guide) moderate

Amplification Plots Dip Below Zero Due to Incorrect Baseline Settings

Amplification plots are clearly abnormal with sections dipping below zero dR; data cannot be used as presented; plots appear distorted

💡 3 causes ✓ 4 fixes
PCR (Sigma Guide) moderate

Abnormal Amplification Plots Due to Excessive Template Concentration

Very low Cq values for concentrated samples; amplification plots are not regularly spaced and appear abnormal; background fluorescence is significantly higher; minimal fluorescence yield through the reaction

💡 3 causes ✓ 4 fixes
PCR (Sigma Guide) moderate

Irregular Standard Curve Spacing Due to Sample Inhibitors

Cq data for standard curve dilutions are irregularly spaced; ΔCq between dilutions is inconsistent and decreases with increasing dilutions; replicates are precise but pattern is abnormal

💡 3 causes ✓ 5 fixes
PCR (Sigma Guide) severe

Insensitive Assay with Abnormal Amplification Due to Probe Secondary Structure

Assay is insensitive and amplification plots look abnormal with pronounced drift of the baseline; fluorescence signals are weak or irregular

💡 3 causes ✓ 4 fixes
PCR (Sigma Guide) severe

PCR ReadyMix Works for PCR but Fails in qPCR

ReadyMix produces amplification in standard PCR but completely fails in real-time qPCR applications; equivalent products from other suppliers work well

💡 3 causes ✓ 3 fixes
PCR (Sigma Guide) 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 causes ✓ 3 fixes