Failure Case Library

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

All Techniques (14) 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)
Flow Cytometry (Paraformaldehyde Fixation) moderate

Inconsistent Fixation Quality from Incorrect PFA Concentration

Samples show variable fixation quality, with some cells over-fixed (high autofluorescence, poor staining) and others under-fixed (continued biological activity). Reproducibility across experiments is compromised.

💡 5 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) critical

Phosphorylation Artifacts from Pre-Staining Surface Antibodies

Intracellular phosphorylation signals are artifactually elevated or altered when surface antibodies are added before fixation. Antibody binding to surface antigens triggers unwanted intracellular signaling cascades that confound phospho-flow results.

💡 5 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) severe

Incomplete Cell Fixation Due to Insufficient Incubation

Cells show inconsistent staining patterns, continued metabolic activity, or poor storage stability when fixation incubation time is too short. Inadequate fixation may also fail to inactivate infectious samples properly.

💡 5 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) severe

Severe Fluorophore Signal Loss with Alcohol Fixatives

Protein-based fluorophores (PE, APC, tandems) show dramatic signal reduction or complete loss when cells are fixed with methanol or ethanol-based fixatives instead of PFA.

💡 4 causes ✓ 5 fixes
Flow Cytometry (Paraformaldehyde Fixation) moderate

Progressive Biological Changes in Unfixed Time-Course Samples

Time-course experiments show artifactual progression or decay of signals when samples are not fixed at each timepoint. Biological processes continue during sample handling, obscuring true temporal snapshots.

💡 5 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) moderate

Sample Degradation During Extended Post-Fixation Storage

Fixed samples show decreased fluorescence intensity, increased autofluorescence, or poor scatter profiles when stored for extended periods (>7 days) before analysis.

💡 5 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) severe

Tandem Fluorophore Signal Quenching After Fixation

PE/Cy7, APC/Cy7, and other tandem dyes show reduced fluorescence intensity after exposure to PFA fixation. Signal loss is more pronounced than with single fluorophores, affecting proper population resolution.

💡 5 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) severe

Loss of Antibody Signal After Pre-Fixation

Antibodies show complete or partial loss of fluorescent signal when cells are fixed with 4% PFA before antibody staining. Target cells that should be positive appear negative or dim compared to unfixed controls.

💡 5 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) critical

Artifactual phosphorylation signals from pre-fixation surface staining

Phospho-flow cytometry results show altered phosphorylation patterns when surface antibodies are added before fixation. Antibody binding to surface antigens triggers intracellular signaling cascades that confound true phosphorylation measurements.

💡 4 causes ✓ 5 fixes
Flow Cytometry (Paraformaldehyde Fixation) moderate

Workflow disruption from inappropriate fixation timing decisions

Experimental workflow becomes incompatible with chosen fixation strategy, leading to scheduling conflicts, sample degradation, or compromised data quality. Researchers cannot complete multi-step protocols in required timeframes.

💡 4 causes ✓ 5 fixes
Flow Cytometry (Paraformaldehyde Fixation) moderate

Suboptimal PFA concentration causing inadequate or excessive fixation

Using incorrect paraformaldehyde concentration results in either incomplete cellular preservation (too low) or excessive epitope masking and fluorophore damage (too high). Standard flow cytometry protocols show inconsistent results across experiments.

💡 4 causes ✓ 6 fixes
Flow Cytometry (Paraformaldehyde Fixation) severe

Tandem fluorophore signal loss after PFA fixation

Protein-based tandem fluorophores (PE/Cyanine7, APC/Cyanine7) exhibit reduced fluorescence intensity after contact with paraformaldehyde fixative. Signal quenching is observed even with standard 1-4% PFA concentrations.

💡 4 causes ✓ 5 fixes
Flow Cytometry (Paraformaldehyde Fixation) critical

Incomplete cellular fixation due to insufficient incubation

Cells show incomplete crosslinking when fixation time is inadequate, resulting in poor preservation, continued enzymatic activity, or inadequate biosafety inactivation of infectious samples. Fixed cells demonstrate degradation during storage or analysis.

💡 4 causes ✓ 5 fixes
Flow Cytometry (Paraformaldehyde Fixation) severe

Loss of antibody signal when staining after PFA fixation

Antibodies show reduced or complete loss of binding signal when cells are fixed with 4% PFA prior to antibody staining. Representative flow cytometry plots demonstrate no detectable fluorescence in post-fixation stained samples compared to unfixed controls.

💡 4 causes ✓ 5 fixes