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)
Immunoprecipitation (CST Guide) severe

Low/No Signal from Insufficient Protein Expression

No detectable signal in IP experiment. Input lysate control shows weak or absent target protein band on western blot.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) critical

Loss of Phosphorylated Protein Signal

Phospho-specific antibody shows no or weak signal in IP experiment, while total protein antibody works. Basal phosphorylation levels appear insufficient for detection.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) moderate

Epitope Masking Prevents Antibody Binding

No IP signal despite confirmed protein expression in input control. Antibody works in western blot of denatured lysate but fails in native IP conditions.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) moderate

Low IP Efficiency from Incorrect Bead Selection

Weak IP signal despite good input control. Low recovery of target protein compared to expected levels based on antibody quality.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) minor

Multiple Bands from Isoforms or PTMs

Multiple specific bands appear at different molecular weights in IP lane. Input control shows same pattern, indicating genuine protein variants rather than non-specific binding.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) severe

IgG Heavy/Light Chains Obscure Target Signal

Strong bands at approximately 50 kDa (heavy chain) and 25 kDa (light chain) obscure target protein signal. Same host species used for IP antibody and western blot detection antibody.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) moderate

Multiple Bands from Non-Specific Protein Binding

Multiple bands appear on western blot after IP. Background bands present in bead-only or IgG control lanes indicate non-specific binding.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) severe

No Signal Due to Stringent Lysis Buffer

No signal detected in co-immunoprecipitation experiment. Target protein appears absent despite expected expression.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) severe

Low/No IP Signal from Insufficient Target Expression

IP experiment yields no detectable signal on western blot. Input lysate control shows weak or absent target protein bands, indicating expression below detection threshold.

💡 3 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) severe

Low Signal for Phosphorylated or Modified Proteins

IP of post-translationally modified proteins yields weak or no signal. Input lysate shows low basal levels of phosphorylated or modified target protein despite total protein presence.

💡 4 causes ✓ 5 fixes
Immunoprecipitation (CST Guide) moderate

Low IP Efficiency from Suboptimal IgG-Bead Binding

IP shows weak target protein recovery despite adequate antibody concentration and protein expression. Bead pellet appears smaller than expected or shows poor antibody capture.

💡 3 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) moderate

Non-Specific Protein Binding to Beads or IgG

Multiple non-specific bands appear on western blot after IP. Background signal present in bead-only or isotype control lanes, indicating off-target protein capture.

💡 4 causes ✓ 4 fixes
Immunoprecipitation (CST Guide) moderate

Target Signal Masked by IgG Heavy/Light Chains

Western blot after IP shows strong bands at ~25 kDa and ~50 kDa obscuring target protein. Target protein migrating near these molecular weights cannot be detected due to overwhelming IgG signal.

💡 3 causes ✓ 5 fixes
Immunoprecipitation (CST Guide) severe

No Signal in Co-IP Due to Stringent Lysis Buffer

No signal detected in co-immunoprecipitation experiment despite adequate protein expression confirmed by input lysate control. Western blot shows no target protein bands after IP.

💡 4 causes ✓ 4 fixes