Failure Case Library

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

All Techniques (13) 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)
Restriction Enzyme Digest severe

Incomplete Restriction Enzyme Digestion

Partial digestion observed with both expected fragments and uncut substrate visible on gel; incomplete linearization of plasmid DNA.

💡 6 causes ✓ 6 fixes
Restriction Enzyme Digest severe

DNA Smearing on Agarose Gel After Digestion

Restriction digest product appears as a smear rather than discrete bands on agarose gel, indicating DNA degradation or enzyme-DNA complex formation.

💡 3 causes ✓ 4 fixes
Restriction Enzyme Digest moderate

Star Activity Producing Extra Bands

Extra DNA bands appear on gel beyond expected digest fragments, indicating cleavage at non-canonical recognition sequences due to relaxed enzyme specificity.

💡 4 causes ✓ 5 fixes
Restriction Enzyme Digest moderate

Inefficient Cleavage Due to Single Recognition Site

Incomplete digestion persists despite adequate enzyme units and incubation time; some restriction enzymes require two recognition sites on the same DNA molecule for efficient cleavage.

💡 2 causes ✓ 4 fixes
Restriction Enzyme Digest minor

Larger Than Expected Bands from Enzyme-DNA Binding

DNA bands migrate slower than expected molecular weight on gel, appearing larger due to restriction enzyme remaining bound to digested DNA fragments.

💡 2 causes ✓ 3 fixes
Restriction Enzyme Digest critical

Restriction Enzyme Complete Failure to Cleave DNA

No cleavage observed in restriction digest reaction; DNA remains uncut on gel, resulting in few or no transformants in downstream cloning applications.

💡 5 causes ✓ 5 fixes
Restriction Enzyme Digest severe

Incomplete Restriction Enzyme Digestion

DNA substrate is not fully cleaved after restriction enzyme incubation. Uncut or partially cut DNA bands persist on agarose gel alongside expected digestion products.

💡 7 causes ✓ 7 fixes
Restriction Enzyme Digest moderate

Star Activity Generating Extra Bands

Extra bands appear on gel beyond expected digestion products. Enzyme cleaves at non-canonical sites with relaxed sequence specificity under suboptimal conditions.

💡 5 causes ✓ 5 fixes
Restriction Enzyme Digest minor

Enzyme-DNA Complex Causing Larger Bands

Larger molecular weight bands than expected appear on gel. Restriction enzyme remains bound to cleaved DNA substrate, retarding migration.

💡 3 causes ✓ 3 fixes
Restriction Enzyme Digest severe

Partial Digest with Multiple Uncut Bands

Gel shows mixture of fully digested, partially digested, and uncut DNA. Some recognition sites cleaved while others remain intact in the same molecule.

💡 5 causes ✓ 5 fixes
Restriction Enzyme Digest moderate

Failure to Cut Near DNA Termini

Restriction enzyme fails to cleave recognition sites located within 6 bp of linear DNA ends, such as PCR product termini. Full-length uncut product observed.

💡 3 causes ✓ 4 fixes
Restriction Enzyme Digest severe

Few or No Transformants After Cloning

Bacterial transformation yields few or no colonies after restriction digest-based cloning. Vector may not be linearized or insert ends incompatible.

💡 4 causes ✓ 4 fixes
Restriction Enzyme Digest moderate

DNA Smear on Agarose Gel

Digested DNA appears as a smear rather than discrete bands on agarose gel. No sharp bands are visible across a wide molecular weight range.

💡 4 causes ✓ 4 fixes