Home › Immunology › Cell Preparation for Flow Cytometry
Steps
  1. 1 Determine cell type and sample source 00:05
  2. 2 Handle cells at appropriate temperature 01:09
  3. 3 Lyse erythrocytes using appropriate buffer 01:27
  4. 4 Process samples promptly or preserve them 02:02
  5. 5 Remove dead cells and debris 02:57
  6. 6 Prepare adherent cells with gentle lifting 03:41
  7. 7 Stimulate cells under optimized conditions 04:00
Immunology BD Biosciences

Cell Preparation for Flow Cytometry

Protocol
Difficulty
intermediate

Steps

1
Determine cell type and sample source

Identify what type of cells you are analyzing, such as whole blood, PBMCs, tissue, or cell lines. Consider that rare lymphoid populations benefit from PBMC isolation, while granulocyte analysis requires whole blood.

▶ 00:05
2
Handle cells at appropriate temperature

Keep whole blood at room temperature, but maintain PBMCs and cells in BD effects lacing solution on ice to preserve cell viability and morphology.

▶ 01:09
3
Lyse erythrocytes using appropriate buffer

Use either BD effects lacing solution (which contains fixative) or BD FarmLite buffer (without fixative) to remove red blood cells. Stain for fixative-sensitive antigens before using BD effects lacing solution.

▶ 01:27
4
Process samples promptly or preserve them

Analyze samples immediately after collection to prevent changes in surface phenotype. If immediate processing is not possible, freeze or fix cells to preserve them for later use.

▶ 02:02
5
Remove dead cells and debris

Filter samples through a cell strainer to remove clumping cells and dead cells. Use a viability marker to gate out dead cells and improve analysis quality and population resolution.

▶ 02:57
6
Prepare adherent cells with gentle lifting

For cultured adherent cells, use gentle lifting media such as EDTA or accutase instead of trypsin to prevent cleavage and loss of sensitive surface markers.

▶ 03:41
7
Stimulate cells under optimized conditions

Stimulate cells directly in whole blood or culture PBMCs and tissue-derived cells with appropriate medium, duration, and temperature. Note that phosphorylation assays require only minutes while cytokine assays require hours of incubation.

▶ 04:00

🚨 Failure Case Library (22) + Submit your own case

critical
Excessive Autofluorescence in Solid Tissue Samples
Solid tissue samples display much higher autofluorescence than PBMCs across multiple channels. Tissue-derived cells show elevated background due to structural proteins, extracellular matrix components, and pigments.
💡 5 · ✓ 5
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 · ✓ 5
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 · ✓ 6
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 · ✓ 5
severe
High Background Signal from Autofluorescent Cell Types
Elevated background fluorescence intensity across multiple channels, particularly affecting green (FITC) and orange (PE) channels. Difficult to distinguish specific antibody staining from background noise.
💡 5 · ✓ 5
severe
Aldehyde-Based Fixation Amplifying Autofluorescence
Fixed cell samples exhibit dramatically elevated autofluorescence compared to live cells, particularly in green and UV channels. Background signal increases after fixation protocol, reducing signal-to-noise ratio.
💡 4 · ✓ 5
severe
Autofluorescence Interfering with Viability Dye Detection
Dead cell discrimination becomes unreliable as autofluorescence overlaps with viability dye emission spectra. False positive or false negative viability calls occur, particularly with green or orange viability dyes.
💡 4 · ✓ 5
severe
Isotype Control Signal Is Abnormally High
The isotype control antibody shows unexpectedly high fluorescence signal, making it difficult to distinguish true positive staining from background in flow cytometry analysis.
💡 6 · ✓ 6
severe
Excessive Background in Myeloid-Rich Cell Populations
Samples enriched for monocytes, macrophages, or dendritic cells show uniformly high fluorescence across all antibody channels including isotype controls, obscuring specific marker detection.
💡 4 · ✓ 5
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 · ✓ 6
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 · ✓ 6
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 · ✓ 5
severe
Poor Resolution of Dim Markers Masked by Autofluorescence
Low-expression markers become indistinguishable from background. Positive and negative populations show poor separation, with dim fluorophores completely masked by cellular autofluorescence.
💡 4 · ✓ 5
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 · ✓ 5
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 · ✓ 6
moderate
High Non-Specific Binding After Cell Fixation
Following fixation with formaldehyde or paraformaldehyde, both test antibodies and isotype controls show elevated background signal and increased non-specific staining patterns.
💡 4 · ✓ 5
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 · ✓ 5
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 · ✓ 6
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 · ✓ 6
moderate
FITC Green Channel Highly Affected by Autofluorescence
FITC-conjugated antibodies show poor signal-to-noise ratio with elevated background in green channel. Blue laser (488 nm) excitation induces strong autofluorescence that directly overlaps with FITC emission spectrum.
💡 4 · ✓ 5
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 · ✓ 6
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 · ✓ 6
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