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Flow Cytometry (CST Guide) moderate

High Signal in Negative Cell Populations

Symptom
Off-target cell populations such as monocytes show unexpectedly high fluorescence signal. Non-specific staining obscures true positive populations.
Common Causes
  1. 1 Fc surface receptors on monocytes or other cells binding Fc portion of primary or secondary antibodies
  2. 2 Excessive primary or secondary antibody causing non-specific binding
  3. 3 Incomplete washing between antibody incubation steps leaving unbound antibody
Solutions
  1. 1 Block cells with Bovine Serum Albumin, Fc receptor blocking reagents, or normal serum from same host as primary/secondary antibody prior to staining
  2. 2 Include secondary-antibody-only control to determine if background originates from primary or secondary antibody
  3. 3 Perform additional wash steps between antibody incubations to remove unbound antibody
Related Video (3)
BioLegend ★ 82
Surface and Intracellular Cytokine Staining for Flow Cytometry
"Covers flow cytometry staining steps including Fc receptor blocking and antibody incubation, directly addressing the cause of non-specific Fc binding on monocytes."
Bilibili (China-Accessible Mirrors) ★ 72
Flow Cytometry Complete Workflow: Sample to Analysis
"Full flow cytometry workflow from sample prep through troubleshooting, useful for understanding where non-specific staining arises and how to correct it."
Bilibili (China-Accessible Mirrors) ★ 68
Zhejiang University Senior's Flow Cytometry Hands-On Tutorial
"Hands-on flow cytometry protocol guidance that can help researchers correctly perform staining and avoid off-target signal in negative populations."
Source: cellsignal.com ↗
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