Home Molecular Biology Deciding on an Approach for Mitigating Autofluorescence
Steps
  1. 1 Understand homogeneous autofluorescence characteristics 00:23
  2. 2 Recognize two unmixing approaches available 01:07
  3. 3 Access unmixing wizard and select autofluorescence 01:25
  4. 4 Gate on population of interest for extraction 01:50
  5. 5 Compare unmixed results with and without extraction 02:26
  6. 6 Evaluate resolution trade-offs for each marker 03:11
  7. 7 Select optimal unmixing approach for your analysis 03:59
Molecular Biology Current Protocols

Deciding on an Approach for Mitigating Autofluorescence

Protocol
Difficulty
intermediate

Steps

1
Understand homogeneous autofluorescence characteristics

Learn to identify when all cells in a sample have the same or very similar autofluorescence spectral characteristics, as demonstrated by a single defined signature in the spectral plot.

▶ 00:23
2
Recognize two unmixing approaches available

Understand that for homogeneous autofluorescence, you can choose to unmix either with or without autofluorescence extraction, as only a single spectral signature can be removed.

▶ 01:07
3
Access unmixing wizard and select autofluorescence

Open the unmixing wizard and select autofluorescence as a fluorescent tag to extract autofluorescence from all samples.

▶ 01:25
4
Gate on population of interest for extraction

In the unmixing wizard, set gates on the unstained sample and ensure you gate only on your population of interest (e.g., lymphocytes) to extract the autofluorescence of cells you will analyze.

▶ 01:50
5
Compare unmixed results with and without extraction

Perform unmixing with autofluorescence extraction, check the n by n matrices, then repeat unmixing without autofluorescence extraction to compare the two approaches.

▶ 02:26
6
Evaluate resolution trade-offs for each marker

Place the two unmixed results side by side and assess whether autofluorescence extraction improves resolution on some markers while potentially worsening it on others, using identically scaled plots.

▶ 03:11
7
Select optimal unmixing approach for your analysis

Decide whether to use autofluorescence extraction based on which approach provides better overall marker resolution for your population of interest, considering that the same autofluorescence signature may perform differently depending on the cell population being analyzed.

▶ 03:59

🚨 Failure Case Library (8) + Submit your own case

critical
Improper Channel and Fluorophore Assignment
Everything glows in green/yellow channels. Dim targets overwhelmed by autofluorescence. Blue and green channels showing high background across tissue types. Spectral crowding and bleed-through between channels.
💡 5 · ✓ 6
severe
Red Blood Cell and Heme-Related Autofluorescence
Strong autofluorescence across multiple channels in blood-rich tissues such as spleen, liver, brain, bone marrow, and vascularized tumors. Heme and porphyrins dominate signal especially when tissue is not thoroughly perfused.
💡 4 · ✓ 5
severe
Collagen and Elastin Structural Protein Autofluorescence
Strong broad-spectrum autofluorescence in collagen and elastin-rich tissues including skin, lung, vessel walls, and fibrotic tissue. Emission persists through fixation and processing.
💡 4 · ✓ 5
severe
Age-Related Lipofuscin Accumulation
Exceptionally broad excitation and emission spectra affecting multiple channels in aged tissues such as brain, heart, skeletal muscle, and retina. Age-dependent lysosomal pigment cannot be confined to single channel.
💡 4 · ✓ 5
severe
Melanin Pigment Interference
Unpredictable autofluorescence and signal quenching in pigmented tissues such as skin and retina. Melanin both autofluoresces and quenches true signal in unpredictable patterns.
💡 4 · ✓ 5
severe
True Signal Loss After Autofluorescence Quenching
Signal drops or disappears after applying Sudan Black B or other quenching treatments. Target staining reduced along with background. Tissue morphology may be affected.
💡 5 · ✓ 6
moderate
Fixation-Induced Aldehyde Fluorescence
Strong blue-green autofluorescence haze in formalin or glutaraldehyde-fixed tissues. Background increases with fixation duration and disproportionately contaminates lower-wavelength channels. Amplified by paraffin embedding and overfixation.
💡 5 · ✓ 6
moderate
Metabolic Cofactor Autofluorescence
Endogenous fluorescence from NADH, FAD, and other metabolic cofactors in high-metabolism tissues such as kidney, liver, pancreas, and spleen. Complex extracellular matrices contribute additional background.
💡 4 · ✓ 5
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