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The BioCat Exosome Isolation Hub

Evidence-based choices for clean, reproducible EV preps, built for downstream RNA, proteomics, and lipidomics

Exosomes underpin precision-medicine readouts across plasma/serum, urine, saliva, and cell culture media. The right isolation method balances purity, yield, hands-on time, and scalability, so your NTA traces, Westerns, small-RNA-seq, and MS data hold up under review. Recent guidance and vendor data below help you pick confidently.

Accelerate exosome isolation with products that enable fast, multiplexed exosome enrichment and purification from a wide range of biofluids.

dUC

Differential Ultracentrifugation

Differential Ultracentrifugation
SEC

Size Exclusion Chromatography

Size Exclusion Chromatography
SmartSEC

SmartSEC™ Purification

SmartSEC™ Purification
Precipitation

Polymer Precipitation

Polymer Precipitation
SiC

Silicon Carbide (SiC) Purification

Silicon Carbide (SiC) Purification

Quick-reference method selection guide

Your situation → dUC SEC (classic) SmartSEC Single SmartSEC Mini SmartSEC HT ExoQuick / ULTRA SiC (Norgen)
Purity first (proteomics/
biomarkers)		 ◑ (with gradient) ✓✓ ✓✓ ✓✓ ✓✓ ◑ (ULTRA better) ✓✓
Throughput / 96-well cohorts ✗ ◑ ✗ ✗ ✓✓ ✓ ◑
Tiny input (≤50 µL) ✗ ✗ ✗ ✓✓ (≥10 µL) ✗ ◑ ◑
Low hands-on time ✗ ◑ ✓ ✓ ✓ ✓✓ ✓
RNA-centric (all sizes, low bias) ◑ ✓ ✓ ✓ ✓ ✓ ✓✓
Budget simplicity / no rotor ◑ ✓ ✓ ✓ ✓ ✓✓ ✓✓
 
Table key:
  • ✓✓ Strong fit/best-in-class
  • ✓ Good fit/recommended
  • ◑ Conditional/usable with caveats
  • ✗ Not recommended

Notes: “with gradient” = add a density gradient; “ULTRA better” = ExoQuick ULTRA version preferred; “≥10 µL” = minimum input.

Differential Ultracentrifugation (dUC)

Why use it: Flexible baseline method that many labs can implement; density cushions/gradients improve selectivity.
Watch-outs: Invisible pellets, co-pelleting of proteins/lipoproteins, long spins; always confirm by markers and orthogonal QC.
Best for: Discovery work when time/equipment are available; can be combined with a polishing step (e.g., SEC).

 

dUC

Size Exclusion Chromatography (SEC)

Why use it: Gentle, reproducible separation that reduces soluble protein and lipoprotein carryover—great for proteomics and clinical plasma/serum; also validated for cell-culture media (CCM).
How it runs: Equilibrate, load, collect fractions, keep the EV-rich/low-protein window (map with A280 and/or NTA).
Best for: Cleaner inputs for MS, biomarker studies, and cross-study comparability.

 

SEC

SmartSECTM Purification

What it is: Chromatography-based SEC evolution with a contaminant-trapping feature to overcome conventional SEC limitations; available in Single spin-columns (100-250µL), Mini spin-columns (as little as 10 µL input) and HT 96-well plates for plasma/serum.

When to choose: Precious/low-volume bioliquids (Mini) or high-throughput cohort plasma/serum (HT) with consistent well-to-well EV yields.

Need to remove excess lipoproteins? the SmartSEC-DeLipoTM kit, engineered to provide unmatched purity and quality while efficiently depleting lipoprotein contaminants..

SmartSEC Purification
SmartSEC

ExoQuick Polymer Precipitation

Why use it: Fast, scalable, easy to train; ideal for screening and qPCR-first workflows.
ExoQuick ULTRA extension: Adds a built-in column clean-up to drop albumin/Ig and other soluble contaminants; 250–500 µL serum/plasma inputs typical.
Best for: Throughput wins and rapid prototyping; consider an SEC/SmartSEC polish if heading to proteomics. 

ExoQuick Polymer precipitation
Precipitation

Silicon Carbide (SiC) Purification

What it is: Spin-column workflow using a proprietary SiC membrane and pH-conditioning to capture intact exosomes via surface-protein charge, then gently release them—an approach described in patent CA2929268A1 (Methods for Extracellular Vesicle Isolation and Selective Removal), which details SiC-based binding of EVs at a preselected pH and elution by pH shift. 

When to choose: RNA-centric studies across plasma/serum, urine, saliva, and CCM; detergent-free ExoR release buffer is compatible with most proteomic workflows.

Best for: Short, instrument-light protocol; end-to-end kits (collection → EV → RNA) for consistent reporting.

Silicon Carbide (SiC) Purification
SiC

Frequently Asked Questions

How do I decide between SEC and SmartSEC?

If you need the gentleness and protein-reduction of SEC plus either tiny inputs (rare fluids) or consistent plate-based plasma throughput, SmartSEC Mini/HT tighten usability without giving up SEC-like purity. Keep EV-rich fractions only; confirm with A280/NTA fraction mapping.

Does SmartSEC work for cell-culture media (CCM), not just plasma/serum?

Yes, SmartSEC Single and SmartSEC Mini are validated across biofluids and developmental models; use them when volumes are scarce or precious. For larger volumes, there is also the SmartSEC-TC.

What’s the real difference between classic precipitation and precipitation/ExoQuick and ExoQuick ULTRA

Classic precipitation is fast but co-enriches soluble proteins; precipitation/ExoQuick and ExoQuick ULTRA add an integrated column step to clean up the prep—ideal when you’ll run Westerns, NGS, or proteomics (still consider an extra SEC polish for the cleanest MS). 

Is Norgen’s ExoR buffer compatible with proteomics?

Yes. ExoR is detergent-free and generally compatible with proteomic downstreams; check your instrument method and run a pilot digest.

For precision-medicine biomarker discovery, which method is safest?

Favor SEC/SmartSEC (cleaner inputs) or SiC (gentle capture with broad RNA recovery) to protect subtle signals in plasma/serum; report markers/negatives per MISEV2023.

Can I combine methods?

Yes. Common combos: dUC → SEC (purity bump), precipitation → SEC (reduce polymer/protein carryover), or SiC → direct RNA (skip extra clean-ups). Document the full chain.

Minimum inputs?

SmartSEC Mini: as low as 10 µL. SmartSEC HT/ExoQuick ULTRA: ~250–500 µL serum/plasma. SiC kits span plasma/serum, urine, saliva, and CCM with format-specific volumes, see kit pages.

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References and helpful links

  1. Welsh, J. A., Goberdhan, D. C. I., O’Driscoll, L., Théry, C., & Witwer, K. W. (2024). MISEV2023: An updated guide to EV research and applications. Journal of Extracellular Vesicles, 13(2), e12416. https://doi.org/10.1002/jev2.12416
  2. System Biosciences. (n.d.). SmartSEC™ Mini EV Isolation System. Retrieved September 6, 2025, from https://www.systembio.com/products/exosome-research/exosome-isolation/smartsec/smartsec-mini-ev-isolation-system
  3. System Biosciences. (n.d.). SmartSEC™ HT EV Isolation System for Serum & Plasma. Retrieved September 6, 2025, from https://www.systembio.com/products/exosome-research/exosome-isolation/smartsec/smartsec-ht-ev-isolation-system-for-serum-plasma
  4. System Biosciences. (n.d.). ExoQuick® ULTRA—Exosome isolation. Retrieved September 6, 2025, from https://www.systembio.com/products/exosome-research/exosome-isolation/exoquick-ultra
  5. Subha, Z. (2025, June 12). Exosomes in precision medicine. Norgen Biotek Corp. https://norgenbiotek.com/blog/exosomes-precision-medicine
  6. Norgen Biotek Corp. (n.d.). Plasma/Serum Exosome Purification Kit. Retrieved September 6, 2025, from https://norgenbiotek.com/product/plasmaserum-exosome-purification-kit
  7. Norgen Biotek Corp. (n.d.). Plasma/Serum Exosome Purification and RNA Isolation Kits. Retrieved September 6, 2025, from https://norgenbiotek.com/product/plasmaserum-exosome-purification-and-rna-isolation-kits
  8. Norgen Biotek Corp. (n.d.). Cell Culture Media Exosome Purification Kits. Retrieved September 6, 2025, from https://norgenbiotek.com/product/cell-culture-media-exosome-purification-kits
  9. Norgen Biotek Corp. (n.d.). Complete Workflows. Retrieved September 6, 2025, from https://norgenbiotek.com/resources/complete-workflows
  10. System Biosciences. (n.d.). Exosome Isolation Kits & Products (ExoQuick® family). Retrieved September 6, 2025, from https://www.systembio.com/products/exosome-research/exosome-isolation