Table 3.

Summary of the methods used for isolation and purification of plasma and serum EVs in the context of liquid biopsy.

Method		Advantages	Limitations
Ultracentrifugation	Differential centrifugation	Commonly and routinely applied Method protocol well established [120,121]	Long and challenging procedure High rate of contamination with plasma protein complexes [119,121]
	Density gradient centrifugation	Commonly used Higher purity than differential centrifugation [120,121]	Difficult procedure Purity improved but not suitable for biomarker detection [120,121]
Ultrafiltration		High purity rate used for cleaning up before SEC [120]	Not commonly used Frequent loss of recovered material [119,120]
Precipitation		High recovery yield [125]	Low purity rate due to protein contamination [125]
SEC		High quality and purity rate Outperforms other methods for useful detection of disease biomarkers Used as a final “cleaning” step for accurate biomarker detection in hematological malignancies [118,120,125,127]	Relatively lower recovery yield [125]

Abbreviations: Size-Exclusion Chromatography (SEC).