Diagnosis of Prostate Cancer Metastasis via Extracellular Vesicles Isolated Using Two-Phase Interface as...

Area of Science:

• Biotechnology
• Biomaterials Science
• Biophysics

Background:

• Extracellular vesicles (EVs) are vital biomarkers, but their isolation requires improved methods.
• Current isolation techniques for EVs lack efficiency and purity.
• Aqueous two-phase systems (ATPS) show promise for EV separation but their mechanism is unclear.

Purpose of the Study:

• To elucidate the EV isolation mechanism in ATPS.
• To enhance the efficiency and purity of EV isolation using ATPS.
• To develop a novel membrane-less filter for EV isolation and biomarker analysis.

Main Methods:

• Utilized Kramers' theory and Fick's law to model EV behavior in ATPS.
• Employed simulations and experiments to understand the liquid-liquid interface's role in EV separation.
• Introduced a vortex to enhance particle transport via convection for accelerated isolation.

Main Results:

• The liquid-liquid interface in ATPS functions as a membrane-less size-selective filter for EVs.
• Vortex-enhanced convection significantly accelerated EV isolation compared to diffusion alone.
• Achieved >80% EV recovery from blood plasma with >90% removal of major lipoproteins and albumin within 1 hour.
• Distinguished metastatic from non-metastatic prostate cancer using EV biomarkers with higher accuracy than PSA tests.

Conclusions:

• ATPS with vortex-enhanced convection offers a highly efficient and pure method for EV isolation.
• This membrane-less filtration system enables rapid EV biomarker quantification.
• The developed method shows potential for improved clinical diagnostics, particularly for prostate cancer detection.