Isolating Rare Cells and Circulating Tumor Cells with High Purity by Sequential eDAR

Area of Science:

• Biomedical Engineering
• Cancer Research
• Cell Biology

Background:

• Circulating tumor cells (CTCs) are crucial biomarkers for metastatic cancer detection and treatment monitoring.
• Current CTC isolation methods face challenges due to low cell abundance and heterogeneity, impacting purity and sensitivity.
• Previous ensemble-decision aliquot ranking (eDAR) platforms showed high throughput and recovery but require further purity enhancement.

Purpose of the Study:

• To develop and demonstrate a sequential eDAR platform for highly pure rare cell and CTC isolation from whole blood.
• To improve the purity of isolated CTCs for more reliable downstream molecular and cellular analyses.
• To enable the collection of single CTCs for in-depth investigation.

Main Methods:

• Implementation of a sequential sorting strategy combined with flow stretching using herringbone features.
• Utilizing the parabolic flow profile in conjunction with a second sorting step to enhance purity.
• Integration of these techniques into the established eDAR platform for rare cell isolation.

Main Results:

• The sequential eDAR platform achieves significantly higher purity in rare cell isolation from whole blood compared to previous methods.
• The novel design effectively sorts and stretches fluid elements, improving the separation of CTCs.
• The platform demonstrates capability for collecting individual CTCs in a multiwell plate format.

Conclusions:

• The sequential eDAR platform represents a significant advancement in CTC isolation technology, offering high purity.
• This improved purity facilitates more accurate downstream analysis of CTCs, aiding metastatic cancer research.
• The platform's ability to isolate single CTCs opens new avenues for personalized cancer diagnostics and therapeutics.