Liquid biopsy for minimal residual disease detection in leukemia using a portable blast cell biochip

Abstract

Long-term management for leukemia is challenging due to the painful and invasive procedure of bone marrow (BM) biopsy. At present, non-invasive liquid (blood) biopsy is not utilized for leukemia, due to lower counts of leukemia blast cells in the blood. Here, we described a robust system for the simultaneous detection and enrichment of rare blast cells. Enrichment of blast cells was achieved from blood with a one-step microfluidic blast cell biochip (BCB) sorting system, without specific targeting of proteins by antibodies. Non-target cells encountered a differential net force as compared to stiffer blast cells and were removed. The efficiency of the BCB promotes high detection sensitivity (1 in 106 cells) even from patients with minimal residual disease. The procedure was validated using actual blast cells from patients with various types of leukemia. Outcomes were compared to current evaluation standards, such as flow cytometry, using BM aspirates. Blast cell detection efficiency was higher in 55.6% of the patients using the BCB as compared to flow cytometry, despite the lower concentrations of blast cells in liquid biopsy. These studies promote early-stage detection and routine monitoring for minimal residual disease in patients.