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.

Highlights

  • Bone marrow aspirate (BMA) is a complex mixture of aspirated bone marrow (BM) cells, small tissue fragments, and peripheral blood

  • We have previously demonstrated the use of inertial microfluidics for sorting circulating tumor cells from peripheral blood of patients with solid tumors,[7,8] as well as infected malaria blood cells with relevance in disease detection.[9]

  • Design and fabrication of the blast cell biochip (BCB) We designed a microfluidic biochip for the detection of rare in actin filament release as well as its polymerization, and, an increase in cell stiffness

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Summary

Introduction

Bone marrow aspirate (BMA) is a complex mixture of aspirated BM cells, small tissue fragments, and peripheral blood. The gold standard is BM biopsy,[3] a procedure that is undesirable for several reasons: (1) high costs, (2) complexity of the surgical procedure, (3) discomfort from the invasive procedure, and (4) increased risk of mortality. Due to these factors, monitoring mutations or blast cell levels from BM biopsies is a tedious process as these procedures must be carried out on a routine basis. Clinicians are keen to introduce rapid, less invasive, and efficient screens for leukemia by employing the use of microfluidic-based assays, which is operated with minimal reagents and samples.[4]

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