Abstract
Processing of complex cell preparations such as blood and peripheral blood progenitor cell (PBPC) transplants using label-free technologies is challenging. Transplant-contaminating neuroblastoma cells (NBCs) can contribute to relapse, and we therefore aimed to provide proof-of-principle evidence that label-free acoustophoretic separation can be applied for diagnostic NBC enrichment and removal (“purging”) from human blood and PBPC products. Neuroblastoma cells spiked into blood and PBPC preparations served as model systems. Acoustophoresis enabled to enrich NBCs from mononuclear peripheral blood cells and PBPC samples with recovery rates of up to 60–97%. When aiming at high purity, NBC purities of up to 90% were realized, however, compromising recovery. Acoustophoretic purging of PBPC products allowed substantial tumour cell depletion of 1.5–2.3 log. PBPC loss under these conditions was considerable (>43%) but could be decreased to less than 10% while still achieving NBC depletion rates of 60–80%. Proliferation of cells was not affected by acoustic separation. These results provide first evidence that NBCs can be acoustically separated from blood and stem cell preparations with high recovery and purity, thus indicating that acoustophoresis is a promising technology for the development of future label-free, non-contact cell processing of complex cell products.
Highlights
Complex biological samples such as blood and stem cell products are routinely processed to prepare cells for subsequent analytical or therapeutic purposes
Circulating tumour cells (CTCs) and stem cell product-contaminating neuroblastoma cells (NBCs), which can be detected in the blood of about 70% of high-risk neuroblastoma patients and 50% of stem cell collections[15,18,19,20], respectively, carry important diagnostic and prognostic information, which motivates the development of efficient tumour cell isolation methods
The composition of stem cell preparations differed between healthy donors (Fig. 2a, middle and lower right, orange line; Fig. S2) and patients, as well as between different patient peripheral blood progenitor cell (PBPC) (Fig. 2a, middle and lower right, blue lines; Fig. S2), which resulted in variations in size distributions of the cell populations
Summary
Complex biological samples such as blood and stem cell products are routinely processed to prepare cells for subsequent analytical or therapeutic purposes. Acoustophoretic separation is primarily based on size, density, and compressibility of the particles in relation to the suspending medium (see equations 1 and 2, Fig. S1 and the video animations for illustration of the separation principle in the supplementary information) This allows to more selectively separate specific cell types without the use of antibody labelling technology, provided that the acoustic properties of the target cells are sufficiently different from the non-target cell population. Circulating tumour cells (CTCs) and stem cell product-contaminating NBCs, which can be detected in the blood of about 70% of high-risk neuroblastoma patients and 50% of stem cell collections[15,18,19,20], respectively, carry important diagnostic and prognostic information, which motivates the development of efficient tumour cell isolation methods. Transplantation of a tumour cell depleted or even tumour cell free stem cell graft seems preferable to avoid retransfusion of viable tumour cells
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