Label-free neuroblastoma cell separation from hematopoietic progenitor cell products using acoustophoresis - towards cell processing of complex biological samples

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.

Label-free separation of neuroblastoma patient-derived xenograft (PDX) cells from hematopoietic progenitor cell products by acoustophoresis

“…The acoustophoresis and microchip setup is shown in Fig. 1 A and was described in detail previously [ 12 , 17 , 18 ]. In this study, a microchip with a 26-mm-long prealignment channel and 43-mm-long main separation channel (long chip) manufactured by Micronit (Enschede, Netherlands) [ 18 ] was used for most experiments (Fig.…”

“…Herein, we report advances in label-free acoustic tumor cell separation from PBPC products in a clinically relevant setting, i.e., enrichment of patient-derived neuroblastoma xenograft (PDX) cells for diagnostics and depletion of PDX cells from PBPC grafts, respectively. PDX cells are established from high-risk neuroblastomas and represent a highly valuable neuroblastoma model because cells retain the original molecular and phenotypic characteristics [ 14 – 16 ], in contrast to conventional cancer cell lines that were used in our prior study [ 17 ].…”

Contactless acoustic micro/nano manipulation: a paradigm for next generation applications in life sciences

“…In recent years, many SAW-II devices have been commercialized into industrial products like Ascent Bio-Nano TM [70] and AcouSort TM [66,71]. A commonly reported configuration of AcouSort TM device enables segregation of bio-analytes from blood plasma in a multi-step fashion [66,67,71].…”

Sorting of Particles Using Inertial Focusing and Laminar Vortex Technology: A Review

“…Among the active methods, acoustophoresis (acoustic levitation) is based upon applying an acoustic force, by means of continuous ultrasound waves [16]. Here, particles suspended in a liquid are exposed to an acoustic standing wave, which causes them to move in the sound field.…”