A Label Free Disposable Device for Rapid Isolation of Rare Tumor Cells from Blood by Ultrasounds.

Itziar González,Rosa Monge,Adela Castillejo,Bruno Sainz,Luis Fernández,Alberto Pinto,Sonia Alcalá,Julie Earl,Jose Soto,Alfredo Carrato

doi:10.3390/mi9030129

Abstract

The use of blood samples as liquid biopsy is a label-free method for cancer diagnosis that offers benefits over traditional invasive biopsy techniques. Cell sorting by acoustic waves offers a means to separate rare cells from blood samples based on their physical properties in a label-free, contactless and biocompatible manner. Herein, we describe a flow-through separation approach that provides an efficient separation of tumor cells (TCs) from white blood cells (WBCs) in a microfluidic device, “THINUS-Chip” (Thin-Ultrasonic-Separator-Chip), actuated by ultrasounds. We introduce for the first time the concept of plate acoustic waves (PAW) applied to acoustophoresis as a new strategy. It lies in the geometrical chip design: different to other microseparators based on either bulk acoustic waves (BAW) or surface waves (SAW, SSAW and tSAW), it allows the use of polymeric materials without restrictions in the frequency of work. We demonstrate its ability to perform high-throughput isolation of TCs from WBCs, allowing a recovery rate of 84% ± 8% of TCs with a purity higher than 80% and combined viability of 85% at a flow rate of 80 μL/min (4.8 mL/h). The THINUS-Chip performs cell fractionation with low-cost manufacturing processes, opening the door to possible easy printing fabrication.

Highlights

The presence of circulating tumor cells (CTCs) in peripheral blood has been associated with a reduced progression survival in many cancer types [1,2]
We describe a flow-through separation approach that provides an efficient separation of tumor cells (TCs) from white blood cells (WBCs) in a microfluidic device, “THINUS-Chip” (Thin-Ultrasonic-Separator-Chip), actuated by ultrasounds
We introduce for the first time the concept of plate acoustic waves (PAW) applied to acoustophoresis as a new strategy

Summary

Introduction

The presence of circulating tumor cells (CTCs) in peripheral blood has been associated with a reduced progression survival in many cancer types [1,2]. We introduce for the first time the concept of plate-vibrations in the development of a new polymeric acoustophoretic chip actuated by a single piezoelectric transducer to perform high-throughput isolation of tumor cells from flowing blood samples: “THINUS-Chip” (Thin-Ultrasonic-Separator-Chip) It offers the advantages of BAW or SAW microseparators together and overcomes their respective disadvantages: it allows the use of polymeric materials for the chip structure, with lower manufacturing cost than the BAW devices and lower frequencies than those required by the SAW isolators, i.e., close to 1 MHz. A prerequisite of the BAW separators is that the channel dimensions are in concert with the ultrasound frequency [34]. Its simple geometrical design and structural properties open a line for a near future easy printing

Materials and Methods

Working Principle for High-Throughput Separation

Cell Viability after Separation through the THINUS-Chip

Findings

Discussion and Conclusions