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

tumor cell isolation
ultrasound
low-cost
microfluidics
plate acoustic waves
Itziar González, Julie Earl, Luis J. Fernández , Bruno Sainz , Alberto Pinto, Rosa Monge, Sonia Alcalá, Adela Castillejo, Jose L. Soto, Alfredo Carrato
Micromachines s 2018, 9, 129; doi:10.3390/mi9030129
https://doi.org/10.3390/mi9030129

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.

micromachines-2018-9
a) A schematic view of the present cancer cell isolation in the polymeric THINUS-chip, with a collection of the bigger particles along the center of the channel, while the small particles continue their flow motion undisturbed by the acoustic field, and (b) the fabricated cancer cell isolation chip.
micromachines-2018-9-1
Results of the quantified capture efficiency of the cancer cell separation (%) of pancreas cancer cells (Panc-1) spiked in RBC-lysed blood samples obtained in the THINUS-Chip at f = 952 kHz and Vp-p = 28 V. The values given are means, the error bars denoting min and max values.

 

Acknowledgments

This work was partially supported by the Ministry of Economy and Competence of Spain (MINECO) under two projects: BIO2011-30535-C04-01: Development of a high-throughput ultrasonic technology for the isolation of circulating tumor cells from peripheral blood samples; and DPI2017-90147-R: Low intensity a Low Intensity ultrasounds for early diagnosis and modulation of tumor and stroma.

RESULT

proyecto/s relacionado/s

  • Low intensity ultrasounds for early detection and modulation of tumor and stroma
    Programa Estatal de I+D+i Orientada a los Retos de la Sociedad (AEI), Fondos Feder
Departamento de Acústica y Evaluación No Destructiva (DAEND)
  • GAA: Grupo de Acústica ambiental
  • G CARMA: Grupo de Caracterización de materiales mediante evaluación no destructiva
  • ULAB: Ultrasonidos para el análisis de líquidos y bioingeniería
Departamento de Tecnologías de la Información y Las Comunicaciones (DTIC)
  • GiCP: Grupo de investigación en Ciberseguridad y Protección de la Privacidad
  • GICSI: Grupo de investigación en Criptología y Seguridad de la Información
    • LCQE: Laboratorio de Comunicaciones Cuánticas
  • PSUM: Grupo de Procesamiento de Señal en sistemas Ultrasónicos Multicanal
Departamento de Sensores y Sistemas Ultrasónicos (DSSU)
  • GSTU: Grupo de Sistemas y tecnologías ultrasónicas
  • NoySI: Grupo de Nanosensores y Sistemas Inteligentes
  • RESULT: Resonadores ultrasónicos para cavitación y micromanipulación
  • SENSAVAN: Grupo de Tecnología de Sensores Avanzados
  • QE: Electrónica Cuántica
Laboratorios
  • Laboratorio de Acústica
  • Laboratorio de Metrología Ultrasónica Médica (LMUM)
  • Laboratorio de Comunicaciones Cuánticas
  • Laboratory for International Collaboration in Advanced Biophotonics Imaging

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