SORTCELL

Developing a microfluidic system for isolating and enriching circulating tumour cells (CTCs) in liquid biopsies

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Broadcast during the Navarra Televisión SINAI Space
Report on Navarra Capital "El CIMA y NAITEC diseñan un dispositivo que aísla células cancerígenas para facilitar la detección precoz"

PUBLICACIONES

Artículos científicos

Alejandro Rodríguez-Pena, Estibaliz Armendariz, Alvaro Oyarbide, Xabier Morales, Sergio Ortiz-Espinosa, Borja Ruiz-Fernández de Córdoba, Denis Cochonneau, Iñaki Cornago, Dominique Heymann, Josepmaría Argemi, Delia D’Avola, Bruno Sangro, Fernando Lecanda, Ruben Pio, Iván Cortés-Domínguez, Carlos Ortiz-de-Solórzano (2022): “Design and validation of a tunable inertial microfluidic system for the efficient enrichment of circulating tumor cells in blood”, Bioeng Transl Med, 2022 Apr 29;7(3):e10331. doi: 10.1002/btm2.10331. eCollection 2022 Sep.

SABER MÁS DEL PROYECTO

INTRODUCTION
According to the latest reports by the World Health Organisation, between 50% and 70% of cancer cases are impossible to prevent. For that reason, early detection is the best strategy to use to keep fighting the disease, because it makes it possible to attack cancer in the early stages decreasing the likelihood of it spreading to other parts of the body, producing metastasis, which is the cause of 90% of cancer deaths. Along those lines, developing screening techniques has become a high priority field of research, especially for kinds of cancer for which there are no effective detection tools due to the delay in clinically detectable symptomatology. Liquid biopsy is one of the screening methods with the greatest potential, because it provides information in a non-invasive way during the early stages of the disease, making it possible to stratify tumours and design personalised treatments. The test consists of a peripheral blood draw from patients for analysis. The goal of the test is to detect circulating tumour cells, among other components, that reach the blood stream after breaking away from the primary tumour.

Currently, there are very few commercial methods for detecting CTCs that can guarantee effective isolation of the cells or their viability. A set of those methods uses markers to detect the tumour population in the blood, but their effectiveness is limited due to the loss of some tumour subpopulations that are not marked by those methods. Another family of methods is based on detecting the morphology of the cells, or their physical properties. Despite being methodologies with a more general application, they have not been optimised and they have limitations because they leave out populations of small tumour cells (<13um), which are very interesting because they are associated with a worse prognosis for the disease.

GOALS
Because of the limitations of the current solutions, in this project we proposed to make use of the knowledge and experience gained in a previous project (ISOCELL, PC080-081), which ended 30/11/2019, for developing and validating a pre-industrial demonstration prototype of a microfluidic system designed for liquid biopsy analysis, which makes it possible to isolate and enrich CTCs in patients with cancer.
To achieve that general goal, to specific goals described below were set:
– Fabricate, validate and characterise a CTC separation module based on dielectric properties.
– Fabricate, validate and characterise the efficiency of a medium change module (serum to medium that conducts electricity and vice-versa), that makes it possible to condition the CTC transport medium between the stages of the device
– Integrate an existing inertial separation module for doing a fast initial separation of CTCs based on size with the dielectrophoresis module through the medium change module, thus creating a functional demonstration prototype of an integrated system for
isolating CTCs
– Validate the functionality of the integrated demonstration prototype, and characterise its efficiency with samples that are cell mixtures of lung cancer cell lines and healthy peripheral blood in known proportions

RESULTS
In general, the assessment of the activities is satisfactory. Despite presenting a project that takes on a very difficult technological and biological challenge, as well as the complications that arose during the project, there is currently a demonstration prototype that makes it possible to enrich CTCs in patient samples. The functionality of the prototype was validated in biological samples. Specifically, concept tests were done with samples from patients with hepatocellular carcinoma (HCC) and CTCs were detected in them. In addition, given the modular design of the prototype, it will be possible to include the rest of the stages into it in a simple way, after being optimised.