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Liquid biopsy is a non-invasive technique for studying cancer biomarkers present in body fluids. However, biomarkers can be hard to find using current methods. Advances in nanotechnology and microfluidics – processing small quantities of fluids using tiny channels – could lead to the earlier detection of cancer metastasis and relapse, to enable better and more cost-effective monitoring.
This was just one challenge addressed by ground-breaking research funded through the NANOTRAINFORGROWTH II project. The project supported fellowships for experienced researchers at the International Iberian Nanotechnology Laboratory (INL), Europe’s first research organisation dedicated to nanoscience and nanotechnology.
‘Within the context of the NANOTRAINFORGROWTH II grant, nanotechnology and microfluidics are being applied to develop a real-time, high-throughput and multiplex cancer monitoring platform,’ says project lead Sara Abalde-Cela, of INL in Braga, Portugal. Thanks to the project, a device for detecting cancer biomarkers is being prepared for the market.
Detecting cancer biomarkers
One group of cancer biomarkers targeted by liquid biopsy are circulating tumour cells (CTCs). These travel from the primary tumour and invade other organs, causing metastasis, or the development of secondary malignant growths. The Medical Devices group at INL recently developed a microfluidic platform that can isolate these very rare cells, which are present in the blood of cancer patients.
However, several challenges remained. One was to extract much more information from these cells, which called for advanced interrogation techniques such as Surface-enhanced Raman scattering (SERS) spectroscopy, a powerful and sensitive detection method.
Abalde-Cela believes the novel combination of SERS spectroscopy with nanotechnology and microfluidics will overcome current bottlenecks faced by researchers in the field of liquid biopsy.
A key innovation involved producing engineered nanoparticles that act as ‘barcodes’ for different cell membrane receptors. This enables improved analysis of CTCs and their various surface proteins simultaneously. Furthermore, CTCs have been encapsulated in microdroplets for single-cell analysis and metabolite tracking, as a way of predicting tumour growth.
‘In the future, all these methods will be integrated into a single medical device for the analysis of real samples,’ says Abalde-Cela. This development would open up the possibility of transferring these methods to the clinic.
Personalised patient care
The platform allows for the monitoring of cancer during treatment, using advanced liquid biopsy. It also provides physicians with more information for adapting therapies to treat patients in a personalised way.
‘Traditional biopsies can only be done at the moment of diagnosis and surgery, while imaging techniques to monitor relapse cannot be performed as often as needed and they usually miss early spreading,’ Abalde-Cela says. ‘This platform will allow for a non-invasive, fast and more sensitive diagnosis of metastasis evolution and relapse in patients who might otherwise be considered cured. Each analysis will cost approximately EUR 500.’
Thanks to the advances that Abalde-Cela’s fellowship at INL helped to achieve, a start-up company – RUBYnanomed – was created in January 2018. The first product the company hopes to bring to market is the RUBYchip device for isolating CTCs from blood. A prototype device is being validated at hospitals in Spain and Portugal, for five types of cancer, and the company has approximately 1 500 pre-orders for 2019.
NANOTRAINFORGROWTH II received funding from the EU’s Marie Skłodowska-Curie Actions programme. Other fellowships funded by the project at INL are advancing innovative applications of nanotechnology in fields such as energy, food and the environment.