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An innovative method to detect cancerous cells in blood

Current methods for identifying specific types of cells in blood require laborious biomarker labelling techniques. An EU-funded project has developed an innovative label-free system based on electrical signals for detecting rare tumour cells.

Health

Rare cells that originate in tumours can travel in the bloodstream and sometimes spread to other organs in the body. But because circulating tumour cells (CTCs) are so rare, detecting them is like finding a needle in a haystack. “Only a few cells in 1 ml of blood are CTCs while there are millions or even billions of other cells including white blood cells and red blood cells,” says pureCTC project coordinator Wim de Malsche, a professor in the department of chemical engineering at the Free University of Brussels (VUB), Belgium. “It is not that easy to detect all kinds of cancers.” Existing systems for detecting specific types of cells all involve prior biomarker labelling. But with wide variation in CTCs this would be cumbersome and complex to use. In order to bypass labelling and produce a generic method that can detect CTCs from many different types of cancers, the project developed a microfluidic platform for high throughput screening to identify and isolate CTCs at the single-cell level using electrochemical methods.

Label-free system

Different cancer cells have different electrical properties that can be detected by electrical signals. A technique known as electrochemical impedance spectroscopy was used to identify the CTCs. “As those cells flow by, you apply an oscillating electrical signal and you get an output from that. Based on that signature you can discriminate those cancer cells from white blood cells and red blood cells,” de Malsche explains. “We have developed a platform that consists of two coupled devices,” says Sertan Sukas, currently a postdoctoral researcher at the department of biomedical engineering at Eindhoven University of Technology, the Netherlands. He received a Marie Skłodowska-Curie programme grant for 2 years to set up a special interdisciplinary laboratory at VUB for the project. “The first component is to stream the blood sample in and do pre-enrichment, using acoustofocusing or acoustophoresis; the second part is the detector which consists of integrated electrodes for impedance sensing,” Sukas says. Acoustophoresis uses sound waves to move particles. The single cells can then be streamed through the detector’s electrodes to identify the electrical properties on a cell-by-cell basis.

Early phase

Experiments were based on blood from healthy people mixed with cancer cells. “At laboratory scale we have proof of concept,” Sukas says. “We are still at an early phase and have only worked with cancer cell lines for now. But later on, the electrical properties can be matched to the properties of the cells,” Sukas explains. “We have not yet been able to work with patient samples from hospitals, so we need to go to the next step to show it clinically.” “We will try to identify a few types of cancer and create a library. But we don’t have that data yet – to do that first you need an optimised sensor and we are still working on that.” As Sukas says: “In the end, we developed a sensitive electrical detection system which shows the potential of discriminating CTC tumour cells from the rest of the blood cells and also has the potential to be used as a haematology analyser, typically to inform about the content of the white blood cells.” “Using a label-free system allows you to do further analysis,” Sukas adds, noting it is more sensitive than a typical biomarker labelling system. A patent application is pending on the device.

Keywords

pureCTC, blood cells, cancer, cancer cells, tumour, biomarker, acoustophoresis, microfluidic, impedance sensing

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