Cardiovascular disease biomarkers in blood detected at nano levels An ever-increasing demand for point-of-care testing (POCT) devices has given rise to the PHOCNOSIS analysis technology for early diagnosis of cardiovascular diseases (CVDs). Digital Economy Health © Phira_60_shutterstock CVD is the leading cause of death in the EU, accounting for 1.9 million deaths each year (40 % of all deaths) with an estimated associated cost of almost EUR 196 billion each year. However, CVD can be successfully treated when detected early and managed according to best practices. Double ‘nano-attack’ on targeted biomarkers “Our EU-funded PHOCNOSIS project has devised a nanotechnology-based analysis device for the minimally invasive diagnosis of CVD,” outlines project coordinator Jaime García-Rupérez. The approach relies on the combination of nanophotonics and micro-/nanofluidics. The sensing elements in the system consist of nanophotonic structures with a very reduced size able to provide a high sensitivity. As García-Rupérez explains: “This means that the analysis chips can contain thousands of sensing elements in an extremely reduced area.” To further increase the sensitivity to detect the required concentrations of the target biomarkers, the nanophotonic sensors were combined with an electrically controlled nanofluidic system based on depletion zone isotachophoresis, or dz-ITP. This technique can significantly increase the concentration of the target analytes at a certain location. Integration of the two nanosystems for the future Although the operation of the nanofluidic and nanophotonic systems have been demonstrated independently, it has not been possible in the project period to integrate the two. “When working on their integration, we observed that the electrical signals used to control the nanofluidic concentrator produced a significant increase of the optical losses for the nanophotonic sensors,” explains the coordinator. The researchers tried unsuccessfully to change the electrical signals to keep the concentrator working while maintaining acceptable optical losses. However, sufficient testing was not possible in the time available. Ironically, the researchers’ opinion is that this undesirable effect may have applications in other scenarios such as optical signal control and processing. Once the PHOCNOSIS researchers can solve these problems, they expect being able to deploy a device that could analyse 2 to 3 drops of a patient’s blood in just 10-15 minutes to diagnose early signs of CVD. Another relevant option the PHOCNOSIS team devised was to use fluorescent labels with the concentrator. Very good results were obtained using this approach. Work along these lines will continue and the target development will be a low-cost, compact and easy-to-use system. “The sample to be analysed simply has to be placed in an analysis cartridge and introduced in the automated reader platform,” adds García-Rupérez. Summing up the situation, it is worth noting that there is a platform prototype already in place, which might also be used for other applications where the detection of not-so-low concentrations or not-so-small analytes is required in other assays, such as for bacteria detection in food or environmental industries. This could be achieved by calibration of the assay targeted by the sensing chips. García-Rupérez considers that the use of fluorescent labels with the nanofluidic concentration system may have more direct application in the medical diagnostic field. “Overall, the progress in the different research fields involved in the PHOCNOSIS project has been remarkable and has allowed us to learn a lot for future work with POCT devices,” he concludes. Keywords PHOCNOSIS, CVD, nanophotonic, nanofluidic, cardiovascular disease, chip, point-of-care testing
