A device for monitoring heart failure from saliva

  • An international team with involvement of ICMAB and IMB-CNM researchers develops a medical device capable of monitoring heart failure from saliva samples.
  • The instrument contains a biosensor chip which teams up with functionalized magnetic nanoparticles in order to detect heart failure-related biomarkers found in saliva.
  • The device, developed in the framework of the European project KardiaTool, can be used as a quick Point-of-Care saliva test that does not require the assistance of any specialized personnel for patient testing.

Heart failure is the main cause of mortality in Western societies. Ischemic heart disease is the main cause of mortality in the world, according to data of the World Health Organization. Since the year 2000, heart failure is also a disease on the rise: data shows that it accounted for 2 million of the global deaths back then, rising up to almost 9 million in 2019, of the close to 17.8 million deceases due to heart disease overall. Some reported estimates suggest that over 120 million patients worldwide may be suffering of ischemic heart disease. In Spain, the Spanish Statistical Office (INE) shows that heart failure-related diseases were the main cause of mortality in Spain until 2020.

For the timely and effective tratment of heart disease, a convenient, realiable and easy to deploy diagnosis method can be key. Currently, the monitoring is done by the quantification of biomarkers in a blood analysis. Addressing this matter, an international research team with participation of the Institute of Materials Science of Barcelona (ICMAB, CSIC) and the Institute of Microelectronics of Barcelona (IMB-CNM) has developed a rapid diagnostic device for the detection of heart failure through saliva samples. Using the developed device for heart failure detection through saliva samples would be a quick, simple to use tool to enhance diagnosis and treatment.

A lab-on-a-chip to detect biomarkers in saliva

The device acts as a portable laboratory able to separate and detect biomarkers in the saliva. It is made of microelectronic systems, integrated sensors, biochemicals and magnetic nanoparticles. It is a quick, low-cost and portable instrument based on nanotechnology to use as a Point-of-Care system to detect heart failure, the main cause of mortality in Europe up until 2019. It is the result of the European project KardiaTool, with published results in the journals Analytica Chimica Acta, Chemosensors and Molecules.

Albert Alcacer IMB-CNM
Albert Alcacer, IMB-CNM researcher, showing the device built at their facilities.

The system contains a microelectronic biosensor based on silicon nitride manufactured in the Clean Room of the Institute of Microelectronics of Barcelona (IMB-CNM, CSIC), the ImmunoFET. It contains an ion selective field effect transistor (ISFET) and is capable of detecting in saliva the presence of tumor necrosis factor-α (TNF-α), a small protein that is one of the biomarkers that indicates heart failure. The team has experimented with artificial and human saliva, demonstrating a high sensitivity to the concentration of TNF-α.

“The biosensor devices are integrated in a lab-on-chip that will allow performing a complete immunoassay for the measurement of the biomarker concentrations”, explains Joan Bausells, PI of the IMB-CNM contribution to the project and NANONEMS group leader. “The use of ISFET devices for the biosensors takes advantage of the intrinsic electronic amplification properties of the transistor to increase the sensitivity,” adds the researcher.

The contribution of the ICMAB focused on the synthesis of the magnetic nanoparticles used in the device: “Since the concentration of the biomarkers in saliva is smaller than in blood, we need to do a pre-concentration. To this end, we use magnetic nanoparticles functionalized with the adequate antibodies, synthesized at ICMAB, that can capture these biomarkers”, says Francesc Teixidor, ICMAB researcher and LMII group leader. “These nanoparticles had to be stable enough to not precipitate and to circulate along the microfluidic channels, a big challenge to overcome!” adds the researcher.

Jewel Ann Maria Xavier, ICMAB researcher, showing a preparation of the magnetic nanoparticles contributed by ICMAB-CSIC.
Jewel Ann Maria Xavier, ICMAB researcher, showing a preparation of the magnetic nanoparticles contributed by ICMAB-CSIC.

“The automatic device developed within the project does not require specialized personnel and is a tool that can rapidly indicate the severity of heart failure condition. We think that it can be very useful to doctors, especially to plan and evaluate the efficacy of the different treatments for the patients”, adds Francesc Teixidor.

A collaboration of 14 European institutions to detect heart failure is part of KardiaTool, an international project funded by the European Commission within the Horizon 2020 Research and Innovation program. It has been granted € 4.9 M since 2018. The project counts with the participation of 14 institutions from 9 European countries including the University Claude Bernard Lyon (UCBL, France), Foundation for Research and Technology Hellas (FORTH, Greece), Spanish National Research Council (CSIC, Spain), University of Pisa (UNIPI, Italy), Fraunhofer-Gesellschaft (Germany), BioTray (France), Micronit Microtechnologies B.V. (Micronit, The Netherlands), IMEC (Belgium), University of Ioannina (UOI, Greece), ValoTec (France), Consiglio Nazionale delle Ricerche (CNR, Italy), EnaChip Inc. (Enachip, US), University of Surrey (US, UK), University College Dublin (UCD, Ireland). IMB-CNM and ICMAB are the leading CSIC centres involved since the beginning and the sole Spanish contributors to the project.

Image credits:

Research pictures were kindly provided by ICMAB, and re-used with permission.