Concept

The challenge

Modern medicine makes consistent efforts to develop methods and tools that can provide insight into the mechanisms of our strongest health enemies, which are at the moment the cancer and the cardiovascular disease (CVD), including the stroke. High-end imaging modalities like the sonography, the computed tomography (CT), the magnetic resonance imaging (MRI) and the positron emission tomography (PET) are still the basic non-invasive tools for a conclusive diagnosis of these diseases, but they are too complex and expensive, and at least in the case of the CT and the PET too harmful too, to be used as everyday monitoring tools. Moreover, having the nature of an imaging tool, these modalities can effectively make images of the results of these diseases such as the presence of solid tumors or blood clots, but they cannot offer true insight into the mechanisms that are present at the molecular level and promote the progression, the recurrence or the resistance to the medical therapy of these diseases. As a matter of fact, most if not all the information that is needed to decipher these mechanisms is believed to be present inside the human blood in the form of circulating cells, vesicles and molecules. What is however required are powerful tools to take us from the macroscopic to the microscopic level of imaging, enabling the sensing and the quantification of this blood content. The extracellular vesicles (EVs) in particular are membrane-enclosed vesicles that are secreted by the cells, and have a key role in the cell waste removal process and the cell-to-cell communication. Their use as circulating markers can offer insightful information about the physiological and pathological state of their cells of origin, and by extension, about the presence and progression state of diseases. The possibility to detect EVs in blood samples has been thus identified as one of the most disruptive and potentially impactful targets in modern medicine. However, with the size of most EVs between 50 and 200 nm, this possibility is still a true challenge. Flow-Cytometry (FCM) based on optical scattering represents the most promising candidate for small-size EV detection, but the current commercial FCM instruments, even the most advanced, can only detect particles with size down to 150-200 nm.

The vision

With this medical and technical background, PHOREVER steps in with the ambitious vision to develop a multi-sensing platform that will enable for the first-time 

1.

the detection of EVs
with size down to 80 nm

2.

the detection of EVs with
disease-specific proteins (biomarkers) as cargo on their membrane surface

3.

the calculation of the corresponding EV concentrations in human blood samples

With this medical and technical background, PHOREVER steps in with the ambitious vision to develop a multi-sensing platform that will enable for the first-time a) the detection of EVs with size down to 80 nm, b) the detection of EVs with disease-specific proteins (biomarkers) as cargo on their membrane surface, and c) the calculation of the corresponding EV concentrations in human blood samples. This disruptive detection performance will be enabled by the combination of three distinct sensing modalities: the FCM as the main sensing modality for the detection and size classification of particles in blood samples, the optical coherence tomography (OCT) as a second sensing modality for the micro-imaging of the sensing area and the application of a coherent gate for drastic noise reduction in the FCM measurements, and the fluorescence sensing as a third modality for the detection of the target biomarkers on the surface of the EVs after a proper stain process with fluorescent antibodies. Based on the development and the use of two photonic integrated circuits (PICs) and three microfluidic chips as the key components of the multi-sensing platform, its expected breakthrough will not be only with respect to the detection performance but also the intended type of use. The platform will be powerful, but still cheap and compact, and will be designed as a point of care (POC) device for diagnosis, progression monitoring and treatment assessment of diseases such as the cancer and the CVD. 

The potential medical impact of this multi-sensing platform is huge, but the actual impact will depend on a case-by-case basis on the background of the medical use cases. Two specific use cases will be investigated within the project. The first will be the case of the pancreatic cancer with focus on the monitoring of the progression stage of the disease, the assessment of the metastasis risk, and the evaluation of the treatment efficacy. The second will be the case of the stroke with focus on the fast diagnosis of the stroke incident and the fast identification of the stroke type using the multi-sensing platform of PHOREVER as a POC device before the actual arrival at the hospital. Since in the case of the pancreatic cancer, the effort by the medical community to identify a protein as a vulgate biomarker is still ongoing, the focus within the project will be on the correlation of the total EV concentration in the blood samples to the actual medical data of the patient. On the other hand, since the corresponding efforts in the stroke case have already resulted in the identification of effective biomarkers that can be carried as cargo by EVs, the focus within the project will be on the detection of the corresponding subclass of EVs and the correlation of their concentration to the stroke incident parameters. In either case, a set of data analysis tools empowered by artificial intelligence (AI) algorithms will be used for the processing of the measurements from the multi-sensing platform, and for their correlation to the corresponding medical data. Within this context, the step-wise approach for the realization of the development plan of PHOREVER, both at the technology and at the biomedical level is outlined through the following eight objectives. 

Contact Details

Dr. Lefteris Gounaridis

 

lgou@mail.ntua.gr

PHOREVER Project

Topic: HORIZON-CL4-2022-DIGITAL-EMERGING-01-03 – Advanced multi-sensing systems (Photonics Partnership) (RIA)
Programme Call: HORIZON-CL4-2022-DIGITAL-EMERGING-01
Project number: 101093171
Start date: 1 January 2023
Duration: 42 months
EU contribution: € 4 973 882,50

Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them.