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Newsletter of June 2020
 

"MADIA has concluded its EC engaged and funded work on March 31st 2020.
The project has successfully fulfilled its main objectives – it has entirely demonstrated the highest diagnostic potential of the proposed technology, confirming the most ambitious objectives, such as fJ/ml detection capability."
 - Project Coordinator – Valentin Alek Dediu - 

NEURODEGENERATIVE DISEASES AND THE “MADIA KEY”

There is an urgent need to develop new effective early diagnostic strategies for Alzheimer’s disease (AD) and Parkinson ́s disease (PD). It is widely recognised that alongside the discovery of new pharmacological treatments, the efficacy of currently available treatments could be improved by early intervention. To tackle this challenge, the multidisciplinary research EU Horizon project Magnetic Diagnostic Assay (MADIA) project, according to its proposed technology, intended to develop a novel ultra-sensitive device for improving the AD and PD biomarkers (BM) detection in blood and cerebrospinal fluid (CSF).

Therefore, the identification and measurement of new and high sensitive biomarkers (BMs) will impact the management of AD and PD to:
  • help to capture high-risk individuals before symptoms develop and monitor the disease progression;
  • discriminate between AD or PD and other dementias for an accurate patient stratification;
  • determine the clinical efficacy of novel therapies and for safety monitoring.
The MADIA contribution aims at identifying innovative biomarkers which further validated may add accuracy to the up-to-day diagnostic criteria.

Main Challenges

MADIA had very challenging and very complex objectives, which required a truly multidisciplinary approach. The selective bio-functionalization had to be adapted for any given biomarker - it also had to be extremely specific (>90%) and simultaneously able to provide a stable binding between nanoparticles and biomarkers, allowing for their further dynamic processing and analysis. Next, this binding efficiency should be necessarily maintained and ultra-low concentrations, where the distance between the two species is enormous for their size. And here MADIA planned to introduce in the game the magnetophoresis, to be able to augment the meeting probabilities by orders of magnitude.

In addition to these two beyond the state of the art challenges, the magnetic sensors should be able to detect the nanoparticles with accuracy beyond the best standard magnetic devices, such as SQUIDs or other magnetometers. Such devices are typically able to detect between nano and picograms of magnetic material, while MADIA diagnostic ambitions required the detection well below the picogram level. To solve this, MADIA took advantage of microfluidics and nanotechnology and was able to bring the nanoparticles in the close vicinity of the sensors, and also, to upgrade the sensor's sensitivity beyond the state of the art achievements. Finally, all the components would be merged by smart engineering solutions for the realisation of the diagnostic unit and supporting tools.
To summarize, MADIA had successfully:
  • Achieved extraordinary detection sensitivity for relevant biomarkers
  • Moved the diagnostic skills for AD and PD to the earlier disease phases 
  • Laid the foundation for a cheap and versatile point-of-care diagnostic technology

Technology

The core of MADIA technology is to supplement the Biomarkers with magnetic labels, making them “visible” to magnetic sensors. The selective functionalisation of superparamagnetic nanoparticles enables the nanoparticles with the capability to recognize the specific biomarker and binds to it, forming the biomarker-nanoparticle conjugates. The aggregation process is magnetically driven, boosting the aggregation efficiency to 90% even for samples with biomarker concentration below the current detection limits. The conjugates are further extracted by properly shaped magnetic gradients, enhancing the concentration of linked biomarkers by orders of magnitude. Finally, the conjugates are analysed by arrays of magnetic sensors, which define their concentration and size. 

Main Events

Workshop on ‘Smart Bio-electronic and Wearable Systems’ in Brussels, Belgium

 
The workshop on Smart Bio-electronic and Wearable Systems (22nd - 23rd October 2019) covered the topic about smart systems across Key Digital Technologies, with an emphasis on bio-electronics, bio-photonics and flexible and wearable electronics. A prototype of MADIA's device was also demonstrated as in the image below. MADIA was presented in the workshop by CNR, Scriba and Orthokey.
 
More information about the workshop can be found here

"Nanotechnologies and Smart Systems for the Early Diagnostics" Workshop in Bologna, Italy


The workshop “Nanotechnologies and Smart Systems for the Early Diagnostics” was organized in the framework of the H2020 MADIA (Grant Agreement N° 732678), to foster the dialogue between actors from academy, industry and civil society, on technological trends and needs in the field of early diagnosis.

The workshop was co-organized by CNR, INNOVA and Scriba Nanotecnologie in June 2019, Bologna, Italy. Invited speakers and panellists of the workshop are experts from the industry. Among them: Militeni BiotechThema SrlST Microelectronics and Sorin Group Italia. 
Furthermore, also huge participation of the academic and institutions world was registered: the European Commissionthe University of Foggiathe University of Bolognathe Italian Red CrossSapienza Universitythe University of Cataniathe University of Lisbon.the University of Modena and Reggio Emiliathe Aristotle University of ThessalonikiEBRI

The workshop focused on nanotechnology for diagnostics, considered the strong interest in exploring possible applications of the most recent technologies developed for early diagnostic in the medical field. Among them, wearable and implantable devices will be also presented and discussed. The main topic of the event included:
  • Advances in diagnostics in neurodegenerative diseases
  • Nanotechnologies in diagnostics
  • Wearable and implantable diagnostic devices
  • Regulatory in the commercialization of diagnostic devices
More information can be found here
Alek Dediu and Aleardo Furlani were discussing the panel
Dr. Sabrina Conoci was giving the industrial perspective on early diagnostics

Healthy Futures Entrepreneurs' Network, Brighton, UK


In July 2018, the entire MADIA Consortium participated in a very strategic event organized by the University of Brighton. It has been an important example of the possible collaboration between public authorities, business and academia. A very good initiative for health enterprise and innovation. Most of the MADIA Partners had their own stand where, also in synergy with other projects in some cases, the MADIA results have been presented and many contacts with the Industry world have been taken.

To better know about the event, please, go
here



Hannover Messe Exhibition, Germany

 
In April 2018 Scriba NanoNanotecnologie was present at the Hannover Mess Exhibition, with a stand divided into two parts, one for their products and the other one for the R&D Project. They then presented MADIA project on the web site of the event and during the exhibition with roll-up, flyers and prototype. In particular, visitors received a flyer describing the objectives of the project and they were deepened verbally based on the requests received.
Target Audience: research and technology-based companies.

To better know about this very important annual event, please, go here.

"Neurodegenerative Disorders: the challenge of early diagnosis" Workshop in Rome, Italy

The Workshop "Neurodegenerative Disorders: the challenge of early diagnosis" was held on 19th January 2018, in the University La Sapienza of Rome, Italy by the Consortium. It was attended from a large number of participants, around 200 persons, the MADIA partners and the Coordinator of the project, most researchers, medical doctors, neurologists, University students, biotech companies, industries, Patients association.

The aim of the workshop was to present all the latest innovations in early diagnosis, treatment, translational R&D, drug development and clinical trials in Alzheimer’s, Parkinson’s and other related neurological disorders.
A central theme of the conference was to further advance innovative strategies in early diagnosis of Neurodegenerative Diseases, organised in four sections, from diagnosis, from care to cure:
  • Epidemiology of Neurodegenerative disorders
  • Parkinson’s and Alzheimer diseases: current status and future perspectives
  • Addressing open questions in biomarkers for early diagnosis
  • Therapeutics for Patients and Patient prospects and present MADIA challenge.
Thus, the MADIA Coordinator, Prof. Alek Dediu, presented challenging the diagnostic limits by the magnetic lab on a chip assay.

More information about the event can be found
here

Achievements

  • Establishment of an innovative diagnostic method based on the statistical detection of biomarkers-nanoparticle aggregates and able to work at ultralow biomarker densities
  • Development of innovative bio-functionalization technologies based on selected aptamers and antibodies and featuring highest selectivity and binding efficiency towards standard and innovative biomarkers
  • Development of innovative routes and tools for the efficient capturing of biomarkers from patient samples and/or the considerable enhancement of their concentration for unprecedented early diagnostic capability
  • Upgrade of magnetic sensor systems towards unprecedented sensitivities and accuracies compatible with ultralow concentration detection in bio-medical diagnostic systems

Future Perspectives

Early diagnosis of neurodegenerative diseases acknowledges the key advantages of their early management, improves the understanding of underlying mechanisms and identifies new targets for innovative treatments. In addition, it improves the stratification of patients who access clinical trials resulting in a better outcome. It is also extremely important to improve diagnostic sensitivity in biological samples that can be obtained through non-invasive methods, such as blood, saliva and others. This the reason why the MADIA Team would like to continue to cooperate and it is interested to upgrade further the developed technologic devices, bringing them to a pre-commercial prototype level: formal agreements between different partners and groups of partners are being established to proceed on this route.

 
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