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Biomedical engineering for cancer and brain disease diagnosis and therapy development

Final Report Summary - ENGCABRA (Biomedical engineering for cancer and brain disease diagnosis and therapy development)

Final Report: 1 April 2011 - 30 September 2015
Marie Curie Initial Training Network
No. PITN-GA-2010-264417

Coordinator: Prof. Michael J. Vellekoop
Institute for Microsensors, -actuators and –systems (IMSAS)
Microsystems Center Bremen (MCB)
University of Bremen, Germany

Summary of objectives
General objective: The project focused on the realization of novel methods and devices for analysis of cellular and molecular mechanisms related to cancer and brain diseases.
Project objectives :
1- To design and realize devices to detect single or small clusters of melanoma cells, both in biopsies and in lymphatic drainage and to develop new therapies based on information resulting from these sensing methods.
2- To investigate and realize devices for heat analysis of cells (differential calorimetric scanning on a chip).
3- To develop a screening and/or monitoring protocol for certain cancer types. Detection of new and existing cancer markers at a very early stage of the disease.
4- To combine state-of-the-art electrical engineering and microelectronics with electro-physiology, immunohistochemistry and pharmacology to introduce a new paradigm in brain disease detection and therapy development.

Work performed within the project
Partners with different background have cooperated to study biological processes and to realize devices for analysis of cell tissue, blood, lymph fluid and brain tissue.
The research has resulted in four demonstrators (hardware) that reflect the results of the investigations: a biopsymeter, chips for fast differential scanning calorimetry, high-density multiple electrode arrays (MEAs), and a silicon nanowire field effect transistor.
-ITN Training-
In addition to the hostdriven training, we organized network trainings (4-6 days per year) on topics from different disciplines such as biotechnology, medical, electrical engineering, physics, and microsystems. Further, a summerschool, meetings with industry, a meeting with representatives of a patent office, and a network workshop with other fellows were conducted. Moreover, secondments were organized.
-Workshops open to the public-
Fellows presented their work orally and through a poster session to the general public in a technical museum. At the final network meeting a poster session was organized by the fellows in the entrance hall of a university faculty.

Main scientific results
• New method for long-term brain slice cultivation on MEAs (roller system)
• First time visualization of real-time brain cell communication in slices
• There is currently no other technology or method available that allows for tracking axonal potentials over larger distances and at multiple sites.
• New method and device for infrared determination of CH2-stretch in biopsies
• First time local determination of cell-structure deviations indicating melanoma in biopsies
• First time cell detection by infrared measurements in microfluidic channels applying heavy water
• New pathway identified for NKG2D ligand ulbp2 regulation
• First time biological liquid analysis performed by fast differential scanning calorimetry (FDSC)
• First time cancer established in patients serum by FDSC

The project has resulted in:
• 19 journal publications (several journal publications are still in preparation)
• 37 international conference presentations
• 31 invited presentations
• Complete website
Articles in newspapers: The research resulted in tens of publications in newspapers and blogs. The biopsymeter was, for example, published in Kreiszeitung (Germany, 28.03.2015) Weser Wirtschaft (Germany, April 2015), Die Presse (Austria, April 2015).
The brain research has been published in 2015 EE Times, 2013 ETH life, and 2011 NZZ:
Radio: An item on the project in general and the biopsymeter in specific was broadcasted on Deutschlandfunk (21.05.2015) a nationwide radio channel with several millions of listeners.

All deliverables were completed and submitted. One milestone was not completely reached yet; tests for cell detection in lymph fluid were conducted with a model fluid instead. Research is on-going.

Potential impact and use
The project brought about four demonstrators. Scientific results of one demonstrator are being commercialized by a company (SME). For two other demonstrators the setup of two startup companies is in an advanced phase.