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Continuous two-dimensional Stretch monitoring of fresh tissue Biopsies

Periodic Reporting for period 1 - StretchBio (Continuous two-dimensional Stretch monitoring of fresh tissue Biopsies)

Reporting period: 2021-09-01 to 2022-08-31

The StretchBio project aims at contributing towards personalised medicine through the development of an advanced nanosystem for drug screening in biopsies of solid tumours. The overall aim of the project is the design, development, fabrication and proof of concept of an advanced label-free and compact nanosystem for the continuous monitoring and quantification of mechanical stresses in ex vivo fresh tissue biopsies.

This new technology will allow testing of the changes of tissues upon their treatment with anticancer drugs for improved drug screening. The proposed solution will be made of photonic crystals based on arrays of nanopillars, and the light transmission through them will clearly and quantifiably correlate with the health situation of the biopsy.

StretchBio will mainly focus on fundamental scientific aspects leading to a low TRL proof-of-concept device. Nevertheless, the long-term impact of the proposed route to screen tumours is undoubted, paving the way towards less invasive techniques to deal with cancer. This will result in both improved quality of life for EU citizens, and competitive advantage for European pharma companies developing future cancer treatments.

As said before, the overall aim of the StretchBio project is the design, development, fabrication and proof of concept of an advanced label-free and compact nanosystem for the continuous monitoring and quantification of mechanical stresses in ex vivo fresh tissue biopsies. Having this in mind, the project outputs can be grouped into two main objectives:

1. Development of theoretical and technical basis for the StretchBio concept (device fabrication);

2. Validation of two-dimensional stress measurements in cancer-relevant tissue samples with dimensions compatible with core needle biopsies (device validation).

To achieve the abovementioned objectives, an interdisciplinary team with heterogeneous expertise (i.e. biology, physics, nanotechnology, etc) has been set up.
StretchBio started on September 2021 and will continue until the end of August 2025. The project is structured in eight work packages (WPs), out of which five, namely WP2 to WP6, are technical. On the other hand, WP1 addresses the ethical aspects, WP7 covers the management and coordination of the overall activity, and WP8 focuses on dissemination, training and exploitation activities.

In WP2 the photonic crystals, on which the proposed nanodevice is based, are considered from a theoretical point of view, while the fabrication and testing strategy is developed in WP3. WP4 focuses on the compatibility and adhesion between the nanopillar materials and the living tissues. The light sources, detectors, and the coupling to the nanodevice are treated in WP5. In the last technical work package, WP6, the validation of the whole nanosystem and the performance assessment is addressed. As this is being written, work is running in all WPs.

For reporting period RP1, efforts have been mainly focused on attaining the first project objective (device fabrication), while the second one (device validation) will be searched in the next stages of the project once the technology is more mature (reporting periods RP2 and RP3).

The following results have been achieved so far:

a) Objective 1.1: Designing photonic devices formed by arrays of nanopillars, containing one or more narrower nanopillars, and simulating the light transmission variations upon the mechanical deflection of the narrower nanopillars. Completed.

b) Objective 1.2: Fabricating the photonic devices and measuring the light transmission through them upon mechanical deflection, providing two-dimensional force distribution maps, which will constitute a force nanosensor. Partially completed due to limitations of the use of Electron Beam Facility for samples production.

c) Objective 1.3: Developing the theoretical background of the interaction between the nanopillar arrays and the ex vivo tissues. Preliminary but promising results validated. Further studies required

d) Objective 1.4: Developing a compact optical excitation and readout system for the nanosensor. The first prototype has been envisaged and designed.

On the other hand, as far as dissemination and exploitation go, the consortium has taken its first steps to designing and put into practice a meaningful plan to reach the project stakeholders in the coming years. The implementation has been however limited due to the fact that project outputs are still in their infancy. Nevertheless, in this regard, the following milestones have been achieved.

1) Visual project guidelines created (ex. logo);

2) Communication channels up and running (ex. project website and Twitter account);

3) Dedicated ZENODO portal and first contributions to the Open Data initiative;

4) First communications initiatives completed (ex. press release and contributions to outreach activities such as the European Researcher's Night);

5) First scientific dissemination activities (ex. contributions to international conferences such as MRS Fall Meeting 2021 and MNE 2022);

6) Preliminary contacts with EIC representatives to evaluate the future exploitation strategy, and;

7) Contribution to the EU Innovation Radar Initiative.
Monitoring of mechanical stresses in tissues ex vivo is key for understanding their effect on tumour growth and for the development of novel anti-cancer drugs aiming to rescue normal tissue elasticity and improve drug delivery to cancer cells. Before StretchBio, the existing methods to do this only provided an indirect non-quantitative assessment of tissues' mechanical stresses. On the other hand, the fabrication of nanopillars, such as those required for the photonic crystal to shape the photonic crystal necessary to evaluate tissues stresses is, in principle, well-known state-of-the-art technology.

Nevertheless, StretchBio is drastically beyond the current state-of-the-art in drug screening for cancer, which relies on time-consuming molecular biology techniques such as immunohistochemistry, mutational analysis, gene expression analysis or metabolomics. By placing the ex vivo tissue on top of the envisaged nanosystem, the continuous monitoring and quantification of the mechanical tensions occurring in the tissue will be recorded while it is kept in a liquid medium. These types of label-free measurements in such environments have never been performed. The target applications of the StretchBio concept can be found in the drug screening field for personalized medicine, representing an innovative approach to identify new target drugs for cancer and also for other multiple disorders that affect the cell and tissue membrane properties through the changes in their mechanical properties.

It goes without saying that any step forward in our fight against cancer will have a clear impact on the well-being of citizens and will result in a differentiating factor for the European pharma industry. Besides, from the regular project activity, tangent progress beyond the state of the art is also expected in other fields. As an example, new designs for improved photonic crystals are right now under evaluation. The full potential of StretchBio will realize in the coming reporting periods.
StretchBio Prototype
StretchBio Logo