Novel 1D photonic metal oxide nanostructures for early stage cancer detection

Project Information

CanBioSe

Grant agreement ID: 778157

DOI

10.3030/778157

Project closed

EC signature date 22 November 2017

Start date 1 January 2018

End date 31 December 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 1 116 000,00

EU contribution

€ 1 116 000,00

Coordinated by

LATVIJAS UNIVERSITATE
Latvia

Periodic Reporting for period 2 - CanBioSe (Novel 1D photonic metal oxide nanostructures for early stage cancer detection)

Reporting period: 2020-01-01 to 2023-12-31

Summary of the context and overall objectives of the project

The CanBioSe project research and innovation goals are targeted to develop a new portable tool for early stage cancer detection which can solve one of the important health challenges in EU society. The project is targeted to strengthen international and intersectoral collaboration, sharing new ideas, knowledge transfer from research to market, and vice versa in the field of nanostructured metal oxide optical biosensors for cancer cell detection.

The project partners will provide research and training activities in the fields of nanotechnology, surface functionalization, bioengineering, microfluidics and biosensor testing, market analysis and commercialisation. The provided research and management training to experienced researchers and early stage researchers will be quite beneficial. It will strengthen their personal skills and CVs via the new scientific papers and conference theses and strengthen a development of EU research human resources. We foresee a long lasting collaboration between the partners, based on co-supervising students and the preparation of novel collaborative project proposals. Also foreseen is a dissemination of the project results to the scientific society and wide auditories.

Scientific work will include: One dimensional (1D) polimer nanofibers will be deposited by an electrospinning technique. Photonic nanomaterials, based on metal oxide based nanostructures (ZnO, ZnO/Al2O3 nanolaminates, Au/ZnO and ZnO/Au) will coat the 1D nanofibers. Metal oxides and Au nanoparticles will be deposited with Atomic Layer Deposition (ALD) and electrophoresis, respectively. Bioselective layer will be formed by immobilization of specific antibodies on the biosensor surface. Photoluminescence and optical spectroscopy will be used for recording the biosensor signal. Biosensor testing will be performed on cancer cells (human chronic lymphocyte leukemia (CLL) leucosis and acute lymphoblastic leucosis). The biosensor will be integrated with microfluidic system in order to minimize dimensions and simplify the use of the detection system.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the first year of the CanBioSe project the scientific work performed and main results achieved are:

1.1D nanofibers have been prepared by using different polymers such as PAN, HA, collagen and gelatin. PAN showed the optimal structure and mechanical properties for further ALD deposition.
ZnO, ZnO-MXene, ZnO/Au and ZnO/Al2O3 nanolayers with different thickness deposited on PAN nanofiber scaffolds. Structure properties of the deposited layers have been investigated by XRD, SEM, XPS, Raman, FTIR and TEM and published in peer review papers.
Optical properties of 1D nanofibers have been investigated by photoluminescence and diffuse reflectance. The samples with optimal structure and optical properties have been selected. The achieved results were presented at workshops and research papers.
2. Surface properties of the 1D nanostructures have been modified by the following methods:
-plasma treatment
-silanization
-thiolization.
As result of the surface treatment, the -NH2 and -COOH functional groups have been formed on the surface of the 1D nanofibers.
Antigens, antibodies and enzymes have been attached to the surface of the 1D nanostructures via covalent immobilization. The presence of the bioselective layer on the surface of the 1D nanostructures have been confirmed by ellipsometry, FTIR, Raman and photoluminescence methods. The samples with best performance for bioselective layer forming have been tested as biosensors.
3. Experimental miocrofluidic system for photoluminescence measurements of sensor signal in liquid has been developed and tested. The system was assembled with sample holding chamber, microfluidic system using syringe pump. The system can be assembled with lasers and LEDs.
4. Biosamples have been prepared via cell culture growth, biomanipulation, fluorescence microscopy of bioprobes cells and separation of cell subpopulations and biomarkers by flow cytometry.
Project partners have been testing the sensor signal to cancer cells and biomarkers by using photoluminescence spectroscopy method. The sensitivity, selectivity and limits of the detection have been calculated. The sensitivity for biomarkers and cells was in the range of 0.01-1 ng/ml and 1000-100000 cells/ml, what is in a good range, compared to the data from the literature. The sensor results have been published in peer reviewed journals. The proposed microfluidic sensor system has some advantages, such as simplicity and low cost.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Progress beyond the state of the art:
Novel 1D ZnO nanostructures with advanced structure and optical properties have been fabricated by LU, AMU, VU and ENSCM. Through tailoring of deposition parameters, optical signal (photoluminescence) is 2-4 folds stronger than other optical materials
Fundamental properties of these nanostructures have been investigated in collaboration between LU, AMU, VU, FBK and ENSCM and industrial partners 3D strong, Biosensors, NanoPrime, NanoPharma and MRC.
The surface of the developed 1D ZnO nanostructures have been modified by Au nanoparticles and MXenes, polymer layers and functional groups to assist immobilization of the biomolecules. Sensitivity tests against antigens and cancer cells have been performed by using photoluminescence spectroscopy on LU, SensoGrafa, Biosensor and CSD facilities. The developed immunosensors, based on 1D ZnO and 1D ZnO composite nanostructures showed good sensor response towards the target cancer biomarkers and cells.
Microfluidic system was designed and developed within collaboration between FBK, LU, VU, Biosensors, SensoGrafa. Transfer of the cells to microfluidic systems and development of the portable optical detection scheme showed good prospects for development of new point of care diagnostic systems.

Expected results until the end of the project:
Fabricated new 1D metal oxide nanostructures with tailored properties as platforms for optical biosensors.
Formed antibody, antigen and enzyme bioselective layers with high stability and selectivity on the surface of 1D metal oxide nanostructures.
Investigated sensitivity and kinetics of the 1D photonic biosensors to different concentrations of target molecules (cellular receptors and molecular markers of cancer cells).
Studied mechanisms of interaction between biomolecules and the biosensor surface.
Developed portable biosensor system for cancer detection, integrated with microfluidic flow and optical fiber detection systems.

Potential impact
The impact of the project is following:
1.Socio-economic impact - the project has developed new methodology for early stage cancer detection, and that will impact the health care of EU citizens. Development of novel integration devices will impact the EU industry. New results will stimulate development of EU research in fields of nano- and biotechnology.
2.Career development and strengthening of research potential - new skills were transferred to early stage researchers (123 secondments) in order to improve their competitiveness. Effective knowledge transfer increases scientific potential of participating countries. New proposed projects stimulate staff exchange, new papers and applications. 47 publications have been published, 10 new projects were submitted; more than 10 international conferences have been attended; 1 international conference, 5 workshops and 4 conference sections have been organized.

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