CETAL | ELI-RO Projects ( PNCDI III 2015-2020) | ELI-RO 01

ELI-RO 01/2020 Project

English (Engleză)
Project title: Laser-driven very high-energy electron beam FLASH irradiation: real-time dosimetry-on-chip and biological effects / FLASH-on-chip

Periode: 01 Oct 2020 - 30 Sept 2023

Contact Person:
Project Director: Dr. Felix SIMA (INFLPR)

Coordinator:
National Institute for Laser, Plasma and Radiation Physics - I.N.F.L.P.R.
Atomiștilor 409, Măgurele, Romania

Abstract (Objectives):

In this project, we propose to simultaneously perform dosimetry measurements using real-time on-chip methods and evaluate the biological effects of FLASH-RT induced by either VHEE or conventional X-ray radiation on melanoma cells grown on the same miniaturized lab-on-chip device. Specifically, the main goals of the project are to determine FLASH irradiation dose of either VHEE obtained by a PW laser-driven electron acceleration in gas or by X-ray radiation using conventional radiation sources and to evaluate cancer cells response to the applied dose (reactive oxygen species production, DNA double-strand breaks generation, cell proliferation). This will be performed in a miniaturized chip housing both cell cultures and dosimetry elements. Secondary project aims will consist of (i) developing new X-ray or electron radiation calibration assays for the eventual determination of FLASH dose and (ii) the development of a tumor-on-chip model consisting of co-cultures of melanoma and normal tissue cells. Finally, we propose a correlation analysis between FLASH irradiation and dose-response effect on the tumor and normal tissue cells, respectively.

Phases:

2020 - Optimization of irradiation set-ups and microchip validation;

2021 - Protocols and irradiation experiments on cancer cells: dosimetry calibration;

2022 - Comparative studies with FLASH irradiation and effects on cancer cells: VHEE vs X ray;

2023 - FLASH irradiation on cancer cells: dose effect.

Română (Romanian)
Titlul proiectului: Iradieri FLASH cu fascicule de electroni de energie foarte mare accelerati cu laser: dozimetrie pe chip in timp real si efecte biologice / FLASH-on-chip

Perioada: 01 Oct 2020 - 30 Sept 2023

Persoana de contact:
Director Proiect: Dr. Felix SIMA (INFLPR)

Coordonator:
Institutul Național pentru Fizica Laserilor, Plasmei și Radiației - I.N.F.L.P.R.
Atomiștilor 409, Măgurele, ROMÂNIA

Abstract (Obiective):

În acest proiect propunem desfășurarea unor măsurători simultane de dozimetrie utilizând metode de analiză în timp real în timpul iradierii FLASH-RT cu VHEE sau raze X și evaluarea efectelor biologice asupra celulelor canceroase de tip melanom crescute în aceleași dispozitive miniaturale de tipul lab-on-chip. Concret, scopurile principale ale proiectului sunt determinarea dozei de iradiere FLASH a radiațiilor VHEE rezultate în urma accelerării electronilor la interacția fasciculelor laser ultra-intense cu mediu gazos sau a radiațiilor de raze X obținute folosind surse convenționale și, respectiv, evaluarea răspunsului celular la valoarea dozei aplicate (producție de specii reactive de oxigen, generare de rupturi dublu-catenare ale ADN-ului, proliferare celulara). Aceste experimente vor fi efectuate într-un dispozitiv miniatural ce găzduiește culturile celulare și elementele de evaluare dozimetrică. Alte ținte ale proiectului constau în (i) dezvoltarea unor metode noi de calibrare a radiațiilor de raze X și, respectiv, de electroni, pentru determinarea dozei de iradiere de tip FLASH și (ii) dezvoltarea unui model tumor-on-chip constituit din co-culturi de celule sănătoase alături de celule canceroase. În final, ne propunem sa corelam nivelul dozei de iradiere FLASH cu efectul ei asupra celulelor tumorale și respectiv sănătoase.

Etape:

2020 - Optimizarea montajului experimental de iradiere si validarea microcipului;

2021 - Protocoale si experimente de iradiere pe celule tumorale: calibrari dozimetrice;

2022 - Studii comparative ale efectelor iradierilor FLASH asupra celulelor tumorale: VHEE vs radiatie X;

2023 - Iradieri FLASH ale celulelor tumorale: efectul dozei.

RESULTS:

Publications:
[1] F. Jipa, S. Orobeti, C. Butnaru, M. Zamfirescu, E. Axente, F. Sima, K. Sugioka, Picosecond Laser Processing of Photosensitive Glass for Generation of Biologically Relevant Microenvironments, Applied Sciences 10 (24), 8947, 2020.
[2] I. Porosnicu, C. M. Butnaru, I. Tiseanu, E. Stancu, C. V. A. Munteanu, B. Bita, O. G. Duliu, F. Sima, Y2O3 Nanoparticles and X-ray Radiation-Induced Effects in Melanoma Cells, Molecules 26 (11), 3403, 2021.
[3] C. E. Staicu, F. Jipa, I. Porosnicu, A. Bran, E. Stancu, C. Dobrea, B. M. Radu, E. Axente, I. Tiseanu, K. Sugioka, F. Sima, Glass lab-on-a-chip platform fabricated by picosecond laser for testing tumor cells exposed to X-ray radiation, Applied Physics A: Materials Science and Processing, 128, 77, 2022.

[4] First in vitro experiments using laser-induced very high energy electron FLASH irradiation – potential for anti-cancer therapeutic strategies S. Orobeti, L. E. Sima, I. Porosnicu, C. Diplasu, G. Giubega, G. Cojocaru, R. Ungureanu, C. Dobrea, M. Serbanescu, A. Mihalcea, E. Stancu, C.E. Staicu, F. Jipa, A. Bran, E. Axente, S. Sandel, M. Zamfirescu, I. Tiseanu, F. Sima, accepted June 2024, Scientific Reports, https://doi.org/10.21203/rs.3.rs-3893842/v1.

Patents:
[1] F. Jipa, C.E. Staicu, I. Dinca (Porosnicu), A. Bran, E. Stancu, C. Dobrea, E. Axente, I. Tiseanu, F. Sima, “Dispozitiv microfluidic din sticla fotosensibila pentru testarea celulelor tumorale la radiatii ionizante si element de dozimetrie in-situ”, OSIM, A/00235, May 10, 2023.

Conference presentations:
[1] C. E. Staicu, C. M. Butnaru, F. Jipa, E. Axente, B. M. Radu, F. Sima, In vitro viability and proliferation tests of photosensitive glasses processed by picosecond laser assisted etching, Workshop CETAL, Magurele, Romania, December 17-18, 2020.
[2] F. Jipa, C. Butnaru, S. Orobeti, C. Staicu, E. Axente, M. Zamfirescu, K. Sugioka, F. Sima, Ultrafast laser processing of photosensitive glasses for biological applications, Workshop CETAL, Magurele, Romania, December 17-18, 2020.
[3] G. Giubega, R. Ungureanu, G. Cojocaru, C. Staicu, F. Jipa, C. Diplasu, E. Stancu, M. Serbanescu, A. Marcu, E. Axente, M. Zamfirescu, F. Sima , “Laser-driven electron acceleration for FLASH radiotherapy”, Poster presentation at Satellite meeting of the 47th European Physics Society (EPS) Conference, EPS 2020 (2021), Conference on Plasma Physics (virtual), organized by University of Salamanca, 28-29 June, 2021.
[4] F. Sima, I. Porosnicu, C. Staicu, C.M. Butnaru, F. Jipa, C. Nita, E. Axente, E. Stancu, I. Tiseanu, “Glass lab-on-a-chip platform fabricated by picosecond laser for testing tumor cells exposed to X-ray radiation”, 16th International Conference on Laser Ablation (COLA2021/2022), Hybrid format, Matsue, Japan & online, (virtual oral presentation), 24 – 29 April, 2022.
[5] F. Jipa, C. E. Staicu, C. Nita, E. Axente, I. Porosnicu, I. Tiseanu, K. Sugioka, F. Sima, “Glass biochips fabricated by ultrafast laser processing for evaluation of ionizing radiation effect on cancer cells”, 1st International Conference on Lasers, Plasma, and Radiation – Science and Technology (ICLPR-ST2022), Hybrid format, Bucharest, Romania & online, (poster presentation), 7 – 10 June, 2022.
[6] E. Axente, F. Jipa, S. Orobeti, M. A. Bran, C. Butnaru, M. Zamfirescu, E. Axente, F. Sima, K. Sugioka, “Picosecond laser-assisted processing of photosensitive glass for the fabrication of cellular microenvironments”, 1st International Conference on Lasers, Plasma, and Radiation – Science and Technology (ICLPR-ST2022), Hybrid format, Bucharest, Romania & online, (poster presentation), 7 – 10 June, 2022.
[7] Felix Sima, Florin Jipa, Stefana Orobeti, Cristina Staicu, Emanuel Axente, Hiroyuki Kawano, Koji Sugioka, “Shaping 2D and 3D transparent materials with sub-micron precision by ultrafast laser technologies: application to cancer research”, CurvoBio2022 Workshop, Berlin, Germany, (invited presentation), 24-26 August 2022.
[8] F. Sima, Mid-term report, Laser-driven very high-energy electron beam FLASH irradiation: real-time dosimetry-on-chip and biological effects / FLASH-on-chip - project presentation: scientific progress and perspectives (Public Session), IFA, Magurele, November 17, 2022.
[9] F. Jipa, C. Staicu, I. Porosnicu, C. Dobrea, I. Tiseanu, A. Bran, E. Axente, F. Sima, K. Sugioka, “Laser fabrication of glass microfluidic biochips for testing melanoma cells response under X-ray irradiation”, 24th International Symposium on Laser Precision Microfabrication, Hirosaki, Aomori, Japan (oral presentation), 13-16 June 2023.
[10] I. Dinca, C. Dobrea, C. Staicu, F. Jipa, E. Stancu, F. Sima, I. Tiseanu,"New Strategy for delivering pulsed X-ray irradiation for preclinical radiotherapy research", 21st International Balkan Workshop on Applied Physics, Constanta, Romania (poster presentation), 11-14 July 2023.
[11] F. Sima, End-term report, Laser-driven very high-energy electron beam FLASH irradiation: real-time dosimetry-on-chip and biological effects / FLASH-on-chip - project presentation: scientific progress and perspectives (Public Session), IFA, Magurele, November 7-8, 2023.

Awards:
4th place Best Poster Competition Awards - I. Dinca, "New Strategy for delivering pulsed X-ray irradiation for preclinical radiotherapy research", 21st International Balkan Workshop on Applied Physics, Constanta, Romania, 11-14 July 2023.

International Cooperation:
Laserlab EU project Working groups: Expert Group on Lasers for Cancer Research (https://www.laserlab-europe.eu/expert-groups/laser-for-cancer-research/laser-science-for-cancer-research), Initiation of an European project to be submitted in 2024;
Invited participation to Foresight Workshop on Opportunities with laser-based Technologies 24 & 25 July 2023, Riga, Latvia – Presentation on Microfluidic biochips & high resolution time lapse microscopy: application to cancer research (https://www.laserlab-europe.eu/events-1/laserlab-events/2023/expert-groups_agenda_20230724.pdf).

CETAL | ELI-RO Projects ( PNCDI III 2015-2020) | ELI-RO 01

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