Nano-assisted digitalizing of cancer phenotyping for immunotherapy

Informations projet

ImmunoChip

N° de convention de subvention: 101045415

DOI

10.3030/101045415

Date de signature de la CE 18 Octobre 2022

Date de début 1 Janvier 2023

Date de fin 31 Decembre 2027

Financé au titre de

• European Research Council (ERC)

Coût total

€ 1 993 875,00

Contribution de l’UE

€ 1 993 875,00

Coordonné par

HELMHOLTZ-ZENTRUM DRESDEN-ROSSENDORF EV
Germany

Periodic Reporting for period 1 - ImmunoChip (Nano-assisted digitalizing of cancer phenotyping for immunotherapy)

Période du rapport: 2023-01-01 au 2025-06-30

Résumé du contexte et des objectifs généraux du projet

Every day cancer takes about 30000 lives worldwide, despite multiple treatments developed in the last 50 years. True revolution in the therapy is demonstrated by the immunooncology relying on multiple routes to activate the immune system. Apart from the developing biology driven multi-omics, at present, there is no predictive technological platform combining both, highly sensitive analysis of the cancer immunity and the planning of the strategy for potential therapy.

It is necessary to establish new patient-care standards, based on new drug administering policies, ultrasensitive diagnostics integrated in gadgets, to provide maximally personalized tests. In this respect, the ERC project ‘ImmunoChip’ successfully works on the development of the new strategies for on-chip integrated nano- microbiosensors for the cancer (a) diagnostics, (b) treatment development; (c) monitoring.

More specifically, ERC project ‚ImmunoChip‘aims to develop the nanotechnology driven sensor platform that enables the multiparametric tests for the cancer patients, enabling tracking of the diagnostic biomarkers, extending it to prognostics capability and optimal therapy testing. In particular, the information about the immunosuppressive activity of the cancer microenvironment, immune checkpoints, T cells, efficiency of the immunotherapy, should be collected into respective data patterns. For the successful realization, several important objectives should be fulfilled: (1) development of the multiplexed electronic biosensor with the exceptional sensitivity and microfluidics; (2) development of the multiple bioassays via specific surface modifications to track the diverse information about the patient sample; (3) interpretation of the multiparametric data.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The key achievements are as follows:
1. we develop portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold nanoparticle-based bioconjugates introduced as a part of the immunoassay. We detect he interleukin 6 playing an important role as a target for immunotherapy. (Biosensors & Bioelectronics 241, 115701 (2023); Next Nanotechnology 3, 100025 (2023)).
2. we introduce the concept ‘high frequency quantification of the biomarkers’, using a droplets microfluidics, and enable detection and continuous monitoring the enzymatic biomarkers, such as amylase, lactate, (Biosensors & Bioelectronics 251, 116034 (2024)).
3. we showcase the innovative use of extended‐gate field‐effect‐transistor (EG‐FET) biosensors for monitoring the concentration and pharmacokinetics of immunotherapeutic drugs in vivo. This approach shows the importance of point‐of‐care electronic biosensors as a groundbreaking solution contributing to better decision‐making in precision oncology. (Small Science 2400515, (2025)).
Publications:
The results related to the project are published as 18 high-profile papers incl. Advanced Science, Small Science, Advanced Healthcare Materials, Biosensors & Bioelectronics, ACS Sensors, etc. Publications are featured as 2x cover pages (Advanced Healthcare Materials and Biotechnology Journal).
3x works have been highlighted with the press releases of HZDR. In particular, one of them, (Biosensors and Bioelectronics 241, 115701 (2023)) is featured by dozens of important news outlets around the world (https://www.hzdr.de/db/Cms?pOid=71199&pNid=99). The interviews and articles were published at MDR Sachsen, Bild, etc.
Presentations:
The results are presented at more than 40 conferences, workshops and colloquia with the posters, contributed talks and invited talks. 23 invited talks given by the team members (PhD students, postdocs and PI) during first two years of the project.
Awards:
I am very proud that our researchers team excellently represents our activity to the scientific community and get the well-deserved recognitions: e.g. Young Researcher Award at EMRS spring meeting 2023 (Diana Sandoval), Humboldt Research Fellowship (Ahmed Alsadig), Helmholtz Professorship (Larysa Baraban), ERC Researchers are the winners of the ultimate bioengineering challenge (Janicijevic/Zhao/Peng),organized by Nature Review Bioengineering (Dec. 2024), and 3x Best poster prizes.
Projects:
The results obtained in the frame of this project provided a solid base for generation of the new ideas, which allowed to attract the following national and EU-funded third party projects:
1) DFG proposal 'Nanosensors for bacterial evolution', start 1.11.2023.
2) Marie Curie Doctoral Network ‘STRIM’, start 1.04.2025.
3) Helmholtz association: Helmholtz Professorship for the female researchers, start 1.05.2024.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

ERC project ‚ImmunoChip‘ develops the micro and nanotechnology driven sensor platform that will enable the multiparametric tests for the cancer patients, enabling not only tracking of the diagnostic biomarkers, but to extend it to the prognostics capability and optimal therapy testing. There are several important highlights, positioning our work beyond state of the art in the field:
1. in particular, we have demonstrated the first 32x multiplexed biosensor platform based on extended gate field effect transistor. Importantly, the platform comprises of three separate modules that make the system suitable for the point of care testing. Namely, these are the disposable chip, a readout module based on a single transistor operating in constant charge mode, and a multiplexer to scan sensing electrodes one-by-one. (Biosensors & Bioelectronics 241, 115701 (2023)).
2. Development of the microphysiological 3D tumor model for prostate cancer, taking into account the elements of the tumor microenvironment. This model resembles the micrometastases of prostate cancer in (a) liver and (b) bones, according to histopathology data (mice model and patients). (article revised, archive: X. Peng et al revised, bioRxiv, 2024.08. 16.608227 https://doi.org/10.1101/2024.08.16.608227).
3. we pioneered the format and the use of droplets based microfluidics chips as a tool for high frequency quantitative biomarkers detection. We have realized the real time diagnostics and monitoring of the lactate and amylase in post operative clinical patients using droplets microfluidics (traditional applications lie in the fundamental science, e.g. in cell biology or microbiology) (Biosensors & Bioelectronics 251, 116034 (2024)). This opens the way towards new standards of the real time and bed side biomarkers monitoring in the clinic.
4. Regulatory affairs: we have initiated the preparation of regulatory documentation for compliance with the In-vitro Diagnostic Device Regulation (IVDR) for droplets based microfluidic detection device (see point 3 above). The device has been structured into two components: the main detection and analysis device (BiomarkerTrack) and its accessory (DrainCollector), which is used to collect patient samples directly from the drain fluid bag. The intended purpose of the device and its accessory has been clearly defined. This includes details such as the medical indication, intended patient population, intended user, intended use environment, principles of functioning/operation, and limitations of use.
The later one have been initiated in cooperation with the regulatory department of University Clinic Dresden and Medical Faculty of TU Dresden.
These efforts are necessary to accelerate the clinical translation of the successfully developed diagnostics principles and prototypes.

Overview of the research directions