A game change in continuous biosensing: Molecularly engineered affinity-based nanoswitches for personal monitoring

Project Information

CONSENSE

Grant agreement ID: 955623

DOI

10.3030/955623

Project closed

EC signature date 17 August 2020

Start date 1 March 2021

End date 31 August 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 4 029 293,82

EU contribution

€ 4 029 293,82

Coordinated by

TECHNISCHE UNIVERSITEIT EINDHOVEN
Netherlands

Periodic Reporting for period 2 - CONSENSE (A game change in continuous biosensing: Molecularly engineered affinity-based nanoswitches for personal monitoring)

Reporting period: 2023-03-01 to 2025-08-31

Summary of the context and overall objectives of the project

Healthcare is in demand of real-time sensing technologies to continuously guard the state of patients based on real-time, precise, and reliable data. Fluctuations in biomolecular levels are conventionally determined through laboratory assays that analyze samples collected at multiple time points. However, these laboratory-based methodologies have long turnaround times, typically a day or more, making it impossible to develop measurement-and-control strategies with frequent measurements and rapid feedback. Therefore, novel generic biosensor technologies are needed for the continuous monitoring of biomarkers for the monitoring of disease status and treatment effects.

The overarching aim of CONSENSE is to develop affinity-based biosensing technologies for the continuous monitoring of biomarkers by combining advanced engineering of biomolecular nanoswitches and optical detection by training 15 Early-Stage Researchers (ESRs) in the necessary scientific and transferable skills. The specific scientific objectives are:
• Construct nanoscale biomolecular architectures that undergo conformational changes upon binding of a target molecule (WP1).
• Develop optical read-out platforms that allow continuous optical monitoring of target molecules by detecting analyte-induced conformational switching (WP2).
• System integration and preclinical validation (WP3).

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

In the CONSENSE project, 15 ESRs worked on their research projects in the field of affinity-based biosensing technologies based on advanced engineering of biomolecular nanoswitches and optical detection. The work in WP1 focused on developing efficient methodologies to design and isolate molecular binders, developing strategies to make functional constructs with proteins and nucleic acids, and designing competitive and sandwich-type measurement formats. The work in WP2 addressed the development of optical sensing platforms suitable for nanoswitches and continuous biosensing, focusing on platforms with particle motion technology, nanoparticle-on-film, nanohole array, and fiber optic surface plasmon resonance. The work in WP3 covered the development of integrated continuous biosensing systems based on particle motion and fiber optics, as well as preclinical validation methodologies for continuous sensing, with a focus on demonstrator systems and in vitro cell-based model systems of the human immune response.

The ESRs received training through their local PhD programmes and the network-wide training events. The ESRs received training in scientific, transferable and business skills. Furthermore, ESRs went on secondments, for training purposes as well as to strengthen collaboration between the network partners. This resulted in collaborative research, with several scientific publications written by two or more beneficiaries.

The network implemented communication and dissemination activities with strong involvement of the ESRs. The CONSENSE website (www.consense-itn.eu) was established and contained regular contributions from the ESRs. The Outreach Support Team, formed by five ESRs, established a Twitter account and shared relevant content through these channels. Furthermore, the ESRs contributed to various national and international conferences.

CONSENSE consortium meetings were co-localised with events of the annual international SensUs biosensing competition (www.sensus.org). This turned out to be very effective for both CONSENSE and SensUs. One of the results has been the development of a new recurring symposium series: the International Symposium on Continuous Real-time Biomolecular Sensing (CRBS). The 1st and 2nd CRBS editions were co-organised by CONSENSE and SensUs, in 2024 and 2025. The recordings are online available, see https://symposium.sensus.org.

A total of 15 papers were published in peer-reviewed journals, such as ACS Sensors, Advanced Materials, and Science. A total of 15 papers were in the publication process (submitted, under review, in revision, or accepted), of which 9 papers were already published on preprint servers. Another 17 manuscripts were still in preparation. Thus, a total of 47 peer-reviewed publications are expected to come out of the project. About half of the publications were collaborative outputs of two or more beneficiaries within the consortium. One of these publications is an Application White Paper entitled ‘Continuous Biosensing to Monitor Acute Systemic Inflammation, a Diagnostic Need for Therapeutic Guidance’ with co-authorships from 7 CONSENSE partners, published in ACS Sensors, a high-impact journal in the field of biosensing [1].

Four ESRs have successfully defended their PhD thesis, and a further three will be defending their PhD theses within the next three months and will gain their PhD degree. All other ESRs are on a path toward finalizing and defending their PhD theses.

[1] G. Gouveia et al, ACS Sensors (2025), DOI: https://doi.org/10.1021/acssensors.4c02569.

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)

In CONSENSE, results beyond the state-of-the-art have been achieved in all aspects of the CONSENSE programme: biomolecular engineering studies, optical detection research, integrations of biomolecular and optical functionalities, system studies, and demonstrations of time-dependent profiles in cell-based systems. The developed technologies for measuring and understanding the time-dependencies of biosystems are important for achieving progress in fields such as fundamental biology, industrial bioprocessing, and patient monitoring, as explained in our own White Paper [1] and underscored in recent review papers published by other groups [2,3].

The CONSENSE results are expected to have a wider scientific, economic and social impact. The scientific results produced in the project have strengthened the scientific levels, inter-disciplinary approaches, and inter-national collaborations of all network partners, in a field with high economic and societal impact. Several novel technological directions have been developed, based on approaches that were already patented or for which new patents are being applied, which will lead to further development opportunities and translation to society. The company beneficiary (spin-off company) was able to drive its research further and increase its scope of applications, increasing the viability and impact of the company. The 15 CONSENSE ESRs are expected to further contribute to the European innovation space. Notably, three ESRs have found employment in spin-off companies. We conclude that the CONSENSE researchers and the developed technologies have strong potential to make impact on the innovations and the healthcare of the future.

[1] G. Gouveia et al, ACS Sensors (2025), DOI: https://doi.org/10.1021/acssensors.4c02569
[2] J.M. Donnelly et al, Science (2025), DOI: https://doi.org/10.1126/science.ady6497
[3] Y. Liao et al, Materials Horizons (2024), DOI: https://doi.org/10.1039/d4mh01174k

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