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

Periodic Reporting for period 1 - CONSENSE (A game change in continuous biosensing: Molecularly engineered affinity-based nanoswitches for personal monitoring)

Okres sprawozdawczy: 2021-03-01 do 2023-02-28

Healthcare is in demand of real-time sensing technologies to continuously guard the state of patients based on real-time, precise, and reliable data. Sensors for patient monitoring are well known, e.g. sensors for monitoring heart rate, muscle actions, electrocardiography (ECG), body temperature, blood pressure, and respiratory rate. However, these sensors all rely on physical effects rather than on the underlying biomolecular processes. The ability to continuously monitor biomolecular parameters such as peptides, proteins, and nucleic acids has the potential to revolutionise health care for continuous monitoring of disease status and treatment effects. Novel generic biosensor technologies are needed for the continuous monitoring of biomarkers at nanomolar to picomolar concentrations for the monitoring of disease status and treatment effects, particularly in the field of medical immunology.

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 large and robust 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).
In the first two years of the project, 15 ESRs were hired and started working on their projects in innovative continuous biosensing. The work in WP1 covered the development of efficient methodologies to design and isolate molecular binders, developing strategies to make functional constructs with proteins and nucleic acids, and developing competitive and sandwich-type measurement formats. The work in WP2 addressed the development of optical sensing platforms suitable for nanoswitches and continuous biosensing, focussing 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 biosensors, with a focus on demonstrator systems and in vitro cell-based model systems of the human immune response to be able to validate developed monitoring technologies.

The ESRs further received training through their local PhD programmes and four network-wide training events. Due to travel restrictions caused by the COVID-19 pandemic, most of the network-wide events were organised in a hybrid format. The ESRs received training in scientific, transferable and business skills. Furthermore, some of the ESRs could already go on their first secondment, strengthening collaboration between the network partners while progressing in their research projects.

The network also implemented the first communication and dissemination activities with the strong involvement of the ESRs. The CONSENSE website (www.consense-itn.eu) was established early in the project and has since been further developed with regular contributions from the ESRs. The Outreach Support Team, formed by five ESRs, has established a Twitter account and regularly shares relevant content through these channels. The ESRs have also contributed to various national and international conferences.
Preliminary results in RP1 show progress in developing continuous biosensing approaches for biomolecular monitoring and outline how integrated solutions may impact the fields of healthcare and industry. Continuous biosensing will give information not only on relative concentrations of biomarkers but also on the rate at which they change, which would become valuable for distinguishing different disease stages/types, personalised treatments, and monitoring-and-control applications. In the next period, CONSENSE will continue the training of ESRs and the multidisciplinary research efforts toward developing sensing concepts, technological innovations, and validation methodologies.
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