Periodic Reporting for period 2 - ImplantSens (Mass-transfer independent long-term implantable biosensors)
Période du rapport: 2021-04-01 au 2023-09-30
The objective of ImplantSens was to empower the next generation of scientists and entrepreneurs with multi-disciplinary training in the research area of implantable biosensors, a topic of fundamental interest for the future of Europe. Accurate, long-term in vivo measurements of bio-analytes such as glucose remain a until-now not solved challenge due to the hostile environment the body creates for any implanted foreign body. Device implantation triggers a cascade of inflammatory responses in the body as it responds to the presence of the implanted sensor. In the final stage of this response, the implant becomes encapsulated by a vascular and collagenous capsule which leads to the gradual loss of the function of the implanted biosensor and, most importantly, to a constant modulation of the diffusional flux of the analyte towards the sensor surface.
A biosensor usually comprises an active sensor layer, consisting of one or more enzymes producing a terminal product that can be detected at the chosen transducer. The generated signal depends on the amount and activity of the immobilized enzyme and the concentration of the analyte at the site of the enzyme which, in turn, is a function of the concentration gradient between the analyte reservoir and sensor compartment as well as the diffusional mass transport towards the sensing layer. This diffusional mass transport is modulated by the formation of additional semi-permeable layers such as the encapsulation layers formed by the foreign body response. The signal will decrease over time due to the inevitable changes in the mass transport properties of all the layers separating the sensor compartment from the analyte reservoir.
Hence, the ultimate question that had to be addressed by the 11 ESRs of ImplantSens is: How is it possible to measure the analyte concentration within the sensor compartment under conditions such that the concentration gradient is equilibrated and no net diffusional flux occurs?
The beneficiaries of the consortium consisted of 11 internationally recognized research groups and industrial partners from 7 European countries. In building this consortium complementary scientific excellence was essential to provide the required interdisciplinary basis to solve the inherent problems encountered in developing long-term stable implantable electrochemical biosensors.
The research program was divided into 7 work packages that defined overarching scientific questions with cross-disciplinary participation of the ESRs to provide a broad scientific training program. The network offered a sophisticated additional training program based on a blended learning concept composed of local, network, and e-learning elements which is far beyond what is typically offered in a graduate program at a university. The technical and scientific training was complemented with comprehensive training in science communication, effective public engagement, creative thinking, entrepreneurship, and self-development to enable the exploitation of the scientific output while guaranteeing wide dissemination of the generated knowledge as well as preparing the fellows for future challenges.
A biosensor usually comprises an active sensor layer, consisting of one or more enzymes producing a terminal product that can be detected at the chosen transducer. The generated signal depends on the amount and activity of the immobilized enzyme and the concentration of the analyte at the site of the enzyme which, in turn, is a function of the concentration gradient between the analyte reservoir and sensor compartment as well as the diffusional mass transport towards the sensing layer. This diffusional mass transport is modulated by the formation of additional semi-permeable layers such as the encapsulation layers formed by the foreign body response. The signal will decrease over time due to the inevitable changes in the mass transport properties of all the layers separating the sensor compartment from the analyte reservoir.
Hence, the ultimate question that had to be addressed by the 11 ESRs of ImplantSens is: How is it possible to measure the analyte concentration within the sensor compartment under conditions such that the concentration gradient is equilibrated and no net diffusional flux occurs?
The beneficiaries of the consortium consisted of 11 internationally recognized research groups and industrial partners from 7 European countries. In building this consortium complementary scientific excellence was essential to provide the required interdisciplinary basis to solve the inherent problems encountered in developing long-term stable implantable electrochemical biosensors.
The research program was divided into 7 work packages that defined overarching scientific questions with cross-disciplinary participation of the ESRs to provide a broad scientific training program. The network offered a sophisticated additional training program based on a blended learning concept composed of local, network, and e-learning elements which is far beyond what is typically offered in a graduate program at a university. The technical and scientific training was complemented with comprehensive training in science communication, effective public engagement, creative thinking, entrepreneurship, and self-development to enable the exploitation of the scientific output while guaranteeing wide dissemination of the generated knowledge as well as preparing the fellows for future challenges.
In WP1 and WP2, enzymes with high stability and activity were developed, which are suitable for switching the enzyme activity between an ON and an OFF state. Selected enzymes were further tested in new sensor architectures. In WP3, sensor architectures for electrochemically induced switching of immobilized enzymes were designed. A method for electrochemical switching of the enzymatic glucose conversion was developed, suitable redox polymers for co-immobilizing the enzymes on nanometre-sized electrodes were synthesized, and the sensor architecture was successfully tested. The synthesized redox polymers are available and were distributed within the consortium.
WP4 focused on the development of macroporous, mesoporous, and nanoband electrodes. Several electrode types with different morphology have been prepared. Immobilisation of enzymes on these surfaces and optimisation of enzyme immobilisation was accomplished. In WP5 the performance of the sensor architectures was analysed and optimised. Moreover, modeling of the substrate concentration within the redox polymer/enzyme hydrogel was performed, providing insight into the complexity of mass-transport processes in switchable biosensors. A variety of different sensor architectures were further tested with respect to their long-term stability and biocompatibility (WP6 and WP7) and test systems for working under homeostatic conditions have been established.
WP8 includes the training activities of ImplantSens consisting of a combination of local training and network training. All planned training activities have been delivered through online and on-site events. WP9 deals with the management tasks of ImplantSens whereas WP10 summarizes all dissemination activities. Our ESRs have not only presented their research in various outreach activities but also participated in scientific events with 46 contributions and published 25 peer-reviewed papers.
WP4 focused on the development of macroporous, mesoporous, and nanoband electrodes. Several electrode types with different morphology have been prepared. Immobilisation of enzymes on these surfaces and optimisation of enzyme immobilisation was accomplished. In WP5 the performance of the sensor architectures was analysed and optimised. Moreover, modeling of the substrate concentration within the redox polymer/enzyme hydrogel was performed, providing insight into the complexity of mass-transport processes in switchable biosensors. A variety of different sensor architectures were further tested with respect to their long-term stability and biocompatibility (WP6 and WP7) and test systems for working under homeostatic conditions have been established.
WP8 includes the training activities of ImplantSens consisting of a combination of local training and network training. All planned training activities have been delivered through online and on-site events. WP9 deals with the management tasks of ImplantSens whereas WP10 summarizes all dissemination activities. Our ESRs have not only presented their research in various outreach activities but also participated in scientific events with 46 contributions and published 25 peer-reviewed papers.
ImplantSens aimed to educate a group of young scientists with the potential to successfully work in academic and non-academic environments via the combination of timely research and an innovative training programme. Working together on this project had a tremendous impact not only on the participating ESRs but also on their supervisors and host institutions.
Through the combination of local training and network training through online and on-site events, we were able to deliver all planned training activities to our fellows and to finally educate a group of young scientists with the potential to successfully work in academia and non-academic environments. The scientific training of the fellows was complemented by courses on transferable skills including scientific communication, creative thinking, management, and leadership, which are considered to be crucial for a successful future career in the academic and/or industrial sector. The active involvement of ESRs in the organization of the training and networking events served as an ideal opportunity for the development of management and organizational skills. The training program also provided ESRs with training in important entrepreneurial skills as well as knowledge of intellectual property rights. The close contact with industry, combined with internationally competitive research prepared them for future employment in the public and private sectors. Finally, the multinational and interdisciplinary interaction between the groups of ImplantSens improved remarkably the cross‐cultural and social competencies of the ESRs. This complementary training improves the career prospects of all ESRs and adds significantly to their employability. 6 fellows already finished their PhD and are currently working as scientists at universities and chemical companies; we expect the others to finalize their PhD within the next year.
All participating host institutions and the ESRs’ supervisors gained significant in-house experience and intellectual property which ensures competitive future research in their field of expertise. The interdisciplinary research within ImplantSens opened new collaborations and the opportunity for further joint research projects.
Especially the participating companies benefited in several ways from ImplantSens itself as well as from the dissemination activities within the project.
Through the combination of local training and network training through online and on-site events, we were able to deliver all planned training activities to our fellows and to finally educate a group of young scientists with the potential to successfully work in academia and non-academic environments. The scientific training of the fellows was complemented by courses on transferable skills including scientific communication, creative thinking, management, and leadership, which are considered to be crucial for a successful future career in the academic and/or industrial sector. The active involvement of ESRs in the organization of the training and networking events served as an ideal opportunity for the development of management and organizational skills. The training program also provided ESRs with training in important entrepreneurial skills as well as knowledge of intellectual property rights. The close contact with industry, combined with internationally competitive research prepared them for future employment in the public and private sectors. Finally, the multinational and interdisciplinary interaction between the groups of ImplantSens improved remarkably the cross‐cultural and social competencies of the ESRs. This complementary training improves the career prospects of all ESRs and adds significantly to their employability. 6 fellows already finished their PhD and are currently working as scientists at universities and chemical companies; we expect the others to finalize their PhD within the next year.
All participating host institutions and the ESRs’ supervisors gained significant in-house experience and intellectual property which ensures competitive future research in their field of expertise. The interdisciplinary research within ImplantSens opened new collaborations and the opportunity for further joint research projects.
Especially the participating companies benefited in several ways from ImplantSens itself as well as from the dissemination activities within the project.