Periodic Reporting for period 1 - ImplantSens (Mass-transfer independent long-term implantable biosensors)
Période du rapport: 2019-04-01 au 2021-03-31
The objective of ImplantSens is to empower the next generation of scientists and entrepreneurs with multi¬disciplinary training in the framework of implantable biosensors, a topic of fundamental interest for the future of Europe. Accurate, long-term in vivo measurement of biochemical analytes, such as glucose, remains a significant challenge because the body represents a very hostile environment for a biosensor. 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 gradual loss of the function of the implanted biosensor.
In a biosensor we usually have an active sensor layer, comprising of one or more enzymes producing a terminal product which can be detected by 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 to the implanted sensor. The signal will decrease over time due to the inevitable changes of the mass transport properties of all the layers separating the sensor compartment from the analyte reservoir.
Hence, the ultimate question that has to be answered of 11 ESRs of ImplantSens is: How it is possible to measure the analyte concentration within the sensor compartment under condition such that the concentration gradient is equilibrated and no net diffusional flux occurs? Under these conditions, the concentration inside the sensor compartment and in the analyte reservoir will be equal and independent of the diffusional restrictions imposed by encapsulation of the sensor.
The beneficiaries of the consortium consist of 8 internationally recognized research groups from 5 European countries as well as 3 SMEs from 3 European countries. In building this consortium complementary scientific excellence was essential to gain the interdisciplinary basis to solve the inherent problems encountered in developing long-term stable implantable electrochemical biosensors.
The research program is divided in 7 workpackages which define overarching scientific questions with cross-disciplinary participation of the ESRs in order to offer a broad scientific training programm. The network offers 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 will be 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 a biosensor we usually have an active sensor layer, comprising of one or more enzymes producing a terminal product which can be detected by 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 to the implanted sensor. The signal will decrease over time due to the inevitable changes of the mass transport properties of all the layers separating the sensor compartment from the analyte reservoir.
Hence, the ultimate question that has to be answered of 11 ESRs of ImplantSens is: How it is possible to measure the analyte concentration within the sensor compartment under condition such that the concentration gradient is equilibrated and no net diffusional flux occurs? Under these conditions, the concentration inside the sensor compartment and in the analyte reservoir will be equal and independent of the diffusional restrictions imposed by encapsulation of the sensor.
The beneficiaries of the consortium consist of 8 internationally recognized research groups from 5 European countries as well as 3 SMEs from 3 European countries. In building this consortium complementary scientific excellence was essential to gain the interdisciplinary basis to solve the inherent problems encountered in developing long-term stable implantable electrochemical biosensors.
The research program is divided in 7 workpackages which define overarching scientific questions with cross-disciplinary participation of the ESRs in order to offer a broad scientific training programm. The network offers 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 will be 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.
ImplantSens has already made substantial progress, to date, all envisaged deliverables and milestones have been reached. ImplantSens has already developed glucose-converting redox enzymes that have been optimised concerning the stability and activity. A method for electrochemically switching on and off enzymatic glucose conversion was developed and suitable redox polymers for co-immobilising the enzymes on nanometre-sized electrodes were synthesised. This has been integrated into a sensor architecture which was successfully tested. Several electrode types with different morphology have been prepared and it has been demonstrated that immobilisation of enzymes on porous electrode materials is possible. An optimisation strategy of the electrode to improve sensor performance has been developed together with a modelling system. Test apparatus for working under homeostatic conditions have been established and first studies on the biocompatibility of enzymes and hydrogels have started. All fellows received training in scientific and generic skills at their host institutes as well as via virtual network events.
All fellows are still in the first half of their PhD thesis. The impact, however, on their life may be already significant. They all had to leave their home country and experienced new culture, language, colleagues etc. Due to the Covid19 crisis the fellows are affected through constrained travel arrangements, both local and international, hampering initial adjustment to the new local environment (professional, social and cultural). ImplantSens instigated alternate network arrangements with contacts via email, phone, and video conference among the fellows and supervisors. In addition, the fellows have all participated in an online-workshop on team building not only to build-up a strong and sustainable network but also to help them to navigate the current situation.
Not only the fellows of ImplantSens but also the supervisors had to adapt to the pandemic situation and had to apply predominantly digital tools to train, supervise, discuss, present and manage which will certainly impact on future activities.
The supervisory board decided to accept so-called associated fellows, PhD students of the beneficiaries, who are at the same level of experience and are working in a similar scientific area as the ImplantSens fellows. Two associated fellows have been nominated, who are already part of the network. Therefore, the ImplantSens network is not only strengthened amongst the fellow, but also expanding.
We anticipate further progress in the development and evaluation of implantable sensors with more focus on the switching capabilities of enzymes and evaluation of the developed sensors.
Not only the fellows of ImplantSens but also the supervisors had to adapt to the pandemic situation and had to apply predominantly digital tools to train, supervise, discuss, present and manage which will certainly impact on future activities.
The supervisory board decided to accept so-called associated fellows, PhD students of the beneficiaries, who are at the same level of experience and are working in a similar scientific area as the ImplantSens fellows. Two associated fellows have been nominated, who are already part of the network. Therefore, the ImplantSens network is not only strengthened amongst the fellow, but also expanding.
We anticipate further progress in the development and evaluation of implantable sensors with more focus on the switching capabilities of enzymes and evaluation of the developed sensors.