Ultra-robust, flexible organic sensors for application in lactic acid sensing and selective biosensing

Periodic Reporting for period 2 - Robust OTFT sensors (Ultra-robust, flexible organic sensors for application in lactic acid sensing and selective biosensing)

Période du rapport: 2018-07-01 au 2019-06-30

The overall objective of this project is the development of novel, highly-stable sensors architectures based on semiconducting polymers that are cheaper and more capable than their inorganic counterpart. The goal is to make true use of organic semiconductor’s unique properties as a soft and stretchable material for the application in reliable biosensors for wearable health monitoring and personalized medical applications.

- One example is the development of sweat sensors for constant monitoring of patients' cortisol concentration which is indicative of their psychological health and varies greatly between patients and throughout the day. Cortisol is linked to psychological illnesses such as depression and a constant monitoring can allow for a targeted and personalized treatment with targeted drug delivery. So far this constant monitoring is not possible since tests can only be done in a laboratory.

- Another example is the use of biosensors for the screening for DNA/RNA for a fast detection and screening of cancer. An array of biosensors could greatly simplify the tests making it more viable and easier to test a larger number of patients at a higher frequency

The objective of this project is the development of a sensors architecture that can be produced cheaply and can be modified for targeted sensing of the above-mentioned analytes (cortisol, RNA etc.). Here the main goal is to develop a platform that exhibits long time stability such that it can record and monitor small signals induced by the binding of a bio-molecule reliably over the course of days. For some applications such as cortisol sensing it is furthermore desirable to have the sensor in close contact witht he human skin (i.e. for skin patches that can monitor the concentration of an analyte over the course of hours or even days) and therefore it is desirable to make the architecture flexible and if possible, stretchable.

Conclusion of the action: Over the course of the action, a new sensor was developed that can reliably sense biomarkers which are relevant for long-term health monitoring applications. It was possible to develop a new transistor-based sensor, that is showing stable operation in biological solutions and detect small concentrations of sample biomarkers reliably and selectively (The latter is a great challenge in the field of biosensing). The new architecture opens up a range of possibilities for the use in human healthcare, monitoring of health conditions (such as detecting, and monitoring biomarkers associated with depression) and has the potential to be used to record vital signs (such as in ECG electrodes).

During the outgoing phase of the Fellowship, a new sensors architecture was designed that has the potential to address the above-mentioned objectives. The project work led to the discovery of a intrinsically and fully stretchable polymer semiconductor that can operate without a loss of performance even when exposed to strains >50%. This is a significant finding and has implications beyond the original project scope. The results are novel and have significant impact in the community and beyond such that they are currently submitted for publication. The new polymer class described above could be used in a newly developed sensor architecture that is based on a transistor design with a polar, ionic elastomer dielectric which is highly stable in analyte solutions (such as water, biological buffer solutions). The polar dielectric forms an electric double layer making it highly sensitive while simultaneously encapsulating the device against the analyte solution. By specific functionalization, the design can be made highly selective to specific analytes such as proteins, RNA, DNA, PH etc. with long term stability enabling health monitoring applications. The long-term stability of the architecture has been demonstrated and its functionality as a sensor has been shown with the proof of concept protein BSA.

During the return phase, the architecture has been further optimized and a range of stability and reliability checks have been conducted. The architecture is now capable of reliably detecting biomarkers in various environments with a sensitivity of 1mV. The next step represents the use of the designed architecture for the sensing of cortisol, which is currently done in continous cooperation with Stanford University. The results achieved thus far, are currently being prepared for publication. Further follow up results based on the designed architecture are expected over the next years.

The new architecture developed within the framework of this Marie-Curie Fellowship offers a powerful tool for the selective sensing of analytes. This is one of the key challenges in the research field of biosensing and a big step towards higher reliability. Here, the use of an elastomer ionic dielectric overcomes these selectivity issues while simultaneously allowing for a maximum signal amplification. The new platform additionally offers long-term stability needed for real-world applications beyond the research laboratory environment as well as flexibility and stretchability needed for wearable skin patches and health monitors. Integrated within the bigger framework of wearable and personalized health applications, the sensor design can tap into research done on surface modification and functionalization for improving the selectivity to relevant analytes for real world health applications. In this respect the newly established collaboration between Stanford University and the University of Cambridge profs to be extremely helpful. The research is therefore expected to have a broader impact in the development of real-world personalized medical applications such as the monitoring of psychological health or the quick and cheap screening for cancer biomarkers and currently work is under way to test these potential applications.

Update at the end of the project: It has been possible to design and optimize a new, flexible biosensing architecture that is selective only to specific analytes. This has been a substantial challenge so far, as most current generation sensors are limited in their selectivity. This is because these devices are sensitive to influences other than those that should be detected (such as a change in the buffer conditions of a solution or biological liquid such as sweat or blood). The sensor developed in this project is only responsive to capacitance changes caused by the binding of a charged analyte but does not respond to any other influences. This could be demonstrated reliably towards the end of the action. The architecture furthermore, shows record stability and does not degrade even over extended periods of several days/weeks. This is enabled by combining a new ionic dielectric layer with a highly stable semiconductor and an entirely newly developed architecture. As such, the reported design exceeds the current state-of-the art devices in both their selectivity as well as stability and can directly be used in on-skin applications such as sweat sensing. This will enable new opportunities in health monitoring of biomarkers and disease agents in the future. Additionally, there is scope for developing this sensor into a new type of ECG electrode which can monitor vital signs far more accurately than the state of the art. This will form the scope of a follow-up project of the action.

Novel biosensor architecture and response to sensing BSA protein

Periodic Reporting for period 2 - Robust OTFT sensors (Ultra-robust, flexible organic sensors for application in lactic acid sensing and selective biosensing)

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