Dual-modality field-effect/magnetic immunosensor chip for label-free biomarker detection (FEMIC)

• Applicants: Dr. Corinna Kaulen; Professor Dr. Hans-Joachim Krause; Professor Dr. Michael J. Schöning
• Subject Area: Microsystems ; Biomedical Systems Technology ; Synthesis and Properties of Functional Materials ; Measurement Systems
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445454801

The main objective of the proposed project is the development of a reusable dual-modality field-effect/magnetic immunosensor chip for detection of multiple biomarkers. The semiconductor field-effect platform is very well-suited for label-free electrical detection of biomarkers by their molecular charge, whereas frequency mixing magnetic detection is a contactless technique probing the binding state of magnetic nanoparticles (MNPs). Such a combined immunosensor using two completely different transducer principles will drastically reduce possible false signals and thus, will provide a more reliable detection of target biomarkers. Only if signals recorded by both methods change in expected direction (Boolean logic AND gate), the result will be considered as positive.Advantages provided by the proposed concept include:- easy and low-cost fabrication of immunochips by using a simple immuno-sensitive field-effect capacitor (ImmunoFEC) as transducer;- the use of MNPs not only for magnetic detection but also for capturing and separation of target biomarkers from samples and their concentration on the immunochip surface;- capability for detection of biomarkers in both low- and high-ionic strength samples;- absence of non-specific adsorption of biomolecules on the ImmunoFEC surface because the immunochemical reaction event is separated from the sensing surface;- reusability and possibility of detection of multiple biomarkers using the same immunochip;- acceleration of adsorption of biomarker-antibody-conjugated MNPs by the magnet and a reduced time-to-result.ImmunoFECs modified with MNPs have not been used for label-free detection of protein biomarkers by their intrinsic molecular charge so far. The new approach shall be exemplarily examined for the detection of several clinically relevant biomarkers (e.g., glycated hemoglobin, hemoglobin, C-reactive protein). MNPs stabilized by hydrophilic coatings will be synthesized in different sizes and characterized according to their nonlinear magnetic responses. They will be conjugated with antibodies for specific biomarker detection. Physical and electrochemical characterization of ImmunoFECs will provide information on surface modification with biomarker-antibody-conjugated MNPs and regeneration steps. A theoretical model of how the ImmunoFEC modified with biomarker-antibody-conjugated MNPs works will be developed. Basic working characteristics (sensitivity, detection limit, specificity, reusability, etc.) of the dual-modality immunochip will be systematically studied and compared with theoretical predictions.The proposal might have distinct impact bringing field-effect and magnetic detection principle together for possible future diagnostic tools such as point-of-care applications. The intended collaboration enables target-oriented work on this multidisciplinary approach and combines complementary scientific expertise in a perfect match.

• DFG Programme: Research Grants