Detection and sensing of predictive biomarkers for periodontitis

The project “Biomarker detection and sensing” forms an essential part of Foresight by developing and providing sensors and detection technologies for the periodontitis biobiomarkers identified by the “Experimental discovery” group. The project is chemistry/physics oriented including five partners with highly complementary expertise comprising artificial receptor design, biosensor science and technology and nanoplasmonic sensors.

The Foresight overall approach is based on the identification and validation of predictive molecular biomarkers intimately involved in the disease process. This requires tools to measure them in vivo.  In this project we foresee the development of a sensor platform which will enable their widespread screening and validation paving the way for high quality clinical studies and in extention early detection for rapid chair-side prediction of risk for severe disease. Lacking a priori knowledge of which factor will be of predictive significance (protease activity or specific biomarker levels) we will take a broad approach combining different biomarker recognition principles with different signal transduction principles.

The project will address the following questions:

• Can our nanoplasmonic sensors detect clinically relevant overall or specific protease activity?
• Can our optical or electrochemical MIP based affinity sensors detect clinically relevant levels of gingipains?
• Can affinity and activity sensors be combined in one sensor platform?
• Can we develop affinity sensors capable of detecting clinically relevant levels of host derived biomarkers?

To address these questions the following actions will be taken:

Development of activity sensors

Nanoplasmonic sensors for measurement of protease activity will be developed using either a fiber optic or paper/stick based sensor format to measure changes in the refractive index at the tip of the optical fiber or paper.

Development of MIP affinity sensors

Molecularly imprinted polymer (MIP) affinity sensors for measurement of gingipains Rgp and Kgp or host derived biomarkers will be developed by the contact printing or the nanogel imprinting approach of intact proteins or solvent exposed epitopes. Both optical (fluorescence or nanoplasmonic) or electrochemical (capacitive) signal transduction will be investigated. Combination of affinity and activity sensors will be assessed.

Sensor validation

The sensor prototypes will be validated by benchmarking with other bioassays and provided to the subproject “Verification and clinical validation of biomarkers” for further verification. Verification will here be performed on samples that closely represent individuals in which the clinical risk assessment will be deployed. Candidate biomarker specificity will be assessed in samples from groups of individuals with ‘high risk’ and ‘low risk’, respectively.