Development of a cantilever sensor chip as a point-of-care (POC) device for label-free, rapid, and multiplexed detection of cancer protein biomarkers

• Applicant: Professor Dr.-Ing. Gerald A. Urban, since 6/2014
• Subject Area: Microsystems ; Medical Physics, Biomedical Technology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 244492497

High-throughput identification and quantitative detection of disease-specific protein biomarkers forms the foundation of many diagnostic tests to direct therapy in diverse area of clinical medicine such as cancer. Various protein detection platforms have been developed to provide a multi-analytes, specific, and sensitive assay; among them the enzyme-linked immunosorbent assay (ELISA) is a golden standard. While the label-based techniques are widely utilized in those platforms for signal transduction, the label incorporation itself can be highly heterogeneous and the labeling procedure is laborious, lengthy, and adds significant cost and time for development. Therefore, there is great interest in developing label-free techniques for biological analysis. Micro/nano-cantilever-based sensors have been considered as one of the most promising label-free techniques because of the simple and efficient sensing mechanism by translating molecular interactions into mechanics. By utilizing a change in contact angle of a liquid meniscus on a solid surface through molecular interactions such as antigen-antibody binding, we could show that a tiny molecular interaction force is converted to a capillary force-a much larger physical quantity. This physical phenomenon could be served not only as a new mechanism for label-free protein detection but also as a practical method for a sensing platform design. We have previously demonstrated a cantilever sensor design by utilizing such a sensing mechanism for a label-free protein immunoassay with detection limit as low as 1 pg/mL and a short detection time within 10 minutes. In this project we will further investigate (i) new surface modification strategies for efficient molecular recognition as well as surface passivation, (ii) new cantilever design and fabrication process to improve the signal-to-noise ratio and linear dynamic range of sensor, and (iii) integrated microfluidics for sample processing on a single sensor chip for label-free, rapid, and multiplexed detection of cancer protein biomarkers. The proposed sensor chip design leads to the construction of an easy-to-use immunosensing platform intended for facile handling, minimal sample/reagent requirements and compatibility with diverse biomarkers. Biological samples from cancer patients are planned to be applied to the sensor chip to detect a panel of 5 cancer protein biomarkers, in an effort to provide a point-of-care (POC) test alternative to current centralized testing for biomarkers.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Thomas Brabletz
• Ehemaliger Antragsteller: Dr. Tsung-I Yin, until 6/2014