Entwicklung eines Cantilever-basierten Sensorchips für einen label-freien, Multiplex-Schnelltest zur Detektion von Protein-Biomarkern zur Krebserkennung
Medizinische Physik, Biomedizinische Technik
Zusammenfassung der Projektergebnisse
The aim of this project was to develop a cantilever sensor chip as a point-of-care (POC) device for label-free, rapid, and multiplexed detection of cancer protein biomarkers. Based on preliminary works, a new cantilever designs, surface modification strategies, and integrated microfluidics on a single sensor chip should be designed and realized. The proposed application aims for an easy-to-use immunosensor platform featuring easy handling, minimal sample/reagent requirements and ability to detect biomarkers. The transduction principle of this immunosensor is based on a force measurement with microcantilevers exploiting the contact angle principle. The deflection force acting onto a microcantilever is greatly enhanced by a liquid meniscus across a small slit around the cantilever. Microfluidic channels can be utilized to expose one sensing cantilever in a full bridge layout to the analyte, while a reference cantilever only measures background signals, e.g. change in temperature. The resulting resistance change due to piezoresistive effects can be measured. Another option is to selectively equip one cantilever with an immobilization layer, where binding events can occur and not on the reference cantilever, to generate a differential signal. In our chip layout, we included seven full bridge microcantilever structures per chip for possible parallelized or multiparametric measurement. We realized the microcantilever fabrication with a silicon-based, wafer-level clean room fabrication process. In contrast to previous approaches, no CMOS-compatible or silicon-on-insulator technology and processing was used in order to keep fabrication more simple and cost-efficient, which is more suitable for a disposable bioanalytical device. The microcantilevers were released by XeF2 etching, resulting in a closed-back variant reducing the danger of the meniscus breaking and liquid leaking behind the cantilever. With this technological approach we achieved comparable signal quality to other systems which utilized an integrated CMOS pre-amplifier on chip. Hereby, we reduced not only the complexity and thus cost of the chip, but also used only off-the-shelf instrumentation, which is relevant for application of a bioanalytical device. Integration of the cantilever chips with a microfluidic measurement cell allowed the characterization of microcantilevers as a transduction principle for bio-/immunosensors. However, based on these findings, it is questionable whether it is possible to achieve a sensitivity sufficient for the immunosensing application.
Projektbezogene Publikationen (Auswahl)
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Microfluidic microcantilever array sensor platform for real-time detection of binding processes in bioanalytics, 28th Anniversary World Congress on Biosensors, Miami, FL, USA, 2018
A. Weltin, J. Kieninger, G. A. Urban
