Polymeric micro-cantilever sensors for biomedical applications

The invention of atomic force microscopy spurred the development of micro-cantilever-based sensors. Their applications in biomedicine require disposable, low-cost cantilevers for single usage. Polymeric micro-cantilever arrays might be a beneficial alternative to the established silicon-based microstructures which tags a price of about 100 USD per array. The thesis demonstrates that injection-molded polymeric micro-cantilever arrays have characteristics, which compare reasonably well to silicon ones and permit the quantification of medically relevant species. In a first step, cantilevers with micrometer dimensions and aspect ratios as large as 10 were successfully injection molded from polymers including polypropylene and polyvinylidenfluoride. In addition, a hybrid mold concept developed through this work, allowed easy modification of the surface topography leading to a wide range of surface patterned micro-cantilevers. The fabricated micro-cantilevers are gold-coated for optical readout and ease of functionalization. Prior to functionalization, the micro-cantilevers are surface cleaned using ultraviolet-ozone treatment. The effects of the surface cleaning process on the mechanical and chemical stability were systematically studied by varying the exposure time. A process time of 20 min was found suitable as a trade-off between cleaning and stability.
In a second step, the injection molded micro-cantilevers were characterized for their mechanical and morphological properties. Their performance was similar to the established silicon cantilevers with Q-factors in the range of 10-20. Nanoindentation techniques were used to evaluate the elastic modulus of the micro-cantilevers. Synchrotron radiation-based scanning small- and wide-angle X-ray scattering (SAXS, WAXS) techniques were used to quantify crystallinity and anisotropy in polymer micro-cantilevers with micrometer resolution in real space. SAXS measurements confirmed the lamellar nature of the injection-molded semi-crystalline micro-cantilevers showing the expected strong degree of anisotropy along the injection direction. The homogenous cantilever material exhibits a lamellar periodicity increasing with mold temperature but not with injection speed.
In a last step, we demonstrate that polypropylene cantilevers can be used as biosensors for medical purposes in the same manner as the established silicon ones to detect single-stranded DNA sequences and metal ions in real-time. A differential signal of 7 nm was detected for the hybridization of 1 µM complementary DNA sequences. For 100 nM copper ions the differential signal was found to be (36 ± 5) nm. Nano-mechanical sensing of medically relevant, nanometer-size species is essential for fast and efficient diagnosis.
The developed low-cost micro-cantilever arrays adapted to the geometric requirements of the Cantisens platform will significantly widen the spectrum of applications. Rather simple further adaptations to the fabrication process will allow an easy tailoring for their application in other systems. It may result in dedicated bedside systems for the benefit of patients.