Inkjet printing is a versatile method to apply surface modification procedures in a spatially controlled, cost-effective and mass-fabrication compatible manner. Utilizing this technology, we investigate two different approaches for functionalizing label-free optical waveguide based biosensors: a) surface modification with amine-based functional polymers (biotin-modified polyethylenimine (PEI-B)) employing active ester chemistry and b) modification with dextran based hydrogel thin films employing photoactive benzophenone crosslinker moieties. Whereas the modification with PEI-B ensures high receptor density at the surface, the hydrogel films can serve both as a voluminous matrix binding matrix and as a semipermeable separation layer between the sensor surface and the sample. We use the two surface modification strategies both individually and in combination for binding studies towards the detection of the protein inflammation biomarker, C-reactive protein (CRP). For the specific detection of CRP, we compare two kinds of capture molecules, namely biotinylated antibodies and biotinylated CRP-specific DNA based aptamers. Both kinds of capture molecules were immobilized on the PEI-B by means of streptavidin-biotin affinity binding. As transducer, we use an integrated four-channel silicon nitride (Si3N4) waveguide based Mach-Zehnder interferometric (MZI) photonic sensing platform operating at a wavelength of 850nm (TM-mode).
Label-free optical schemes for molecular biosensing hold a strong promise for point-of-care applications in medical research and diagnostics. Apart from diagnostic requirements in terms of sensitivity, specificity, and multiplexing capability, also other aspects such as ease of use and manufacturability have to be considered in order to pave the way to a practical implementation. We present integrated optical waveguide as well as magnetic nanoparticle based molecular biosensor concepts that address these aspects. The integrated optical waveguide devices are based on low-loss photonic wires made of silicon nitride deposited by a CMOS compatible plasma-enhanced chemical vapor deposition (PECVD) process that allows for backend integration of waveguides on optoelectronic CMOS chips. The molecular detection principle relies on evanescent wave sensing in the 0.85 μm wavelength regime by means of Mach-Zehnder interferometers, which enables on-chip integration of silicon photodiodes and, thus, the realization of system-on-chip solutions. Our nanoparticle-based approach is based on optical observation of the dynamic response of functionalized magneticcore/ noble-metal-shell nanorods (‘nanoprobes’) to an externally applied time-varying magnetic field. As target molecules specifically bind to the surface of the nanoprobes, the observed dynamics of the nanoprobes changes, and the concentration of target molecules in the sample solution can be quantified. This approach is suitable for dynamic real-time measurements and only requires minimal sample preparation, thus presenting a highly promising point-of-care diagnostic system. In this paper, we present a prototype of a diagnostic device suitable for highly automated sample analysis by our nanoparticle-based approach.
We present our developments on integrated optical waveguide based as well as on magnetic nanoparticle based label-free
biosensor concepts. With respect to integrated optical waveguide devices, evanescent wave sensing by means of Mach-
Zehnder interferometers are used as biosensing components. We describe three different approaches: a) silicon photonic
wire waveguides enabling on-chip wavelength division multiplexing, b) utilization of slow light in silicon photonic
crystal defect waveguides operated in the 1.3 μm wavelength regime, and c) silicon nitride photonics wire waveguide
devices compatible with on-chip photodiode integration operated in the 0.85 μm wavelength regime. The nanoparticle
based approach relies on a plasmon-optical detection of the hydrodynamic properties of magnetic-core/gold-shell
nanorods immersed in the sample solution. The hybrid nanorods are rotated within an externally applied magnetic field
and their rotation optically monitored. When target molecules bind to the surfaces of the nanorods their hydrodynamic
volumes increase, which directly translates into a change of the optical signal. This approach possesses the potential to
enable real-time measurements with only minimal sample preparation requirements, thus presenting a promising point-of-
care diagnostic system.