Guenther Koppitsch

Optical biosensor technologies for molecular diagnostics at the point-of-care

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.

Integrated optical waveguide and nanoparticle based label-free molecular biosensing concepts

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.

Design and Optimization of High-Channel Si3N4 Based AWGs for Medical Applications

We present the design and optimization of 80-channel, 50-GHz Si3N4 based AWG. The AWG was designed for TM-polarized light with a central wavelength of 850 nm. The simulations showed that, while the standard channel count AWGs (up to 40) feature gut optical properties and are relatively easy to design, increasing the channel counts (> 40 channels) leads to a rapid increase in the AWG size and this, in turn causes the deterioration of optical performance like higher insertion loss and, in particular, higher channel crosstalk. Optimizing the design we are able to design 80-channel, 50-GHz AWG with satisfying optical properties.

Design and simulation of 20-channel 50-GHz Si3N4-based arrayed waveguide grating applying AWG-parameters tool

We present the design of 20-channel, 50-GHz Si3N4 based AWG applying our proprietary AWG-Parameters tool. For the simulations of the AWG layout we used PHASAR photonics tool from Optiwave. The simulated transmission characteristics were then evaluated applying our AWG-Analyzer tool. We studied the influence of one of the design parameters – the separation between input/output waveguides, dx on the channel crosstalk. The results show that there is some minimum waveguide separation necessary to keep the crosstalk between transmitting channels low. The AWGs were designed for TM-polarized light with a central wavelength of 850 nm. They will later be used in a photonic integrated circuit dedicated to medical diagnostic imaging applications.

Preparation of Mach-Zehnder interferometric photonic biosensors by inkjet printing technology

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).

Silicon nitride waveguide integration platform for medical diagnostic applications

The impressive progress of silicon photonic integrated device technology during the past fifteen years has been primarily driven by the requirements of optical data- and telecommunication. Research and development in silicon photonics has therefore been focused on the telecom wavelengths in the 1.55 μm and 1.31 μm regions and on silicon-on-insulator (SOI) material as waveguide integration platform. The rising cost burden of the traditional healthcare system as well as the increasing health consciousness among people is stimulating the decentralization of healthcare and is creating a strong demand for novel medical diagnostic devices suitable for point-of-care testing. This opens up new possibilities for integrated nanophotonic sensing devices operating in the visible and <; 1.1 μm near infrared region. In this talk, we will present our ongoing research activities on the development of a CMOS-compatible photonic integrated circuit technology platform. This platform relies on silicon nitride waveguides fabricated by low-temperature plasma enhanced chemical vapor deposition (PECVD), which allows their monolithic co-integration with silicon photodiodes and CMOS based electronic read-out circuitry. We have achieved propagation losses of less than 1 dB/cm at a wavelength of 850nm in silicon nitride waveguides processed directly on an optoelectronic CMOS chip employing chemical-mechanical planarization (CMP). We will present the design and experimental validation of various nanophotonic building blocks required for the implementation of medical diagnostic sensing devices. We will show results of optical biosensing experiments based on integrated Mach-Zehnder interferometers and demonstrate how inkjet material printing technology can be effectively used to locally functionalize the optical waveguide transducer components. Moreover, we will discuss the potential of this silicon nitride waveguide based nanophotonic integration platform for the miniaturization of optical coherence tomography systems.