Uwe Bog

Low-cost label-free biosensors using photonic crystals embedded between crossed polarizers

There is a strong need for low-cost biosensors to enable rapid, on-site analysis of biological, biomedical, or chemical substances. We propose a platform for label-free optical biosensors based on applying the analyte onto a surface-functionalized photonic crystal slab and performing a transmission measurement with two crossed polarization filters. This dark-field approach allows for efficient background suppression as only the photonic crystal guided-mode resonances interacting with the functionalized surface experience significant polarization rotation. We present a compact biosensor demonstrator using a low-cost light emitting diode and a simple photodiode capable of detecting the binding kinetics of a 2.5 nM solution of the protein streptavidin on a biotin-functionalized photonic crystal surface.

On-chip microlasers for biomolecular detection via highly localized deposition of a multifunctional phospholipid ink

We report on a novel approach to realize on-chip microlasers, by applying highly localized and material-saving surface functionalization of passive photonic whispering gallery mode microresonators. We apply dip-pen nanolithography on a true three-dimensional structure. We coat solely the light-guiding circumference of pre-fabricated poly(methyl methacrylate) resonators with a multifunctional molecular ink. The functionalization is performed in one single fabrication step and simultaneously provides optical gain as well as molecular binding selectivity. This allows for a direct and flexible realization of on-chip microlasers, which can be utilized as biosensors in optofluidic lab-on-a-chip applications. In a proof-of-concept we show how this highly localized molecule deposition suffices for low-threshold lasing in air and water, and demonstrate the capability of the ink-lasers as biosensors in a biotin-streptavidin binding experiment.

Large-Scale Parallel Surface Functionalization of Goblet-type Whispering Gallery Mode Microcavity Arrays for Biosensing Applications

A novel surface functionalization technique is presented for large-scale selective molecule deposition onto whispering gallery mode microgoblet cavities. The parallel technique allows damage-free individual functionalization of the cavities, arranged on-chip in densely packaged arrays. As the stamp pad a glass slide is utilized, bearing phospholipids with different functional head groups. Coated microcavities are characterized and demonstrated as biosensors.

Densely Packed Microgoblet Laser Pairs for Cross-Referenced Biomolecular Detection

Microgoblet laser pairs are presented for cross‐referenced on‐chip biomolecular sensing. Parallel readout of the microlasers facilitates effective mutual filtering of highly localized refractive index and temperature fluctuations in the analyte. Cross‐referenced detection of two different types of proteins and complete chemical transducer reconfiguration is demonstrated. Selective surface functionalization of the individual lasers with high spatial accuracy is achieved by aligned microcontact stamping.

Nanograting transfer for light extraction in organic light-emitting devices

Damage-free transfer of nanogratings as waveguide mode extraction elements onto the top of top-emission organic light-emitting devices(OLEDs) was realized with the assistance of cyclic olefin copolymer molds. Photoluminescence and electroluminescence measurements together with transfer matrix calculations were used to identify the extracted waveguide modes. The presented one-step, wet-free, and etchless nanotransfer approach can avoid damage on the top-emission OLEDstructure and does not adversely affect the OLED performance. It offers the possibility for the independent optimization of OLEDfabrication and nanofabrication, and has potential applications in organic optoelectronic devices, especially top-emission OLEDs.

Design of plasmonic grating structures towards optimum signal discrimination for biosensing applications

Sensors based on surface plasmon resonances (SPRs) have proven themselves as promising devices for molecular investigations - still there is potential to determine the geometrical parameter set for optimal sensing performance. Here we propose a comprehensive design rule for one-dimensional plasmonic grating structures. We present an analytical approach, which allows for estimation of the grating parameters for best SPR coupling efficiency for any geometry and design wavelength. On the example of sinusoidal gratings, we expand this solution and discuss numerically and experimentally, how the grating modulation depth can be refined to achieve optimal signal resolution. Finally, we propose a benchmark factor to assess the sensor performance, which can be applied to any sensing scheme utilizing resonances, allowing for comparison of different technological platforms.

Clickable Antifouling Polymer Brushes for Polymer Pen Lithography

Protein-repellent reactive surfaces that promote localized specific binding are highly desirable for applications in the biomedical field. Nonspecific adhesion will compromise the function of bioactive surfaces, leading to ambiguous results of binding assays and negating the binding specificity of patterned cell-adhesive motives. Localized specific binding is often achieved by attaching a linker to the surface, and the other side of the linker is used to bind specifically to a desired functional agent, as e.g. proteins, antibodies, and fluorophores, depending on the function required by the application. We present a protein-repellent polymer brush enabling highly specific covalent surface immobilization of biorecognition elements by strain-promoted alkyne-azide cycloaddition click chemistry for selective protein adhesion. The protein-repellent polymer brush is functionalized by highly localized molecular binding sites in the low micrometer range using polymer pen lithography (PPL). Because of the massive parallelization of writing pens, the tunable PPL printed patterns can span over square centimeter areas. The selective binding of the protein streptavidin to these surface sites is demonstrated while the remaining polymer brush surface is resisting nonspecific adsorption without any prior blocking by bovine serum albumin (BSA). In contrast to the widely used BSA blocking, the reactive polymer brushes are able to significantly reduce nonspecific protein adsorption, which is the cause of biofouling. This was achieved for solutions of single proteins as well as complex biological fluids. The remarkable fouling resistance of the polymer brushes has the potential to improve the multiplexing capabilities of protein probes and therefore impact biomedical research and applications.

Integrated photonic lab-on-chip systems for biomedical applications

Currently, one may find a wide variety of approaches for integrated lab-on-chip systems developed for applications in the biomedical field. Our contributions within the area of polymer based photonic systems are presented here. We are utilizing mass production techniques and head for lab-on-a-chip systems with solely optical and fluidic interfaces, avoiding electrical interconnects. Fluidic structures are implemented in the chips mainly by using the same technologies, which are chosen to create the optical elements. While photonic structures may require dimensions in the sub-100 nm range, microfluidic channels are more than one order of magnitude above this regime. Nevertheless, our approach allows for a limited number of process steps by simultaneous multiscale fabrication. Organic semiconductor lasers are generated by evaporating a thin film of photoactive material on top of a distributed feedback (DFB) grating. Gratings are replicated by hot embossing into poly(methyl methacrylate) (PMMA) bulk material. The lasing wavelength in the visible light regime of the on-chip lasers is selected by altering the thickness of the vacuum deposited organic semiconductor active material or the DFB grating period. Waveguides are monolithically integrated in PMMA via photodegradation through deep ultraviolet irradiation. The coupling of laser light into these waveguides is optimized. Hence, laser light is guided to an interaction zone with a biological sample in the microfluidic channel on chip. Micro-optical cavities are designed and processed to be functionalized for detecting biological binding events in the channel. Surface functionalization, e.g. by Dip-Pen Nanolithography, is carried out for integrated label-free detection as well as for fluorescence excitation.

Site‐Specific Surface Functionalization via Microchannel Cantilever Spotting (µCS): Comparison between Azide–Alkyne and Thiol–Alkyne Click Chemistry Reactions

Different types of click chemistry reactions are proposed and used for the functionalization of surfaces and materials, and covalent attachment of organic molecules. In the present work, two different catalyst-free click approaches, namely azide-alkyne and thiol-alkyne click chemistry are studied and compared for the immobilization of microarrays of azide or thiol inks on functionalized glass surfaces. For this purpose, the surface of glass is first functionalized with dibenzocyclooctyne-acid (DBCO-acid), a cyclooctyne with a carboxyl group. Then, the DBCO-terminated surfaces are functionalized via microchannel cantilever spotting with different fluorescent and nonfluorescent azide and thiol inks. Although both routes work reliably for surface functionalization, the protein binding experiments reveal that using a thiol-alkyne route will obtain the highest surface density of molecular immobilization in such spotting approaches. The obtained achievements and results from this work can be used for design and manufacturing of microscale patterns suitable for biomedical and biological applications.

Polymer Pen Lithography with Lipids for Large-Area Gradient Patterns

Gradient patterns comprising bioactive compounds over comparably (in regard to a cell size) large areas are key for many applications in the biomedical sector, in particular, for cell screening assays, guidance, and migration experiments. Polymer pen lithography (PPL) as an inherent highly parallel and large area technique has a great potential to serve in the fabrication of such patterns. We present strategies for the printing of functional phospholipid patterns via PPL that provide tunable feature size and feature density gradients over surface areas of several square millimeters. By controlling the printing parameters, two transfer modes can be achieved. Each of these modes leads to different feature morphologies. By increasing the force applied to the elastomeric pens, which increases the tip-surface contact area and boosts the ink delivery rate, a switch between a dip-pen nanolithography (DPN) and a microcontact printing (μCP) transfer mode can be induced. A careful inking procedure ensuring a homogeneous and not-too-high ink-load on the PPL stamp ensures a membrane-spreading dominated transfer mode, which, used in combination with smooth and hydrophilic substrates, generates features with constant height, independently of the applied force of the pens. Ultimately, this allows us to obtain a gradient of feature sizes over a mm2 substrate, all having the same height on the order of that of a biological cellular membrane. These strategies allow the construction of membrane structures by direct transfer of the lipid mixture to the substrate, without requiring previous substrate functionalization, in contrast to other molecular inks, where structure is directly determined by the printing process itself. The patterns are demonstrated to be viable for subsequent protein binding, therefore adding to a flexible feature library when gradients of protein presentation are desired.