Although much is known about chemotaxis- induced by gradients of soluble chemical cues - the molecular mechanisms involved in haptotaxis (migration induced by substrate-bound protein gradients) are largely unknown. We used micropatterning to produce discontinuous gradients consisting of μm-sized fibronectin-dots arranged at constant lateral but continuously decreasing axial spacing. Parameters like gradient slope, protein concentration and size or shape of the fibronectin dots were modified to determine optimal conditions for directional cell migration in gradient patterns. We demonstrate that fibroblasts predominantly migrate uphill towards a higher fibronectin density in gradients with a dot size of 2 × 2 μm, a 2% and 6% slope, and a low fibronectin concentration of 1 μg ml-1. Increasing dot size to 3.5 × 3.5 μm resulted in stationary cells, whereas rectangular dots (2 × 3 μm) orientated perpendicular to the gradient axis preferentially induce lateral migration. During haptotaxis, the Golgi apparatus reorients to a posterior position between the nucleus and the trailing edge. Using pharmacological inhibitors, we demonstrate that actomyosin contractility and microtubule dynamics are a prerequisite for gradient recognition indicating that asymmetric intracellular forces are necessary to read the axis of adhesive gradients. In the haptotaxis signalling cascade, RhoA and Cdc42, and the atypical protein kinase C zeta (aPKCζ), but not Rac, are located upstream of actomyosin contractility.

We demonstrate the applicability of polymeric whispering gallery mode resonators fabricated on silicon as biosensors. Optical measurements on the passive resonators in the visible spectral range yield Q-factors as high as 1.3×107. Local, covalent surface functionalization, is achieved by spatially controlled UV-exposure of a derivative of the photoreactive crosslinker benzophenone. Protein detection is shown using the specific binding of the biotin-streptavidin system.

Cell populations often display heterogeneous behavior, including cell-to-cell variations in morphology, adhesion and spreading. However, better understanding the significance of such cell variations for the function of the population as a whole requires quantitative single-cell assays. To investigate adhesion variability in a CHO cell population in detail, we measured integrin-mediated adhesion to laminin and collagen, two ubiquitous ECM components, by AFM-based single-cell force spectroscopy (SCFS). CHO cells generally adhered more strongly to laminin than collagen but population adhesion force distributions to both ECM components were broad and partially overlapped. To determine the levels of laminin and collagen binding in individual cells directly, we alternatingly measured single cells on adjacent microstripes of collagen and laminin arrayed on the same adhesion substrate. In repeated measurements (≥60) individual cells showed a stable and ECM type-specific adhesion response. All tested cells bound laminin more strongly, but the scale of laminin over collagen binding varied between cells. Together, this demonstrates that adhesion levels to different ECM components are tightly yet differently set in each cell of the population. Adhesion variability to laminin was non-genetic and cell cycle-independent but scaled with the range of α6 integrin expression on the cell surface. Adhesive cell-to-cell variations due to varying receptor expression levels thus appear to be an inherent feature of cell populations and should to be considered when fully characterizing population adhesion. In this approach, SCFS performed on multifunctional adhesion substrates can provide quantitative single-cell information not obtainable from population-averaging measurements on homogeneous adhesion substrates.

We report laser action from conical polymeric microcavities. A thin film of the organic semiconductor tris(8-hydroxyquinoline) aluminum (Alq 3 ) doped with the laser dye 4-dicyanmethylene-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran (DCM) on top of the microcones enables low-threshold lasing when pumped with a conventional blu-ray laser diode. This combination might pave the way towards compact, low-cost integrated laser-based sensing systems.

We report on lasing in conical microcavities, which are made out of the low-loss polymer poly (methyl methacrylate) (PMMA) doped with the dye rhodamine 6G, and directly fabricated on silicon. Including a thermal reflow step during fabrication enables a significantly reduced surface roughness, resulting in low scattering losses of the whispering gallery modes (WGMs). The high cavity quality factors (above 2.10(6) in passive cavities) in combination with the large oscillator strength gain material enable lasing threshold energies as low as 3 nJ, achieved by free-space excitation in the quasi-stationary pumping regime. Lasing wavelengths are detected in the visible wavelength region around 600 nm. Finite element simulations indicate that lasing occurs in fundamental TE/TM cavity modes, as these modes have - in comparison to higher order cavity modes - the smallest mode volume and the largest overlap with the gain material. In addition, we investigate the effect of dye concentration on lasing wavelength and threshold by comparing samples with four different concentrations of rhodamine 6G. Observations are explained by modifying the standard dye laser model.

We report on a new type of high-Q microresonator made of poly(methyl methacrylate) (PMMA) with a conical shape. First results on biosensing with proteins are presented.

We report the fabrication of high-Q polymeric microdisks on silicon via direct laser writing utilizing two-photon absorption induced polymerization. The quality factors of the passive cavities are above 10(6) in the 1300 nm wavelength region. The flexible three-dimensional (3D) lithography method allows for the fabrication of different cavity thicknesses on the same substrate, useful for rapid prototyping of active and passive optical microcavities. Microdisk lasers are realized by doping the resist with dye, resulting in laser emission at visible wavelengths.

We report on the planar and three-dimensional (3D) lithographic fabrication and optical characterization of microcavity lasers made of polymers doped with dyes with laser thresholds as low as 3 nJ per pulse at visible wavelengths.

We investigate lasing from high-Q, polymeric goblet-type microcavities covered by an organic semiconductor gain layer. We analyze the optical modes in the high-Q cavities using finite element simulations and present a numerical method to determine the cutoff thickness of the gain layer above which the whispering gallery modes are strongly confined in this layer. Fabricated devices show reduced lasing thresholds for increasing gain layer thicknesses, which can be explained by a higher filling factor of the optical modes in the gain layer. Furthermore, reduced lasing threshold is accompanied by a red-shift of the laser emission.

We report on the fabrication and optical characterization of whispering-gallery microcavity lasers with an organic semiconductor gain layer and laser thresholds as low as 1 nJ per pulse, operating at visible wavelengths.

We report on a new type of whispering gallery mode (WGM) resonator made of out of low-loss polymer poly (methyl methacrylate) (PMMA). These optical cavities are fabricated using standard semiconductor processing methods in combination with a specific thermal reflow process. During this subsequent thermal treatment, surface tension leads to the goblet like geometry of the resonator and to an ultra smooth surface. The Q-factor of these goblet resonators is above 2·106 in the 1310 nm wavelength range. In order to demonstrate the applicability of the goblet resonators for bio sensing, Bovine Serum Albumin was detected by monitoring the shift of resonator modes due to protein adsorption.

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.

We report on lasing in rhodamine 6G-doped, conical polymeric microcavities with high quality factors fabricated on a silicon substrate. Threshold pump energies as low as 3 nJ are achieved by free-space excitation in the quasistationary pumping regime with lasing wavelengths around 600 nm. Finite element simulations confirm that lasing occurs in whispering gallery modes which corresponds well to the measured multimode laser-emission. The effect of dye concentration on lasing threshold and lasing wavelength is investigated and can be explained using a standard dye laser model.

We report on the fabrication of high-Q microresonators made of poly(methyl methacrylate) (PMMA) with a conical shape due to a thermal reflow step. The cavity quality factor is above 2-106 in the 1300 nm wavelength range.

We report on the utilization of whispering-gallery mode resonators in optical sensing. In particular, we focus on fabrication and characterization of conical PMMA microresonators directly processed on a silicon substrate with Q-factors above 2·106.