Fluorescent Tools for the Imaging of Dopamine D2 -Like Receptors.

The family of dopamine D2 -like receptors represents an interesting target for a variety of neurological diseases, e. g. Parkinson's disease (PD), addiction, or schizophrenia. In this study we describe the synthesis of a new set of fluorescent ligands as tools for visualization of dopamine D2 -like receptors. Pharmacological characterization in radioligand binding studies identified UR-MN212 (20) as a high-affinity ligand for D2 -like receptors (pKi (D2long R)=8.24, pKi (D3 R)=8.58, pKi (D4 R)=7.78) with decent selectivity towards D1 -like receptors. Compound 20 is a neutral antagonist in a Go1 activation assay at the D2long R, D3 R, and D4 R, which is an important feature for studies using whole cells. The neutral antagonist 20, equipped with a 5-TAMRA dye, displayed rapid association to the D2long R in binding studies using confocal microscopy demonstrating its suitability for fluorescence microscopy. Furthermore, in molecular brightness studies, the ligand's binding affinity could be determined in a single-digit nanomolar range that was in good agreement with radioligand binding data. Therefore, the fluorescent compound can be used for quantitative characterization of native D2 -like receptors in a broad variety of experimental setups.

Shedding Light on the D1 -Like Receptors: A Fluorescence-Based Toolbox for Visualization of the D1 and D5 Receptors.

Dopamine D1 -like receptors are the most abundant type of dopamine receptors in the central nervous system and, even after decades of discovery, still highly interesting for the study of neurological diseases. We herein describe the synthesis of a new set of fluorescent ligands, structurally derived from D1 R antagonist SCH-23390 and labeled with two different fluorescent dyes, as tool compounds for the visualization of D1 -like receptors. Pharmacological characterization in radioligand binding studies identified UR-NR435 (25) as a high-affinity ligand for D1 -like receptors (pKi (D1 R)=8.34, pKi (D5 R)=7.62) with excellent selectivity towards D2 -like receptors. Compound 25 proved to be a neutral antagonist at the D1 R and D5 R in a Gs heterotrimer dissociation assay, an important feature to avoid receptor internalization and degradation when working with whole cells. The neutral antagonist 25 displayed rapid association and complete dissociation to the D1 R in kinetic binding studies using confocal microscopy verifying its applicability for fluorescence microscopy. Moreover, molecular brightness studies determined a single-digit nanomolar binding affinity of the ligand, which was in good agreement with radioligand binding data. For this reason, this fluorescent ligand is a useful tool for a sophisticated characterization of native D1 receptors in a variety of experimental setups.

The Impact of Membrane Protein Diffusion on GPCR Signaling.

Spatiotemporal signal shaping in G protein-coupled receptor (GPCR) signaling is now a well-established and accepted notion to explain how signaling specificity can be achieved by a superfamily sharing only a handful of downstream second messengers. Dozens of Gs-coupled GPCR signals ultimately converge on the production of cAMP, a ubiquitous second messenger. This idea is almost always framed in terms of local concentrations, the differences in which are maintained by means of spatial separation. However, given the dynamic nature of the reaction-diffusion processes at hand, the dynamics, in particular the local diffusional properties of the receptors and their cognate G proteins, are also important. By combining some first principle considerations, simulated data, and experimental data of the receptors diffusing on the membranes of living cells, we offer a short perspective on the modulatory role of local membrane diffusion in regulating GPCR-mediated cell signaling. Our analysis points to a diffusion-limited regime where the effective production rate of activated G protein scales linearly with the receptor-G protein complex's relative diffusion rate and to an interesting role played by the membrane geometry in modulating the efficiency of coupling.

33 W continuous output power semiconductor disk laser emitting at 1275 nm.

We demonstrate a semiconductor disk laser emitting at 1275nm, employing a wafer fused AlInGaAs/InP-AlAs/GaAs gain mirror. A built-in Au-reflector was used to reflect the pump light not absorbed in a single pass through the gain chip active region. The laser exhibited an output power of 33 W for a pump spot with a diameter of 0.86 mm, an output coupler of 2.5%, and a heat-sink temperature of -5°C. When the temperature of the heat-sink was increased to 15 °C, the maximum output power reached a value of ~24 W. The study reveals that the wafer fused gain mirrors have a high optical quality and good uniformity enabling scaling of the maximum emitted power with the diameter of the pump spot, i.e. at least up to the 1 mm diameter.

750 nm 1.5 W frequency-doubled semiconductor disk laser with a 44 nm tuning range.

We demonstrate 1.5 W of output power at the wavelength of 750 nm by intracavity frequency doubling a wafer-fused semiconductor disk laser diode-pumped at 980 nm. An optical-to-optical efficiency of 8.3% was achieved using a bismuth borate crystal. The wavelength of the doubled emission could be tuned from 720 to 764 nm with an intracavity birefringent plate. The beam quality parameter M2 of the laser output was measured to be below 1.5 at all pump powers. The laser is a promising tool for biomedical applications that can take advantage of the large penetration depth of light in tissue in the 700-800 nm spectral range.

High-power flip-chip semiconductor disk laser in the 1.3 µm wavelength band.

We present 6.1 W of output power from a flip-chip semiconductor disk laser (SDL) emitting in the 1.3 µm wavelength region. This is the first demonstration of a flip-chip SDL in this wavelength range with output powers that are comparable to those obtained with intracavity diamond heat spreaders. The flip-chip configuration circumvents the optical distortions and losses that the intracavity diamond heat spreaders can introduce into the laser cavity. This is essential for several key applications of SDLs.

High performance wafer-fused semiconductor disk lasers emitting in the 1300 nm waveband.

We report for the first time on the performance of 1300 nm waveband semiconductor disc lasers (SDLs) with wafer fused gain mirrors that implement intracavity diamond and flip-chip heat dissipation schemes based on the same gain material. With a new type of gain mirror structure, maximum output power values reach 7.1 W with intracavity diamond gain mirrors and 5.6 W with flip-chip gain mirrors, using a pump spot diameter of 300 µm, exhibiting a beam quality factor M(2)< 1.25 in the full operation range. These results confirm previously published theoretical modeling of these types of SDLs.

Control of cavity lifetime of 1.5 µm wafer-fused VCSELs by digital mirror trimming.

Digital chemical etching is used to trim the output mirror thickness of wafer-fused VCSELs emitting at a wavelength near 1.5µm. The fine control of the photon cavity lifetime thus achieved is employed to extract important device parameters and optimize the combination of the threshold current, output power, and direct current modulation characteristics. The fabrication process is compatible with industrial production and should help in improving device yield and in reducing manufacturing costs.

Transverse mode discrimination in long-wavelength wafer-fused vertical-cavity surface-emitting lasers by intra-cavity patterning.

Transverse mode discrimination is demonstrated in long-wavelength wafer-fused vertical-cavity surface-emitting lasers using ring-shaped air gap patterns at the fused interface between the cavity and the top distributed Bragg reflector. A significant number of devices with varying pattern dimensions was investigated by on-wafer mapping, allowing in particular the identification of a design that reproducibly increases the maximal single-mode emitted power by about 30 %. Numerical simulations support these observations and allow specifying optimized ring dimensions for which higher-order transverse modes are localized out of the optical aperture. These simulations predict further enhancement of the single-mode properties of the devices with negligible penalty on threshold current and emitted power.

1.56 µm 1 watt single frequency semiconductor disk laser.

A single frequency wafer-fused semiconductor disk laser at 1.56 µm with 1 watt of output power and a coherence length over 5 km in fiber is demonstrated. The result represents the highest output power reported for a narrow-line semiconductor disk laser operating at this spectral range. The study shows the promising potential of the wafer fusion technique for power scaling of single frequency vertical-cavity lasers emitting in the 1.3-1.6 µm range.

1 W at 785 nm from a frequency-doubled wafer-fused semiconductor disk laser.

We demonstrate an optically pumped semiconductor disk laser operating at 1580 nm with 4.6 W of output power, which represents the highest output power reported from this type of laser. 1 W of output power at 785 nm with nearly diffraction-limited beam has been achieved from this laser through intracavity frequency doubling, which offers an attractive alternative to Ti:sapphire lasers and laser diodes in a number of applications, e.g., in spectroscopy, atomic cooling and biophotonics.

8 mW fundamental mode output of wafer-fused VCSELs emitting in the 1550-nm band.

We report record-high fundamental mode output power of 8 mW at 0 °C and 1.5 mW at 100°C achieved with wafer-fused InAlGaAs-InP/AlGaAs-GaAs 1550 nm VCSELs incorporating a re-grown tunnel junction and un-doped AlGaAs/GaAs distributed Bragg reflectors. A broad wavelength tuning range of 15 nm by current variation and wavelength setting in a spectral range of 40 nm on the same VCSEL wafer are demonstrated as well. This performance positions wafer-fused VCSELs as prime candidates for many applications in low power consumption, "green" photonics.

Polarisation stabilisation of vertical cavity surface emitting lasers by minimally invasive focused electron beam triggered chemistry.

Local electron triggered reactions of functional surface adsorbates were used as a maskless, dry, and minimally invasive nanolithography concept to stabilize the polarisation of individual vertical cavity surface emitting lasers (VCSELs) on a wafer in a post-processing step. Using a 30 keV focused electron beam of a scanning electron microscope and injecting volatile organo-metallic (CH(3))(2)Au(tfa) molecules, polarisation gratings were directly written on VCSELs by dissociating the surface adsorbed molecules. The electron triggered adsorbate dissociation resulted in electrically conductive Au-C nano-composite material, with gold nanocrystals embedded in a carbonaceous matrix. A resistivity of 2500 µΩcm was measured at a typical composition of 30 at.% Au. This material proved successful in suppressing polarisation switching when deposited as line gratings with a width of 200 nm, a thickness of 50 nm, and a pitch of 500 nm and 1 µm. Refractive index measurements suggest that the optical attenuation by the deposited Au-C material is much lower than by pure Au thus giving a low emission power penalty while keeping the polarisation stable.

Intra-cavity patterning for mode control in 1.3 µm coupled VCSEL arrays.

We report coupled VCSEL arrays, emitting at 1.3 µm wavelength, in which both the optical gain/loss and refractive index distributions were defined on different vertical layers. The arrays were electrically pumped through a patterned tunnel junction, whereas the array pixels were realized by intra-cavity patterning using sub-wavelength air gaps. Stable oscillations in coupled modes were evidenced for 2x2 array structures, from threshold current up to thermal roll-over, using spectrally resolved field pattern analysis.

3 W of 650 nm red emission by frequency doubling of wafer-fused semiconductor disk laser.

3 W at genuine red wavelength of 650 nm has been achieved from a semiconductor disk laser by frequency doubling. An InP based active medium was fused with a GaAs/AlGaAs distributed Bragg reflector resulting in an integrated monolithic gain mirror. 6.6 W of output power at the fundamental wavelength of 1.3 µm represents the best achievement reported to date for this type of lasers.

Power-scalable 1.57 microm mode-locked semiconductor disk laser using wafer fusion.

We report the first (to our knowledge) wafer-fused high-power passively mode-locked semiconductor disk laser operating at 1.57 microm wavelength. An InP-based active medium was fused with GaAs/AlGaAs distributed Bragg reflector on a 2 inch wafer level, resulting in an integrated monolithic gain mirror. An intracavity wedged diamond heat-spreader capillary bonded to the gain chip provides efficient heat removal from the gain structure without disturbing the spectrum of the mode-locked laser. The laser produces over 0.6 W of average output power at 15 degrees C with 16 ps pulse width. The total output power accounting for all output beams emerging from the cavity was 0.86 W. The results reveal an essential advantage of wafer fusion processing of disparate materials over monolithically grown InP-based gain structures and demonstrate the high potential of this technique for power scaling of long-wavelength semiconductor disk lasers.

10-Gb/s and 10-km error-free transmission up to 100 degrees C with 1.3-microm wavelength wafer-fused VCSELs.

10-Gb/s modulation speed and transmission over 10-km SM fiber with BER < 10(-11) up to 100 degrees C temperature are achieved with optimized wafer-fused GaAs/AlGaAs-InP/InAlGaAs VCSELs incorporating re-grown tunnel junction. These VCSELs operate in the 1310-nm waveband and emit more than 1-mW single mode power in the full temperature range.

1.3-microm optically-pumped semiconductor disk laser by wafer fusion.

We report a wafer-fused high power optically-pumped semiconductor disk laser operating at 1.3 microm. An InP-based active medium was fused with a GaAs/AlGaAs distributed Bragg reflector, resulting in an integrated monolithic gain mirror. Over 2.7 W of output power, obtained at temperature of 15 degrees C, represents the best achievement reported to date for this type of lasers. The results reveal an essential advantage of the wafer fusing technique over both monolithically grown AlGaInAs/GaInAsP- and GaInNAs-based structures.

1.3 microm-wavelength phase-locked VCSEL arrays incorporating patterned tunnel junction.

We report the fabrication and the performance of phase-locked VCSEL arrays emitting near 1310 nm wavelength. The arrays were fabricated using double wafer fusion by patterning a tunnel junction layer, which serves to define the individual single mode array elements. Phase-locking in both one-dimensional and two-dimensional array configurations was confirmed by means of far field and spectral measurements as well as theoretical modeling. CW output powers of more than 12 mW were achieved.

2.6 W optically-pumped semiconductor disk laser operating at 1.57-microm using wafer fusion.

We report a wafer fused high power optically pumped semiconductor disk laser incorporating InP-based active medium fused to a GaAs/AlGaAs distributed Bragg reflector. A record value of over 2.6 W of output power in a spectral range around 1.57 microm was demonstrated, revealing the essential advantage of the wafer fusing technique over monolithically-grown all-InP-based structures. The presented approach allows for integration of lattice-mismatched compounds, quantum-well and quantum-dot based media. This would provide convenient means for extending the wavelength range of semiconductor disk lasers.