Large area robotically assisted optical coherence tomography (LARA-OCT).

We demonstrate large-area robotically assisted optical coherence tomography (LARA-OCT), utilizing a seven-degree-of-freedom robotic arm in conjunction with a 3.3 MHz swept-source OCT to raster scan samples of arbitrary shape. By combining multiple fields of view (FOV), LARA-OCT can probe a much larger area than conventional OCT. Also, nonplanar and curved surfaces like skin on arms and legs can be probed. The lenses in the LARA-OCT scanner with their normal FOV can have fewer aberrations and less complex optics compared to a single wide field design. This may be especially critical for high resolution scans. We directly use our fast MHz-OCT for tracking and stitching, making additional machine vision systems like cameras, positioning, tracking or navigation devices obsolete. This also eliminates the need for complex coordinate system registration between OCT and the machine vision system. We implemented a real time probe-to-surface control that maintains the probe alignment orthogonal to the sample by only using surface information from the OCT images. We present OCT data sets with volume sizes of 140 × 170 × 20 mm3, captured in 2.5 minutes.

High-resolution rectoscopy using MHz optical coherence tomography: a step towards real time 3D endoscopy.

Colonoscopy and endoscopic ultrasound play pivotal roles in the assessment of rectal diseases, especially rectal cancer and inflammatory bowel diseases. Optical coherence tomography (OCT) offers a superior depth resolution, which is a critical factor for individualizing the therapeutic concept and evaluating the therapy response. We developed two distinct rectoscope prototypes, which were integrated into a 1300 nm MHz-OCT system constructed at our facility. The rapid rotation of the distal scanning probe at 40,000 revolutions per minute facilitates a 667 Hz OCT frame rate, enabling real-time endoscopic imaging of large areas. The performance of these OCT-rectoscopes was assessed in an ex vivo porcine colon and a post mortem human in-situ colon. The OCT-rectoscope consistently distinguished various layers of the intestinal wall, identified gut-associated lymphatic tissue, and visualized a rectal polyp during the imaging procedure with 3D-reconstruction in real time. Subsequent histological examination confirmed these findings. The body donor was preserved using an ethanol-glycerol-lysoformin-based technique for true-to-life tissue consistency. We could demonstrate that the novel MHZ-OCT-rectoscope effectively discriminates rectal wall layers and crucial tissue characteristics in a post mortem human colon in-situ. This real-time-3D-OCT holds promise as a valuable future diagnostic tool for assessing disease state and therapy response on-site in rectal diseases.

Four-wave mixing seeded by a rapid wavelength-sweeping FDML laser for nonlinear imaging at 900 nm and 1300 nm.

Four-wave mixing (FWM) enables the generation and amplification of light in spectral regions where suitable fiber gain media are unavailable. The 1300 nm and 900 nm regions are of especially high interest for time-encoded (TICO) stimulated Raman scattering microscopy and spectro-temporal laser imaging by diffracted excitation (SLIDE) two-photon microscopy. We present a new, to the best of our knowledge, FWM setup where we shift the power of a home-built fully fiber-based master oscillator power amplifier (MOPA) at 1064 nm to the 1300-nm region of a rapidly wavelength-sweeping Fourier domain mode-locked (FDML) laser in a photonic crystal fiber (PCF) creating pulses in the 900-nm region. The resulting 900-nm light can be wavelength swept over 54 nm and has up to 2.5 kW (0.2 µJ) peak power and a narrow instantaneous spectral linewidth of 70 pm. The arbitrary pulse patterns of the MOPA and the fast wavelength tuning of the FDML laser (419 kHz) allow it to rapidly tune the FWM light enabling new and faster TICO-Raman microscopy, SLIDE imaging, and other applications.

828 kHz retinal imaging with an 840†nm Fourier domain mode locked laser.

This paper presents a Fourier domain mode locked (FDML) laser centered around 840 nm. It features a bidirectional sweep repetition rate of 828 kHz and a spectral bandwidth of 40 nm. An axial resolution of ∼9.9 µm in water and a 1.4 cm sensitivity roll-off are achieved. Utilizing a complex master-slave (CMS) recalibration method and due to a sufficiently high sensitivity of 84.6 dB, retinal layers of the human eye in-vivo can be resolved during optical coherence tomography (OCT) examination. The developed FDML laser enables acquisition rates of 3D-volumes with a size of 200 × 100 × 256 voxels in under 100 milliseconds. Detailed information on the FDML implementation, its challenging design tasks, and OCT images obtained with the laser are presented in this paper.

Continuous spectral zooming for in vivo live 4D-OCT with MHz A-scan rates and long coherence.

We present continuous three-dimensional spectral zooming in live 4D-OCT using a home-built FDML based OCT system with 3.28 MHz A-scan rate. Improved coherence characteristics of the FDML laser allow for imaging ranges up to 10 cm. For the axial spectral zoom feature, we switch between high resolution and long imaging range by adjusting the sweep range of our laser. We present a new imaging setup allowing for synchronized adjustments of the imaging range and lateral field of view during live OCT imaging. For this, a novel inline recalibration algorithm was implemented that enables numerical k-linearization of the raw OCT fringes for every frame instead of every volume. This is realized by acquiring recalibration data within the dead time of the raster scan at the turning points of the fast axis scanner. We demonstrate in vivo OCT images of fingers and hands at different resolution modes and show real three-dimensional zooming during live 4D-OCT. A three-dimensional spectral zooming feature for live 4D-OCT is expected to be a useful tool for a wide range of biomedical, scientific and research applications, especially in OCT guided surgery.

Fungicide and insecticide exposure adversely impacts bumblebees and pollination services under semi-field conditions.

Sulfoximines, the next generation systemic insecticides developed to replace neonicotinoids, have been shown to negatively impact pollinator development and reproduction. However, field-realistic studies on sulfoximines are few and consequences on pollination services unexplored. Moreover, the impacts of other agrochemicals such as fungicides, and their combined effects with insecticides remain poorly investigated. Here, we show in a full factorial semi-field experiment that spray applications of both the product Closer containing the insecticide sulfoxaflor and the product Amistar containing the fungicide azoxystrobin, negatively affected the individual foraging performance of bumblebees (Bombus terrestris). Insecticide exposure further reduced colony growth and size whereas fungicide exposure decreased pollen deposition. We found indications for resource limitation that might have exacerbated pesticide effects on bumblebee colonies. Our work demonstrates that field-realistic exposure to sulfoxaflor can adversely impact bumblebees and that applications before bloom may be insufficient as a mitigation measure to prevent its negative impacts on pollinators. Moreover, fungicide use during bloom could reduce bumblebee foraging performance and pollination services.

Cavity length control for Fourier domain mode locked (FDML) lasers with µm precision.

In highly dispersion compensated Fourier domain mode locked (FDML) lasers, an ultra-low noise operation can only be achieved by extremely precise and stable matching of the filter tuning period and light circulation time in the cavity. We present a robust and high precision closed-loop control algorithm and an actively cavity length controlled FDML laser. The cavity length control achieves a stability of ∼0.18 mHz at a sweep repetition rate of ∼418 kHz which corresponds to a ratio of 4×10-10. Furthermore, we prove that the rapid change of the cavity length has no negative impact on the quality of optical coherence tomography using the FDML laser as light source.

Chelated Fischer carbene complexes of annulated thiophenes: synthesis, structure and electrochemistry.

Two (thieno[3,2-b]thiophene) and three annulated thiophenes (dithieno[2,3-b;3',2'-d]thiophene and dithieno[3,2-b;2',3'-d]thiophene) were employed as building blocks to synthesize linear or semi-circular chelated mononuclear biscarbene and dinuclear tetracarbene complexes. The electronic properties of the annulated thienylene chelated carbene complexes were investigated by cyclic voltammetry experiments and compared to non-chelated Fischer-type monocarbene complexes. Density functional theory (DFT) calculations were used to assign the redox events and to probe the extent of electron delocalisation as well as the possibility of electronic (intramolecular metal-metal) communication as a result of intervalence. The differences of these electronic properties in the conjugated chelated carbene complexes are compared to chelated carbene compounds without a linear conjugated pathway.

Mono-, di- and tetrarhenium Fischer carbene complexes with thienothiophene substituents.

The oxidative cleaving of a rhenium-rhenium bond by bromine in binuclear Fischer carbene complexes proves to be an effective method to prepare mononuclear bromido-carbene complexes. The reaction of mono- and dilithiated thieno[2,3-b]thiophene (2,3-b-TTH2) and thieno[3,2-b]thiophene (3,2-b-TTH2) with [Re2(CO)10] affords dirhenium nonacarbonyl ethoxycarbene complexes, [Re2(CO)9{C(OEt)2,3-b-TTH}] (1a) and [Re2(CO)9{C(OEt)3,2-b-TTH}] (1b), and the tetrarhenium bis(ethoxycarbene) complexes from the dilithiated thiophene substrates, [Re2(CO)9-µ-{C(OEt)-2,3-b-TT-C(OEt)}Re2(CO)9] (2a) and [Re2(CO)9-µ-{C(OEt)-3,2-b-TT-C(OEt)}Re2(CO)9] (2b) featuring bridging thiophene linkers. Rhenium-rhenium bond cleavage by bromine of the monocarbene complexes yielded the scarce class of monorhenium bromido-carbene complexes, cis-[Re(CO)4{C(OEt)2,3-b-TTH}Br] (3a) and cis-[Re(CO)4{C(OEt)3,2-b-TTH}Br] (3b), while the corresponding reaction of the biscarbene tetrarhenium carbonyl complex of thieno[2,3-b]thiophene afforded the cleaving of both metal-metal bonds to give the novel dirhenium biscarbene dibromido complex with a thienothiophene spacer, [Re(CO)4Br-µ-{C(OEt)-2,3-b-TT-C(OEt)}Re(CO)4Br] (4a). A new indirect aminolysis route is described to prepare the chlorido dimethylaminocarbene complex 5acis-[Re(CO)4{C(NMe2)2,3-b-TTH}Cl], with unexpected cleavage of the Re-Re bond. Single crystal X-ray diffraction studies were performed on 1a, 2a, 3a, 5a, 1b and 3b. Spectroscopic and electrochemical methods are employed to investigate the electronic effect of the different conjugation pathways in the different thienothiophenyl carbene substituents, and the replacement of the rhenium pentacarbonyl fragment with a bromido ligand.

Synthesis and properties of mono- and dimetal Fischer multicarbene complexes derived from thiophene and thieno[2,3-b]thiophene.

Access to multicarbene complexes of a fused thienothiophene substrate was obtained by the use of the tetrabrominated thieno[2,3-b]thiophene precursor in a lithium-bromide exchange reaction, followed by nucleophilic attack on metal hexacarbonyls (M = Cr, W). Subsequent alkylation afforded unique triscarbene complexes [M(CO)4{{C(OEt)}2C6H1S2C(OEt)}M(CO)5] (M = Cr 12, W 13) featuring three non-equivalent carbene ligands on a single thiophene linker, as well as the bischelated tetracarbene complexes [M(CO)4{{C(OEt)}2C6S2{C(OEt)}2}M(CO)4] (M = Cr 14, W 15). The triscarbene complexes 12 and 13 are the first examples of multi-alkoxycarbene complexes featuring three non-equivalent carbene ligands. The reaction also afforded the chelated mononuclear biscarbene complexes [M(CO)4{C(OEt)}2C6H2S2] (M = Cr 10, W 11) in low yields. Similarly, employing tetrabromothiophene as precursor yielded the mononuclear chelate biscarbene complexes [M(CO)4{C(OEt)}2C4H2S] (M = Cr 6, W 7) and the dinuclear tetracarbene complexes [M(CO)4{{C(OEt)}2C4S{C(OEt)}2}M(CO)4] (M = Cr 8, W 9). Modification of the classic Fischer carbene synthetic methodology to a process of stepwise additions of lithiating agent and metal carbonyls to thieno[2,3-b]thiophene, facilitates the formation of the mixed metal biscarbene complex [W(CO)5C(OEt){C6H2S2}C(OEt)Cr(CO)5] 5, as analogue of the homonuclear biscarbene complexes [M(CO)5C(OEt){C6H2S2}C(OEt)M(CO)5], (M = Cr 3, W 4). The monocarbene complexes [M(CO)5{C(OEt)C6H3S2}], (M = Cr 1, W 2) were also obtained in high yields, and the molecular structures of the tungsten complexes, with the exception of 9 and 11, were confirmed by single crystal X-ray diffraction studies.

Rhenium ethoxy- and hydroxycarbene complexes with thiophene substituents.

Reaction of mono- and dilithiated thiophene (a), bithiophene (b) and 2,5-dibromothiophene (c) with [Re(2)(CO)(10)] afforded, after subsequent alkylation with triethyloxonium tetrafluoroborate, tetra- and binuclear Fischer carbene complexes, [Re(2)(CO)(9){C(OEt){C(4)H(2)S}(n)X}], n = 1, X = H (1a); n = 2, X = H (1b); n = 1, X = Br (1c); n = 1, X = C(OEt)Re(2)(CO)(9), (2a); n = 2, X = C(OEt)Re(2)(CO)(9) (2b), as major products. The dirhenium acylate intermediates from this reaction not only gave the expected novel ethoxycarbene complexes with alkylation but after rhenium-rhenium bond breaking afforded a number of minor products. The (1)H NMR spectrum of the crude reaction mixture revealed the formation of four metal hydride complexes and aldehydes. Protonation with HBF(4) instead of alkylation with Et(3)OBF(4) significantly increased the yields of the hydride complexes, which enabled the positive identification of three of these complexes. In addition to the known compounds [Re(CO)(5)H] and [Re(3)(CO)(14)H] (3), a unique complex displaying a hydroxycarbene fragment connected to an acyl fragment via an O-H···O hydrogen bond and a Re···H···Re bond linking the two Re centers, [(µ-H){Re(CO)(4)C(OH){C(4)H(2)S}(n)H}{Re(CO)(4)C(O){C(4)H(2)S}(n)H}], n = 1 (4a) or n = 2 (4b), were isolated. The formation of thiophene aldehydes, H{C(O)}(m){C(4)H(2)S}(n)C(O)H (m = 0 or 1 and n = 1 or 2), were observed and the novel monocarbene complexes with terminal aldehyde groups, [Re(2)(CO)(9){C(OEt){C(4)H(2)S}(n)C(O)H}], n = 1 (5a) and n = 2 (5b) could be isolated. A higher yield of 5b was obtained after stirring crystals of 2b in wet THF. The crystal structures of 1a, 2a, 4a and 5b are reported.

Synthesis, characterization, and structural studies of multimetallic ferrocenyl carbene complexes of group VII transition metals.

Fischer carbene complexes of the group VII transition metals (Mn and Re) containing at least two or three different transition metal substituents, all in electronic contact with the carbene carbon atom, were synthesized. The structural features and their relevance to bonding in the carbene multimetal compounds were investigated, as they represent indicators of possible reactivity sites in polymetallic carbene assemblies. For complexes of the type [ML(x){C(OR)R'}] (ML(x) = MnCp(CO)(2) or Re(2)(CO)(9)), ferrocenyl (Fc) was chosen as the R' substituent, while the OR substituent was systematically varied between an ethoxy or a titanoxy group, to yield the complexes 1a (ML(x) = MnCp(CO)(2), R = Et, R' = Fc), 2a (ML(x) = MnCp(CO)(2), R = TiCp(2)Cl, R' = Fc), 3a (ML(x) = Re(2)(CO)(9), R = Et, R' = Fc), and 4a (ML(x) = Re(2)(CO)(9), R = TiCp(2)Cl, R' = Fc). Direct lithiation of the ferrocene with n-BuLi/TMEDA at elevated temperatures, followed by the Fischer method of carbene preparation, resulted in formation of the novel biscarbene complexes with bridging ferrocen-1,1'-diyl (Fc') substituents [{π-Fe(C(5)H(4))(2)-C,C'}{C(OEt)ML(x)}(2)] (1b, ML(x) = MnCp(CO)(2); 3b, ML(x) = Re(2)(CO)(9)) or the unusual bimetallacyclic bridged biscarbene complexes [{π-TiCp(2)O(2)-O,O'}{π-Fe(C(5)H(4))(2)-C,C'}{CML(x)}(2)] (2b, ML(x) = MnCp(CO)(2); 4b, ML(x) = Re(2)(CO)(9)). The target compounds that were isolated displayed a variety of different geometric isomers and conformations. The greater reactivity of the binary dirhenium acylates in solution, compared to that of the cyclopentadienyl manganese acylate, resulted in a complex reaction mixture. Although the stabilization of hydroxycarbene or hydrido-acyl intermediates of dirhenium carbonyls could not be achieved, their existence in solution was confirmed by the isolation of [(π-H)(2)-(Re(CO)(4){C(O)Fc})(2)] (8), the unique dichloro-bridged biscarbene complex fac-[(π-Cl)(2)-(Re(CO)(3){C(OEt)Fc})(2)] (6), the known hydrido complex [Re(3)(CO)(14)H] (5), the acyl complex [Re(CO)(5){C(O)Fc}] (7), and the aldehyde-functionalized eq-[Re(2)(CO)(9){C(OTiCp(2)Cl)(Fc'CHO)}] (9).

Thiophene decorated with Fischer carbene ligands.

The activation of a section, or of all the carbons of thiophene by bromine in lithium-halogen exchange reactions, was implemented in a step-wise manner to facilitate the preparation of novel multiple Fischer carbene-bearing thiophene compounds.

Synthesis and reactivity of metal carbene complexes with heterobiaryl spacer substituents.

Mono- and binuclear Fischer carbene complexes, [M(CO)5{C(OR)Ar-ArX}], X = H, {C(OR)M'(CO)5}; M, M' = W or Cr; R = Me, Et or (CH2)4OMe; Ar = thiophene, N-methylpyrrole or furan units 1-20, were synthesized. For this purpose, mono-, bi- or stepwise lithiated bithiophene, N,N'-dimethylbipyrrole, thienylfuran and N-methyl(thienyl)pyrrole were reacted with chromium and tungsten hexacarbonyl precursors. Dilithiation in the 2- and 9-positions of N-methyl(thienyl)pyrrole could not be achieved. Alkylation of acyl metallates with triethyloxonium tetrafluoroborate or methyl trifluoromethanesulfonate in THF afforded not only the expected carbene complexes with ethoxy or methoxy substituents, but in the case of bithiophene with methyl trifluoromethanesulfonate, carbene complexes with alkoxy substituents incorporating a ring-opened tetrahydrofuran moiety. X-Ray crystallographic structure determinations were performed on [W(CO)5{C(OMe)(thienylfuran)}] (14), [W(CO)5{C(OMe)(N-methylthienylpyrrole)}] (20) and [{W(CO)5}2{mu-C(OEt)(N,N'-dimethylbipyrrolylC(OEt)}] (12) to assess the role of the heterobiaryl substituent on the structural features of the carbene ligand in the complexes. Complexes [{Cr(CO)5}2{mu-C(OMe)bithienylC(OEt)}] (3), [(CO)5Cr{mu-C(OMe)bithienylC(OMe)}W(CO)5] (5) and [{Cr(CO)5}2 {mu-C(OMe)thienylfuranC-(OMe)}] (15) were reacted with 3-hexyne to study their behaviour in benzannulation reactions. The major products generated by the biscarbene complexes were regio-selectively determined by the nature of the metal site and that of the heteroatom in the arene rings. The monocarbene complexes [Cr(CO)5{C(OMe)thienylfuran] (13) and [Cr(CO)5{C(OEt)(N-methylthienylpyrrole)}] (19) were refluxed in THF for 2 hours in the presence of [Pd(PPh4)4] to afforded the carbene-carbene coupled olefinic products and small amounts of the corresponding 2-ethyl(biheteroaryl)acetate. By contrast, the biscarbene complex of thienylfuran (15), afforded only the 2,9-diester of thienylfuran.

Binuclear biscarbene complexes of furan.

Carbene complexes of chromium and tungsten with a bridging furan substituent were synthesized from lithiated furan precursors and metal hexacarbonyls. The binuclear biscarbene complexes [(CO)5M{C(OEt)-C4H2O-C(OEt)}M'(CO)5](M = M'= Cr (3), W (4)) were obtained as well as the corresponding monocarbene complexes [M{C(OEt)-C(4)H3O}(CO)5](M = Cr (1), W (2)). A method of protecting the carbene moiety during the metal acylate stage was used to increase not only the yields of the binuclear Fischer biscarbene complexes 3 and 4 but to establish a method to synthesize analogous mixed heterobinuclear carbene complexes (M = W, M'= Cr (5)) in high yields. The binuclear biscarbene complexes 3 and 5 were reacted with 3-hexyne and yielded the corresponding benzannulated monocarbene complexes [M{C(OEt)-C14H17O3}(CO)5](M = Cr (6), W(7)). Complex 5 reacted regioselectively with the benzannulation reaction occurring at the chromium-carbene centre. The major products from refluxing 3 in the presence of [Pd(PPh3)4] were a monocarbene-ester complex [Cr{C(OEt)-C4H2O-C(O)OEt}(CO)5](8), the 2,5-diester of furan (9) and a carbene-carbene coupled olefin EtOC(O)-C4H2O-C(OEt)=C(OEt)-C4H2O-C(O)OEt (10). X-Ray structure analysis of 4 and 6 confirmed the molecular structures of the compounds in the solid state and aspects of electron conjugation between the transition metals and the furan substituents in the carbene ligands were investigated.