0.5 gigapixel microscopy using a flatbed scanner: erratum

When one uses USAF target to calibrate the resolution of an imaging system, the periodicity of the smallest resolvable line should be used to define the limit. However, in the original paper, the line width of the resolution target was used to characterize the resolution of our microscope system, resulting in an overestimation of the performance of the imaging system. In this erratum, we correct the parts that state incorrect resolution and also re-evaluate the performance of our micoscope.OCIS codes: (120.4820) Optical systems, (170.0180) Microscopy, (170.4730) Optical pathologyIn section 4 of the original paper [1], we characterized the resolution of our imaging system using a USAF target. In the experiment, group 9 element 3 (0.78 μm line width) of the resolution target was resolved, and we stated that ‘This establishes the resolution of our prototype system under the quasi-monochromatic 530 nm illumination, as 0.78 μm over the entire FOV.’ Here, we correct the statement as follows: This establishes the resolution of our prototype system under the quasi-monochromatic 530 nm illumination as 1.56 μm over the entire FOV. We also stated that ‘the effective pixel size at the object plane should be less than 0.39 μm (0.78 μm divided by 2).’ We correct the statement as: the effective pixel size at the object plane should be less than 0.78 μm (1.56 μm divided by 2).Because of the change of the resolution, the space-bandwidth product (SBP) of the imaging system needs to be recalculated. The imaging system has a field-of-view (FOV) of 10 mm × 7.5 mm, with effective pixel size of 0.78 μm x 0.78 μm, resulting in an SBP of 0.12 gigapixel. We hereby state that the previous estimation of a 0.5 gigapixel microscopy is incorrect. Instead, we got a microscope system with 0.12 gigapixel. In the following paragraphs, we listed all the incorrect statements and correct them accordingly.In the abstract, we stated that: ‘We show that such an imaging system is capable of capturing a 10 mm × 7.5 mm FOV image with 0.78 μm resolution, resulting in more than 0.5 billion pixels across the entire image... To demonstrate its application, 0.5 gigapixel images of histology slides were acquired using this system.’ We correct the statement as: We show that such an imaging system is capable of capturing a 10 mm × 7.5 mm FOV image with 1.56 μm resolution, resulting in more than 0.12 billion pixels across the entire image... To demonstrate its application, 0.12 gigapixel images of histology slides were acquired using this system.In the second last paragraph of section 1, we stated that: ‘We show that such a system is capable of capturing a 0.5-gigapixel pixel image with a FOV of 75 mm² and a resolution of 0.78 μm. Remarkably, the CCTV lens has a SBP of at least 0.5 gigapixel (10⁹pixels), two orders of magnitude larger than conventional microscope objectives.’ We correct the statement as: We show that such a system is capable of capturing a 0.12-gigapixel pixel image with an FOV of 75 mm² and a resolution of 1.56 μm. Remarkably, the CCTV lens has an SBP of at least 0.12 gigapixel (10⁹pixels), one order of magnitude larger than conventional microscope objectives.The title of section 2 was: ‘The prototype setup of the 0.5 gigapixel microscopy imaging system’, but it should be ‘The prototype setup of the 0.12 gigapixel microscopy imaging system’.In section 6, we stated that ‘In summary, we report a wide-FOV (10 mm × 7.5 mm) microscopy system which can generate a 0.5 gigapixel image with 0.78 μm resolution across the entire FOV.’ We correct the statement as: In summary, we report a wide-FOV (10 mm × 7.5 mm) microscopy system which can generate a 0.12 gigapixel image with 1.56 μm resolution across the entire FOV. We stated that: ‘Compared to typical 10 × and 4 × objectives, our system has both superior SBP and resolution.’ We correct the statement as: Compared to typical 4 × objectives, our system has both superior SBP and resolution.We also need to relabel the position of our CCTV lens in the space-bandwidth product plot shown in Fig. 7. The relabeled coordinate is shown as follows:Open in a separate windowFig. 7The SBP-resolution summary for microscope objectives and our current CCTV lensbased system.     

Ultra-thin and flexible endoscopy probe for optical coherence tomography based on stepwise transitional core fiber

We present an ultra-thin fiber-body endoscopy probe for optical coherence tomography (OCT) which is based on a stepwise transitional core (STC) fiber. In a minimalistic design, our probe was made of spliced specialty fibers that could be directly used for beam probing optics without using a lens. In our probe, the OCT light delivered through a single-mode fiber was efficiently expanded to a large mode field of 24 μm diameter for a low beam divergence. The size of our probe was 85 μm in the probe’s diameter while operated in a 160-μm thick protective tubing. Through theoretical and experimental analyses, our probe was found to exhibit various attractive features in terms of compactness, flexibility and reliability along with its excellent fabrication simplicity.OCIS codes: (110.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.3890) Medical optics instrumentation, (060.2350) Fiber optics imaging     

Closed-loop optical stabilization and digital image registration in adaptive optics scanning light ophthalmoscopy

Eye motion is a major impediment to the efficient acquisition of high resolution retinal images with the adaptive optics (AO) scanning light ophthalmoscope (AOSLO). Here we demonstrate a solution to this problem by implementing both optical stabilization and digital image registration in an AOSLO. We replaced the slow scanning mirror with a two-axis tip/tilt mirror for the dual functions of slow scanning and optical stabilization. Closed-loop optical stabilization reduced the amplitude of eye-movement related-image motion by a factor of 10–15. The residual RMS error after optical stabilization alone was on the order of the size of foveal cones: ~1.66–2.56 μm or ~0.34–0.53 arcmin with typical fixational eye motion for normal observers. The full implementation, with real-time digital image registration, corrected the residual eye motion after optical stabilization with an accuracy of ~0.20–0.25 μm or ~0.04–0.05 arcmin RMS, which to our knowledge is more accurate than any method previously reported.OCIS codes: (110.1080) Active or adaptive optics, (120.3890) Medical optics instrumentation, (170.3880) Medical and biological imaging, (170.4470) Ophthalmology, (330.2210) Vision - eye movements     

Spermidine enhanced resistance of Chlorella to high levels of CO2 and light intensity for improving photosynthetic growth rate

In order to promote the photosynthetic growth rate of Chlorella in the presence of flue gas CO₂ from coal-fired power plants, spermidine was first used to enhance cellular resistance to a high CO₂ concentration (15%) and high light intensity (30 000 lux). It was found that low concentrations (100–300 μM) of spermidine significantly enhanced the photosynthetic growth rate of Chlorella. The accelerated cell division decreased the cell diameter from 3.64 μm to 2.71 μm and the fractal dimension from 1.60 to 1.49, and the activity of total superoxide dismutase (T-SOD) increased from 0.48 U mL⁻¹ to 5.33 U mL⁻¹. Expression levels of key enzymes of photosystems I and II, ATP synthase and transportase markedly increased, thereby enhancing the electron transport and energy supply that reduced oxidative damage. Finally, an enhanced cellular resistance to the high CO₂ concentration and high light intensity increased the biomass yield from 0.11 g L⁻¹ to 1.71 g L⁻¹ (300 μM).

Spermidine enhanced resistance of Chlorella to high levels of CO₂ and light intensity.     

Development of micropillar array electrodes for highly sensitive detection of biomarkers

Micropillar array electrodes (μAEs) have been widely applied in electrochemical detection owing to their advantages of increased mass transport, lower detection limit, and potential to be miniaturized. This paper reports the fabrication, simulation, surface modification, and characterization of PDMS-based μAEs coated with gold films. The μAEs consist of 9 × 10 micropillars with a height of either 100 μm, 300 μm, or 500 μm in a 0.09 cm² region. Numerical simulation was employed to study the influence of geometrical parameters on the current density. The μAEs were fabricated by soft lithography and characterized using both SEM and cyclic voltammetry. Experiments revealed that high pillars enabled enhanced voltammetric current density regardless of the scan rates. The platinum–palladium/multi-walled carbon nanotubes (Pt–Pd/MWCNTs) were coated on the μAEs to improve their electrochemical detection capability. The μAEs demonstrated 1.5 times larger sensitivity compared with the planar electrode when hydrogen peroxide was detected. Furthermore, μAE500 with Pt–Pd/MWCNTs was employed to detect sarcosine, a potential biomarker for prostate cancer. The linear range and limit of detection for sarcosine were from 5 to 60 μM and 1.28 μM, respectively. This detection range covers the concentration of sarcosine in human tissues (0–60 μM). These results suggest that the μAEs have better detection performance in comparison to planar electrodes due to their large surface area and pillar height. This paper provides essential guidelines for the application of μAEs in high sensitivity electrochemical detection of low abundance analytes.

PDMS-based micropillar array electrodes with increased surface area and surface modification were developed to detect biomarkers with high sensitivity.     

Clinical superficial Raman probe aimed for epithelial tumor detection: Phantom model results

Abstract: A novel clinical Raman probe for sampling superficial tissue to improve in vivo detection of epithelial malignancies is compared to a non-superficial probe regarding depth response function and signal-to-noise ratio. Depth response measurements were performed in a phantom tissue model consisting of a polyethylene terephthalate disc in an 20%-Intralipid^® solution. Sampling ranges of 0-200 and 0-300 μm were obtained for the superficial and non-superficial probe, respectively. The mean signal-to-noise ratio of the superficial probe increased by a factor of 2 compared with the non-superficial probe. This newly developed superficial Raman probe is expected to improve epithelial cancer detection in vivo.OCIS codes: (170.3890) Medical optics instrumentation, (170.5660) Raman spectroscopy, (300.6450) Spectroscopy, Raman     

Performance and stability comparison of Aemion™ and Aemion+™ membranes for vanadium redox flow batteries

Anion exchange membranes (AEMs) have shown a significant rise in performance and durability within recent years for applications such as electrolysis and fuel cells. However, in vanadium redox-flow batteries, their use is of particular interest to lower costs and self-discharge rates compared to conventional perfluorinated sulfonic acid-based ionomers such as Nafion. In this work we evaluate the properties of two commercial AEMs, Aemion™ and Aemion+™, based on ex situ characterizations, an accelerated stress test degradation study (>1000 hours storage in highly oxidizing VO₂⁺ electrolyte at 35 °C) and electrochemical battery cycle tests. All membranes feature low ionic resistances of below 320 mΩ cm², enabling battery cycling at 100 mA cm⁻². Aemion shows considerable VO²⁺ formation within a VO₂⁺ stress test, whereas Aemion+ remains almost unaffected in the 1058 h stress test. Evaluating self-discharge data, cycling performance and durability data, Aemion+™ (50 μm thickness) features the best properties for vanadium redox-flow battery operation.

Cycling behaviour of Aemion™ (50 μm), Aemion+™ (50 μm), Aemion+™ (15 μm) and Nafion® 212 (50 μm) at 100 mA cm⁻². (a) Coulombic efficiency, (b) energy efficiency and (c) membrane resistance.     

Silver nanoribbons achieved by picosecond ablation using cylindrical focusing and SERS-based trace detection of TNT

We report the fabrication of silver nanoribbons by picosecond laser ablation of bulk silver (Ag) targets submerged in double distilled water (DDW) using a cylindrical focusing geometry. The laser ablation was performed by ∼2 picosecond laser pulses and the corresponding light sheet engendered by a cylindrical lens of focal length ∼4.5 cm. The input pulse energies employed at a wavelength ∼800 nm in the experiments were ∼1000 μJ, ∼1200 μJ, and ∼1400 μJ. In contrast to the case of ablation with spherical lenses, cylindrical lens ablation produced nanoparticles (NPs) and nanostructures (NSs) in 20% less time. The data obtained from the optical characterizations exemplify that localized surface plasmon resonance (LSPR) was observed at 406 nm, 408 nm, and 410 nm for the input energies of ∼1000 μJ, ∼1200 μJ, and ∼1400 μJ, respectively. Interestingly, it was observed that the ablation performed at an input energy of ∼1200 μJ demonstrated the fabrication of Ag nanoribbons rather than the formation of Ag NPs. Selected area electron diffraction (SAED) data of the nanoribbons recorded revealed their crystalline phase and linear morphology. Ag nanomaterials (NPs and ribbons) synthesized in these experiments were employed to detect the explosive molecules of 2,4,6-trinitrotoluene (TNT) at a concentration 25 nM using the technique of surface enhanced Raman scattering. The enhancement factor in the case of Ag nanoribbons (width of ∼20–30 nm, length of ∼0.6–2 μm), obtained using the cylindrical focussing geometry at input pulse energies of ∼1200 μJ, was estimated to be ∼10⁷ for the 1362 cm⁻¹ mode, corresponding to the symmetric NO₂ stretch of TNT.

We synthesised silver nanomaterials by laser ablation of Ag in DDW with ∼2 ps pulses using cylindrical focussing geometry. Ag nanoribbons were obtained at ∼1200 μJ input pulse and were utilized to detect TNT via surface enhanced Raman scattering studies.     

In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo.OCIS codes: (170.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.1610) Clinical applications, (170.4580) Optical diagnostics for medicine     

Co2+ detection,cell imaging,and temperature sensing based on excitation-independent green-fluorescent N-doped carbon dots

Green-fluorescent N-doped carbon dots (N-CDs) have been successfully fabricated using hydrothermal treatment of tyrosine and urea. The N-CDs obtained showed excitation-independent emission, superior stability and strong photoluminescence with a quantum yield of ca. 9.8%. Based on these striking behaviors, the as-prepared N-CDs have been utilized in Co²⁺ detection and temperature sensing. Due to an inner filter effect, the N-CDs obtained were dramatically quenched by Co²⁺ with linear ranges of 0.1 μM–10 μM, 25 μM–275 μM and 300 μM–400 μM, and they had a detection limit of 0.15 μM. The use of the as-prepared N-CDs has been extended to visualize Co²⁺ fluctuations in living cells. Additionally, the N-CDs obtained have also been applied for use as a temperature sensor with a linear range of 25–80 °C.

Green-fluorescent N-doped carbon dots (N-CDs) have been successfully fabricated using hydrothermal treatment of tyrosine and urea.     

Miniature objective lens with variable focus for confocal endomicroscopy

Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that can rapidly image large areas of luminal organs at microscopic resolution. One of the main challenges for large-area SECM imaging in vivo is maintaining the same imaging depth within the tissue when patient motion and tissue surface irregularity are present. In this paper, we report the development of a miniature vari-focal objective lens that can be used in an SECM endoscopic probe to conduct adaptive focusing and to maintain the same imaging depth during in vivo imaging. The vari-focal objective lens is composed of an aspheric singlet with an NA of 0.5, a miniature water chamber, and a thin elastic membrane. The water volume within the chamber was changed to control curvature of the elastic membrane, which subsequently altered the position of the SECM focus. The vari-focal objective lens has a diameter of 5 mm and thickness of 4 mm. A vari-focal range of 240 μm was achieved while maintaining lateral resolution better than 2.6 μm and axial resolution better than 26 μm. Volumetric SECM images of swine esophageal tissues were obtained over the vari-focal range of 260 μm. SECM images clearly visualized cellular features of the swine esophagus at all focal depths, including basal cell nuclei, papillae, and lamina propria.OCIS codes: (220.3620) Lens system design, (170.1790) Confocal microscopy, (170.2150) Endoscopic imaging, (170.3890) Medical optics instrumentation, (170.2680) Gastrointestinal, (170.4730) Optical pathology     

Solution processed high performance perovskite solar cells based on a silver nanowire-titanium dioxide hybrid top electrode

Longer silver nanowires (AgNWs) > 50 μm and even 90 μm in length have been produced via a polyol method by just changing the stirring speed at a temperature of 130 °C. As-synthesized longer AgNWs are further utilized to construct transparent conductive AgNWs films by a facile drop-casting technique that attained a sheet resistance of 14.5 Ω sq⁻¹ and transmittance over 85%, which is higher than ITO film. The use of a AgNWs/TiO₂ hybrid electrode decreases the sheet resistance to 8.3 Ω sq⁻¹, which is attributed to the enhancement of connections between AgNWs by filling the empty spaces between nanowires and TiO₂ nanoparticles. Transparent perovskite solar cells (PSCs) on the basis of these AgNWs and AgNWs/TiO₂ hybrid top electrodes were made and examined. Due to the light scattering nature of TiO₂ nanoparticles, optical transmittance of the AgNWs/TiO₂ hybrid electrode enhances to some extent after the coating of a TiO₂ layer. Both cell efficiencies and stability of the PSCs are enhanced by using the AgNWs/TiO₂ top electrode. A power conversion efficiency (PCE) of 10.65% was attained for perovskite devices based on only the AgNW electrode with a sheet resistance of 14.5 Ω sq⁻¹. A PCE of 14.53% was achieved after coating with TiO₂ nanoparticles, indicating the layer effect of TiO₂ coating.

Longer silver nanowires (AgNWs) > 50 μm and even 90 μm in length have been produced via a polyol method by just changing the stirring speed at a temperature of 130 °C.     

Ultrahigh speed endoscopic optical coherence tomography using micromotor imaging catheter and VCSEL technology

We developed a micromotor based miniature catheter with an outer diameter of 3.2 mm for ultrahigh speed endoscopic swept source optical coherence tomography (OCT) using a vertical cavity surface-emitting laser (VCSEL) at a 1 MHz axial scan rate. The micromotor can rotate a micro-prism at several hundred frames per second with less than 5 V drive voltage to provide fast and stable scanning, which is not sensitive to the bending of the catheter. The side-viewing probe can be pulled back to acquire a three-dimensional (3D) data set covering a large area on the specimen. The VCSEL provides a high axial scan rate to support dense sampling under high frame rate operation. Using a high speed data acquisition system, in vivo 3D-OCT imaging in the rabbit GI tract and ex vivo imaging of a human colon specimen with 8 μm axial resolution, 8 μm lateral resolution and 1.2 mm depth range in tissue at a frame rate of 400 fps was demonstrated.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.2150) Endoscopic imaging, (170.2680) Gastrointestinal, (140.3600) Three-dimensional image acquisition, (110.2350) Fiber optics imaging, (120.5800) Scanners, (120.3890) Medical optics instrumentation     

Rate of Change of Carotid Intima‐Media Thickness with Magnesium Administration in Abcc6?/? Mice

Pseudoxanthoma elasticum (PXE), caused by mutations in the ABCC6 gene, demonstrates progressive build‐up of calcium phosphate and proteoglycans in the skin, eye, and arteries, and is associated to myocardial infarctions, stroke, blindness, and elevated carotid intima‐media thickness (CIMT). Although CIMT reduction with magnesium (Mg) has been documented in a mouse model for PXE (Abcc6^−/−), it is not clear if Mg is effective in humans with PXE to reduce CIMT. To examine this, we calculated the rate of change of CIMT (washout) in 15‐ and 12‐month‐old Abcc6^−/− mice fed standard rodent diet with or without Mg supplementation for 2 months. Using means in untreated 15‐ and 12‐month‐old Abcc6^−/− mice (145 and 120 μm, respectively), the rate of change was 8.3 μm/month. Using means in treated 15‐ and 12‐month‐old Abcc6^−/− mice (118 and 104.6 μm, respectively), the rate of change was 4.5 μm. Compared to normal progression of CIMT in humans without PXE, PXE has advanced atherosclerosis and possibly a higher CIMT rate of change. This experiment may portend, at least in PXE, the rationale for a 1‐year oral Mg CIMT clinical trial and may be useful for application in other progressive mineralizing disorders like atherosclerosis.     

Telavancin Demonstrates Activity against Methicillin-Resistant Staphylococcus aureus Isolates with Reduced Susceptibility to Vancomycin,Daptomycin, and Linezolid in Broth Microdilution MIC and One-Compartment Pharmacokinetic/Pharmacodynamic Models

Methicillin-resistant Staphylococcus aureus (MRSA) isolates have arisen with reduced susceptibility to several anti-MRSA agents. Telavancin (TLV), a novel anti-MRSA agent, retains low MICs against these organisms. Our objective was to determine the MICs for TLV, daptomycin (DAP), vancomycin (VAN), and linezolid (LZD) against daptomycin-nonsusceptible (DNS) S. aureus, vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), and linezolid-resistant (LZD^r) S. aureus. We also evaluated these agents against each phenotype in pharmacokinetic/pharmacodynamic (PK/PD) models. Seventy DNS, 100 VISA, 180 hVISA, and 25 LZD^r MRSA isolates were randomly selected from our library and tested to determine their MICs against TLV, DAP, VAN, and LZD via broth microdilution and a Trek panel. Four isolates were randomly selected for 168-h in vitro models to evaluate treatment with TLV at 10 mg/kg of body weight/day, DAP at 10 mg/kg/day, VAN at 1 g every 12 h (q12h), and LZD at 600 mg q12h. The MIC_50/90 for TLV, DAP, VAN, and LZD against 70 DNS S. aureus isolates were 0.06/0.125 μg/ml, 2/4 μg/ml, 1/2 μg/ml, and 2/2 μg/ml, respectively. Against 100 VISA isolates, the MIC_50/90 were 0.06/0.125 μg/ml, 1/1 μg/ml, 4/8 μg/ml, and 1/2 μg/ml, respectively. Against 170 hVISA isolates, the MIC_50/90 were 0.06/0.125 μg/ml, 0.5/1 μg/ml, 1/2 μg/ml, and 1/2 μg/ml, respectively. Against 25 LZD^r isolates, the MIC_50/90 were 0.03/0.06 μg/ml, 1/1 μg/ml, 2/2 μg/ml, and 8/8 μg/ml, respectively. The TLV MIC was >0.125 μg/ml for 10/365 (2.7%) isolates. In PK/PD models, TLV was universally bactericidal at 168 h and statistically superior to all antibiotics against DNS S. aureus strain R2334. These data further establish the potency of TLV against resistant MRSA. The model data demonstrate in vitro bactericidal activity of TLV against hVISA, VISA, DNS S. aureus, and LZD^r S. aureus strains. Further clinical research is warranted.     

A 5-mm piezo-scanning fiber device for high speed ultrafast laser microsurgery

Towards developing precise microsurgery tools for the clinic, we previously developed image-guided miniaturized devices using low repetition rate amplified ultrafast lasers for surgery. To improve the speed of tissue removal while reducing device diameter, here we present a new 5-mm diameter device that delivers high-repetition rate laser pulses for high speed ultrafast laser microsurgery. The device consists of an air-core photonic bandgap fiber (PBF) for the delivery of high energy pulses, a piezoelectric tube actuator for fiber scanning, and two aspheric lenses for focusing the light. Its inline optical architecture provides easy alignment and substantial size reduction to 5 mm diameter as compared to our previous MEMS-scanning devices while realizing improved intensity squared (two-photon) lateral and axial resolutions of 1.16 μm and 11.46 μm, respectively. Our study also sheds light on the maximum pulse energies that can be delivered through the air-core PBF and identifies cladding damage at the input facet of the fiber as the limiting factor. We have achieved a maximum energy delivery larger than 700 nJ at 92% coupling efficiency. An in depth analysis reveals how this value is greatly affected by possible slight misalignments of the beam during coupling and the measured small beam pointing fluctuations. In the absence of these imperfections, self-phase modulation becomes the limiting factor for the maximum energy delivery, setting the theoretical upper bound to near 2 μJ for a 1-m long, 7-μm, air-core PBF. Finally, the use of a 300 kHz repetition rate fiber laser enabled rapid ablation of 150 µm x 150 µm area within only 50 ms. Such ablation speeds can now allow the surgeons to translate the surgery device as fast as ~4 mm/s to continuously remove a thin layer of a 150 µm wide tissue. Thanks to a high optical transmission efficiency of the in-line optical architecture of the device and improved resolution, we could successfully perform ablation of scarred cheek pouch tissue, drilling through a thin slice. With further development, this device can serve as a precise and high speed ultrafast laser scalpel in the clinic.OCIS codes: (170.1020) Ablation of tissue, (140.7090) Ultrafast lasers, (180.4315) Nonlinear microscopy, (170.3890) Medical optics instrumentation, (190.4370) Nonlinear optics, fibers     

Variations in Amino Acid Composition of Antisense Peptide-Phosphorodiamidate Morpholino Oligomer Affect Potency against Escherichia coli In Vitro and In Vivo

The potency of antisense peptide-phosphorodiamidate morpholino oligomers (PPMOs) was improved by varying the peptide composition. An antisense phosphorodiamidate morpholino oligomer (PMO) complementary to the mRNA of the essential gene acpP (which encodes the acyl carrier protein required for lipid biosynthesis) in Escherichia coli was conjugated to the 5′ ends of various cationic membrane-penetrating peptides. Each peptide had one of three repeating sequence motifs: C-N-N (motif 1), C-N (motif 2), or C-N-C (motif 3), where C is a cationic residue and N is a nonpolar residue. Variations in the cationic residues included arginine, lysine, and ornithine (O). Variations in the nonpolar residues included phenylalanine, valine, β-alanine (B), and 6-aminohexanoic acid (X). The MICs of the PPMOs varied from 0.625 to >80 μM (about 3 to 480 μg/ml). Three of the most potent were the (RX)₆B-, (RXR)₄XB-, and (RFR)₄XB-AcpP PMOs, which were further tested in mice infected with E. coli. The (RXR)₄XB-AcpP PMO was the most potent of the three conjugates tested in mice. The administration of 30 μg (1.5 mg/kg of body weight) (RXR)₄XB-AcpP PMO at 15 min postinfection reduced CFU/ml in blood by 10² to 10³ within 2 to 12 h compared to the numbers in water-treated controls. All mice treated with 30 μg/dose of (RXR)₄XB-AcpP PMO survived infection, whereas all water-treated mice died 12 h postinfection. The reduction in CFU/ml in blood was proportional to the dose of PPMO from 30 to 300 μg/ml. In summary, the C-N-C motif was more effective than the other two motifs, arginine was more effective than lysine or ornithine, phenylalanine was more effective than 6-aminohexanoic acid in vitro but not necessarily in vivo, and (RXR)₄XB-AcpP PMO reduced bacterial infection and promoted survival at clinically relevant doses.     

Performance study of μDMFC with foamed metal cathode current collector

Micro Direct Methanol Fuel Cells (μDMFCs) often have application in moveable power due to their green and portable nature. In a μDMFC''s structure, a current collector of the μDMFC needs to have high corrosion resistance such that the μDMFC can work for a long time in a redox reaction and respond to variable environmental conditions. To this end, four cathode current collectors were prepared. The materials selected were foam stainless steel (FSS) and foam titanium (FT), with fields of hole type and grid type. The performance of μDMFC with different cathode collector types was investigated by I–V–P polarization curves, Electrochemical Impedance Spectroscopy (EIS), and discharge test. The experimental results show that the maximum power density of the hole-type FSS cathode current collector μDMFC (HFSS-μDMFC) is 49.53 mW cm⁻² at 70 °C in the methanol solution of 1 mol L⁻¹, which is 70.15% higher than that of the hole-type FT cathode current collector μDMFC (HFT-μDMFC). The maximum power density of the grid-type FSS cathode current collector μDMFC (GFSS-μDMFC) is 22.60 mW cm⁻², which is 11.99% higher than that of the grid-type FT cathode current collector μDMFC (GFT-μDMFC). The performance of the HFSS-μDMFC is optimal in the methanol solution of 1 mol L⁻¹.

Micro Direct Methanol Fuel Cells (μDMFCs) often have application in moveable power due to their green and portable nature.     

Penetration of chlorhexidine into human skin

This study evaluated a model of skin permeation to determine the depth of delivery of chlorhexidine into full-thickness excised human skin following topical application of 2% (wt/vol) aqueous chlorhexidine digluconate. Skin permeation studies were performed on full-thickness human skin using Franz diffusion cells with exposure to chlorhexidine for 2 min, 30 min, and 24 h. The concentration of chlorhexidine extracted from skin sections was determined to a depth of 1,500 μm following serial sectioning of the skin using a microtome and analysis by high-performance liquid chromatography. Poor penetration of chlorhexidine into skin following 2-min and 30-min exposures to chlorhexidine was observed (0.157 ± 0.047 and 0.077 ± 0.015 μg/mg tissue within the top 100 μm), and levels of chlorhexidine were minimal at deeper skin depths (less than 0.002 μg/mg tissue below 300 μm). After 24 h of exposure, there was more chlorhexidine within the upper 100-μm sections (7.88 ± 1.37 μg/mg tissue); however, the levels remained low (less than 1 μg/mg tissue) at depths below 300 μm. There was no detectable penetration through the full-thickness skin. The model presented in this study can be used to assess the permeation of antiseptic agents through various layers of skin in vitro. Aqueous chlorhexidine demonstrated poor permeation into the deeper layers of the skin, which may restrict the efficacy of skin antisepsis with this agent. This study lays the foundation for further research in adopting alternative strategies for enhanced skin antisepsis in clinical practice.     

Pharmacology of a New 1-Oxa-β-lactam (LY127935) in Normal Volunteers

The pharmacokinetics of 1-oxa-β-lactam (LY127935), a new semisynthetic β-lactam antibiotic, was studied in four healthy adult volunteers (mean age of 27 years, mean body surface area ± standard error [SE] of 1.87 ± 0.08 m², and mean creatinine clearance ± SE of 116 ± 12 ml/min per 1.73 m²). Immediately after completion of a 1-g, 20-min intravenous (i.v.) infusion, the mean serum level ± SE was 70.7 ± 8.5 μg/ml. After a 1-g intramuscular (i.m.) injection, peak serum levels occurred from 30 min to 1 h, and the mean peak serum level ± SE was 52.3 ± 1.6 μg/ml. Beginning at 1 h, the serum concentrations after i.m. administration were higher than those after i.v. administration. At 8 h, the mean serum level ± SE was 3.8 ± 0.6 μg/ml after completion of the i.v. infusion and 4.8 ± 0.7 μg/ml after the i.m. injection. The mean serum half-lives for the β phase i.v. and i.m. administration were similar (2.3 ± 0.7 h and 2.4 ± 0.2 h, respectively). The mean apparent volume of distribution ± SE was 16.6 ± 1.9 liters per 1.73 m². The mean serum clearance ± SE of LY127935 was 85.4 ± 12.7 ml/min per 1.73 m², and the mean renal clearance ± SE was 54.5 ± 4.4 ml/min per 1.73 m.² Urine concentrations of LY127935 were at least 140 μg/ml in each volunteer during the first 12 h after i.m. or i.v. administration. The mean percentages of the dose recovered in the urine ± SE within 2 h after i.v. or i.m. administration were similar (30 ± 4 and 34 ± 11, respectively). Only 67 ± 3% and 75 ± 13% were recovered in the urine within 24 h after i.v. and i.m. administration, respectively.