Structural basis for Cas9 off-target activity.

The target DNA specificity of the CRISPR-associated genome editor nuclease Cas9 is determined by complementarity to a 20-nucleotide segment in its guide RNA. However, Cas9 can bind and cleave partially complementary off-target sequences, which raises safety concerns for its use in clinical applications. Here, we report crystallographic structures of Cas9 bound to bona fide off-target substrates, revealing that off-target binding is enabled by a range of noncanonical base-pairing interactions within the guide:off-target heteroduplex. Off-target substrates containing single-nucleotide deletions relative to the guide RNA are accommodated by base skipping or multiple noncanonical base pairs rather than RNA bulge formation. Finally, PAM-distal mismatches result in duplex unpairing and induce a conformational change in the Cas9 REC lobe that perturbs its conformational activation. Together, these insights provide a structural rationale for the off-target activity of Cas9 and contribute to the improved rational design of guide RNAs and off-target prediction algorithms.

A double-blind, randomized, two-part, two-period crossover study to evaluate the pharmacokinetics of caffeine versus d9-caffeine in healthy subjects.

The deuterium kinetic isotope effect has been used to affect the cytochrome P450 metabolism of the deuterated versions of substances. This study compares the pharmacokinetics of caffeine, a Generally Recognized As Safe food and beverage ingredient, versus d9-caffeine, a potential caffeine alternative, and their respective metabolites at two dose levels in 20 healthy adults. A single dose of 50 mg or 250 mg of caffeine, or a molar-equivalent dose of d9-caffeine, were orally administered in solution with blood samples collected for up to 48 h post-dose. Plasma concentrations of parent and metabolites were analyzed using validated LC-MS/MS methods. Both d9-caffeine and caffeine were rapidly absorbed; however, d9-caffeine exhibited a higher (ca. 29%-43%) Cmax and 4-5-fold higher AUClast than caffeine, and lower Cmax, lower AUClast, and a 5-10-fold reduction in the relative exposure to the active metabolites of caffeine. Results were consistent in normal and rapid metabolizers, and both substances were well tolerated.

Facile Generation of Thermally Activated Delayed Fluorescence and Fabrication of Highly Efficient Non-Doped OLEDs Based on Triazine Derivatives.

A series of donor-acceptor-donor triazine-based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain highly efficient blue-emitting OLEDs with non-doped emitting layers (EMLs). The targeted molecules use a triazine core as the electron acceptor, and a benzene ring as the conjugated linker with different electron donors to alternate the energy level of the HOMO to further tune the emission color. The introduction of long alkyl chains on the triazine core inhibits the unwanted intermolecular D-D/A-A-type π-π interactions, resulting in the intermolecular D-A charge transfer. The weak aggregation-caused quenching (ACQ) effect caused by the suppressed intermolecular D-D/A-A-type π-π interaction further enhances the emission. The crowded molecular structure allows the electron donor and acceptor to be nearly orthogonal, thereby reducing the energy gap between triplet and singlet excited states (ΔEST ). As a result, blue-emitting devices with TH-2DMAC and TH-2DPAC non-doped EMLs showed satisfactory efficiencies of 12.8 % and 15.8 %, respectively, which is one of the highest external quantum efficiency (EQEs) reported for blue TADF emitters (λpeak <475 nm), demonstrating that our tailored molecular designs are promising strategies to endow OLEDs with excellent electroluminescent performances.

Coupling of a light-emitting diode with surface plasmon polariton or localized surface plasmon induced on surface silver gratings of different geometries.

A metal grating on top of a light-emitting diode (LED) with a designed grating period for compensating the momentum mismatch can enhance the surface plasmon polariton (SPP) coupling effect with the quantum wells (QWs) to improve LED performance. Here, we demonstrate the experimental results showing that the induced localized surface plasmon (LSP) resonance on such a metal grating can dominate the QW coupling effect for improving LED performance, particularly when grating ridge height is large. The finding is illustrated by fabricating Ag gratings on single-QW, green-emitting LEDs of different p-type thicknesses with varied grating ridge height and width such that the distance between the grating ridge tip and the QW can be controlled. Reflection spectra of the Ag grating structures are measured and simulated to identify the SPP or LSP resonance behaviors at the QW emission wavelength. The measured results of LED performances show that in the LED samples under study, both SPP and LSP couplings can lead to significant enhancements of internal quantum efficiency and electroluminescence intensity. At the designated QW emission wavelength, with a grating period theoretically designed for momentum matching, the LSP coupling effect is stronger, when compared with SPP coupling.

Efficiency enhancement of light color conversion through surface plasmon coupling.

The efficiency enhancement of light color conversion from blue quantum well (QW) emission into red quantum dot (QD) emission through surface plasmon (SP) coupling by coating CdSe/ZnS QDs on the top of an InGaN/GaN QW light-emitting diode (LED) is demonstrated. Ag nanoparticles (NPs) are fabricated within a transparent conductive Ga-doped ZnO interlayer to induce localized surface plasmon (LSP) resonance for simultaneously coupling with the QWs and QDs. Such a coupling process generates three enhancement effects, including QW emission, QD absorption at the QW emission wavelength, and QD emission, leading to an overall enhancement effect of QD emission intensity. An Ag NP geometry for inducing an LSP resonance peak around the middle between the QW and QD emission wavelengths results in the optimized condition for maximizing QD emission enhancement. Internal quantum efficiency and photoluminescence (PL) decay time measurements are performed to show consistent results with LED performance characterizations, even though the QD absorption of PL excitation laser may mix with the SP-induced QD absorption enhancement effect in PL measurement.

Further emission efficiency improvement of a commercial-quality light-emitting diode through surface plasmon coupling.

It is usually believed that surface plasmon (SP) coupling is practically useful only for improving the performance of a light-emitting diode (LED) with a low intrinsic internal quantum efficiency (IQE). In this Letter, we demonstrate that the performance of a commercial-quality blue LED with a high IQE (>80%) can still be significantly improved through SP coupling based on a surface Ag nanoparticle (NP) structure. The performance improvement of such an LED is achieved by increasing the Mg doping concentration in its p-AlGaN electron blocking layer to enhance the hole injection efficiency such that the p-GaN layer thickness can be significantly reduced without sacrificing its electrical property. In this situation, the distance between surface Ag NPs and quantum wells is decreased and hence SP coupling strength is increased. By reducing the distance between the surface Ag NPs and the top quantum well to 66 nm, the IQE can be increased to almost 90% (an ∼11% enhancement) and the electroluminescence intensity can be enhanced by ∼24%.

Dependencies of surface plasmon coupling effects on the p-GaN thickness of a thin-p-type light-emitting diode.

The high performance of a light-emitting diode (LED) with the total p-type thickness as small as 38 nm is demonstrated. By increasing the Mg doping concentration in the p-AlGaN electron blocking layer through an Mg pre-flow process, the hole injection efficiency can be significantly enhanced. Based on this technique, the high LED performance can be maintained when the p-type layer thickness is significantly reduced. Then, the surface plasmon coupling effects, including the enhancement of internal quantum efficiency, increase in output intensity, reduction of efficiency droop, and increase of modulation bandwidth, among the thin p-type LED samples of different p-type thicknesses that are compared. These advantageous effects are stronger as the p-type layer becomes thinner. However, the dependencies of these effects on p-type layer thickness are different. With a circular mesa size of 10 µm in radius, through surface plasmon coupling, we achieve the record-high modulation bandwidth of 625.6 MHz among c-plane GaN-based LEDs.

Effect of the CF3 Substituents on the Charge-Transfer Kinetics of High-Efficiency Cyclometalated Ruthenium Sensitizers.

Six thiocyanate-free complexes, DUY1-DUY6, were synthesized, and their application in a dye-sensitized solar cell was studied to explore the effect of the CF3 substituent positioned in the ancillary ligand and the structure of the anchoring ligand on the physicochemical properties, charge-transfer kinetics, and photovoltaic properties of ruthenium sensitizers. When the electron-withdrawing groups were installed on the cyclometalating ligands and their π conjugation of the ancillary ligand was extended, the frontier orbital energy levels of the ruthenium complex appeared to be sufficient for effective electron injection and dye regeneration, at the same time having high light-harvesting ability. Two electron-withdrawing CF3 groups meta to the cyclometalated position reduce the electron density at the metal center less seriously than o-CF3 and p-CF3 groups. The sensitizers containing a m-CF3 group also reveal a more favorable distribution of ß lowest unoccupied spin orbital for interaction between the oxidized dyes and the iodide ion, which promotes dye regeneration. The absorption profiles of DUY1-DUY4 adsorbed a TiO2 film extended to longer wavelength compared to those in an N,N-dimethylformamide solution, especially DUY1 and DUY2 dyes, which have λmax red shifts of up to 30 nm. The DUY2-dyed cell exhibited the highest efficiency of 9.03%, while the power conversion efficiencies of DUY1-, DUY3-, DUY4-, and N719-based devices were 7.40%, 7.01%, 8.92%, and 8.63%, respectively. DUY5 and DUY6 (the side products of DUY3 and DUY4) without anchoring groups have very weak physical adsorption on a TiO2 anode. The corresponding cells exhibit very low efficiency (<0.1%), although both dyes have high light-harvesting ability and proper frontier orbital energy levels.

Regularly patterned multi-section GaN nanorod arrays grown with a pulsed growth technique.

The growth of regularly patterned multi-section GaN nanorod (NR) arrays based on a pulsed growth technique with metalorganic chemical vapor deposition is demonstrated. Such an NR with multiple sections of different cross-sectional sizes is formed by tapering a uniform cross section to another through stepwise decreasing of the Ga supply duration to reduce the size of the catalytic Ga droplet. Contrast line structures are observed in either a scanning electron microscopy or transmission electron microscopy image of an NR. Such a contrast line-marker corresponds to a thin Ga-rich layer formed at the beginning of GaN precipitation of a pulsed growth cycle and illustrates the boundary between two successive growth cycles in pulsed growth. By analyzing the geometry variation of the contrast line-markers, the morphology evolution in the growth of a multi-section NR, including a tapering process, can be traced. Such a morphology variation is controlled by the size of the catalytic Ga droplet and its coverage range on the slant facets at the top of an NR. The comparison of emission spectra between single-, two-, and three-section GaN NRs with sidewall InGaN/GaN quantum wells indicates that a multi-section NR can lead to a significantly broader sidewall emission spectrum.

Evaluating the blue-shift behaviors of the surface plasmon coupling of an embedded light emitter with a surface Ag nanoparticle by adding a dielectric interlayer or coating.

The surface plasmon (SP) coupling behaviors of an embedded light emitter or radiating dipole in GaN with a surface Ag nanoparticle (NP) in four structures of different added dielectric geometries, including an extended dielectric interlayer (DI) and a DI of a finite width between the Ag NP and GaN, a dielectric coating on the Ag NP, and no dielectric addition, are numerically compared. Either an added DI or dielectric coating can lead to the blue shift of localized surface plasmon (LSP) dipole resonance peak or the spectral peak of radiated power enhancement ratio with respect to that of the structure without dielectric addition. A smaller dielectric refractive-index or a larger dielectric thickness results in a larger blue-shift range. Under the condition of the same dielectric refractive-index and thickness, the structure of a DI with a finite width leads to the largest blue-shift range, followed by the structure of an extended DI and then the structure of a dielectric coating. In a practical application, for a given emission wavelength of a blue-emitting quantum well, the emission enhancement effect through SP coupling depends on the LSP resonance strength at this wavelength. Our study also shows that although the LSP resonance peak can be blue-shifted by reducing the size of a surface Ag NP, its SP coupling strength is dramatically reduced. Adding a DI or dielectric coating is a more practical approach for shifting the major LSP resonance mode of a surface Ag NP from the green into blue range.

Modulation behaviors of surface plasmon coupled light-emitting diode.

The modulation bandwidths of the light-emitting diodes (LEDs) of different mesa sizes with and without surface plasmon (SP) coupling effect are compared. Due to the significant increase of carrier decay rate, within the size range of LED square-mesa from 60 through 300 micron and the injected current-density range from 139 through 1667 A/cm², the SP coupling can lead to the enhancement of modulation bandwidth by 44-48%, independent of the variations of LED mesa size or injected current level. The enhancement ratios of modulation bandwidth of the samples with SP coupling with respect to those of the samples without SP coupling are lower than the corresponding ratios of the square-root of photoluminescence decay rate due to the increases of their RC time constants (the product of device resistance and capacitance). The increases of the RC time constants in the samples with SP coupling are attributed to the increases of their device resistance levels when the Ag nanoparticles and GaZnO dielectric interlayer are added to the LED surface for effectively inducing SP coupling.

Multi-section core-shell InGaN/GaN quantum-well nanorod light-emitting diode array.

The growth of a two-section, core-shell, InGaN/GaN quantum-well (QW) nanorod- (NR-) array light-emitting diode device based on a pulsed growth technique with metalorganic chemical vapor deposition is demonstrated. A two-section n-GaN NR is grown through a tapering process for forming two uniform NR sections of different cross-sectional sizes. The cathodoluminescence (CL), photoluminescence (PL), and electrolumines-cence (EL) characterization results of the two-section NR structure are compared with those of a single-section NR sample, which is prepared under the similar condition to that for the first uniform NR section of the two-section sample. All the CL, PL, and EL spectra of the two-section sample (peaked between 520 and 525 nm) are red-shifted from those of the single-section sample (peaked around 490 nm) by >30 nm in wavelength. Also, the emitted spectral widths of the two-section sample become significantly larger than their counterparts of the single-section sample. The PL spectral full-width at half-maximum increases from ~37 to ~61 nm. Such variations are attributed to the higher indium incorporation in the sidewall QWs of the two-section sample due to the stronger strain relaxation in an NR section of a smaller cross-sectional size and the more constituent atom supply from the larger gap volume between neighboring NRs.

Thermally induced variations of strain condition and emission behavior in flat and bendable light-emitting diodes on different substrates.

The emission behaviors of four light-emitting diodes (LEDs) of different substrate structures, including a lateral LED grown on sapphire, a vertical LED wafer-bonded onto Si (111), a bendable LED Ag-epoxied onto a flat metal, and another bendable LED Ag-epoxied onto a metal of a curved surface, under different duty cycles of current injection are compared. Their different variation trends of emission behavior with injection duty cycle are attributed to the different thermally-induced strain conditions in the epitaxial layers, which are controlled by their substrate structures, in increasing injection duty cycle or current level. The results of Raman scattering measurements during LED operation show that a stronger tensile strain is generated under heating for reducing the quantum-confined Stark effect and hence increasing emission efficiency when the epitaxial layer is not tightly bonded onto a hard substrate. Such a behavior is particularly stronger when the epitaxial layer is bent.

Multi-mechanism efficiency enhancement in growing Ga-doped ZnO as the transparent conductor on a light-emitting diode.

The combined effects of a few mechanisms for emission efficiency enhancement produced in the overgrowth of the transparent conductor layer of Ga-doped ZnO (GaZnO) on a surface Ag-nanoparticle (NP) coated light-emitting diode (LED), including surface plasmon (SP) coupling, current spreading, light extraction, and contact resistivity reduction, are demonstrated. With a relatively higher GaZnO growth temperature (350 °C), melted Ag NPs can be used as catalyst for forming GaZnO nanoneedles (NNs) through the vapor-liquid-solid growth mode such that light extraction efficiency can be increased. Meanwhile, residual Ag NPs are buried in a simultaneously grown GaZnO layer for inducing SP coupling. With a relatively lower GaZnO growth temperature (250 °C), all the Ag NPs are preserved for generating a stronger SP coupling effect. By using a thin annealed GaZnO interlayer on p-GaN before Ag NP fabrication, the contact resistivity at the GaZnO/p-GaN interface and hence the overall device resistance can be reduced. Although the use of this interlayer blue-shifts the localized surface plasmon resonance peak of the fabricated Ag NPs from the quantum well emission wavelength of the current study (535 nm) such that the SP coupling effect becomes weaker, it is useful for enhancing the SP coupling effect in an LED with a shorter emission wavelength.

Regularly patterned non-polar InGaN/GaN quantum-well nanorod light-emitting diode array.

The growth and process of a regularly patterned nanorod (NR)- light-emitting diode (LED) array with its emission from sidewall non-polar quantum wells (QWs) are demonstrated. A pyramidal un-doped GaN structure is intentionally formed at the NR top for minimizing the current flow through this portion of the NR such that the injection current can be effectively guided to the sidewall m-plane InGaN/GaN QWs for emission excitation by a conformal transparent conductor (GaZnO). The injected current density at a given applied voltage of the NR LED device is similar to that of a planar c-plane or m-plane LED. The blue-shift trend of NR LED output spectrum with increasing injection current is caused by the non-uniform distributions of QW width and indium content along the height on a sidewall. The photoluminescence spectral shift under reversed bias confirms that the emission of the fabricated NR LED comes from non-polar QWs.

Dependencies of the emission behavior and quantum well structure of a regularly-patterned, InGaN/GaN quantum-well nanorod array on growth condition.

To achieve green emission from the sidewall non-polar quantum wells (QWs) of a GaN nanorod (NR) light-emitting diode, regularly patterned InGaN/GaN QW NR arrays are grown under various growth conditions of indium supply rate, QW growth temperature, and QW growth time for comparing their emission wavelength variations of the top-face c-plane and sidewall m-plane QWs based on photoluminescence and cathodoluminescence (CL) measurements. Although the variation trends of QW emission wavelength by changing those growth conditions in the NR structure are similar to those in the planar structure, the emission wavelength range of the QWs on an NR is significantly shorter than that in a planar structure under the same growth conditions. Under the growth conditions for a longer NR QW emission wavelength, the difference of emission wavelength between the top-face and sidewall QWs is smaller. Also, the variation range of the emission wavelength from the sidewall QWs over different heights on the sidewall becomes larger. On the other hand, strain state analysis based on transmission electron microscopy is undertaken to calibrate the average QW widths and average indium contents in the two groups of QW of an NR. The variation trends of the calibrated QW widths and indium contents are consistent with those of the CL emission wavelengths from various portions of NR QWs.

Efficiency improvement of a vertical light-emitting diode through surface plasmon coupling and grating scattering.

The enhancement of output intensity, the generation of polarized output, and the reduction of the efficiency droop effect in a surface plasmon (SP) coupled vertical light-emitting diode (LED) with an Ag nano-grating structure located between the p-GaN layer and the wafer bonding metal for inducing SP coupling with the InGaN/GaN quantum wells (QWs) are demonstrated. In fabricating the vertical LED, the patterned sapphire substrate is removed with a photoelectrochemical liftoff technique. Based on the reflection measurement from the metal grating structure and the numerical simulation result, it is found that the localized surface plasmon (LSP) resonance induced around the metal grating crest plays the major role in the SP-QW coupling process although a hybrid mode of LSP and surface plasmon polariton can be generated in the coupling process. By adding a surface grating structure to the SP-coupled vertical LED on the n-GaN side, the output intensity is further enhanced, the output polarization ratio is further increased, and the efficiency droop effect is further suppressed.

Independent variations of applied voltage and injection current for controlling the quantum-confined Stark effect in an InGaN/GaN quantum-well light-emitting diode.

A reverse-biased voltage is applied to either device in the vertical configuration of two light-emitting diodes (LEDs) grown on patterned and flat Si (110) substrates with weak and strong quantum-confined Stark effects (QCSEs), respectively, in the InGaN/GaN quantum wells for independently controlling the applied voltage across and the injection current into the p-i-n junction in the lateral configuration of LED operation. The results show that more carrier supply is needed in the LED of weaker QCSE to produce a carrier screening effect for balancing the potential tilt in increasing the forward-biased voltage, when compared with the LED of stronger QCSE. The small spectral shift range in increasing injection current in the LED of weaker QCSE is attributed not only to the weaker QCSE, but also to its smaller device resistance such that a given increment of applied voltage leads to a larger increment of injection current. From a viewpoint of practical application in LED operation, by applying a reverse-biased voltage in the vertical configuration, the applied voltage and injection current in the lateral configuration can be independently controlled by adjusting the vertical voltage for keeping the emission spectral peak fixed.

Phosphor-free, white-light LED under alternating-current operation.

A light-emitting diode structure, consisting of a p-GaN layer, a CdZnO/ZnO quantum-well (QW) structure, a high-temperature-grown ZnO layer, and a GaZnO layer, is fabricated. Under forward bias, the device effectively emits green-yellow light, from the QW structure, at the rim of device mesa. Under reverse bias, electrons in the valence band of the p-GaN layer move into the conduction band of the GaZnO layer, through a QW-state-assisted tunneling process, to recombine with the injected holes in the GaZnO layer, for emitting yellow-red and shallow ultraviolet light over the entire mesa area. Also, carrier recombination in the p-GaN layer produces blue light. By properly designing the thickness of the high-temperature grown ZnO layer, the emission intensity under forward bias can be controlled such that, under alternating-current operation at 60 Hz, the spatial and spectral mixtures of the emitted lights of complementary colors, under forward and reverse biases, result in white light generation based on persistence of vision.

Vertical light-emitting diodes with surface gratings and rough surfaces for effective light extraction.

For enhancing the light extraction of a light-emitting diode, surface grating fabrication based on a simple method of combining photoelectrochemical (PEC) etching with phase mask interferometry has been demonstrated. To understand the optimum grating period in forming a surface grating on a vertical light-emitting diode (VLED), we construct a Llyod's interferometer within PEC electrolyte (KOH) to fabricate surface gratings of various periods on VLEDs for comparing their light extraction efficiencies. Also, to compare the effectiveness of light extraction enhancement between surface grating and rough surface, VLEDs with the rough surfaces fabricated with two different KOH wet etching methods are fabricated. The comparisons of VLED characterizations show that among those grating VLEDs, the light extraction is more effective in a VLED of a smaller grating period. Also, compared with VLEDs of rough surfaces, the grating VLEDs of short grating periods (<2 µm) have the higher light extraction efficiencies, even though the root-mean-square roughness of the rough surface is significantly larger than the grating groove depth.