Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development.

Leveraging AAVs' versatile tropism and labeling capacity, we expanded the scale of in vivo CRISPR screening with single-cell transcriptomic phenotyping across embryonic to adult brains and peripheral nervous systems. Through extensive tests of 86 vectors across AAV serotypes combined with a transposon system, we substantially amplified labeling efficacy and accelerated in vivo gene delivery from weeks to days. Our proof-of-principle in utero screen identified the pleiotropic effects of Foxg1, highlighting its tight regulation of distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% by lentivirus, to achieve analysis of over 30,000 cells in one experiment and enable massively parallel in vivo Perturb-seq. Compatible with various phenotypic measurements (single-cell or spatial multi-omics), it presents a flexible approach to interrogate gene function across cell types in vivo, translating gene variants to their causal function.

Quantitative evaluation of biomechanical properties of optic nerve head by using acoustic radiation force optical coherence elastography.

Significance: Previous studies have demonstrated that the biomechanical properties of the optic nerve head (ONH) are associated with a variety of ophthalmic diseases; however, they have not been adequately studied. Aim: We aimed to obtain a two-dimensional (2D) velocity distribution image based on the one-to-one correspondence between velocity values and position using the acoustic radiation force optical coherence elastography (ARF-OCE) technique combined with a 2D phase velocity algorithm. Approach: An ARF-OCE system has the advantages of non-invasive detection, high resolution, high sensitivity, and high-speed imaging for quantifying the biomechanical properties of the ONH at different intraocular pressures (IOPs) and detection directions. The 2D phase velocity algorithm is used to calculate the phase velocity values at each position within the imaging region, and then the 2D velocity distribution image is realized by mapping the velocity values to the corresponding structure based on the one-to-one relationship between velocity and position. The elasticity changes can be read directly according to the quantitative relationship between Lamb wave velocity and Young's modulus. Results: Our quantitative results show that the phase velocity and Young's modulus of the ONH increase by 32.50% and 129.44%, respectively, with increasing IOP, which is in general agreement with the results of previous studies, but they did not produce large fluctuations with the constant change of the ONH direction. These results are consistent with the changes of elastic information in the 2D velocity distribution image. Conclusions: The results suggest that the ARF-OCE technology has great potential in detecting the biomechanical properties of the ONH at different IOPs and directions, and thus may offer the possibility of clinical applications.

Polarity reversal and strain modulation of Janus MoSSe/GaN polar semiconductor heterostructures.

Beyond three-dimensional (3D) architectures, polar semiconductor heterostructures are developing in the direction of two-dimensional (2D) scale with mix-dimensional integration for novel properties and multifunctional applications. Herein, we stacked 2D Janus MoSSe and 3D wurtzite GaN polar semiconductors to construct MoSSe/GaN polar heterostructures by polarity configurations. The structural stability was enhanced as binding energy changed from -0.08 eV/-0.17 eV in the N polarity to -0.24 eV/-0.42 eV in the Ga polarity. In particular, the polarity reversal of GaN in contact with Janus MoSSe not only determined the charge transfer direction but also significantly increased the electrostatic potential difference from 0.71 eV/0.78 eV in the N polarity to 3.13 eV/2.24 eV in the Ga polarity. In addition, strain modulation was further utilized to enhance interfacial polarization and tune the electronic energy band profiles of Janus MoSSe/GaN polar heterostructures. By applying in-plane biaxial strains, the AA and AA' polarity configurations induced band alignment transition from type I (tensile) to type II (compressive). As a result, both the polarity reversal and strain modulation provide effective ways for the multifunctional manipulation and facile design of Janus MoSSe/III-nitrides polar heterostructures, which broaden the Janus 2D/3D polar semiconducting devices in advanced electronics, optoelectronics, and energy harvesting applications.

Massively parallel in vivo Perturb-seq reveals cell type-specific transcriptional networks in cortical development.

Systematic analysis of gene function across diverse cell types in vivo is hindered by two challenges: obtaining sufficient cells from live tissues and accurately identifying each cell's perturbation in high-throughput single-cell assays. Leveraging AAV's versatile cell type tropism and high labeling capacity, we expanded the resolution and scale of in vivo CRISPR screens: allowing phenotypic analysis at single-cell resolution across a multitude of cell types in the embryonic brain, adult brain, and peripheral nervous system. We undertook extensive tests of 86 AAV serotypes, combined with a transposon system, to substantially amplify labeling and accelerate in vivo gene delivery from weeks to days. Using this platform, we performed an in utero genetic screen as proof-of-principle and identified pleiotropic regulatory networks of Foxg1 in cortical development, including Layer 6 corticothalamic neurons where it tightly controls distinct networks essential for cell fate specification. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% (mediated by lentivirus), and achieve analysis of over 30,000 cells in one experiment, thus enabling massively parallel in vivo Perturb-seq. Compatible with various perturbation techniques (CRISPRa/i) and phenotypic measurements (single-cell or spatial multi-omics), our platform presents a flexible, modular approach to interrogate gene function across diverse cell types in vivo, connecting gene variants to their causal functions.

2D-materials-integrated optoelectromechanics: recent progress and future perspectives.

The discovery of two-dimensional (2D) materials has gained worldwide attention owing to their extraordinary optical, electrical, and mechanical properties. Due to their atomic layer thicknesses, the emerging 2D materials have great advantages of enhanced interaction strength, broad operating bandwidth, and ultralow power consumption for optoelectromechanical coupling. The van der Waals (vdW) epitaxy or multidimensional integration of 2D material family provides a promising platform for on-chip advanced nano-optoelectromechanical systems (NOEMS). Here, we provide a comprehensive review on the nanomechanical properties of 2D materials and the recent advances of 2D-materials-integrated nano-electromechanical systems and nano-optomechanical systems. By utilizing active nanophotonics and optoelectronics as the interface, 2D active NOEMS and their coupling effects are particularly highlighted at the 2D atomic scale. Finally, we share our viewpoints on the future perspectives and key challenges of scalable 2D-materials-integrated active NOEMS for on-chip miniaturized, lightweight, and multifunctional integration applications.

Dual-Nanopipettes for the Detection of Single Nanoparticles and Small Molecules.

Nanopore sensing is blooming due to its label-free and high sensitivity features. As a novel nanopore, a droplet is formed at the orifice of a dual-nanopipette, which allows for the translocation of analytes through the two channels at a relatively low speed and the promotion of signal-to-noise ratio. However, nanopore sensing based on the principle of current blockage requires the pore size to be comparable to that of the single entity, which poses a huge challenge for the direct detection of small molecules. In this work, gold nanoparticles (Au NPs) modified with sulfhydryl poly(ethylene glycol) (PEG-SH) or aptamers were detected successfully. The size difference of Au NPs and the interaction between Au NPs and dual-nanopipettes could be distinguished sensitively. Furthermore, Au NPs modified with designed aptamers will produce different blocking current after capturing the corresponding small molecules (e.g., dopamine and serotonin). Even non-electroactive ions, such as potassium ions, can also be detected, which is difficult to sense based on redox reactions, and further illustrates that the change of surface properties of nanoparticles is responsible for the detection. This work expands the application of nanopipette sensing for Au NPs and provides a universal platform for the small-molecule detection, which has the potential application in biosensing.

Two-Step Deposition of an Ultrathin GaN Film on a Monolayer MoS2 Template.

Ultrathin gallium nitride (GaN) application can be profoundly influenced by its quality, especially the issue of amorphous interfacial layers formed on conventional substrates. Herein, we report a two-step deposition of an ultrathin GaN film via the plasma-enhanced atomic layer deposition (PEALD) technique on a mono-MoS2 template over a SiO2/Si substrate for quality improvement, by starting the deposition temperature at 260 °C and then ramping it to 320 °C. It was found that a lower initiating deposition temperature could be conducive to maintaining the mono-MoS2 template to support the subsequent growth of GaN. Compared to the control group of one-step high-temperature deposition at 320 °C, ideal layer-by-layer film growth is achieved at the low temperature of the two-step method instead of island formation, leading to the direct crystallization of GaN on the substrate with a rather sharp interface. Structural and chemical characterizations show that this two-step method produces a preferred [0001] orientation of the film originating from the interface region. Additionally, the improved two-step ultrathin GaN displays a smooth surface roughness as low as 0.58 nm, a low oxygen impurity concentration of 3.6%, and a nearly balanced Ga/N stoichiometry of 0.95:1. Our work paves a possible way to the feasible fabrication of ultrathin high-quality PEALD-GaN, and it is promising for better performance of relevant devices.

Interfacial carrier transport properties of a gallium nitride epilayer/quantum dot hybrid structure.

Electron transport layers (ETLs) play a key role in the electron transport properties and photovoltaic performance of solar cells. Although the existing ETLs such as TiO2, ZnO and SnO2 have been widely used to fabricate high performance solar cells, they still suffer from several inherent drawbacks such as low electron mobility and poor chemical stability. Therefore, exploring other novel and effective electron transport materials is of great importance. Gallium nitride (GaN) as an emerging candidate with excellent optoelectronic properties attracts our attention, in particular its significantly higher electron mobility and similar conduction band position to TiO2. Here, we mainly focus on the investigation of interfacial carrier transport properties of a GaN epilayer/quantum dot hybrid structure. Benefiting from the quantum effects of QDs, suitable energy level arrangements have formed between the GaN and CdSe QDs. It is revealed that the GaN epilayer exhibits better electron extraction ability and faster interfacial electron transfer than the rutile TiO2 single crystal. Moreover, the corresponding electron transfer rates of 4.44 × 108 s-1 and 8.98 × 108 s-1 have been calculated, respectively. This work preliminarily shows the potential application of GaN in quantum dot solar cells (QDSCs). Carefully tailoring the structure and optoelectronic properties of GaN, in particular realizing the low-temperature deposition of high-quality GaN on various substrates, will significantly promote the construction of highly efficient GaN-ETL based QDSCs.

Continuous-wave electrically injected GaN-on-Si microdisk laser diodes.

Silicon photonics has been calling for an electrically pumped on-chip light source at room temperature for decades. A GaN-based microdisk laser diode with whispering gallery modes grown on Si is a promising candidate for compact on-chip light source. By suppressing the unintentional incorporation of carbon impurity in the p-type AlGaN cladding layer of the laser, we have significantly reduced the operation voltage and threshold current of the GaN-on-Si microdisk laser. Meanwhile the radius of the microdisk laser was shrunk to 8 µm to lower the thermal power. The overall junction temperature of the microdisk laser was effectively reduced. As a result, the first continuous-wave electrically pumped InGaN-based microdisk laser grown on Si was achieved at room temperature.

Mitotic Implantation of the Transcription Factor Prospero via Phase Separation Drives Terminal Neuronal Differentiation.

Compacted heterochromatin blocks are prevalent in differentiated cells and present a barrier to cellular reprogramming. It remains obscure how heterochromatin remodeling is orchestrated during cell differentiation. Here we find that the evolutionarily conserved homeodomain transcription factor Prospero (Pros)/Prox1 ensures neuronal differentiation by driving heterochromatin domain condensation and expansion. Intriguingly, in mitotically dividing Drosophila neural precursors, Pros is retained at H3K9me3+ pericentromeric heterochromatin regions of chromosomes via liquid-liquid phase separation (LLPS). During mitotic exit of neural precursors, mitotically retained Pros recruits and concentrates heterochromatin protein 1 (HP1) into phase-separated condensates and drives heterochromatin compaction. This establishes a transcriptionally repressive chromatin environment that guarantees cell-cycle exit and terminal neuronal differentiation. Importantly, mammalian Prox1 employs a similar "mitotic-implantation-ensured heterochromatin condensation" strategy to reinforce neuronal differentiation. Together, our results unveiled a new paradigm whereby mitotic implantation of a transcription factor via LLPS remodels H3K9me3+ heterochromatin and drives timely and irreversible terminal differentiation.

Interfacial Tailoring for the Suppression of Impurities in GaN by In Situ Plasma Pretreatment via Atomic Layer Deposition.

A method for suppressing impurities in GaN thin films grown via plasma-enhanced atomic deposition (PEALD) through the in situ pretreatment of Si (100) substrate with plasma was developed. This approach leads to a superior GaN/Si (100) interface. After pretreatment, the thickness of the interfacial layer between GaN films and the substrates decreases from 2.0 to 1.6 nm, and the oxygen impurity content at the GaN/Si (100) interface reduces from 34 to 12%. The pretreated GaN films exhibit thinner amorphous transition GaN layer of 5.3 nm in comparison with those nonpretreated of 18.0 nm, which indicates the improvement of crystallinity of GaN. High-quality GaN films with enhanced density are obtained because of the pretreatment. This promising approach is considered to facilitate the growth of high-quality thin films via PEALD.

A large-scale, ultrahigh-resolution nanoemitter ordered array with PL brightness enhanced by PEALD-grown AlN coating.

III-nitride solid-state microdisplays have significant advantages, including high brightness and high resolution, for the development of advanced displays, high-definition projectors, head-mounted displays, large-capacity optical communication systems, and so forth. Herein, a high-brightness InGaN/GaN multiple-quantum-well (MQW) nanoemitter array with an ultrahigh resolution of 31 750 dpi was achieved by combining a top-down fabrication with surface passivation of plasma-enhanced atomic layer deposition (PEALD)-grown AlN coating. With regard to the nanometer-level top-down etching, the surface damage or defects on the newly-formed sidewall play a significant role in the photoluminescence (PL) quality. Note that these arrays can be effectively passivated by the PEALD-grown AlN coating with an over 345% PL enhancement. In addition, a sharp band bending at the interface of the luminescent InGaN QW and the AlN coating layer can electrically drift away the photogenerated electrons from the surface traps; this leads to enhancement of the bulk PL radiative recombination with a fast PL decay rate. Therefore, we have demonstrated a feasible way for realizing an advanced nanoemitter array with both high brightness and ultrahigh resolution for future smart displays, high-resolution imaging, big-data optical information systems and so on.

Electric-field driven photoluminescence probe of photoelectric conversion in InGaN-based photovoltaics.

The spatial distribution of electric field in photovoltaic multiple quantum wells (MQWs) is extremely important to dictate the mutual competition of photoelectric conversion and optical transition. Here, electric-field-driven photoluminescence (PL) in both steady-state and transient-state has been utilized to directly investigate the internal photoelectric conversion processes in InGaN-based MQW photovoltaic cell. As applying the reversed external electric field, the compensation of the quantum confined stark effect (QCSE) in InGaN QW is beneficial to help the photoabsorbed minor carriers drift out from the localized states, whereas extremely weakening the PL radiative recombination. A directly driven force by the reversed external electric field decreases the transit time of photocarriers drifting in InGaN QW. And hence, the overall dynamic PL decay including both the slow and fast processes gradually speeds up from 19.2 ns at the open-circuit condition to 3.9 ns at a negative bias of -3 V. In particular, the slow PL decay lifetime declines more quickly than that of the fast one. It is the delocalization of photocarriers by electric-field drift that helps to further enhance the high-efficiency photoelectric conversion except for the tunneling transport in InGaN-based MQW photovoltaics. Therefore, it can be concluded that the electric-field PL probe may provide a direct method for evaluating the photoelectric conversion in multilayer quantum structures and related multijunction photovoltaic cells.

PEALD-Grown Crystalline AlN Films on Si (100) with Sharp Interface and Good Uniformity.

Aluminum nitride (AlN) thin films were deposited on Si (100) substrates by using plasma-enhanced atomic layer deposition method (PEALD). Optimal PEALD parameters for AlN deposition were investigated. Under saturated deposition conditions, the clearly resolved fringes are observed from X-ray reflectivity (XRR) measurements, showing the perfectly smooth interface between the AlN film and Si (100). It is consistent with high-resolution image of the sharp interface analyzed by transmission electron microscope (TEM). The highly uniform thickness throughout the 2-inch size AlN film with blue covered surface was determined by spectroscopic ellipsometry (SE). Grazing incident X-ray diffraction (GIXRD) patterns indicate that the AlN films are polycrystalline with wurtzite structure and have a tendency to form (002) preferential orientation with increasing of the thickness. The obtained AlN films could open up a new approach of research in the use of AlN as the template to support gallium nitride (GaN) growth on silicon substrates.

Aligned carbon nanotubes for high-efficiency Schottky solar cells.

The development of low-cost and high-efficiency silicon Schottky solar cells has drawn considerable interest in recent years. A facial approach for the fabrication of carbon nanotube-silicon (CNT-Si) Schottky solar cells by using aligned double-walled CNTs drawn from a CNT array is demonstrated. The aligned CNTs help to form high CNT-Si junction density and provide efficient charge-transport paths. The power conversion efficiency (PCE) reaches 10.5%, which is higher than that of solar cells fabricated using pristine and random CNT networks. Furthermore, the cell fabrication is scalable, and the solar cells fabricated in one batch show very small PCE fluctuations.