Ultrahigh-printing-speed photoresists for additive manufacturing.

Printing technology for precise additive manufacturing at the nanoscale currently relies on two-photon lithography. Although this methodology can overcome the Rayleigh limit to achieve nanoscale structures, it still operates at too slow of a speed for large-scale practical applications. Here we show an extremely sensitive zirconium oxide hybrid-(2,4-bis(trichloromethyl)-6-(4-methoxystyryl)-1,3,5-triazine) (ZrO2-BTMST) photoresist system that can achieve a printing speed of 7.77 m s-1, which is between three and five orders of magnitude faster than conventional polymer-based photoresists. We build a polygon laser scanner-based two-photon lithography machine with a linear stepping speed approaching 10 m s-1. Using the ZrO2-BTMST photoresist, we fabricate a square raster with an area of 1 cm2 in ~33 min. Furthermore, the extremely small chemical components of the ZrO2-BTMST photoresist enable high-precision patterning, leading to a line width as small as 38 nm. Calculations assisted by characterizations reveal that the unusual sensitivity arises from an efficient light-induced polarity change of the ZrO2 hybrid. We envisage that the exceptional sensitivity of our organic-inorganic hybrid photoresist may lead to a viable large-scale additive manufacturing nanofabrication technology.

High-throughput multiplexed fluorescence lifetime microscopy.

Fluorescence lifetime microscopy has been widely used in quantifying cellular interaction or histopathological identification of different stained tissues. A novel, to the best of our knowledge, approach for high-throughput multiplexed fluorescence lifetime imaging is presented. To establish a high-throughput fluorescence lifetime acquisition system, a uniformed illumination optical focus array was generated by a novel computer-generated hologram algorithm based on matrix triple product. This, in conjunction with an array detector and multichannel time-correlated single-photon counting, enables the full use of the acquisition ability of each detector. By utilizing interval segmentation of photon time detection, a high-throughput multiplexed fluorescence lifetime imaging is achieved. Experimental results demonstrate that this method achieves a fivefold increase in the collection throughput of fluorescence lifetime and is capable of simultaneous dual-target fluorescence lifetime measurement.

3D nanoprinting for fiber-integrated achromatic diffractive lens.

Achromatic performance is crucial for numerous multi-wavelength optical fiber applications, including endoscopic imaging and fiber sensing. This paper presents the design and nanoprinting of a fiber-integrated achromatic diffractive lens within the visible spectrum (450-650 nm). The 3D nanoprinting is achieved by a high-resolution direct laser writing technology, overcoming limitations in the optical performance caused by the lack of an arbitrary 3D structure writing capability and an insufficient feature resolution in the current manufacturing technology for visible light broadband achromatic diffractive lenses. A three-step optimization algorithm is proposed to effectively balance optical performance with writing difficulty. The characterization results demonstrate excellent achromatic focusing performance, paving the way towards the development of nanoprinted flat optical devices for applications such as optical fiber traps, miniature illumination systems, and integrated photonic chips.

High-Precision and Rapid Direct Laser Writing Using a Liquid Two-Photon Polymerization Initiator.

Two-photon polymerization based direct laser writing (DLW) is an emerging micronano 3D fabrication technology wherein two-photon initiators (TPIs) are a key component in photoresists. Upon exposure to a femtosecond laser, TPIs can trigger the polymerization reaction, leading to the solidification of photoresists. In other words, TPIs directly determine the rate of polymerization, physicochemical properties of polymers, and even the photolithography feature size. However, they generally exhibit extremely poor solubility in photoresist systems, severely inhibiting their application in DLW. To break through this bottleneck, we propose a strategy to prepare TPIs as liquids via molecular design. The maximum weight fraction of the as-prepared liquid TPI in photoresist significantly increases to 2.0 wt %, which is several times higher than that of commercial 7-diethylamino-3-thenoylcoumarin (DETC). Meanwhile, this liquid TPI also exhibits an excellent absorption cross section (64 GM), allowing it to absorb femtosecond laser efficiently and generate abundant active species to initiate polymerization. Remarkably, the respective minimum feature sizes of line arrays and suspended lines are 47 and 20 nm, which are comparable to that of the-state-of-the-art electron beam lithography. Besides, the liquid TPI can be utilized to fabricate various high-quality 3D microstructures and manufacture large-area 2D devices at a considerable writing speed (1.045 m s-1). Therefore, the liquid TPI would be one of the promising initiators for micronano fabrication technology and pave the way for future development of DLW.

Autosomal chromosome microdeletions in three adolescent girls with premature ovarian insufficiency: a case report.

BACKGROUND: Premature ovarian insufficiency (POI) in the pediatric age group is most commonly related to X chromosome abnormalities such as Turner syndrome. Autosomal chromosome microdeletions in ovarian failure are relatively rare. The present study identified new autosomal deletions in three girls with POI. CASE: We present three adolescent girls aged 14-15 years who had not attained menarche. Upon physical examination, there was a lack of breast tissue and no prominent secondary sexual characteristics. Clinical evaluation, hormonal tests, abdominal ultrasonography, and chromosome karyotyping were performed. Chromosome microarray analysis (CMA) was also performed to detect DNA copy number changes. Luteinizing hormone level was significantly increased, while follicular stimulating hormone level was > 25 IU/L with low estradiol levels. Autosomal deletions were detected in all three cases by CMA. The first patient had 0.454 Mb deletion on 15q25.2, the second patient had 1.337 Mb deletion on 19p13.3, and the third patient had 0.163 Mb deletion on 16p11.2. CONCLUSIONS: POI is rare in children and is most commonly associated with X chromosome abnormalities. However, normal karyotype does not exclude the presence of chromosomal abnormality. CMA should be considered in cases with POI to detect microdeletions in autosomal chromosomes.

First morning voided urinary gonadotropins in children: verification of method performance and establishment of reference intervals.

OBJECTIVES: Urinary luteinizing hormone (uLH) and urinary follicle-stimulating hormone (uFSH) have been shown to be useful screening and management tools for children with central precocious puberty. However, studies on uLH and uFSH reference intervals are scarce. Therefore, we aimed to establish reference intervals for uLH and uFSH, according to age, sex, and pubertal status in apparently healthy children aged 6-11 years. METHODS: We performed detection capability, precision, accuracy by recovery, linearity, agreement analysis, and stability testing to analyze the method performance of uLH and uFSH. The Clinical Laboratory Standards Institute's C28-A3 criteria was used to establish the reference intervals. RESULTS: Both uLH and uFSH were stable at 4 °C for 52.6 h and 64.8 days, respectively. The total imprecision of uFSH is within the manufacturer's claim, while the total imprecision of uLH remained within tolerable bias. Both uLH and uFSH could be measured with acceptable detection capability. The recovery rates of the hormones were 87.6-98.8% and 102.8-103.4%, respectively, and therefore within acceptable limits. There were significant correlations between the serum and urine concentrations (LH: r=0.91, p<0.001; FSH: r=0.90, p<0.001). The reference intervals of uLH and uFSH were established according to age, sex, and pubertal status. CONCLUSIONS: We established reference intervals for uLH and uFSH based on age, sex and pubertal status to provide a non-invasive clinical screening tool for precocious puberty in children aged 6-11 years.

The first central precocious puberty proteomic profiles revealed multiple metabolic networks and novel key disease-associated proteins.

Though central precocious puberty (CPP) as a disease that seriously affects the development of a child is increasing year by year, treatment options remain limited and is the same as the 1980s' method. These are mainly due to the complex pathogenesis of central precocious puberty. Therefore, systems biology approach to identify and explore the multiple factors related to the pathogenesis of central precocious puberty is necessary. Our data established the first proteome profile of CPP revealed 163 down-regulated and 129 were up-regulated differentially expressed proteins. These altered proteins were primarily enriched in three metabolic process including energy metabolism, amino acid metabolism and nitrogenous base metabolism. The identified altered members of the metabolic signaling are valuable and potential novel therapeutic targets of central precocious puberty.

Label-free difference super-resolution microscopy based on parallel detection.

In this paper, a new method is proposed for super-resolution imaging of non-fluorescent samples. This approach is based on the intensity difference between confocal image and negative confocal image, which are simultaneously acquired at one sample scanning. In order to get these two different images simultaneously, the sample was illuminated by two different focused spots from the same laser source: the doughnut spot and the solid spot. The effectiveness of the label-free difference microscopy based on parallel detection was validated by experiments on some samples including 80 nm gold beads, 100 nm silver nanowires, and Blu-ray DVD without fluorescent dyes. By subtraction of the reflected light intensity from the sample, the final resolution of the image without deconvolution was enhanced about 1.6 times compared with confocal imaging. This technique can be applied to surface topography detection of metallographic or other non-fluorescent materials.

Enhancing the axial resolution of two-photon imaging.

An axial-resolution-enhanced two-photon laser scanning microscopy system is presented in this paper. In the proposed method, we use a spatial light modulator (SLM) for the phase modulation of the excitation light. The axially split point spread function (PSF) is generated by loading a 0-π pattern on the SLM. The final quality-enhanced images are acquired by subtracting the two consecutive images acquired by the original PSF and the split PSF. Because of the fluorescence differential processing, the axial elongation of the particles images is suppressed, and the axial resolution is enhanced accordingly. With the axial resolution enhanced, the overlap between layer images is also reduced, which decreases the background noise of the images and enhances the contrast and image quality of the acquired fluorescence images. The capability of axial resolution and contrast enhancement is successfully demonstrated by both theoretical calculation and experimental results.

[Clinical and genetic features of Kallmann syndrome: an analysis of 5 cases].

Kallmann syndrome (KS) is a rare pediatric disease with major manifestations of olfactory dysfunction and hypogonadotropic hypogonadism. Five children (4 boys and 1 girl) with KS reported in this article were aged between 6 months and 19 years at the time when they attended the hospital. All the children had the clinical manifestation of hypogonadotropic hypogonadism; in addition, three children had olfactory dysfunction (two were found to have olfactory bulb dysplasia on magnetic resonance imaging), one had cleft lip and palate, and one had micropenis and cryptorchidism with right renal agenesis during infancy. All the five children had normal karyotype and their parents had normal clinical phenotypes. The uncle of one child had underdeveloped secondary sexual characteristics and olfactory disorder since childhood. High-throughput sequencing found two known heterozygous missense mutations in the FGFR1 gene, i.e., c.1097C>T(p.P366L) and c.809G>C(p.G270A), in two children. One child had a novel frameshift mutation, c.1877_1887/p.S627Tfs*6, in the KAL1 gene; this deletion mutation caused a frameshift in base sequence and produced truncated proteins, which led to a significant change in protein structure, and thus it was highly pathogenic. It is concluded that KS has great clinical and genetic heterogeneity and can be accompanied by incomplete dominant inheritance and that gene detection helps with the diagnosis of this disease.

Isolation of the retinal isomers from the isomerization of all-trans-retinal by flash countercurrent chromatography.

The isolation of the retinal isomers from all-trans-retinal was performed by flash countercurrent chromatography. In each separation, isomerization reaction solution of 200mg all-trans-retinal could be loaded on a 1200 mL of high-speed countercurrent chromatographic column with 5mm bore, eluted by a mobile phase flow rate of 25 mL/min, resulting in 63 mg of 11-cis-retinal, 24 mg of 13-cis-retinal and 26 mg of 9-cis-retinal with purities more than 95%. n-Hexane-acetonitrile (3:1) was used as the solvent system which possesses the advantages of simplicity, re-use of the solvent and multiple injections. This method could be used to prepare 13-cis-retinal, 11-cis-retinal and 9-cis-retinal for the photoisomerization investigation, such as the effect of 11-cis-retinal in the visual system.