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BACKGROUND: Sphingolipids play a crucial role in cellular functions and are essential components of cell membranes, signaling molecules, and lipid metabolism. In particular, ceramide is a key intermediate in sphingolipid metabolism and defects in ceramide metabolism can lead to various inborn errors of metabolism, making ceramides important targets for clinical screening and diagnosis. Detecting altered concentration patterns of sphingolipids is desirable for distinguishing related inborn errors of metabolism for diagnosis and treatment monitoring. METHODS: We developed a liquid chromatography-tandem mass spectrometry method with a pathway-oriented approach to focus on sphingolipids involved in ceramide metabolism. A total of 47 sphingolipids bearing different head groups and side chains were targeted. Precision/reproducibility, linearity, and spike recovery extraction efficiency tests were performed on plasma and serum samples from confirmed cases of sphingolipidosis. RESULTS: Linearity of the method showed the coefficient of determination (r2) for all standards to be >0.99 with a slope of 1.00 ± 0.01. Intra- and interday reproducibility of standards spiked into plasma and serum revealed a coefficient of variation <20%. Spike and recovery assessment showed recovery values of 80%-120% for all standards. Altered levels of sphingolipids from patients with hereditary sensory and autonomic neuropathy caused by pathogenic variants in SPTLC2 and hypomyelinating leukodystrophy related to variants in DEGS1 were detected, in agreement with trends reported in earlier studies confirming the utility of this pathway-centric method. CONCLUSIONS: This method can serve as a useful tool to simultaneously monitor sphingolipids, enabling screening and diagnosis of inborn errors of ceramide metabolism.
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Tailoring the interaction between light and sound has opened new possibilities in photonic integrated circuits (PICs) that range from achieving quantum control of light to high-speed information processing. However, the actuation of sound waves in Si PICs usually requires integration of a piezoelectric thin film. Lead zirconate titanate (PZT) is a promising material due to its strong piezoelectric and electromechanical coupling coefficient. Unfortunately, the traditional methods to grow PZT on silicon are detrimental for photonic applications due to the presence of an optical lossy intermediate layer. In this work, we report integration of a high quality PZT thin film on a silicon-on-insulator (SOI) photonic chip using an optically transparent buffer layer. We demonstrate acousto-optic modulation in silicon waveguides with the PZT actuated acoustic waves. We fabricate interdigital transducers (IDTs) on the PZT film with a contact photolithography and electron-beam lithography to generate the acoustic waves in MHz and GHz ranges, respectively. We obtain a V π L â¼ 3.35 V·cm at 576 MHz from a 350 nm thick gold (Au) IDT with 20 finger-pairs. After taking the effect of mass-loading and grating reflection into account, we measured a V π L â¼ 3.60 V·cm at 2 GHz from a 100 nm thick aluminum (Al) IDT consisting of only four finger-pairs. Thus, without patterning the PZT film nor suspending the device, we obtained figures-of-merit comparable to state-of-the-art modulators based on SOI, making it a promising candidate for a broadband and efficient acousto-optic modulator for future integration.
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Silicon nitride (SiN) is emerging as a competitive platform for CMOS-compatible integrated photonics. However, active devices such as modulators are scarce and still lack in performance. Ideally, such a modulator should have a high bandwidth, good modulation efficiency, low loss, and cover a wide wavelength range. Here, we demonstrate the first electro-optic modulators based on ferroelectric lead zirconate titanate (PZT) films on SiN, in both the O-band and C-band. Bias-free operation, bandwidths beyond 33 GHz and data rates of 40 Gbps are shown, as well as low propagation losses (α ≈ 1 dB cm-1). A half-wave voltage-length product of 3.2 V cm is measured. Simulations indicate that further improvement is possible. This approach offers a much-anticipated route towards high-performance phase modulators on SiN.
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Barium titanate (BaTiO3) thin films are prepared by conventional 2-methoxy ethanol-based chemical solution deposition. We report highly c-axis-oriented BaTiO3 thin films grown on silicon substrates, coated with a lanthanum oxynitrate buffer layer of 8.9 nm. The influence of the intermediate buffer layer on the crystallization of BaTiO3 film is investigated. The annealing temperature and buffer layer sintering conditions are optimized to obtain good crystal growth. X-ray diffraction measurements show the growth of highly oriented BaTiO3 thin films having a single perovskite phase with tetragonal geometry. The scanning electron microscopy and atomic force microscopy studies indicate the presence of smooth, crack-free, uniform layers, with densely packed crystal grains on the silicon surface. A BaTiO3 film of 150-nm thickness, deposited on a buffer layer of 7.2 nm, shows a dielectric constant of 270, remnant polarization (2Pr) of 5 µC/cm2, and coercive field (Ec) of 60 kV/cm.
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A quantitative method has been developed for determining the affinity of substrates for the peptide transporter PepT1, allowing oral availability of drugs via PepT1 to be estimated.