Silicon FMCW LiDAR chip integrated with SLG beam scanner and k-clock interferometer for operation with wavelength-swept laser source.

We fabricated a frequency-modulated continuous-wave light detection and ranging (FMCW LiDAR) chip that integrates a slow-light grating (SLG) beam scanner and an optical interferometer for k-clock generation using silicon photonics. Beam scanning and FMCW light generation were performed simultaneously through a wavelength sweep, while the sweep nonlinearity was compensated by resampling the ranging signal using the k-clock. The interferometer incorporated a 24-cm-long Si waveguide delay line, facilitating ranging up to 7.1 m and the capture of point cloud images. The possibility of ranging longer distances by lengthening the waveguide and increasing the interpolation is discussed.

Ambient light immunity of a frequency-modulated continuous-wave (FMCW) LiDAR chip.

The interference between a frequency-modulated continuous-wave (FMCW) light detection and ranging (LiDAR) and other LiDARs or sunlight was theorized, considering the spatial overlap, frequency overlap, and intensity ratio. It has been concluded that the interference probability between LiDARs can be lower than a safety standard value for autonomous vehicles when the number of the resolution points of a single LiDAR is increased sufficiently and that the interference with incoherent sunlight does not occur. Due to the coherent detection of FMCW, such ambient light immunity is much better than time-of-flight LiDAR. The dependence of the interference on the wavelength range, sweep bandwidth, and sweep period was also observed experimentally using a silicon (Si) photonics FMCW LiDAR chip incorporating slow-light grating beam scanners. It was shown that the interference can be suppressed by increasing the number of resolution points and changing their common parameters moderately. Regarding the contamination of sunlight, unwanted beam shift due to heating was observed, although it will be suppressed simply by wavelength filtering.

The Toughness-Enhanced Atelocollagen Double-Network Gel for Biomaterials.

A tough gel composed of atelocollagen, which lacks an immunogenetic site, is a promising material for biomedical application. In this study, we created a composite hydrogel composed of atelocollagen gel cross-linked with glutaraldehyde (GA) and poly-(N,N-dimethylacrylamide) gel exhibiting biocompatibility based on the double-network (DN) gel principle. The tensile toughness of atelocollagen gel remained constant regardless of the amount of cross-linker (GA) used. In contrast, tensile tests of the DN gel indicated that mechanical properties, such as fracture stress and toughness, were significantly higher than those of the atelocollagen gel. Moreover, fibroblast cells adhered and spread on the gels, the Schiff bases of which were treated via reductive amination for detoxification from GA. These findings demonstrate the potential of the proposed gel materials as artificial alternative materials to soft tissues with sub-MPa fracture stress.

Synthesis, Characterization, and Potential Application of Cyclodextrin-Based Polyrotaxanes for Reinforced Atelocollagen Threads.

Preparing strong and flexible atelocollagen-based materials for biomedical applications is still a challenging task. To address this challenge, this study describes the synthesis and characterization of water-soluble polyrotaxanes (PRs) with different coverage ratios and molecular weights of axle polymers, and their potential applications for PR-reinforced atelocollagen threads (PRATs). A novel method was established for the syntheses of PRs with relatively low coverage ratio at the sub-gram scale, in which the aldehyde groups were employed as crosslinking sites for preparing the PRATs via reductive amination. The aldehyde groups were successfully quantified by 1H nuclear magnetic resonance spectroscopy using 1,1-dimethylhydrazine as an aldehyde marker. Fourier-transform infrared and thermogravimetric analysis measurements supported the characterization of the PRs. Interestingly, tensile testing demonstrated that coverage ratio affected the mechanical properties of the PRATs more strongly than molecular weight. The insights obtained in this study would facilitate the development of soft materials based on atelocollagens and PRs.

Easy-to-Prepare Mini-Chemosensor Array for Simultaneous Detection of Cysteine and Glutathione Derivatives.

We herein propose an easy-to-prepare mini-chemosensor array constructed by two-types of off-the-shelf coumarin dyes for simultaneous classification and quantification of sulfur-containing amino acids (SCAAs) (i.e., l-cysteine, l-cystine, l-homocysteine, glutathione, and glutathione disulfide). The detection mechanism of SCAAs relied on a coordination-based sensor array (CBSA) utilizing the competitive binding among the coumarin dye, a Zn2+ ion and SCAAs. The reversible feature of the coordination bond of the coumarin-Zn2+ resulted in UV/vis spectral shifts and fluorescence enhancement in response to the analytes, offering the multianalyte detection in high accuracy. Furthermore, a mixture of glutathione and l-cysteine was successfully quantified in a sample containing human blood serum. This study would be an important example of the optical chemosensor array toward the rapid and accurate detection of biomarkers.

Suppression of Malachite Green-Induced Toxicity to Human Liver Cells Utilizing Host-Guest Chemistry of Cucurbit[7]uril.

We investigated a host-guest complex between cucurbit[7]uril and malachite green, and its effect on the toxicity to human liver cells. The host-guest complexation was evaluated by a UV/vis titration and electrospray-ionization mass spectrometry. Interestingly, the host-guest complex resulted in remarkable suppression of the toxicity of malachite green in its practical concentration range (ca. ∼6 µM). This study is one step forward to the active control of the biological effects of potent toxicants utilizing host-guest chemistry.

A Water-Gated Organic Thin-Film Transistor for Glyphosate Detection: A Comparative Study with Fluorescence Sensing.

Invited for the cover of this issue is the group of Tsuyoshi Minami at the University Tokyo. The image illustrates that despite being fabricated with the same polythiophene material, a water-gated organic thin-film transistor is a more sensitive device than a fluorescence sensor chip. Read the full text of the article at 10.1002/chem.202003529.

A Water-Gated Organic Thin-Film Transistor for Glyphosate Detection: A Comparative Study with Fluorescence Sensing.

This work reports the design of a highly sensitive solid-state sensor device based on a water-gated organic thin-film transistor (WG-OTFT) for the selective detection of herbicide glyphosate (GlyP) in water. A competitive assay among carboxylate-functionalized polythiophene, Cu2+ , and GlyP was employed as a sensing mechanism. Molecular recognition phenomena and electrical double layer (EDL) (at the polymer/water interface) originated from the field-effect worked cooperatively to amplify the sensitivity for GlyP. The limit of detection of WG-OTFT (0.26 ppm) was lower than that of a fluorescence sensor chip (0.95 ppm) which is the conventional sensing method. In contrast to the previously reported insulated molecular wires to block interchain interactions, molecular aggregates under the field-effect has shown to be effective for amplification of sensitivity through "intra"- and "inter"-molecular wire effects. The opposite strategy in this study could pave the way for fully utilizing the sensing properties of polymer-based solid-state sensor devices.

Supramolecular Sensor for Astringent Procyanidin C1: Fluorescent Artificial Tongue for Wine Components.

An artificial tongue that detects astringent components for a comprehensive evaluation of taste has not been established to date. Herein, we first propose fluorescent polythiophene (PT) derivatives (S1-S3) modified with 3-pyridinium boronic acid as supramolecular chemosensors for wine components including astringent procyanidin C1. After numerous attempts for the synthetic conditions, more than 95 mol % of the PT unit was modified with the pyridinium boronic acid moiety. To evaluate the PT derivatives as chemosensors of the artificial tongue, qualitative and quantitative analyses were performed with four types of wine components (i.e., sweet, sour, bitter, and astringent tastes) in combination with pattern recognition models. Notably, procyanidin C1 in the actual wine sample was successfully detected in a quantitative manner. In other words, we have established an authentic artificial tongue using PT based supramolecular chemosensors.

Fluorescence Anion Chemosensor Array Based on Pyrenylboronic Acid.

A novel fluorescence chemosensor array composed of pyrenylboronic acid-based probes for multi- anion detection has been developed. The pyrenylboronic acid derivatives showed fluorescence quenching or enhancement due to photoinduced electron transfer originating from anion binding. The recognition ability was assessed by fluorescence titrations and electrospray ionization mass spectrometry. Because the array is constructed with cross-reactive probes, the combination of differential binding affinities for anions (i.e., fluoride, acetate, oxalate, malonate, citrate, dihydrogen phosphate, and pyrophosphate) and pattern recognitions, such as linear discriminant analysis, offered a successful simultaneous anion detection with a classification rate of 100%. Furthermore, the chemosensor array allowed for quantitative prediction of oxalate, malonate, and citrate in mixtures using a support vector machine. Importantly, the array system employs low-cost and commercially available reagents as probes. Thus, this study could lead to the development of user-friendly and high-throughput methods to detect a variety of analytes in complicated systems.

Protein Assays on Organic Electronics: Rational Device and Material Designs for Organic Transistor-Based Sensors.

Artificial receptor-based protein assays have various attractive features such as a long-term stability, a low-cost production process, and the ease of tuning the target specificity. However, such protein sensors are still immature compared with conventional immunoassays. To enhance the application potential of synthetic sensing materials, organic field-effect transistors (OFETs) are some of the suitable platforms for protein assays because of their solution processability, durability, and compact integration. Importantly, OFETs enable the electrical readout of the protein recognition phenomena of artificial receptors on sensing electrodes. Thus, we believe that OFETs functionalized with artificial protein receptors will be a powerful tool for the on-site analyses of target proteins. In this Minireview, we summarize the recent progress of the OFET-based protein assays including the rational design strategies for devices and sensing materials.

The potential of lipid-polymer nanoparticles as epigenetic and ROS control approaches for COPD.

Chronic obstructive pulmonary disease (COPD) is a lung disease caused by an inflammatory response to various inhaled toxins, especially cigarette smoke. Reactive oxygen species (ROS) and epigenetic abnormality are intimately related to the pathology of COPD, and the overproduction of ROS results in a decrease of histone deacetylase 2 (HDAC2), leading to glucocorticoid resistance. Therefore, a novel treatment that simultaneously reduces ROS level and glucocorticoid resistance is urgently needed. In this study, we developed a codelivery system using core-shell type lipid-polymer nanoparticles (LPNs) composed of a poly(lactic acid) (PLA) core encapsulating a potent antioxidant Mn-porphyrin dimer (MnPD) and a cationic lipid (DOTAP) shell that binds HDAC2-encoding plasmid DNA (pHDAC2), as a new therapeutic approach toward COPD. The transfection of pHDAC2 combined with the elimination of ROS by MnPD exhibited a significant enhancement of intracellular HDAC2 expression levels, suggesting that the multi-antioxidative activity of MnPD plays a crucial role in the expression of HDAC2. Moreover, treatment with LPNs efficiently ameliorated the steroid resistance in COPD models in vitro as evidenced by the lowered expression levels of IL-8. Recovery from mitochondrial dysfunction may be the mechanism underlying the action of LPNs. The PLA-MnPD/DOTAP/pHDAC2 system proposed offers a new therapeutic approach for COPD based on the synergism of ROS elimination and HDAC2 expression.

Simplest Chemosensor Array for Phosphorylated Saccharides.

We believe that "the simpler we are, the more complete we become" is a key concept of chemical sensing systems. In this work, a "turn-on" fluorescence chemosensor array relying on only two self-assembled molecular chemosensors with ability of both qualitative and quantitative detection of phosphorylated saccharides has been developed. The easy-to-prepare chemosensor array was fabricated by in situ mixing of off-the-shelf reagents (esculetin, 4-methylesculetin, and 3-nitrophenylboronic acid). The fluorescence-based saccharide sensing system was carried out using indicator displacement assay accompanied by photoinduced electron transfer (PeT) under various pH conditions. The simultaneous recognition of 14 types of saccharides including glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) was achieved with a successful classification rate of 100%. We also succeeded in the quantitative analysis of a mixture of glucose (Glc), as an original substrate, G6P and F6P, as enzymatic products in pseudoglycolysis pathway. Finally, levels of Glc and F6P in human induced pluripotent stem (hiPS) cells were indirectly monitored by using our proposed chemosensor array. Glc and F6P in supernatants of hiPS cells were classified by linear discriminant analysis as a pattern recognition model and the observed clusters represent the activity of hiPS cells. The results show the high accuracy of the proposed chemosensor array in detection of phosphorylated and similarly modified saccharides.

Chemical Sensing Platforms Based on Organic Thin-Film Transistors Functionalized with Artificial Receptors.

Organic thin-film transistors (OTFTs) have attracted intense attention as promising electronic devices owing to their various applications such as rollable active-matrix displays, flexible nonvolatile memories, and radiofrequency identification (RFID) tags. To further broaden the scope of the application of OTFTs, we focus on the host-guest chemistry combined with the electronic devices. Extended-gate types of OTFTs functionalized with artificial receptors were fabricated to achieve chemical sensing of targets in complete aqueous media. Organic and inorganic ions (cations and anions), neutral molecules, and proteins, which are regarded as target analytes in the field of host-guest chemistry, were electrically detected by artificial receptors. Molecular recognition phenomena on the extended-gate electrode were evaluated by several analytical methods such as photoemission yield spectroscopy in the air, contact angle goniometry, and X-ray photoelectron spectroscopy. Interestingly, the electrical responses of the OTFTs were highly sensitive to the chemical structures of the guests. Thus, the OTFTs will facilitate the selective sensing of target analytes and the understanding of chemical conversions in biological and environmental systems. Furthermore, such cross-reactive responses observed in our studies will provide some important insights into next-generation sensing systems such as OTFT arrays. We strongly believe that our approach will enable the development of new intriguing sensor platforms in the field of host-guest chemistry, analytical chemistry, and organic electronics.

Simple Colorimetric Chemosensor Array for Oxyanions: Quantitative Assay for Herbicide Glyphosate.

Although the determination of oxyanions due to correlation with metabolic processes and diseases is in high demand, most of the developed methods are suffering from a shortage of a capability of on-site analysis, sensitivity, and user-friendliness. This paper introduces the first colorimetric chemosensor array targeting various anions including glyphosate. The proposed sensor benefits from some notable features such as utilizing only commercially available reagents, recognizing similarly structured compounds by biomaterial-free sensors, and providing a fingerprint-like response originating from pattern recognition. The detection mechanism is based on an anion sensing strategy named coordination binding-based sensor array (CBSA). In CBSA, competitive coordinative bonding of a metal ion (Zn2+) between a catechol dye (i.e., indicator) and target anions occurs, and changes in the optical properties of the dye represent the target's concentration. For data processing, two chemometrical techniques including linear discrimination analysis (LDA) and an artificial neural network (ANN) for pattern classification and regression/prediction purposes were successfully employed, respectively. Finally, the proposed chemosensor was subjected to glyphosate samples (commercial herbicide and tap water samples) and produced satisfactory results.

New class of artificial enzyme composed of Mn-porphyrin, imidazole, and cucurbit[10]uril toward use as a therapeutic antioxidant.

In this study, we investigated a new class of artificial enzymes composed of Mn-porphyrin, imidazole, and cucurbit[10]uril (CB[10]) toward therapeutic antioxidants. Structural characterization by means of NMR indicated that the inclusion mode of metalloporphyrin in CB[10] was sensitive to the chemical structure of metalloporphyrin and that the structure of the artificial enzyme had a similarly to that of native heme catalase. Kinetic analysis for catalytic antioxidative activities demonstrated that the artificial enzyme exhibited highly efficient activity for H2O2 disproportionation (catalase activity) in water. The activity was classified as top-performing among the water-soluble artificial catalases. The artificial enzyme was constructed by simply mixing the components in water. We consider that this is a great advantage over previously reported artificial catalases, which require a multi-step synthesis or that lack water solubility. The pro-oxidative peroxidase activity was remarkably suppressed due to inclusion in CB[10]. Furthermore, a preliminary in vitro study suggested that the artificial enzyme catalytically eliminated reactive oxygen species, including H2O2, in human cell lines. It was presumed that CB[10] contributed to the bioavailability of the artificial enzyme. Overall, the artificial enzyme was shown to have high potential as a therapeutic antioxidant. We consider that the results in this study could lead to a new conceptual advance toward therapeutic antioxidants that could simultaneously improve the catalytic and biological properties of Mn-porphyrins.

Lactoferrin-modified nanoparticles loaded with potent antioxidant Mn-porphyrins exhibit enhanced antioxidative activity in vitro intranasal brain delivery model.

In this study, for efficient intranasal brain delivery, we have prepared lactoferrin (Lf)-modified nanoparticles loaded with an amphiphilic Mn-porphyrin derivative, MndMImP3P (MnP) (Lf-NP-MnP). MndMImP3P was loaded into the nanoparticles with good loading efficiency. The stability of the resulting Lf-NP-MnP was sufficient for intranasal brain delivery. Lf on the surface of Lf-NP-MnP was significantly recognized by the Lf receptor, which leads to enhanced cellular uptake of MnP and efficient transcytosis. Furthermore, Lf-NP-MnP exhibited antioxidative activity in vitro experiment using a transwell assay as a model of intranasal brain delivery. Our result in this study is one step forward for efficient brain delivery of Mn-porphyrin derivatives to cure neurodegenerative diseases.

A bioinspired polymer-bound Mn-porphyrin as an artificial active center of catalase.

The complex comprising a cationic Mn-porphyrin and carboxymethyl poly(1-vinylimidazole) (CM-PVIm) was prepared as an artificial active center of catalase. Interestingly, the catalase activity of the complex depends on the chain length of the polymer and the chemical structure of Mn-porphyrin. This study is one step forward in the development of a new class of water-soluble catalase mimics.

Synthesis of water-soluble dinuclear mn-porphyrin with multiple antioxidative activities.

Superoxide dismutase (SOD) and catalase activities of a drug are of great importance for its effective protection against reactive oxygen species (ROS)-induced injury. Achievement of catalase activity of a synthetic compound remains a challenge. Water-soluble Mn-porphyrins have high SOD and peroxynitrite (ONOO(-)) reducing activities, but not catalase-like activity. Herein, we are able to retain the fair SOD-like activity of a mononuclear Mn-5-(N-methylpyridinium-4-yl)-10,15,20-triphenyl porphyrin (MnM4PyP3P), while gaining in catalase-like activity with its dinuclear complex, 1,3-di[5-(N-methylene-pyridinium-4-yl)-10,15,20-triphenyl porphynato manganese] benzene tetrachloride (MnPD). Mechanistic study indicates that catalase-like activity of MnPD is due to synergism of two Mn active sites, where hydroxo-Mn(IV) complex is formed as an intermediate. The in vivo experiments demonstrate that MnPD significantly restores the treadmill-running ability of SOD-deficient mouse and thus indicates the therapeutic potential of MnPD. Furthermore, MnPD may serve as a mechanistic tool and indicate the new directions in the synthesis of catalase-like mimics.