Publications by authors named "Po-Yen Chen"

127 Publications

Cation-Induced Assembly of Conductive MXene Fibers for Wearable Heater, Wireless Communication, and Stem Cell Differentiation.

ACS Biomater Sci Eng 2021 Jul 23. Epub 2021 Jul 23.

Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.

Emerging wearable electronics, wireless communication, and tissue engineering require the development of conductive fiber-shaped electrodes and biointerfaces. TiCT MXene nanosheets serve as promising building block units for the construction of highly conductive fibers with integrated functionalities, yet a facile and scalable fabrication scheme is highly required. Herein, a cation-induced assembly process is developed for the scalable fabrication of conductive fibers with MXene sheaths and alginate cores (abbreviated as [email protected]). The fabrication scheme of [email protected] fibers includes the fast extrusion of alginate fibers followed by electrostatic assembly of MXene nanosheets, enabling high-speed fiber production. When multiple fabrication parameters are optimized, the [email protected] fibers exhibit a superior electrical conductivity of 1083 S cm, which can be integrated as Joule heaters into textiles for wearable thermal management. By triggering reversible de/hydration of alginate cores upon heating, the [email protected] fibers can be repeatedly contracted and generate large contraction stress that is >40 times higher than the ones of mammalian skeletal muscle. Furthermore, the [email protected] springs demonstrate large contraction strains up to 65.5% and are then fabricated into a reconfigurable dipole antenna to wirelessly monitor the surrounding heat sources. In the end, with the biocompatibility of MXene nanosheets, the [email protected] fibers enable the guidance of neural stem/progenitor cells differentiation and the promotion of neurite outgrowth. With a cation-induced assembly process, our multifunctional [email protected] fibers exhibit high scalability for future manufacturing and hold the prospect to inspire other applications.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00591DOI Listing
July 2021

Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6-35 Months of Age: Results From a Phase 2, Randomized, Observer-blind, Multicenter, Dose-ranging Study.

Pediatr Infect Dis J 2021 Jul 19. Epub 2021 Jul 19.

From the Vaccines Clinical Research and Development, GSK, Rockville, Maryland Vaccine Biostatistics Department, GSK, Rockville, Maryland Department of Pediatrics, Center of Excellence in Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Department of Pediatrics, Mackay Children's Hospital, Taipei, Taiwan Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University Col-lege of Medicine, Taoyuan, Taiwan Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan Division of Pediatric Infectious Diseases, China Medical University College of Medicine, Children's Hospital, Taichung, Taiwan Clinical and Epi Research and Development, GSK, Rockville, Maryland GSK, Wavre, Belgium Clinical Laboratory Sciences, GSK, Rixensart, Belgium Biostatistics and Statistical Programming Department, GSK, Rockville, Maryland Vaccines Research and Development, GSK, Rockville, Maryland Center for Vaccine Innovation and Access, PATH, Washington, District of Columbia Vaccine Discovery and Development, GSK, Rockville, Maryland, USA.

Background: This phase 2 observer-blind, randomized, multicenter, dose-ranging study evaluated immunogenicity and safety of different formulations of an AS03-adjuvanted H5N1 influenza vaccine in children 6-35 months of age.

Methods: One hundred eighty-five children randomized into 5 groups [1.9 µg hemagglutinin (HA)/AS03B, 0.9 µg HA/AS03C, 1.9 µg HA/AS03C, 3.75 µg HA/AS03C or 3.75 µg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03B the highest amount. One year later, all subjects were to receive unadjuvanted 3.75 µg HA as antigen challenge. Immunogenicity was assessed 21 days after primary vaccination (day 42) and 7 days after antigen challenge (day 392). Immunogenicity-fever index, based on hemagglutination inhibition and microneutralization antibody titers at day 42 and fever 7 days after each vaccination, was used to guide the selection of an acceptable formulation.

Results: After primary vaccination, formulations elicited strong homologous immune responses with all subjects' hemagglutination inhibition titers ≥1:40 post-vaccination. Immunogenicity-fever index based on hemagglutination inhibition and microneutralization assays showed that 1.9 µg HA/AS03B ranked the highest. Antibody levels persisted >4 times above baseline 12 months after primary vaccination with all formulations (day 385). Antibodies increased >4-fold after antigen challenge (day 392/day 385) with 1.9 µg HA/AS03B, 0.9 µg HA/AS03C and 1.9 µg HA/AS03C formulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 µg HA/AS03D) to 60.5% (1.9 µg HA/AS03B).

Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 µg HA/AS03B providing the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age.
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http://dx.doi.org/10.1097/INF.0000000000003247DOI Listing
July 2021

Induction of Polyploidy and Metabolic Profiling in the Medicinal Herb .

Plants (Basel) 2021 Jun 17;10(6). Epub 2021 Jun 17.

Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.

, which belongs to the Asteraceae family, is a procumbent, perennial herb. It has medicinal anti-inflammatory properties and has been traditionally used as folk medicine in East and South Asia for treating fever, cough and phlegm. In Taiwan, is a common ingredient of herbal tea. Previous studies showed that the plant leaves contain four major bioactive compounds, wedelolactone, demethylwedelolactone, luteolin and apigenin, that have potent antihepatoxic activity, and are thus used as major ingredients in phytopharmaceutical formulations. In this study, we set up optimal conditions for induction of ploidy in  . Ploidy can be an effective method of increasing plant biomass and improving medicinal and ornamental characteristics. By using flow cytometry and chicken erythrocyte nuclei as a reference, the DNA content (2C) or genome size of was determined to be 4.80 picograms (pg) in this study for the first time. Subsequently, we developed the successful induction of five triploid and three tetraploid plants by using shoot explants treated with different concentrations (0, 0.25, 0.5, 1, 1.5, 2 g/L) of colchicine. No apparent morphological changes were observed between these polyploid plants and the diploid wild-type (WT) plant, except that larger stomata in leaves were found in all polyploid plants as compared to diploid WT. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was used to quantify the four index compounds (wedelolactone, demethylwedelolactone, luteolin, apigenin) in these polyploid plants, and fluctuating patterns were detected. This is the first report regarding polyploidy in the herbal plant .
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http://dx.doi.org/10.3390/plants10061232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235177PMC
June 2021

COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.

Expert Rev Vaccines 2021 Jul 8:1-9. Epub 2021 Jul 8.

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Introduction: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination.

Areas Covered: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS.

Expert Opinion: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity.

Plain Language Summary: Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines.TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality.TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 10/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated.TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.
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http://dx.doi.org/10.1080/14760584.2021.1949294DOI Listing
July 2021

Comparative safety review of current pharmacological treatments for interstitial cystitis/ bladder pain syndrome.

Expert Opin Drug Saf 2021 May 19:1-11. Epub 2021 May 19.

Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a frustrating disease of chronic bladder pain associated with lower urinary tract symptoms. Although there are many proposed treatment algorithms, the uncertainty as to their etiology has a negative impact on the therapeutic outcome. Oftentimes combination therapy of drugs with different mechanisms of action will be utilized to relieve the symptoms. With the various treatment options available to patients and providers, there is an ever-growing need to implement drug efficacy as well as safety to promote best practice in use of the approved drug.: This review will focus on guideline-based pharmacotherapies as described by the AUA and EAU, specifically oral, and intravesical therapies with the most up-to-date published literature. Pharmacotherapies targeting bladder, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on efficacy and drug safety evaluation.: IC/BPS is a syndrome that requires bladder targeting agents to restore the urothelium barrier function and inhibit bladder hypersensitivity as well as various drugs with anti-inflammatory effects, and immune modulation effects. Current pharmacotherapies for IC/BPS have various therapeutic effects and adverse effects depending on the dose and individual response.
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http://dx.doi.org/10.1080/14740338.2021.1921733DOI Listing
May 2021

Highly Stretchable Flame-Retardant Skin for Soft Robotics with Hydrogel-Montmorillonite-Based Translucent Matrix.

Soft Robot 2021 Mar 24. Epub 2021 Mar 24.

Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore.

Flame-retardant coatings are crucial for intelligent systems operating in high-temperature (300-800°C) scenarios, which typically involve multi-joint discrete or continuous kinematic systems. These multi-segment motion generation systems call for conformable yet resilient skin for dexterous work, including firefighting, packaging inflammable substances, encapsulating energy storage devices, and preventing from burning. In fire scenes, a flame-retardant soft robot shall protect integrated electronic components safely and work for navigation and surveillance effectively. Here, we establish fire-resistant robotic mechanisms with montmorillonite (MMT)-biocompatible hydrogel skin, offering effective flame retardancy (∼78°C surface temperature after 3 min in fire) and high post-fire stretchability (∼360% uniaxial tensile strain). Fatigue test results in the MMT-hydrogel polymer matrix to portray a change in post-fire energy consumption of ∼21% (between the first cycle and the 200th cycle), further indicating robustness. MMT-hydrogel synthetic skin medium is then applied to everyday household items and electronics, offering appealing protections in fire scenes (≤10% capacitance loss after 3 min and ≤14% diode light-intensity loss after 1 min in fire). We deploy shape memory alloy (SMA) actuated inchworm-, starfish-, and snail-like locomotion (average velocity ∼12 mm·min) for translating inside fire applications. With the stretchable and flame-retardant translucent barriers, the MMT-hydrogel skinned soft robots demonstrate stable compression/relaxation cycles (25 cycles) within flames (4 min 10 s) while protecting the electronic components inside in fire scene. We solve the agility vs. endurance conundrum in this article with SMA actuation independently via Joule heating without a cross-talk from the surrounding high-temperature arena.
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http://dx.doi.org/10.1089/soro.2020.0003DOI Listing
March 2021

Vincristine exposure impairs skin keratinocytes, ionocytes, and lateral-line hair cells in developing zebrafish embryos.

Aquat Toxicol 2021 Jan 24;230:105703. Epub 2020 Nov 24.

Department of Life Science, School of Life Science, National Taiwan Normal University, 88 Ting-Chow Rd., Sec. 4, Taipei 11677, Taiwan. Electronic address:

Environmental contamination by anticancer pharmaceuticals has been widely reported. These drugs are not readily biodegradable, and their parent compounds and/or metabolites have been detected in surface waters and groundwater throughout the world. Adverse effects of anticancer drugs occur frequently in cancer patients, and a large body of clinical knowledge has accumulated. However, the effects of these drugs on aquatic organisms have not been thoroughly studied. This study aimed to investigate the effects of acute exposure to a common anticancer drug, vincristine (VCR), on zebrafish embryonic development and skin function. After 96 h of VCR exposure (0, 1, 10, 15, and 25 mg/L), significant teratogenic effects were observed, including growth retardation, pericardial edema, spine, tail, and yolk sac malformations (VCR ≥ 15 mg/L), a decreased heart rate, and ocular malformations (VCR ≥ 10 mg/L). The value of the half lethal concentration for zebrafish embryos was 20.6 mg/L. At ≥10 mg/L VCR, systemic ion contents and acid secretion in the skin over the yolk-sac decreased, and these findings were associated with decreases in skin ionocytes (H-ATPase-rich cells and Na-K-ATPase-rich cells). Also, the microridge-structure of skin keratinocytes was significantly damaged. The number of lateral line hair cells was reduced when VCR was ≥10 mg/L, and functional impairment was detected when VCR was as low as 1 mg/L. Results of this in vivo study in zebrafish embryos indicate that acute exposure to VCR can lead to developmental defects, impairment of skin functions, and even fish death.
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http://dx.doi.org/10.1016/j.aquatox.2020.105703DOI Listing
January 2021

Transformation and Characterization of Δ12-Fatty Acid Acetylenase and Δ12-Oleate Desaturase Potentially Involved in the Polyacetylene Biosynthetic Pathway from .

Plants (Basel) 2020 Nov 3;9(11). Epub 2020 Nov 3.

Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.

is commonly used as an herbal tea component or traditional medicine for treating several diseases, including diabetes. Polyacetylenes have two or more carbon-carbon triple bonds or alkynyl functional groups and are mainly derived from fatty acid and polyketide precursors. Here, we report the cloning of full-length cDNAs that encode Δ12-fatty acid acetylenase (designated BPFAA) and Δ12-oleate desaturase (designated BPOD) from , which we predicted to play a role in the polyacetylene biosynthetic pathway. Subsequently, expression vectors carrying BPFAA or BPOD were constructed and transformed into via the -mediated method. Genomic PCR analysis confirmed the presence of transgenes and selection marker genes in the obtained transgenic lines. The copy numbers of transgenes in transgenic lines were determined by Southern blot analysis. Furthermore, 4-5 genes and 2-3 genes were detected in wild-type (WT) plants. Quantitative real time-PCR revealed that some transgenic lines had higher expression levels than WT. Western blot analysis revealed OD protein expression in the selected transformants. High-performance liquid chromatography profiling was used to analyze the seven index polyacetylenic compounds, and fluctuation patterns were found.
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http://dx.doi.org/10.3390/plants9111483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693981PMC
November 2020

Synergistic Antimicrobial Titanium Carbide (MXene) Conjugated with Gold Nanoclusters.

Adv Healthc Mater 2020 10 3;9(19):e2001007. Epub 2020 Sep 3.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.

Bacterial resistance toward antibiotics is a world-wide problem, and one potential solution to fight against the resistance is to develop multi-mechanism antimicrobial agents to achieve synergistic performance. Titanium carbide (MXene) is an emerging 2D nanomaterial with antimicrobial ability to physically damage bacterial membrane and chemically induce oxidative stress, and it can be further conjugated with nanomaterials to improve its antibacterial performance. Herein, a synergistic antimicrobial agent is developed through conjugation of the ultra-small gold nanoclusters (AuNCs) on MXene nanosheets. The conjugated AuNCs are effectively delivered into bacteria after bacterial membrane damage caused by MXene, generating localized reactive oxygen species (ROS) of high concentration to effectively oxidize bacterial membrane lipid for enhanced membrane broken, as well as bacterial DNA for violent fragmentation. Thus, the synergistic physical (via MXene) and chemical (via MXene and AuNCs) antimicrobial mechanisms lead to eventual bacterial death of both Gram-positive and Gram-negative bacteria, with low IC values of 11.7 µg mL of MXene and 0.04 µm of AuNCs. Moreover, the crumpled MXene-AuNCs structure is constructed to inhibit biofilm formation, which hold synergistic antibacterial ability of MXene-AuNCs conjugation, hydrophobic surface to prevent bacterial attachment, and large surface area containing higher density of bactericides.
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http://dx.doi.org/10.1002/adhm.202001007DOI Listing
October 2020

Wireless TiCT MXene Strain Sensor with Ultrahigh Sensitivity and Designated Working Windows for Soft Exoskeletons.

ACS Nano 2020 09 19;14(9):11860-11875. Epub 2020 Aug 19.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585.

Emerging soft exoskeletons pose urgent needs for high-performance strain sensors with tunable linear working windows to achieve a high-precision control loop. Still, the state-of-the-art strain sensors require further advances to simultaneously satisfy multiple sensing parameters, including high sensitivity, reliable linearity, and tunable strain ranges. Besides, a wireless sensing system is highly desired to enable facile monitoring of soft exoskeleton in real time, but is rarely investigated. Herein, wireless TiCT MXene strain sensing systems were fabricated by developing hierarchical morphologies on piezoresistive layers and incorporating regulatory resistors into circuit designs as well as integrating the sensing circuit with near-field communication (NFC) technology. The wireless MXene sensor system can simultaneously achieve an ultrahigh sensitivity (gauge factor ≥ 14,000) and reliable linearity ( ≈ 0.99) within multiple user-designated high-strain working windows (130% to ≥900%). Additionally, the wireless sensing system can collectively monitor the multisegment exoskeleton actuations through a single database channel, largely reducing the data processing loading. We finally integrate the wireless, battery-free MXene e-skin with various soft exoskeletons to monitor the complex actuations that assist hand/leg rehabilitation.
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http://dx.doi.org/10.1021/acsnano.0c04730DOI Listing
September 2020

Broadband NaKLi[LiSiO]:Ce Alkali Lithosilicate Blue Phosphors.

J Phys Chem Lett 2020 Aug 4;11(16):6621-6625. Epub 2020 Aug 4.

Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.

Phosphors with a rigid and symmetrical structure are urgently needed. The alkali lithosilicate family (A[LiSiO]) has been extensively studied with a narrow emission band due to its unique cuboid-coordinated environment and rigid structure. However, here we demonstrate for the first time Ce-doped NaKLi[LiSiO] phosphors with a broad emission band, a high internal quantum efficiency (85.6%), and excellent thermal stability. Photoluminescence indicates the Ce's preference to occupy the Na site, leading to a strong blue color emission with peak maxima at 417 and 450 nm. Temperature- and pressure-dependent photoluminescence reveals thermal stability and a phase transition. Moreover, the X-ray absorption near-edge structure reveals the mixing of Ce and Ce in the materials; this result differs from that of Eu-doped A[LiSiO] phosphors. The charge compensation process is then proposed to explain this difference. This study not only provides insights into Ce-doped UCrC-type phosphors but also explains the charge compensation mechanism of the aliovalent doping process.
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http://dx.doi.org/10.1021/acs.jpclett.0c02064DOI Listing
August 2020

Potential of galled leaves of Goji () as functional food.

BMC Nutr 2020 7;6:26. Epub 2020 Jul 7.

Department of Horticulture and Landscape Architecture, National Taiwan University, Daan, 106 Taipei, Taiwan.

Background: Goji () is a popular traditional health food, and its fruit and root extracts have been found to possess antioxidant, anti-inflammatory, and hypocholesterolemia-inducing abilities. Goji leaves also contain high amounts of phenolic compounds, similar to its fruit, and their extracts also exhibit several pharmaceutical effects. The induction of galls on Goji leaves reduces their photosynthetic ability and fruit yield, which raise their farming costs, thereby leading to economic loss. However, the defense mechanisms induced by infection may elevate the secondary metabolite content of the leaves, which might provide more nutritive compounds.

Method: Content of chlorophyll, carotenoids, polyphenols, and flavonoids in the extracts of normal and infected Goji leaves () were analyzed. The relative content of chlorogenic acid and rutin, two major phenolic compounds in Goji leaves, were determined by LC-MS/MS. Antioxidant activity was presented by demonstrating the DPPH scavenging percentage. The extract of Goji fruit () was also analyzed to show a comparative result.

Results: In this study, we found that in infected Goji leaves, the polyphenol content was significantly increased. The level of chlorogenic acid was increased by 36% in galled leaves. The content of rutin in galled leaves was also elevated. Testing the antioxidant activities also showed that the extracts of galled leaves have higher DPPH scavenging abilities.

Conclusions: Our results demonstrated that galled Goji leaves have higher functional value, and may have potential as being consumed as health food.
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http://dx.doi.org/10.1186/s40795-020-00351-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339520PMC
July 2020

Correlation between Nanoscale Elasticity, Semiconductivity, and Structural Order in Functionalized Polyaniline Thin Films.

Langmuir 2020 Apr 8;36(15):4153-4164. Epub 2020 Apr 8.

Department of Physics, National Taiwan Normal University, Taipei, Taiwan 106, Republic of China.

The correlation between structural order, elasticity, and semiconductivity for butylthio-functionalized polyaniline (PANI-SBu) thin films was investigated using atomic force microscopy (AFM)-based techniques with X-ray diffraction (XRD) and scanning electron microscopy (SEM). After different stirring times, the thin films were cast from the solution of PANI-SBu in -methyl-2-pyrrolidone that was continuously stirred at a constant rate of 150 rpm in an airtight round-bottom flask. According to the XRD and SEM results, the cross-sectional film structure evolved from being generally holey to highly lamellar with an increase in the stirring time. However, some new types of disordered structures began emerging beyond the optimal stirring time, possibly caused by the formation of disordered packing structures as contributed from the overoxidized polyaniline backbones during the additional stirring time. Moreover, according to the investigation results obtained using AFM-based techniques, the out-of-plane elastic moduli and charge mobilities of the PANI-SBu films were consistently smaller for disordered thin films and larger for structurally more ordered ones. The shear force resulting from the mechanical stirring of the PANI-SBu solution may gradually disentangle the polymer chains and thus help transform the individual polyaniline molecule from a coil-like chain conformation to a better extended rodlike chain conformation. Therefore, when cast into a film, the stretched polymer chains facilitate self-organization among the PANI-SBu backbones during the film formation process. Thus, an improved structural order in the film is attained. Our results demonstrate an unambiguous correlation between the structure order, elasticity, and conductivity in PANI-SBu thin films, which may have useful applications in conducting polymer-based flexible electronics.
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http://dx.doi.org/10.1021/acs.langmuir.0c00100DOI Listing
April 2020

Are children less susceptible to COVID-19?

J Microbiol Immunol Infect 2020 Jun 25;53(3):371-372. Epub 2020 Feb 25.

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

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http://dx.doi.org/10.1016/j.jmii.2020.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102573PMC
June 2020

2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China.

J Microbiol Immunol Infect 2020 Jun 19;53(3):481-484. Epub 2020 Feb 19.

Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan. Electronic address:

We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.
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http://dx.doi.org/10.1016/j.jmii.2020.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102546PMC
June 2020

Therapeutic Efficacy of onabotulinumtoxinA Delivered Using Various Approaches in Sensory Bladder Disorder.

Toxins (Basel) 2020 01 23;12(2). Epub 2020 Jan 23.

Division of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.

Cystoscopic onabotulinumtoxinA (onaBoNTA) intradetrusor injection is an efficient and durable modality for treating sensory bladder disorders. However, the inconvenience of using the cystoscopic technique and anesthesia, and the adverse effects of direct needle injection (e.g., haematuria, pain, and infections) have motivated researchers and clinicians to develop diverse injection-free procedures to improve accessibility and prevent adverse effects. However, determining suitable approaches to transfer onaBoNTA, a large molecular and hydrophilic protein, through the impermeable urothelium to reach therapeutic efficacy remains an unmet medical need. Researchers have provided potential solutions in three categories: To disrupt the barrier of the urothelium (e.g., protamine sulfate), to increase the permeability of the urothelium (e.g., electromotive drug delivery and low-energy shock wave), and to create a carrier for transportation (e.g., liposomes, thermosensitive hydrogel, and hyaluronan-phosphatidylethanolamine). Thus far, most of these novel administration techniques have not been well established in their long-term efficacy; therefore, additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques. Finally, researchers may make progress with new combinations or biomaterials to change clinical practices in the future.
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http://dx.doi.org/10.3390/toxins12020075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076745PMC
January 2020

Heterogeneous, 3D Architecturing of 2D Titanium Carbide (MXene) for Microdroplet Manipulation and Voice Recognition.

ACS Appl Mater Interfaces 2020 Feb 4;12(7):8392-8402. Epub 2020 Feb 4.

Department of Chemical and Biomolecular Engineering , National University of Singapore (NUS) , 117585 , Singapore.

Mismatched deformation in a bilayer composite with rigid coating on a soft substrate results in complex and uniform topographic patterns, yet it remains challenging to heterogeneously pattern the upper coatings with various localized structures. Herein, a heterogeneous, 3D microstructure composed of TiCT titanium carbide (MXene) and single-walled carbon nanotubes (SWNTs) was fabricated using a one-step deformation of a thermally responsive substrate with designed open holes. The mechanically deformed SWNT-MXene (s-MXene) structure was next transferred onto an elastomeric substrate, and the resulting s-MXene/elastomer bilayer device exhibited three localized surface patterns, including isotropic crumples, periodic wrinkles, and large papillae-like microstructures. By adjusting the number and pattern, the s-MXene papillae arrays exhibited superhydrophobicity (>170°), strong and tunable adhesive force (52.3-110.6 μN), and ultra-large liquid capacity (up to 35 μL) for programmable microdroplet manipulation. The electrically conductive nature of s-MXene further enabled proper thermal management on microdroplets via Joule heating for miniaturized antibacterial tests. The s-MXene papillae were further fabricated in a piezoresistive pressure sensor with high sensitivity (11.47 kPa). The output current changes of s-MXene sensors were highly sensitive to voice vibrations and responded identically with prerecorded profiles, promising their application in accurate voice acquisition and recognition.
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http://dx.doi.org/10.1021/acsami.9b18879DOI Listing
February 2020

A Review of Printable Flexible and Stretchable Tactile Sensors.

Research (Wash D C) 2019 11;2019:3018568. Epub 2019 Nov 11.

Department of Biomedical Engineering, Medical Mechatronics Laboratory, National University of Singapore, Singapore 117583.

Flexible and stretchable tactile sensors that are printable, nonplanar, and dynamically morphing are emerging to enable proprioceptive interactions with the unstructured surrounding environment. Owing to its varied range of applications in the field of wearable electronics, soft robotics, human-machine interaction, and biomedical devices, it is required of these sensors to be flexible and stretchable conforming to the arbitrary surfaces of their stiff counterparts. The challenges in maintaining the fundamental features of these sensors, such as flexibility, sensitivity, repeatability, linearity, and durability, are tackled by the progress in the fabrication techniques and customization of the material properties. This review is aimed at summarizing the recent progress of rapid prototyping of sensors, printable material preparation, required printing properties, flexible and stretchable mechanisms, and promising applications and highlights challenges and opportunities in this research paradigm.
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http://dx.doi.org/10.34133/2019/3018568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944518PMC
November 2019

Recommendations for the use of Japanese encephalitis vaccines.

Pediatr Neonatol 2020 02 28;61(1):3-8. Epub 2019 Nov 28.

Division of Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taiwan.

Japanese encephalitis (JE) is a mosquito-borne viral infection which is prevalent in Taiwan. The virus circulates in an enzootic cycle in pigs which serve as amplifying hosts. Outbreaks typically occur during summer. A universal vaccination program using 4-shot mouse brain-derived inactivated vaccine has successfully controlled JE epidemics in Taiwan since 1968. More than 90% of JE cases in recent years were older than 20 years in Taiwan. Because of several drawbacks, mouse brain-derived vaccine has been replaced by newer generation JE vaccines, including inactivated Vero cell-derived vaccine and live chimeric vaccine. The present article describes the recommendations in Taiwan for the use of new JE vaccines and the schedules for shifting between different JE vaccines.
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http://dx.doi.org/10.1016/j.pedneo.2019.11.009DOI Listing
February 2020

Respiratory pathogens - Some altered antibiotic susceptibility after implementation of pneumococcus vaccine and antibiotic control strategies.

J Microbiol Immunol Infect 2020 Oct 18;53(5):682-689. Epub 2019 Oct 18.

Department of Pediatrics, Section of Infection, Taichung Veterans General Hospital, Taichung, Taiwan. Electronic address:

Background/purpose: Antimicrobial resistance in Taiwan has been on the rise for two decades. The implementation of pneumococcal conjugate vaccination (PCV13) and enhanced antimicrobial control (2013-2015) by the government may have changed the antibiotic resistance.

Methods: Four respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Moraxella catarrhalis) isolated in a single medical center during 2008-2017 were studied. We defined three temporal stages: (a) the first era (2008-2012), prior to implementation of the national immunization program (PCV13 vaccination), (b) the second era (2013-2015), during which an enhanced antibiotic control strategy was implemented, and (c) the third era (2016-2017), after implementation. Antimicrobial drug sensitivities were collected from two other hospitals: one from east Taiwan, one from west-central Taiwan.

Results: S. pneumoniae was frequently isolated during the first era. It declined progressively during the second era of PCV13 vaccination. S. pyogenes and M. catarrhalis were not frequently isolated. The drug susceptibility of S. pneumoniae to ceftriaxone and vancomycin remained high. The antimicrobial susceptibility of H. influenzae to amoxillin/clavulante declined over the three temporal stages, from 91.9%-79.5%-58.5% (all p < 0.05).

Conclusion: Antimicrobial resistance of H. influenzae increased during the latter part of the study period. The PCV13 vaccination program reduced the invasive pneumococcal disease and reduced the stress on the emergent drug resistance. This enhanced antibiotic control strategy was effective in terms of nosocomial drug resistance but not for community-associated pathogens.
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http://dx.doi.org/10.1016/j.jmii.2019.08.015DOI Listing
October 2020

Respiratory presentation of patients infected with enterovirus D68 in Taiwan.

Pediatr Neonatol 2020 04 12;61(2):168-173. Epub 2019 Sep 12.

School of Medicine, Chung Shan Medical University, Taichung City, Taiwan; Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, Taiwan. Electronic address:

Background: Enterovirus-D68 (EV-D68) has been endemic in Taiwan for some years with a small number of positive cases. Detailed information about respiratory presentation is lacking. This study characterized the clinical course in children admitted to the medical center and regional hospital in Taichung during 2015.

Methods: Retrospective chart review of patients with confirmed EV-D68 infection admitted to the medical center and regional hospital in Taichung with respiratory symptoms in the second half of 2015. Past medical history, clinical presentation, management, and course in hospital were collected and analyzed. Simple demographic data and clinical symptoms were also collected from patients confirmed with EV-D68 infection who visited clinics in Taichung.

Results: Six children were included. Two patients had a prior history of asthma or recurrent dyspnea, and one had other preexisting medical comorbidities. One child was admitted to the pediatric intensive care unit. All the patients were cured. Cough, rhinorrhea, tachypnea and fever were the most common clinical symptoms among inpatients, while influenza-like illness (ILI) was prevalent in outpatients.

Conclusion: EV-D68 infection resulted in respiratory presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of asthma or recurrent dyspnea appear to be more severely affected.
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http://dx.doi.org/10.1016/j.pedneo.2019.09.006DOI Listing
April 2020

Mechanochemical engineering of 2D materials for multiscale biointerfaces.

J Mater Chem B 2019 11 10;7(41):6293-6309. Epub 2019 Jul 10.

School of Engineering, Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA.

Atomically thin nanomaterials represent a unique paradigm for interfacing with biological systems due to their mechanical flexibility, exceptional interfacial area, and ease of chemical functionalization. In particular, these two-dimensional (2D) materials are able to bend, curve, and fold in response to biologically-generated forces or other external stimuli. Such origami-like folding of 2D materials into wrinkled or crumpled topographies allows them to withstand large deformations by accordion-like unfolding, with implications for stretchable and shape-changing devices. Here, we review how mechanically manipulated 2D materials can interact with biological systems across a multitude of length scales. We focus on recent work where wrinkling, crumpling, or bending of 2D materials permits new chemical and material properties, with four case studies: (i) programming biomolecular reactivity and enhanced sensing, (ii) directed adhesion and encapsulation of bacteria or mammalian cells, (iii) stimuli-responsive actuators and soft robotics, and (iv) stretchable barrier technologies and wearable human-scale sensors. Finally, we consider future directions for manufacturing, materials and systems integration, as well as biocompatibility. Taken together, these 2D materials may enable new avenues for ultrasensitive molecular detection, biomaterial scaffolds, soft machines, and wearable technologies.
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http://dx.doi.org/10.1039/c9tb01006hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812607PMC
November 2019

Multifunctional metallic backbones for origami robotics with strain sensing and wireless communication capabilities.

Sci Robot 2019 Aug;4(33)

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.

The tight integration of actuation, sensing, and communication capabilities into origami robots enables the development of new-generation functional robots. However, this task is challenging because the conventional materials (e.g., papers and plastics) for building origami robots lack design opportunities for incorporating add-on functionalities. Installing external electronics requires high system integration and inevitably increases the robotic weight. Here, a graphene oxide (GO)-enabled templating synthesis was developed to produce reconfigurable, compliant, multifunctional metallic backbones for the fabrication of origami robots with built-in strain sensing and wireless communication capabilities. The GO-enabled templating synthesis realized the production of complex noble metal origamis (such as Pt) with high structural replication of their paper templates. The reproduced Pt origami structures were further stabilized with thin elastomer, and the Pt-elastomer origamis were reconfigurable and served as the multifunctional backbones for building origami robots. Compared with traditional paper and plastic materials, the reconfigurable Pt backbones were more deformable, fire retardant, and power efficient. In addition, the robots with conductive Pt-elastomer backbones (Pt robots) demonstrated distinct capabilities-such as on-demand resistive heating, strain sensing, and built-in antennas-without the need for external electronics. The multifunctionality of Pt robots was further demonstrated to extend beyond the capabilities of traditional paper-based robots, such as melting an ice cube to escape, monitoring/recording robotic motions in real time, and wireless communications between robots. The development of multifunctional metallic backbones that couple actuation, sensing, and communication enriches the material library for the fabrication of soft robotics toward high functional integration.
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http://dx.doi.org/10.1126/scirobotics.aax7020DOI Listing
August 2019

Silver nanoparticle exposure impairs ion regulation in zebrafish embryos.

Aquat Toxicol 2019 Sep 26;214:105263. Epub 2019 Jul 26.

Department of Life Science, School of Life Science, National Taiwan Normal University, Taipei, Taiwan. Electronic address:

The potential toxicity of silver nanoparticles (AgNPs) to the early stages of fish is still unclear. This study used zebrafish embryos as a model to investigate the toxic effects of AgNPs on ion regulation by skin ionocytes. Zebrafish embryos were exposed to AgNPs for 96 h (4-100 h post-fertilization (hpf)) or 4 h (96-100 hpf). After 96 h of exposure to 5 and 10 mg/L AgNPs, survival rates had decreased to 42% and 0%, respectively; the body length had also significantly decreased at 5 mg/L. Whole-body Na and K contents significantly decreased at 1 and 3 mg/L, while Ca contents decreased at ≥0.1 mg/L. H secretion by the skin significantly decreased at 1 mg/L. The density of skin ionocytes labeled with rhodamine 123 (a mitochondrion marker) decreased by 25% and 55% at 1 and 3 mg/L, respectively; and 54% of ionocytes (at 3 mg/L) were deformed from an oval to a spinous shape. After 4 h of exposure to 1 and 5 mg/L, whole-body Na and Ca contents, H secretion, and density of ionocytes had also significantly decreased. This study revealed the toxicity of AgNPs to skin ionocytes and ion regulation in the early stages of zebrafish embryos.
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http://dx.doi.org/10.1016/j.aquatox.2019.105263DOI Listing
September 2019

MoS Membranes for Organic Solvent Nanofiltration: Stability and Structural Control.

J Phys Chem Lett 2019 Aug 1;10(16):4609-4617. Epub 2019 Aug 1.

Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive , Singapore 117585.

This paper reveals the chemical, structural, and separation stability of stacked molybdenum disulfide (MoS) membranes and establishes a low-cost and facile approach to developing stable, selective membranes for efficient molecular separation in an organic solvent. MoS nanoflakes that were dominant  by monolayer MoS sheets as prepared via direct chemical exfoliation (chem-MoS) were found to be chemically and structurally instable, with a sharp decrease in the level of solute rejection within a few days. Few-layer MoS nanoflakes were then fabricated using a hydrothermal method (hydro-MoS). A "supportive" drying process involving glycerol pretreatment and drying in an oven was established to allow realignment of nanoflakes and adjustment of interflake spacing. We have shown that the hydro-MoS membranes provide a mean interflake free spacing of ∼1 nm, which is ideal for the separation of a model solute (Rose Bengal, size of ∼1.45 nm) from the solvent isopropanol (size of 0.58 nm) with good long-term stability over a 7 day test.
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http://dx.doi.org/10.1021/acs.jpclett.9b01780DOI Listing
August 2019

Disease antigens detection by silicon nanowires with the efficiency optimization of their antibodies on a chip.

Biosens Bioelectron 2019 Sep 21;141:111209. Epub 2019 Mar 21.

National Applied Research Laboratories,Taiwan Semiconductor Research Institute, Hsinchu, Taiwan. Electronic address:

Enhancing the efficiency of antibody protein immobilized on a silicon nanowire-based chip for their antigens detection is reported. An external electric field (EEF) is applied to direct the orientation of antibodies during their immobilization on a chip. Atomic force microscopy (AFM) is used to measure the binding forces between immobilized antibody and targeting antigen under the influence of EEF at different angles. The maximum binding force under a specific angle (optimal angle; oa) of EEF (EEF) implies the optimal orientation of the antibodies on the chip. In this report, two different cancer carcinoembryonic antigen (CEA)-related cell adhesion molecules 5 (CEACAM5) & 1 (CEACAM1) were used for the examples of disease antigen detection. EEF of anti-CEACAM5 or anti-CEACAM1 immobilized on a general chip was firstly determined. Spectroscopy of AFM revealed that both binding forces were the largest ones with their antigens when EEF was applied as compared with no or other angles of EEF. These antibody proteins accompanied with the application of EEF were secondly immobilized on silicon-nanowires (n = 1000) and the field effects were measured (∆I) as their target antigens were approached. Results showed that ∆I was the largest ones when EEFs (225°/270° and 135°/180° for anti-CEACAM5 and anti-CEACAM1, respectively) were applied as compared with other angles of EEF. These observations imply that the silicon nanowires together with the application of EEF as detection tools could be applied for the cancer diagnostics in the future.
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http://dx.doi.org/10.1016/j.bios.2019.03.042DOI Listing
September 2019

Tunable Moiré Superlattice of Artificially Twisted Monolayers.

Adv Mater 2019 Sep 24;31(37):e1901077. Epub 2019 Jul 24.

Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.

Twisting between two stacked monolayers modulates periodic potentials and forms the Moiré electronic superlattices, which offers an additional degree of freedom to alter material property. Considerable unique observations, including unconventional superconductivity, coupled spin-valley states, and quantized interlayer excitons are correlated to the electronic superlattices but further study requires reliable routes to study the Moiré in real space. Scanning tunneling microscopy (STM) is ideal to precisely probe the Moiré superlattice and correlate coupled parameters among local electronic structures, strains, defects, and band alignment at atomic scale. Here, a clean route is developed to construct twisted lattices using synthesized monolayers for fundamental studies. Diverse Moiré superlattices are predicted and successfully observed with STM at room temperature. Electrical tuning of the Moiré superlattice is achieved with stacked TMD on graphite.
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http://dx.doi.org/10.1002/adma.201901077DOI Listing
September 2019

Risk Factors for Myocardial Infarction and Stroke Among Sepsis Survivors: A Competing Risks Analysis.

J Intensive Care Med 2020 Jan 12;35(1):34-41. Epub 2019 May 12.

Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Objectives: Predictors for post-sepsis myocardial infarction (MI) and stroke are yet to be identified due to the competing risk of death.

Methods: This study included all hospitalized patients with sepsis from National Health Insurance Research Database of Taiwan between 2000 and 2011. The primary outcome was the first occurrence of MI and stroke requiring hospitalization within 180 days following hospital discharge from the index sepsis episode. The association between predictors and post-sepsis MI and stroke were analyzed using cumulative incidence competing risk model that controlled for the competing risk of death.

Results: Among 42 316 patients with sepsis, 1012 (2.4%) patients developed MI and stroke within 180 days of hospital discharge. The leading 5 predictors for post-sepsis MI and stroke are prior cerebrovascular diseases (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.74-2.32), intra-abdominal infection (HR: 1.94, 95% CI: 1.71-2.20), previous MI (HR: 1.81, 95% CI: 1.53-2.15), lower respiratory tract infection (HR: 1.62, 95% CI: 1.43-1.85), and septic encephalopathy (HR: 1.61, 95% CI: 1.26-2.06).

Conclusions: Baseline comorbidities and sources of infection were associated with an increased risk of post-sepsis MI and stroke. The identified risk factors may help physicians select a group of patients with sepsis who may benefit from preventive measures, antiplatelet treatment, and other preventive measures for post-sepsis MI and stroke.
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http://dx.doi.org/10.1177/0885066619844936DOI Listing
January 2020

New Dammarane-type Saponins from .

Molecules 2019 Apr 8;24(7). Epub 2019 Apr 8.

Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei 112, Taiwan.

Six new dammarane-type saponins, gypenosides CP1-6 (), along with 19 known compounds ⁻, were isolated and characterized from the aerial parts of . Among these compounds, eight dammarane-type saponins, , , , , , , , and exhibited the greatest antiproliferative effects against two human tumor cell lines (A549 and HepG2).
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http://dx.doi.org/10.3390/molecules24071375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480664PMC
April 2019

Graphene Oxide-Enabled Synthesis of Metal Oxide Origamis for Soft Robotics.

ACS Nano 2019 May 25;13(5):5410-5420. Epub 2019 Mar 25.

Department of Chemical and Biomolecular Engineering , National University of Singapore (NUS) , 117585 , Singapore.

Origami structures have been widely applied in various technologies especially in the fields of soft robotics. Metal oxides (MOs) have recently emerged as unconventional backbone materials for constructing complex origamis with distinct functionalities. However, the MO origami structures reported in the literature were rigid and not deformable, thus limiting their applications to soft robotics. Herein, we reported a graphene oxide (GO)-enabled templating synthesis to produce complex MO origami structures from their paper origami templates with high structural replication. The MO origami structures were next stabilized with elastomer, and the MO-elastomer origamis were able to be adapted into multiple actuation systems (including magnetic fields, shape-memory alloys, and pneumatics) for the fabrication of MO origami robots. Compared with conventional paper origami robots, the MO robots were lightweight, mechanically compliant, fire-retardant, magnetic responsive, and power efficient. We further demonstrated the legendary phoenix-fire-reborn concept in the soft robotics fields: a paper origami robot sacrificed itself in a fire scene and transformed itself into a downsized AlO robot; the AlO robot was able to crawl through a narrow tunnel where the original paper robot was unfit. These MO reconfigurable origamis provide an expanded material library for building soft robotics, and the functionalities of MO robots can be systematically engineered via the intercalation of various metal ions during the GO-enabled synthesis.
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http://dx.doi.org/10.1021/acsnano.9b00144DOI Listing
May 2019
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