Al Khamici, H, Hossain, K, Cornell, B & Valenzuela, S 2016, 'Investigating Sterol and Redox Regulation of the Ion Channel Activity of CLIC1 Using Tethered Bilayer Membranes', Membranes, vol. 6, no. 4, pp. 51-51.
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The Chloride Intracellular Ion Channel (CLIC) family consists of six conserved proteins in humans. These are a group of enigmatic proteins, which adopt both a soluble and membrane bound form. CLIC1 was found to be a metamorphic protein, where under specific environmental triggers it adopts more than one stable reversible soluble structural conformation. CLIC1 was found to spontaneously insert into cell membranes and form chloride ion channels. However, factors that control the structural transition of CLIC1 from being an aqueous soluble protein into a membrane bound protein have yet to be adequately described. Using tethered bilayer lipid membranes and electrical impedance spectroscopy system, herein we demonstrate that CLIC1 ion channel activity is dependent on the type and concentration of sterols in bilayer membranes. These findings suggest that membrane sterols play an essential role in CLIC1's acrobatic switching from a globular soluble form to an integral membrane form, promoting greater ion channel conductance in membranes. What remains unclear is the precise nature of this regulation involving membrane sterols and ultimately determining CLIC1's membrane structure and function as an ion channel. Furthermore, our impedance spectroscopy results obtained using CLIC1 mutants, suggest that the residue Cys24 is not essential for CLIC1's ion channel function. However Cys24 does appear important for optimal ion channel activity. We also observe differences in conductance between CLIC1 reduced and oxidized forms when added to our tethered membranes. Therefore, we conclude that both membrane sterols and redox play a role in the ion channel activity of CLIC1.
Asadnia, M, Kottapalli, AGP, Karavitaki, KD, Warkiani, ME, Miao, J, Corey, DP & Triantafyllou, M 2016, 'From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance', Scientific Reports, vol. 6, no. 1, p. 32955.
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AbstractWe report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.
Cai, M, Zhou, B, Tian, Y, Zhou, J, Xu, S & Zhang, J 2016, 'Broadband mid-infrared 2.8μm emission in Ho3+/Yb3+-codoped germanate glasses', Journal of Luminescence, vol. 171, pp. 143-148.
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This work reports the mid-infrared emission properties around 2.85 μm in Ho3+/Yb3+ codoped germanate glasses. The glass not only possesses considerably low OH− absorption coefficient (0.24 cm−1), but also exhibits low phonon energy (790 cm−1). A large spontaneous transition probability (36.66 s−1) corresponding to the Ho3+:5I6→5I7 transition has been calculated based on the Judd–Ofelt theory. Besides, a broad 2.85 μm fluorescence has been successfully observed and a reasonably model has been proposed to unravel the origin of the broadening emission band. Moreover, the peak emission cross sections of the glass is as high as 9.2×10−21 cm2, and the maximum gain per unit length at 2.85 μm could be as high as 4.3 dB/cm. Results indicate that the prepared germanate glass is a promising candidate for 2.85 μm mid-infrared laser materials applications.
Chaudhuri, PK, Ebrahimi Warkiani, M, Jing, T, Kenry, K & Lim, CT 2016, 'Microfluidics for research and applications in oncology', The Analyst, vol. 141, no. 2, pp. 504-524.
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Cancer is currently one of the top non-communicable human diseases, and continual research and developmental efforts, particularly in microfluidics technology, are being made to better understand and manage this disease.
Chen, P, Zhong, Z, Jia, H, Zhou, J, Han, J, Liu, X & Qiu, J 2016, 'Magnetic field enhanced upconversion luminescence and magnetic–optical hysteresis behaviors in NaYF4: Yb, Ho nanoparticles', RSC Advances, vol. 6, no. 9, pp. 7391-7395.
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A magnetic field induces the enhancement of upconversion luminescence and magnetic–optical hysteresis behaviors in NaYF4: 20% Yb, 1% Ho nanoparticles.
Cong, Y, Shi, B, Lu, Y, Wen, S, Chung, R & Jin, D 2016, 'RETRACTED ARTICLE: One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell', Scientific Reports, vol. 6, no. 1, pp. 1-11.
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AbstractGene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,1H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy.
Constantine, M, Liew, CK, Lo, V, Macmillan, A, Cranfield, CG, Sunde, M, Whan, R, Graham, RM & Martinac, B 2016, 'Heterologously-expressed and Liposome-reconstituted Human Transient Receptor Potential Melastatin 4 Channel (TRPM4) is a Functional Tetramer', SCIENTIFIC REPORTS, vol. 6.
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Cranfield, CG, Berry, T, Holt, SA, Hossain, KR, Le Brun, AP, Carne, S, Al Khamici, H, Coster, H, Valenzuela, SM & Cornell, B 2016, 'Evidence of the Key Role of H3O+ in Phospholipid Membrane Morphology', LANGMUIR, vol. 32, no. 41, pp. 10725-10734.
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© 2016 American Chemical Society. This study explains the importance of the phosphate moiety and H3O+ in controlling the ionic flux through phospholipid membranes. We show that despite an increase in the H3O+ concentration when the pH is decreased, the level of ionic conduction through phospholipid bilayers is reduced. By modifying the lipid structure, we show the dominant determinant of membrane conduction is the hydrogen bonding between the phosphate oxygens on adjacent phospholipids. The modulation of conduction with pH is proposed to arise from the varying H3O+ concentrations altering the molecular area per lipid and modifying the geometry of conductive defects already present in the membrane. Given the geometrical constraints that control the lipid phase structure of membranes, these area changes predict that organisms evolving in environments with different pHs will select for different phospholipid chain lengths, as is found for organisms near highly acidic volcanic vents (short chains) or in highly alkaline salt lakes (long chains). The stabilizing effect of the hydration shells around phosphate groups also accounts for the prevalence of phospholipids across biology. Measurement of ion permeation through lipid bilayers was made tractable using sparsely tethered bilayer lipid membranes with swept frequency electrical impedance spectroscopy and ramped dc amperometry. Additional evidence of the effect of a change in pH on lipid packing density is obtained from neutron reflectometry data of tethered membranes containing perdeuterated lipids.
Deng, X, Chen, Y, Cheng, Z, Deng, K, Ma, P, Hou, Z, Liu, B, Huang, S, Jin, D & Lin, J 2016, 'Rational design of a comprehensive cancer therapy platform using temperature-sensitive polymer grafted hollow gold nanospheres: simultaneous chemo/photothermal/photodynamic therapy triggered by a 650 nm laser with enhanced anti-tumor efficacy', Nanoscale, vol. 8, no. 12, pp. 6837-6850.
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© The Royal Society of Chemistry 2016. Combining multi-model treatments within one single system has attracted great interest for the purpose of synergistic therapy. In this paper, hollow gold nanospheres (HAuNs) coated with a temperature-sensitive polymer, poly(oligo(ethylene oxide) methacrylate-co-2-(2-methoxyethoxy)ethyl methacrylate) (p(OEGMA-co-MEMA)), co-loaded with DOX and a photosensitizer Chlorin e6 (Ce6) were successfully synthesized. As high as 58% DOX and 6% Ce6 by weight could be loaded onto the HAuNs-p(OEGMA-co-MEMA) nanocomposites. The grafting polymer brushes outside the HAuNs play the role of 'gate molecules' for controlled drug release by 650 nm laser radiation owing to the temperature-sensitive property of the polymer and the photothermal effect of HAuNs. The HAuNs-p(OEGMA-co-MEMA)-Ce6-DOX nanocomposites with 650 nm laser radiation show effective inhibition of cancer cells in vitro and enhanced anti-tumor efficacy in vivo. In contrast, control groups without laser radiation show little cytotoxicity. The nanocomposite demonstrates a way of 'killing three birds with one stone', that is, chemotherapy, photothermal and photodynamic therapy are triggered simultaneously by the 650 nm laser stimulation. Therefore, the nanocomposites show the great advantages of multi-modal synergistic effects for cancer therapy by a remote-controlled laser stimulus.
Du, W, Su, QP, Chen, Y, Zhu, Y, Jiang, D, Rong, Y, Zhang, S, Zhang, Y, Ren, H, Zhang, C, Wang, X, Gao, N, Wang, Y, Sun, L, Sun, Y & Yu, L 2016, 'Kinesin 1 Drives Autolysosome Tubulation', Developmental Cell, vol. 37, no. 4, pp. 326-336.
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© 2016 Elsevier Inc. Autophagic lysosome reformation (ALR) plays an important role in maintaining lysosome homeostasis. During ALR, lysosomes are reformed by recycling lysosomal components from autolysosomes. The most noticeable step of ALR is autolysosome tubulation, but it is currently unknown how the process is regulated. Here, using an approach combining in vivo studies and in vitro reconstitution, we found that the kinesin motor protein KIF5B is required for autolysosome tubulation and that KIF5B drives autolysosome tubulation by pulling on the autolysosomal membrane. Furthermore, we show that KIF5B directly interacts with PtdIns(4,5)P2. Kinesin motors are recruited and clustered on autolysosomes via interaction with PtdIns(4,5)P2 in a clathrin-dependent manner. Finally, we demonstrate that clathrin promotes formation of PtdIns(4,5)P2-enriched microdomains, which are required for clustering of KIF5B. Our study reveals a mechanism by which autolysosome tubulation was generated.
Gerami, A, Mostaghimi, P, Armstrong, RT, Zamani, A & Warkiani, ME 2016, 'A microfluidic framework for studying relative permeability in coal', International Journal of Coal Geology, vol. 159, pp. 183-193.
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A significant unconventional energy resource is methane gas stored in shallow coal beds, known as coal seam gas. The flow and transport of fluid in coal beds occur in a well-developed system of natural fractures, called cleats. In this study, we developed an efficient workflow for the fabrication of microfluidic chips based on X-ray micro-Computed Tomography (micro-CT) images of coal. A dry and wet micro-CT imaging technique is utilized to image coal cleats that would be otherwise non-resolvable. The obtained image of the cleat network is then etched into silicon wafers and used to fabricate poly dimethyl siloxane (PDMS) microfluidic devices. Fluid transport and displacement efficiency are visualized and quantified in real time by injecting water with a flow rate of 1 μl min-1 into the fabricated cleat structure initially saturated with air. A microfluidic approach is used to measure the relative permeability of a realistic coal cleat system by monitoring the liquid recovery at recorded saturations after the breakthrough. Relative permeability curves show the cross and end point values for the water and gas flow, and predict a maximum relative permeability of 0.15 for the water phase. Understanding the relationship between coal cleat structure and the resulting relative permeability is crucial for the optimization of methane gas extraction and to reduce the environmental concerns of excess surface water production. Also, pore network modelling based on the Maximal Ball (MB) concept is applied to predict relative permeability curves numerically. Our experimental results are in good agreement with pore network modelling outcomes and provide consistent and smooth macro-scale relationships along with direct observation of the pore-scale physics. Therefore not only can the microfluidic approach be used as a validation tool for multiphase flow numerical models but it can also provide direct visualization of transport properties unique to coals. Overall, our d...
Gholami, A & Maddahfar, M 2016, 'Synthesis and characterization of barium molybdate nanostructures with the aid of amino acids and investigation of its photocatalytic degradation of methyl orange', Journal of Materials Science: Materials in Electronics, vol. 27, no. 7, pp. 6773-6778.
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Gholami, A & Maddahfar, M 2016, 'Synthesis and characterization of novel samarium-doped CuAl2O4 and its photocatalytic performance through the modified sol–gel method', Journal of Materials Science: Materials in Electronics, vol. 27, no. 4, pp. 3341-3346.
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Hassanzadeh-Barforoushi, A, Shemesh, J, Farbehi, N, Asadnia, M, Yeoh, GH, Harvey, RP, Nordon, RE & Warkiani, ME 2016, 'A rapid co-culture stamping device for studying intercellular communication', Scientific Reports, vol. 6, no. 1, p. 35618.
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AbstractRegulation of tissue development and repair depends on communication between neighbouring cells. Recent advances in cell micro-contact printing and microfluidics have facilitated the in-vitro study of homotypic and heterotypic cell-cell interaction. Nonetheless, these techniques are still complicated to perform and as a result, are seldom used by biologists. We report here development of a temporarily sealed microfluidic stamping device which utilizes a novel valve design for patterning two adherent cell lines with well-defined interlacing configurations to study cell-cell interactions. We demonstrate post-stamping cell viability of >95%, the stamping of multiple adherent cell types, and the ability to control the seeded cell density. We also show viability, proliferation and migration of cultured cells, enabling analysis of co-culture boundary conditions on cell fate. We also developed an in-vitro model of endothelial and cardiac stem cell interactions, which are thought to regulate coronary repair after myocardial injury. The stamp is fabricated using microfabrication techniques, is operated with a lab pipettor and uses very low reagent volumes of 20 μl with cell injection efficiency of >70%. This easy-to-use device provides a general strategy for micro-patterning of multiple cell types and will be important for studying cell-cell interactions in a multitude of applications.
He, F, Li, C, Zhang, X, Chen, Y, Deng, X, Liu, B, Hou, Z, Huang, S, Jin, D & Lin, J 2016, 'Optimization of upconversion luminescence of Nd3+-sensitized BaGdF5-based nanostructures and their application in dual-modality imaging and drug delivery', Dalton Transactions, vol. 45, no. 4, pp. 1708-1716.
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Nd3+-sensitized BaGdF5:20%Yb3+/2%Er3+@BaGdF5:10%Yb3+@BaNdF5@BaGdF5 nanoparticles for dual-model imaging and pH-triggered drug release.
Hesari, Z, Soleimani, M, Atyabi, F, Sharifdini, M, Nadri, S, Warkiani, ME, Zare, M & Dinarvand, R 2016, 'A hybrid microfluidic system for regulation of neural differentiation in induced pluripotent stem cells', Journal of Biomedical Materials Research Part A, vol. 104, no. 6, pp. 1534-1543.
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AbstractControlling cellular orientation, proliferation, and differentiation is valuable in designing organ replacements and directing tissue regeneration. In the present study, we developed a hybrid microfluidic system to produce a dynamic microenvironment by placing aligned PDMS microgrooves on surface of biodegradable polymers as physical guidance cues for controlling the neural differentiation of human induced pluripotent stem cells (hiPSCs). The neuronal differentiation capacity of cultured hiPSCs in the microfluidic system and other control groups was investigated using quantitative real time PCR (qPCR) and immunocytochemistry. The functionally of differentiated hiPSCs inside hybrid system's scaffolds was also evaluated on the rat hemisected spinal cord in acute phase. Implanted cell's fate was examined using tissue freeze section and the functional recovery was evaluated according to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Our results confirmed the differentiation of hiPSCs to neuronal cells on the microfluidic device where the expression of neuronal‐specific genes was significantly higher compared to those cultured on the other systems such as plain tissue culture dishes and scaffolds without fluidic channels. Although survival and integration of implanted hiPSCs did not lead to a significant functional recovery, we believe that combination of fluidic channels with nanofiber scaffolds provides a great microenvironment for neural tissue engineering, and can be used as a powerful tool for in situ monitoring of differentiation potential of various kinds of stem cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1534–1543, 2016.
Hoiles, W, Gupta, R, Cornell, B, Cranfield, C & Krishnamurthy, V 2016, 'The Effect of Tethers on Artificial Cell Membranes: A Coarse-Grained Molecular Dynamics Study', PLOS ONE, vol. 11, no. 10.
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Hossain, K, Al Khamici, H, Holt, S & Valenzuela, S 2016, 'Cholesterol Promotes Interaction of the Protein CLIC1 with Phospholipid Monolayers at the Air–Water Interface', Membranes, vol. 6, no. 1, pp. 15-15.
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© 2016 by the authors; licensee MDPI, Basel, Switzerland. CLIC1 is a Chloride Intracellular Ion Channel protein that exists either in a soluble state in the cytoplasm or as a membrane bound protein. Members of the CLIC family are largely soluble proteins that possess the intriguing property of spontaneous insertion into phospholipid bilayers to form integral membrane ion channels. The regulatory role of cholesterol in the ion‐channel activity of CLIC1 in tethered lipid bilayers was previously assessed using impedance spectroscopy. Here we extend this investigation by evaluating the influence of cholesterol on the spontaneous membrane insertion of CLIC1 into Langmuir film monolayers prepared using 1‐palmitoyl‐2‐oleoylphosphatidylcholine, 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phospho‐ethanolamine and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phospho‐L‐serine alone or in combination with cholesterol. The spontaneous membrane insertion of CLIC1 was shown to be dependent on the presence of cholesterol in the membrane. Furthermore, pre‐incubation of CLIC1 with cholesterol prior to its addition to the Langmuir film, showed no membrane insertion even in monolayers containing cholesterol, suggesting the formation of a CLIC1‐cholesterol pre‐complex. Our results therefore suggest that CLIC1 membrane interaction involves CLIC1 binding to cholesterol located in the membrane for its initial docking followed by insertion. Subsequent structural rearrangements of the protein would likely also be required along with oligomerisation to form functional ion channels.
Hosseinpour-Mashkani, SM, Maddahfar, M & Sobhani-Nasab, A 2016, 'Precipitation Synthesis, Characterization, Morphological Control, and Photocatalyst Application of ZnWO4 Nanoparticles', Journal of Electronic Materials, vol. 45, no. 7, pp. 3612-3620.
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Hou, Z, Deng, K, Li, C, Deng, X, Lian, H, Cheng, Z, Jin, D & Lin, J 2016, '808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd3+-sensitized upconversion emission with enhanced anti-tumor efficacy', Biomaterials, vol. 101, pp. 32-46.
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© 2016 Elsevier Ltd.The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYF4:Yb/Tm@NaYF4:Yb@NaNdF4:Yb@NaYF4 (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiO2, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiO2 shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd3+-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual-photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT.
Huo, L, Zhou, J, Wu, R, Ren, J, Zhang, S, Zhang, J & Xu, S 2016, 'Dual-functional β-NaYF_4: Yb^3+, Er^3+ nanoparticles for bioimaging and temperature sensing', Optical Materials Express, vol. 6, no. 4, pp. 1056-1056.
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Hexagonal-phase NaYF4: Yb3+, Er3+ nanoparticles (NPs) have been widely used as the most efficient NIR-to-visible upconversion (UC) luminescent and probe in bioscience. Here, we exploited not only the function of dual-mode emission of β-NaYF4: Yb3+, Er3+ NPs in the near infrared (NIR) and visible regions with single wavelength excitation at 980 nm, but also the function of physiological temperature sensing with the luminescence of Er3+ in the visible region. The structural and optical characteristics of β-NaYF4: Yb3+, Er3+ NPs were obtained using X-ray diffraction (XRD), scanning electron microscopy (SEM),and fluorescence spectral measurements, respectively; the mechanism for the energy transfer has been suggested with emphasis on the optimized Er/Yb concentration for most efficient UC. Due to the UC and down-shifting NIR properties, we achieved the dual-functional nanoparticles with potential application in physiological range temperature sensing and bioimaging simultaneously.
Iezzi, VL, Büttner, TFS, Tehranchi, A, Loranger, S, Kabakova, IV, Eggleton, BJ & Kashyap, R 2016, 'Temporal characterization of a multi-wavelength Brillouin–erbium fiber laser', New Journal of Physics, vol. 18, no. 5, pp. 055003-055003.
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This paper provides the first detailed temporal characterization of a multi-wavelength-Brillouin-erbium fiber laser (MWBEFL) by measuring the optical intensity of the individual frequency channels with high temporal resolution. It is found that the power in each channel is highly unstable due to the excitation of several cavity modes for typical conditions of operation. Also provided is the real-time measurements of the MWBEFL output power for two configurations that were previously reported to emit phase-locked picosecond pulse trains, concluded from their autocorrelation measurements. Real-time measurements reveal a high degree of instability without the formation of a stable pulse train. Finally, we model the MWBEFL using coupled wave equations describing the evolution of the Brillouin pump, Stokes and acoustic waves in the presence of stimulated Brillouin scattering, and the optical Kerr effect. A good qualitative consistency between the simulation and experimental results is evident, in which the interference signal at the output shows strong instability as well as the chaotic behavior due to the dynamics of participating pump and Stokes waves.
Jia-Jia, ZHOU & Jian-Rong, QIU 2016, 'Upconversion Spectroscopic Investigation of Single Nanoparticles', Journal of Inorganic Materials, vol. 31, no. 10, pp. 1023-1023.
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Jin, D 2016, 'Bright future for upconversion', Nature Photonics, vol. 10, no. 9, pp. 567-569.
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Kabakova, IV, de Hoogh, A, van der Wel, REC, Wulf, M, le Feber, B & Kuipers, L 2016, 'Imaging of electric and magnetic fields near plasmonic nanowires', Scientific Reports, vol. 6, no. 1, p. 22665.
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AbstractNear-field imaging is a powerful tool to investigate the complex structure of light at the nanoscale. Recent advances in near-field imaging have indicated the possibility for the complete reconstruction of both electric and magnetic components of the evanescent field. Here we study the electro-magnetic field structure of surface plasmon polariton waves propagating along subwavelength gold nanowires by performing phase- and polarization-resolved near-field microscopy in collection mode. By applying the optical reciprocity theorem, we describe the signal collected by the probe as an overlap integral of the nanowire’s evanescent field and the probe’s response function. As a result, we find that the probe’s sensitivity to the magnetic field is approximately equal to its sensitivity to the electric field. Through rigorous modeling of the nanowire mode as well as the aperture probe response function, we obtain a good agreement between experimentally measured signals and a numerical model. Our findings provide a better understanding of aperture-based near-field imaging of the nanoscopic plasmonic and photonic structures and are helpful for the interpretation of future near-field experiments.
Khoo, BL, Chaudhuri, PK, Ramalingam, N, Tan, DSW, Lim, CT & Warkiani, ME 2016, 'Single‐cell profiling approaches to probing tumor heterogeneity', International Journal of Cancer, vol. 139, no. 2, pp. 243-255.
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Tumor heterogeneity is a major hindrance in cancer classification, diagnosis and treatment. Recent technological advances have begun to reveal the true extent of its heterogeneity. Single‐cell analysis (SCA) is emerging as an important approach to detect variations in morphology, genetic or proteomic expression. In this review, we revisit the issue of inter‐ and intra‐tumor heterogeneity, and list various modes of SCA techniques (cell‐based, nucleic acid‐based, protein‐based, metabolite‐based and lipid‐based) presently used for cancer characterization. We further discuss the advantages of SCA over pooled cell analysis, as well as the limitations of conventional techniques. Emerging trends, such as high‐throughput sequencing, are also mentioned as improved means for cancer profiling. Collectively, these applications have the potential for breakthroughs in cancer treatment.
Kulasinghe, A, Perry, C, Warkiani, ME, Blick, T, Davies, A, O'Byrne, K, Thompson, EW, Nelson, CC, Vela, I & Punyadeera, C 2016, 'Short term ex-vivo expansion of circulating head and neck tumour cells', Oncotarget, vol. 7, no. 37, pp. 60101-60109.
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Minimally invasive techniques are required for the identification of head and neck cancer (HNC) patients who are at an increased risk of metastasis, or are not responding to therapy. An approach utilised in other solid cancers is the identification and enumeration of circulating tumour cells (CTCs) in the peripheral blood of patients. Low numbers of CTCs has been a limiting factor in the HNC field to date. Here we present a methodology to expand HNC patient derived CTCs ex-vivo. As a proof of principle study, 25 advanced stage HNC patient bloods were enriched for circulating tumour cells through negative selection and cultured in 2D and 3D culture environments under hypoxic conditions (2% O2, 5% CO2). CTCs were detected in 14/25 (56%) of patients (ranging from 1-15 CTCs/5 mL blood). Short term CTC cultures were successfully generated in 7/25 advanced stage HNC patients (5/7 of these cultures were from HPV+ patients). Blood samples from which CTC culture was successful had higher CTC counts (p = 0.0002), and were predominantly from HPV+ patients (p = 0.007). This is, to our knowledge, the first pilot study to culture HNC CTCs ex-vivo. Further studies are warranted to determine the use of short term expansion in HNC and the role of HPV in promoting culture success.
Li, D, Zhang, Y, Wen, S, Song, Y, Tang, Y, Zhu, X, Shen, M, Mignani, S, Majoral, J-P, Zhao, Q & Shi, X 2016, 'Construction of polydopamine-coated gold nanostars for CT imaging and enhanced photothermal therapy of tumors: an innovative theranostic strategy', Journal of Materials Chemistry B, vol. 4, no. 23, pp. 4216-4226.
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A theranostic nanoplatform for in vivo CT imaging and enhanced PTT of tumors is reported.
Liao, J, Yang, Z, Shao, B, Li, J, Qiu, J, Song, Z & Yang, Y 2016, 'Preparation and Photoluminescence Modification of NaGdF<SUB>4</SUB> :Eu<SUP>3</SUP><SUP>+</SUP> Nanorods in a Crystalline Colloidal Array', Science of Advanced Materials, vol. 8, no. 4, pp. 697-702.
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© 2016 by American Scientific Publishers. A crystalline colloidal array was prepared by an ion exchange method, and its structure was characterized. Eu3+ doped NaGdF4 nanorods were added into the crystalline colloidal array, leading to an ordered crystalline colloidal array including the nanorods. The photoluminescence properties of NaGdF4:Eu3+ nanorods in the array were investigated. A significant suppression of photoluminescence of NaGdF4:Eu3+ nanorods in the range of the photonic band gap was observed.
Lin, G, Karnaushenko, DD, Bermúdez, GSC, Schmidt, OG & Makarov, D 2016, 'Droplet Microfluidics: Magnetic Suspension Array Technology: Controlled Synthesis and Screening in Microfluidic Networks (Small 33/2016)', Small, vol. 12, no. 33, pp. 4580-4580.
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Lin, G, Karnaushenko, DD, Bermúdez, GSC, Schmidt, OG & Makarov, D 2016, 'Magnetic Suspension Array Technology: Controlled Synthesis and Screening in Microfluidic Networks', Small, vol. 12, no. 33, pp. 4553-4562.
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Information tagging and processing are vital in information‐intensive applications, e.g., telecommunication and high‐throughput drug screening. Magnetic suspension array technology may offer intrinsic advantages to screening applications by enabling high distinguishability, the ease of code generation, and the feasibility of fast code readout, though the practical applicability of magnetic suspension array technology remains hampered by the lack of quality administration of encoded microcarriers. Here, a logic‐controlled microfluidic system enabling controlled synthesis of magnetic suspension arrays in multiphase flow networks is realized. The smart and compact system offers a practical solution for the quality administration and screening of encoded magnetic microcarriers and addresses the universal need of process control for synthesis in microfluidic networks, i.e., on‐demand creation of droplet templates for high information capacity. The demonstration of magnetic suspension array technology enabled by magnetic in‐flow cytometry opens the avenue toward point‐of‐care multiplexed bead‐based assays, clinical diagnostics, and drug discovery.
Ling, Y, Yan, D-X, Wang, P-F, Wang, M, Wen, Q, Liu, F & Wang, Y-G 2016, 'Highly Efficient Power Conversion from Salinity Gradients with Ion-Selective Polymeric Nanopores', Chinese Physics Letters, vol. 33, no. 9, pp. 096103-096103.
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Liu, B, Li, C, Xie, Z, Hou, Z, Cheng, Z, Jin, D & Lin, J 2016, '808 nm photocontrolled UCL imaging guided chemo/photothermal synergistic therapy with single UCNPs-CuS@PAA nanocomposite', Dalton Transactions, vol. 45, no. 33, pp. 13061-13069.
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Recently, incorporating multiple components into one nanostructured matrix to construct a multifunctional nanomedical platform has attracted more and more attention for simultaneous anticancer diagnosis and therapy.
Liu, B, Zhang, X, Li, C, He, F, Chen, Y, Huang, S, Jin, D, Yang, P, Cheng, Z & Lin, J 2016, 'Magnetically targeted delivery of DOX loaded Cu9S5@mSiO2@Fe3O4-PEG nanocomposites for combined MR imaging and chemo/photothermal synergistic therapy', Nanoscale, vol. 8, no. 25, pp. 12560-12569.
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The combination of multi-theranostic modes in a controlled fashion has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, we have synthesized a smart magnetically targeted nanocarrier system, Cu9S5@mSiO2@Fe3O4-PEG (labelled as CMF), which integrates NIR triggered photothermal therapy, pH/NIR-responsive chemotherapy and MR imaging into one nanoplatform to enhance the therapeutic efficacy. This new multifunctional paradigm has a uniform and monodisperse sesame ball-like structure by decorating tiny Fe3O4 nanoparticles on the surface of Cu9S5@mSiO2 before a further PEG modification to improve its hydrophilicity and biocompatibility. With doxorubicin (DOX) payload, the as-obtained CMF-DOX composites can simultaneously provide an intense heating effect and enhanced DOX release upon 980 nm NIR light exposure, achieving a combined chemo/photothermal therapy. Under the influence of an external magnetic field, the magnetically targeted synergistic therapeutic effect of CMF-DOX can lead to highly superior inhibition of animal H22 tumor in vivo when compared to any of the single approaches alone. The results revealed that this Cu9S5 based magnetically targeted chemo/photothermal synergistic nanocarrier system has great promise in future MR imaging assisted tumor targeted therapy of cancer.
Liu, D, Xu, X, Du, Y, Qin, X, Zhang, Y, Ma, C, Wen, S, Ren, W, Goldys, EM, Piper, JA, Dou, S, Liu, X & Jin, D 2016, 'Three-dimensional controlled growth of monodisperse sub-50 nm heterogeneous nanocrystals', Nature Communications, vol. 7, no. 1, pp. 1-8.
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AbstractThe ultimate frontier in nanomaterials engineering is to realize their composition control with atomic scale precision to enable fabrication of nanoparticles with desirable size, shape and surface properties. Such control becomes even more useful when growing hybrid nanocrystals designed to integrate multiple functionalities. Here we report achieving such degree of control in a family of rare-earth-doped nanomaterials. We experimentally verify the co-existence and different roles of oleate anions (OA−) and molecules (OAH) in the crystal formation. We identify that the control over the ratio of OA− to OAH can be used to directionally inhibit, promote or etch the crystallographic facets of the nanoparticles. This control enables selective grafting of shells with complex morphologies grown over nanocrystal cores, thus allowing the fabrication of a diverse library of monodisperse sub-50 nm nanoparticles. With such programmable additive and subtractive engineering a variety of three-dimensional shapes can be implemented using a bottom–up scalable approach.
Liu, D, Xu, X, Wang, F, Zhou, J, Mi, C, Zhang, L, Lu, Y, Ma, C, Goldys, E, Lin, J & Jin, D 2016, 'Emission stability and reversibility of upconversion nanocrystals', Journal of Materials Chemistry C, vol. 4, no. 39, pp. 9227-9234.
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We report the emission stability and reversibility of NaYF4:Yb3+,Er3+ core and core–shell nanocrystals at different temperatures and pH values.
Liu, L, Zhao, G, Wu, W, Rong, Y, Jin, D, Wang, D, Lou, W & Qin, X 2016, 'Low intratumoral regulatory T cells and high peritumoral CD8+ T cells relate to long-term survival in patients with pancreatic ductal adenocarcinoma after pancreatectomy', Cancer Immunology, Immunotherapy, vol. 65, no. 1, pp. 73-82.
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Lv, Y, Xin, B, Li, J, Chen, K, Jin, D, Lou, W & Xu, X 2016, 'Pancreatic intraglandular metastasis of the ductal adenocarcinoma: cases of 2 and literature review', INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, vol. 9, no. 10, pp. 20324-20330.
Ma, C, Xu, X, Wang, F, Zhou, Z, Wen, S, Liu, D, Fang, J, Lang, CI & Jin, D 2016, 'Probing the Interior Crystal Quality in the Development of More Efficient and Smaller Upconversion Nanoparticles', The Journal of Physical Chemistry Letters, vol. 7, no. 16, pp. 3252-3258.
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© 2016 American Chemical Society. Optical biomedical imaging using luminescent nanoparticles as contrast agents prefers small size, as they can be used at high dosages and efficiently cleared from body. Reducing nanoparticle size is critical for the stability and specificity for the fluorescence nanoparticles probes for in vitro diagnostics and subcellular imaging. The development of smaller and brighter upconversion nanoparticles (UCNPs) is accordingly a goal for complex imaging in bioenvironments. At present, however, small UCNPs are reported to exhibit less emission intensity due to increased surface deactivation and decreased number of dopants. Here we show that smaller and more efficient UCNPs can be made by improving the interior crystal quality via controlling heating rate during synthesis. We further developed a unique quantitative method for optical characterizations on the single UCNPs with varied sizes and the corresponding shell passivated UCNPs, confirming that the internal crystal quality dominates the relative emission efficiency of the UCNPs.
Maddahfar, M, Ramezani, M & Mostafa Hosseinpour-Mashkani, S 2016, 'Barium hexaferrite/graphene oxide: controlled synthesis and characterization and investigation of its magnetic properties', Applied Physics A, vol. 122, no. 8.
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Merklein, M, Casas-Bedoya, A, Marpaung, D, Buttner, TFS, Pagani, M, Morrison, B, Kabakova, IV & Eggleton, BJ 2016, 'Stimulated Brillouin Scattering in Photonic Integrated Circuits: Novel Applications and Devices', IEEE Journal of Selected Topics in Quantum Electronics, vol. 22, no. 2, pp. 336-346.
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The last few years have seen major progress in harnessing on-chip photon-phonon interactions, leading to a wide range of demonstrations of new functionalities. Utilizing not only the optical response of a nonlinear waveguide - but also acoustic resonances - enables the realization of microwave devices with unprecedented performance, otherwise hard to achieve in all-optical processing schemes or electronically. Here, we overview on-chip stimulated Brillouin scattering (SBS) with special emphasis on microwave sources and microwave signal processing schemes. We review the different material platforms and structures for on-chip SBS, ranging from chalcogenide rib waveguides to hybrid silicon/silicon-nitride structures, high-Q photonic-phononic silica microresonators, and suspended silicon nanowires. We show that the paradigm shift in SBS research - from long length of fibers to chip-scale devices - is now moving toward fully integrated photonic-phononic CMOS chips.
Merklein, M, Stiller, B, Kabakova, IV, Mutugala, US, Vu, K, Madden, SJ, Eggleton, BJ & Slavík, R 2016, 'Widely tunable, low phase noise microwave source based on a photonic chip', Optics Letters, vol. 41, no. 20, pp. 4633-4633.
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Spectrally pure microwave sources are highly desired for several applications, ranging from wireless communication to next generation radar technology and metrology. Additionally, to generate very pure signals at even higher frequencies, these advanced microwave sources have to be compact, low in weight, and low energy consumption to comply with in-field applications. A hybrid optical and electronic cavity, known as an optoelectronic oscillator (OEO), has the potential to leverage the high bandwidth of optics to generate ultrapure high-frequency microwave signals. Here we present a widely tunable, low phase noise microwave source based on a photonic chip. Using on-chip stimulated Brillouin scattering as a narrowband active filter allows single-mode OEO operation and ultrawide frequency tunability with no signal degeneration. Furthermore, we show very low close-to-carrier phase noise. This Letter paves the way to a compact, fully integrated pure microwave source.
Mohkam, M, Rasoul-Amini, S, Shokri, D, Berenjian, A, Rahimi, F, Sadraeian, M, Khalvati, B, Gholami, A & Ghasemi, Y 2016, 'Characterization and in vitro probiotic assessment of potential indigenous Bacillus strains isolated from soil rhizosphere', Minerva Biotecnologica, vol. 28, no. 1, pp. 19-28.
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BACKGROUND: Probiotics mainly Bacillus species can be advantageous to the host by promoting its intestinal balance. Attempts were made to isolate and identify Bacillus strains from rhizosphere environment. METHODS: The in vitro probiotic criteria were used for screening and characterizing potential Bacillus probiotics. Morphological, physiological and biochemical characteristics as well as 16S rRNA gene sequence analysis were utilized for identification of the isolates. Seven isolates were chosen based on withstanding to acidic condition (pH 2.5) and various bile salt concentrations (1-4%(w/v)). RESULTS: Isolates found to have the least antimicrobial activity against Listeria monocytogenes PTCC 1163, Staphylococcus aureus ATCC 1912 and Bacillus cereus PTCC 1015; however, no activity against Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 25922 was observed. The Bacillus Isolates showed different variation in auto-aggregation features and adhesion to hydrocarbons ranging from 60% to 90% and 10% to 60%, respectively. Excluding isolate 14 that exhibited resistance to penicillin and ampicillin, all the other Bacillus strains were sensitive to the tested antibiotics. All isolates showed relatively low cytotoxic effect on HepG2 cell line except strains 12 and 14. CONCLUSION: Taking together, among the investigated Bacillus isolates, strains 17 and S10 found to be the most promising candidates to fulfill in vitro probiotic specifications.
Mostafa Hosseinpour-Mashkani, S, Maddahfar, M & Sobhani-Nasab, A 2016, 'Novel silver-doped CdMoO4: synthesis, characterization, and its photocatalytic performance for methyl orange degradation through the sonochemical method', Journal of Materials Science: Materials in Electronics, vol. 27, no. 1, pp. 474-480.
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Nizalapur, S, Ho, KKK, Kimyon, O, Yee, E, Berry, T, Manefield, M, Cranfield, CG, Willcox, M, Black, DS & Kumar, N 2016, 'Synthesis and biological evaluation of N-naphthoyl-phenylglyoxamide-based small molecular antimicrobial peptide mimics as novel antimicrobial agents and biofilm inhibitors', ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 14, no. 14, pp. 3623-3637.
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© The Royal Society of Chemistry 2016. Antimicrobial peptides (AMPs) are a key component of the human immune system. Synthetic AMP mimics represent a novel strategy to counteract the increasing incidence of antimicrobial resistance. Here, we describe the synthesis of novel glyoxamide derivatives via ring-opening reactions of N-hexanoyl, N-benzoyl and N-naphthoylisatins with N,N-dimethylethane-1,2-diamine and N,N-dimethylpropane-1,3-diamine. These were converted to both the hydrochloric acid (HCl) or quaternary ammonium iodide (MeI) salts and their antibacterial activity against Staphylococcus aureus was investigated by their zone-of-inhibition and minimum inhibitory concentration (MIC). The HCl salt 22b exhibited the lowest MIC of 16 μg mL-1, whereas the corresponding MeI salt 22c had a MIC of 39 μg mL-1. We also investigated the in vitro toxicity of active compounds against the MRC-5 normal human lung fibroblasts and their activity against established biofilm in S. aureus.
Pavesi, A, Adriani, G, Tay, A, Warkiani, ME, Yeap, WH, Wong, SC & Kamm, RD 2016, 'Engineering a 3D microfluidic culture platform for tumor-treating field application', Scientific Reports, vol. 6, no. 1, p. 26584.
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AbstractThe limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy.
Rafeie, M, Zhang, J, Asadnia, M, Li, W & Warkiani, ME 2016, 'Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation', Lab on a Chip, vol. 16, no. 15, pp. 2791-2802.
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Blood and blood products are critical components of health care.
Ramalingam, N, Warkiani, ME, Ramalingam, N, Keshavarzi, G, Hao-Bing, L & Hai-Qing, TG 2016, 'Numerical and experimental study of capillary-driven flow of PCR solution in hybrid hydrophobic microfluidic networks', Biomedical Microdevices, vol. 18, no. 4, p. 68.
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Capillary-driven microfluidics is essential for development of point-of-care diagnostic micro-devices. Polymerase chain reaction (PCR)-based micro-devices are widely developed and used in such point-of-care settings. It is imperative to characterize the fluid parameters of PCR solution for designing efficient capillary-driven microfluidic networks. Generally, for numeric modelling, the fluid parameters of PCR solution are approximated to that of water. This procedure leads to inaccurate results, which are discrepant to experimental data. This paper describes mathematical modeling and experimental validation of capillary-driven flow inside Poly-(dimethyl) siloxane (PDMS)-glass hybrid micro-channels. Using experimentally measured PCR fluid parameters, the capillary meniscus displacement in PDMS-glass microfluidic ladder network is simulated using computational fluid dynamic (CFD), and experimentally verified to match with the simulated data.
Roushani, M, Hoseini, SJ, Azadpour, M, Heidari, V, Bahrami, M & Maddahfar, M 2016, 'Electrocatalytic oxidation behavior of NADH at Pt/Fe 3 O 4 /reduced-graphene oxide nanohybrids modified glassy carbon electrode and its determination', Materials Science and Engineering: C, vol. 67, pp. 237-246.
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Sayyadi, N, Justiniano, I, Connally, RE, Zhang, R, Shi, B, Kautto, L, Everest-Dass, AV, Yuan, J, Walsh, BJ, Jin, D, Willows, RD, Piper, JA & Packer, NH 2016, 'Sensitive Time-Gated Immunoluminescence Detection of Prostate Cancer Cells Using a TEGylated Europium Ligand', Analytical Chemistry, vol. 88, no. 19, pp. 9564-9571.
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Shen, M, Zhang, N, Zheng, S, Zhang, W-B, Zhang, H-M, Lu, Z, Su, QP, Sun, Y, Ye, K & Li, X-D 2016, 'Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor', Proceedings of the National Academy of Sciences, vol. 113, no. 40, pp. E5812-E5820.
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Significance Myosin-5a is a molecular motor that functions as a cargo transporter in cells. The motor function of myosin-5a is regulated by calcium via the calmodulin bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a. Here, we solve the crystal structure of a truncated myosin-5a containing the motor domain and the IQ1 complexed with calcium-bound calmodulin. Comparison of the structures of the IQ1 complexed with calmodulin with or without bound calcium reveals the calcium-induced conformational changes of calmodulin. We demonstrated that calmodulin continuously associates with the IQ1 during that calcium transition and that the IQ1 binding substantially changes the thermodynamic and kinetics of calcium transition in calmodulin. These findings provide insight into the mechanism by which calcium regulates myosin-5a.
Shi, Y, Shi, B, Dass, AVE, Lu, Y, Sayyadi, N, Kautto, L, Willows, RD, Chung, R, Piper, J, Nevalainen, H, Walsh, B, Jin, D & Packer, NH 2016, 'Stable Upconversion Nanohybrid Particles for Specific Prostate Cancer Cell Immunodetection', Scientific Reports, vol. 6, no. 1, pp. 1-11.
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AbstractProstate cancer is one of the male killing diseases and early detection of prostate cancer is the key for better treatment and lower cost. However, the number of prostate cancer cells is low at the early stage, so it is very challenging to detect. In this study, we successfully designed and developed upconversion immune-nanohybrids (UINBs) with sustainable stability in a physiological environment, stable optical properties and highly specific targeting capability for early-stage prostate cancer cell detection. The developed UINBs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and luminescence spectroscopy. The targeting function of the biotinylated antibody nanohybrids were confirmed by immunofluorescence assay and western blot analysis. The UINB system is able to specifically detect prostate cancer cells with stable and background-free luminescent signals for highly sensitive prostate cancer cell detection. This work demonstrates a versatile strategy to develop UCNPs based sustainably stable UINBs for sensitive diseased cell detection.
Sobhani-Nasab, A, Maddahfar, M & Hosseinpour-Mashkani, SM 2016, 'Ce(MoO4)2 nanostructures: Synthesis, characterization, and its photocatalyst application through the ultrasonic method', Journal of Molecular Liquids, vol. 216, pp. 1-5.
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Su, QP, Du, W, Ji, Q, Xue, B, Jiang, D, Zhu, Y, Ren, H, Zhang, C, Lou, J, Yu, L & Sun, Y 2016, 'Vesicle Size Regulates Nanotube Formation in the Cell', Scientific Reports, vol. 6, no. 1, pp. 24002-24002.
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AbstractIntracellular membrane nanotube formation and its dynamics play important roles for cargo transportation and organelle biogenesis. Regarding the regulation mechanisms, while much attention has been paid on the lipid composition and its associated protein molecules, effects of the vesicle size has not been studied in the cell. Giant unilamellar vesicles (GUVs) are often used for in vitro membrane deformation studies, but they are much larger than most intracellular vesicles and the in vitro studies also lack physiological relevance. Here, we use lysosomes and autolysosomes, whose sizes range between 100 nm and 1 μm, as model systems to study the size effects on nanotube formation both in vivo and in vitro. Single molecule observations indicate that driven by kinesin motors, small vesicles (100–200 nm) are mainly transported along the tracks while a remarkable portion of large vesicles (500–1000 nm) form nanotubes. This size effect is further confirmed by in vitro reconstitution assays on liposomes and purified lysosomes and autolysosomes. We also apply Atomic Force Microscopy (AFM) to measure the initiation force for nanotube formation. These results suggest that the size-dependence may be one of the mechanisms for cells to regulate cellular processes involving membrane-deformation, such as the timing of tubulation-mediated vesicle recycling.
Tay, A, Pavesi, A, Yazdi, SR, Lim, CT & Warkiani, ME 2016, 'Advances in microfluidics in combating infectious diseases', Biotechnology Advances, vol. 34, no. 4, pp. 404-421.
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One of the important pursuits in science and engineering research today is to develop low-cost and user-friendly technologies to improve the health of people. Over the past decade, research efforts in microfluidics have been made to develop methods that can facilitate low-cost diagnosis of infectious diseases, especially in resource-poor settings. Here, we provide an overview of the recent advances in microfluidic devices for point-of-care (POC) diagnostics for infectious diseases and emphasis is placed on malaria, sepsis and AIDS/HIV. Other infectious diseases such as SARS, tuberculosis, and dengue are also briefly discussed. These infectious diseases are chosen as they contribute the most to disability-adjusted life-years (DALYs) lost according to the World Health Organization (WHO). The current state of research in this area is evaluated and projection toward future applications and accompanying challenges are also discussed.
Umar, J, Hussain, T & Maqsood, M 2016, 'Modeling the mechanical and compression properties of polyamide/elastane knitted fabrics used in compression sportswear', The Journal of The Textile Institute, vol. 107, no. 10, pp. 1240-1252.
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Warkiani, ME, Khoo, BL, Wu, L, Tay, AKP, Bhagat, AAS, Han, J & Lim, CT 2016, 'Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics', Nature Protocols, vol. 11, no. 1, pp. 134-148.
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Circulating tumor cells (CTCs) are rare cancer cells that are shed from primary or metastatic tumors into the peripheral blood circulation. Phenotypic and genetic characterization of these rare cells can provide important information to guide cancer staging and treatment, and thus further research into their characteristics and properties is an area of considerable interest. In this protocol, we describe detailed procedures for the production and use of a label-free spiral microfluidic device to allow size-based isolation of viable CTCs using hydrodynamic forces that are present in curvilinear microchannels. This spiral system enables us to achieve ≥ 85% recovery of spiked cells across multiple cancer cell lines and 99.99% depletion of white blood cells in whole blood. The described spiral microfluidic devices can be produced at an extremely low cost using standard microfabrication and soft lithography techniques (2-3 d), and they can be operated using two syringe pumps for lysed blood samples (7.5 ml in 12.5 min for a three-layered multiplexed chip). The fast processing time and the ability to collect CTCs from a large patient blood volume allows this technique to be used experimentally in a broad range of potential genomic and transcriptomic applications.
Wen, Q, Wang, P-F, Ling, Y, Wang, M, Yan, D-X, Cao, X-Z, Wang, B-Y & Wang, Y-G 2016, 'Influence of UV-Irradiation on Latent Tracks in Polyethylene Terephthalate Films', Chinese Physics Letters, vol. 33, no. 1, pp. 016103-016103.
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Wen, Q, Yan, D, Liu, F, Wang, M, Ling, Y, Wang, P, Kluth, P, Schauries, D, Trautmann, C, Apel, P, Guo, W, Xiao, G, Liu, J, Xue, J & Wang, Y 2016, 'Highly Selective Ionic Transport through Subnanometer Pores in Polymer Films', Advanced Functional Materials, vol. 26, no. 32, pp. 5796-5803.
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Novel transport phenomena through nanopores are expected to emerge as their diameters approach subnanometer scales. However, it has been challenging to explore such a regime experimentally. Here, this study reports on polymer subnanometer pores exhibiting unique selective ionic transport. 12 μm long, parallel oriented polymer nanopores are fabricated in polyethylene terephthalate (PET) films by irradiation with GeV heavy ions and subsequent 3 h exposure to UV radiation. These nanopores show ionic transport selectivity spanning more than 6 orders of magnitude: the order of the transport rate is Li+>Na+>K+>Cs+>>Mg2+>Ca2+>Ba2+, and heavy metal ions such as Cd2+ and anions are blocked. The transport can be switched off with a sharp transition by decreasing the pH value of the electrolyte. Structural measurements and molecular dynamics simulations suggest that the ionic transport is attributed to negatively charged nanopores with pore radii of ≈0.3 nm, and the selectivity is associated with the dehydration effect.
Wu, M, Song, EH, Chen, ZT, Ding, S, Ye, S, Zhou, JJ, Xu, SQ & Zhang, QY 2016, 'Single-band red upconversion luminescence of Yb3+–Er3+via nonequivalent substitution in perovskite KMgF3 nanocrystals', Journal of Materials Chemistry C, vol. 4, no. 8, pp. 1675-1684.
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Single-band red upconversion emission of Er3+ has been successfully achieved in Yb3+/Er3+ codoped KMgF3 nanocrystals via a nonequivalent substitution strategy.
Xu, X, Li, J-A, Xin, B, Zhang, L, Wang, D, Kuang, T, Lou, W & Jin, D 2016, 'Use of a closed suction, perfused drainage system for peripancreatic drainage after pancreaticoduodenectomy', INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, vol. 9, no. 6, pp. 9389-9396.
Yang, CS, Zhang, J, Zhang, L, Huang, J & Wang, Y 2016, 'Mechanisms of body weight reduction and metabolic syndrome alleviation by tea', Molecular Nutrition & Food Research, vol. 60, no. 1, pp. 160-174.
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Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been shown to reduce body weight, alleviate metabolic syndrome, and prevent diabetes and cardiovascular diseases in animal models and humans. Such beneficial effects have generally been observed in most human studies when the level of tea consumption was three to four cups (600–900 mg tea catechins) or more per day. Green tea is more effective than black tea. In spite of numerous studies, the fundamental mechanisms for these actions still remain unclear. From a review of the literature, we propose that the two major mechanisms are: (i) decreasing absorption of lipids and proteins by tea constituents in the intestine, thus reducing calorie intake; and (ii) activating AMP‐activated protein kinase by tea polyphenols that are bioavailable in the liver, skeletal muscle, and adipose tissues. The relative importance of these two mechanisms depends on the types of tea and diet consumed by individuals. The activated AMP‐activated protein kinase would decrease gluconeogenesis and fatty acid synthesis and increase catabolism, leading to body weight reduction and metabolic syndrome alleviation. Other mechanisms and the health relevance of these beneficial effects of tea consumption remain to be further investigated.
Yang, X, Xie, H, Alonas, E, Liu, Y, Chen, X, Santangelo, PJ, Ren, Q, Xi, P & Jin, D 2016, 'Mirror-enhanced super-resolution microscopy', Light: Science & Applications, vol. 5, no. 6, pp. e16134-e16134.
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Axial excitation confinement beyond the diffraction limit is crucial to the development of next-generation, super-resolution microscopy. STimulated Emission Depletion (STED) nanoscopy offers lateral super-resolution using a donut-beam depletion, but its axial resolution is still over 500 nm. Total internal reflection fluorescence microscopy is widely used for single-molecule localization, but its ability to detect molecules is limited to within the evanescent field of ~ 100 nm from the cell attachment surface. We find here that the axial thickness of the point spread function (PSF) during confocal excitation can be easily improved to 110 nm by replacing the microscopy slide with a mirror. The interference of the local electromagnetic field confined the confocal PSF to a 110-nm spot axially, which enables axial super-resolution with all laser-scanning microscopes. Axial sectioning can be obtained with wavelength modulation or by controlling the spacer between the mirror and the specimen. With no additional complexity, the mirror-assisted excitation confinement enhanced the axial resolution six-fold and the lateral resolution two-fold for STED, which together achieved 19-nm resolution to resolve the inner rim of a nuclear pore complex and to discriminate the contents of 120 nm viral filaments. The ability to increase the lateral resolution and decrease the thickness of an axial section using mirror-enhanced STED without increasing the laser power is of great importance for imaging biological specimens, which cannot tolerate high laser power.
Yang, X, Zhanghao, K, Wang, H, Liu, Y, Wang, F, Zhang, X, Shi, K, Gao, J, Jin, D & Xi, P 2016, 'Versatile Application of Fluorescent Quantum Dot Labels in Super-resolution Fluorescence Microscopy', ACS Photonics, vol. 3, no. 9, pp. 1611-1618.
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© 2016 American Chemical Society. Quantum dots (QDs) are well known as bright and photostable inorganic fluorescent probes for microscopy imaging, with many attractive features superior to those found in organic dyes. However, their broadband excitation spectrum and emission blinking property have limited the applicability of QDs in modern super-resolution microscopy techniques. In this work, we systematically investigate practical approaches to overcoming these drawbacks and provide examples of their use across many commercially available super-resolution microscopy systems now accessible to biologists, with examples across the major super-resolution techniques. This work further maps out how QDs can be further engineered to facilitate their applications in the respective super-resolution microscopy techniques.
Yang, Y, Ciampi, S, Zhu, Y & Gooding, JJ 2016, 'Light-Activated Electrochemistry for the Two-Dimensional Interrogation of Electroactive Regions on a Monolithic Surface with Dramatically Improved Spatial Resolution', The Journal of Physical Chemistry C, vol. 120, no. 24, pp. 13032-13038.
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The concept of light-activated electrochemistry (LAE) was recently presented where faradaic electrochemistry could be spatially resolved on a monolithic silicon electrode by illuminating the specific region with light. A major implication from the previous study using illumination from the nonsolution side, or backside, is that the spatial resolution is limited by the finite thickness of silicon wafer. To overcome this restriction, and enable the further application of LAE, in combination with optical imaging for example, herein the spatial resolution of LAE using topside illumination (illumination from the solution side) is explored. The applied potential and irradiated light intensity are found to have significant effects on the spatial resolution. A spatial resolution of ∼30 μm was achieved with optimal parameters, which is a 20 times improvement compared with the previously reported backside illumination design, demonstrating the potential application of the strategy including microarray patterning of silicon or for single cell analysis.
Zarepour, E, Hassan, M, Chou, CT & Ebrahimi Warkiani, M 2016, 'Characterizing terahertz channels for monitoring human lungs with wireless nanosensor networks', Nano Communication Networks, vol. 9, pp. 43-57.
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We characterize terahertz wireless channels for extracting data from nanoscale sensors deployed within human lungs. We discover that the inhalation and exhalation of oxygen and carbon dioxide causes periodic variation of the absorption coefficient of the terahertz channel. Channel absorption drops to its minimum near the end of inhalation, providing a window of opportunity to extract data with minimum transmission power. We propose an algorithm for nanosensors to estimate the periodic channel by observing signal-to-noise ratio of the beacons transmitted from the data sink. Using real respiration data from multiple subjects, we demonstrate that the proposed algorithm can estimate the minimum absorption interval of the periodic channel with 98.5% accuracy. Our analysis shows that by confining all data collections during the estimated low-absorption window of the periodic channel, nanosensors can reduce power consumption by six orders of magnitude. Finally, we demonstrate that for wireless communications within human lungs, 0.1–0.12 THz is the least absorbing spectrum within the terahertz band.
Zhang, J, Yan, S, Yuan, D, Alici, G, Nguyen, N-T, Ebrahimi Warkiani, M & Li, W 2016, 'Fundamentals and applications of inertial microfluidics: a review', Lab on a Chip, vol. 16, no. 1, pp. 10-34.
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We provide a comprehensive review describing the fundamental mechanisms of inertial microfluidics, structure design and applications in biology, medicine and industry.
Zhang, L, Cheng, Q, Zhang, L, Wang, Y, Merrill, GF, Ilani, T, Fass, D, Arnér, ESJ & Zhang, J 2016, 'Serum thioredoxin reductase is highly increased in mice with hepatocellular carcinoma and its activity is restrained by several mechanisms', Free Radical Biology and Medicine, vol. 99, pp. 426-435.
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Zhang, S, Zhou, J, Wu, R, Lei, L, Xiao, Z, Zhang, J & Xu, S 2016, 'Controlling red upconversion luminescence in Gd2O3:Yb3+–Er3+nanoparticles by changing the different atmosphere', RSC Advances, vol. 6, no. 103, pp. 101707-101713.
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Upconversion luminescence properties were investigated by emission intensityvs.excitation power (double logarithmic relationship) and temperature dependent emission spectroscopy.
Zhang, Y, Wen, S, Zhao, L, Li, D, Liu, C, Jiang, W, Gao, X, Gu, W, Ma, N, Zhao, J, Shi, X & Zhao, Q 2016, 'Ultrastable polyethyleneimine-stabilized gold nanoparticles modified with polyethylene glycol for blood pool, lymph node and tumor CT imaging', Nanoscale, vol. 8, no. 10, pp. 5567-5577.
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Facile formed ultrastable Au PSNPs with excellent biocompatibility for in vivo CT imaging.
Zhanghao, K, Chen, L, Yang, X-S, Wang, M-Y, Jing, Z-L, Han, H-B, Zhang, MQ, Jin, D, Gao, J-T & Xi, P 2016, 'Super-resolution dipole orientation mapping via polarization demodulation', Light: Science & Applications, vol. 5, no. 10, pp. e16166-e16166.
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© The Author(s) 2016. Fluorescence polarization microscopy (FPM) aims to detect the dipole orientation of fluorophores and to resolve structural information for labeled organelles via wide-field or confocal microscopy. Conventional FPM often suffers from the presence of a large number of molecules within the diffraction-limited volume, with averaged fluorescence polarization collected from a group of dipoles with different orientations. Here, we apply sparse deconvolution and least-squares estimation to fluorescence polarization modulation data and demonstrate a super-resolution dipole orientation mapping (SDOM) method that resolves the effective dipole orientation from a much smaller number of fluorescent molecules within a sub-diffraction focal area. We further apply this method to resolve structural details in both fixed and live cells. For the first time, we show that different borders of a dendritic spine neck exhibit a heterogeneous distribution of dipole orientation. Furthermore, we illustrate that the dipole is always perpendicular to the direction of actin filaments in mammalian kidney cells and radially distributed in the hourglass structure of the septin protein under specific labelling. The accuracy of the dipole orientation can be further mapped using the orientation uniform factor, which shows the superiority of SDOM compared with its wide-field counterpart as the number of molecules is decreased within the smaller focal area. Using the inherent feature of the orientation dipole, the SDOM technique, with its fast imaging speed (at sub-second scale), can be applied to a broad range of fluorescently labeled biological systems to simultaneously resolve the valuable dipole orientation information with super-resolution imaging.
Zhao, J, Zheng, X, Schartner, EP, Ionescu, P, Zhang, R, Nguyen, T, Jin, D & Ebendorff‐Heidepriem, H 2016, 'Glass Fibers: Upconversion Nanocrystal‐Doped Glass: A New Paradigm for Photonic Materials (Advanced Optical Materials 10/2016)', Advanced Optical Materials, vol. 4, no. 10, pp. 1419-1419.
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Zhao, J, Zheng, X, Schartner, EP, Ionescu, P, Zhang, R, Nguyen, T, Jin, D & Ebendorff‐Heidepriem, H 2016, 'Upconversion Nanocrystal‐Doped Glass: A New Paradigm for Photonic Materials', Advanced Optical Materials, vol. 4, no. 10, pp. 1507-1517.
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The integration of novel luminescent nanomaterials into glassy matrix can lead to new hybrid materials and photonic devices with promising material performance and device functions. Lanthanide‐containing upconversion nanocrystals have become unique candidates for sensing, bioimaging, photon energy management, volumetric displays, and other photonic applications. Here, a versatile direct‐doping approach is developed to integrate bright upconversion nanocrystals in tellurite glass with tailored nanoscale properties. Following our two‐temperature glass‐melting technique, the doping temperature window of 550–625 °C and a 5 min dwell time at 577 °C are determined as the key to success, which balances the survival and dispersion of upconversion nanocrystals in glass. It is identified that the fine spectra of upconversion emissions can be used to diagnose the survival and dissolution fraction of doped nanocrystals in the glass. Moreover, 3D dispersion of nanocrystals in the glass is visualized by upconversion scanning confocal microscopy. It is further demonstrated that a low‐loss fiber, drawn from the highly transparent nanocrystals‐doped glass retains the distinct optical properties of upconversion nanocrystals. These results suggest a robust strategy for fabrication of high‐quality upconversion nanocrystal‐doped glasses. The new class of hybrid glasses allows for fiber‐based devices to be developed for photonic applications or as a useful tool for tailoring light–nanoparticles interactions study.
Zheng, X, Lu, Y, Zhao, J, Zhang, Y, Ren, W, Liu, D, Lu, J, Piper, JA, Leif, RC, Liu, X & Jin, D 2016, 'High-Precision Pinpointing of Luminescent Targets in Encoder-Assisted Scanning Microscopy Allowing High-Speed Quantitative Analysis', Analytical Chemistry, vol. 88, no. 2, pp. 1312-1319.
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Zheng, X, Zhu, X, Lu, Y, Zhao, J, Feng, W, Jia, G, Wang, F, Li, F & Jin, D 2016, 'High-Contrast Visualization of Upconversion Luminescence in Mice Using Time-Gating Approach', Analytical Chemistry, vol. 88, no. 7, pp. 3449-3454.
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© 2016 American Chemical Society. Optical imaging through the near-infrared (NIR) window provides deep penetration of light up to several centimeters into biological tissues. Capable of emitting 800 nm luminescence under 980 nm illumination, the recently developed upconversion nanoparticles (UCNPs) suggest a promising optical contrast agent for in vivo bioimaging. However, presently they require high-power lasers to excite when applied to small animals, leading to significant scattering background that limits the detection sensitivity as well as a detrimental thermal effect. In this work, we show that the time-gating approach implementing pulsed illumination from a NIR diode laser and time-delayed imaging synchronized via an optical chopper offers detection sensitivity more than 1 order of magnitude higher than the conventional approach using optical band-pass filters (S/N, 47321/6353 vs 5339/58), when imaging UCNPs injected into Kunming mice. The pulsed laser illumination (70 μs ON in 200 μs period) also reduces the overall thermal accumulation to 35% of that under the continuous-wave mode. Technical details are given on setting up the time-gating unit comprising an optical chopper, a pinhole, and a microscopy eyepiece. Being generally compatible with any camera, this provides a convenient and low cost solution to NIR animal imaging using UCNPs as well as other luminescent probes. (Figure Presented).
Zhou, B, Huang, F, Cai, M, Tian, Y, Zhou, J, Xu, S & Zhang, J 2016, 'Mid-Infrared 2.86-$\mu \text{m}$ Emission Characteristics in Highly Dy3+ Doped Fluoroaluminate Glass', IEEE Photonics Technology Letters, vol. 28, no. 4, pp. 429-432.
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A highly Dy3+ doped (10 mol%) fluoroaluminate glass was successfully fabricated by melt-quenching method for the first time. The intensity of 2.86-μm emission increases with the Dy3+ ions concentration without fluorescence quenching because of the large dispersibility of Dy3+ ions in this glass network without clustering. Radiative and emission parameters were calculated based on the Judd-Ofelt theory, which show that the 10 mol% highly doped sample possesses a high calculated spontaneous transition probability (32.01 S-1) together with a large emission cross section (5.94 × 10-21 cm2) of Dy3+: 6H13/2 →6H15/2 transition. In addition, the increasing Qt (t = 2,4,6) values, which caused by a complex outermost electron configuration of Dy3+ ions, have been further discussed to analyze the partial glass structure.
Zhou, H, Che, X, Bao, G, Wang, N & Bai, X 2016, 'Design, Synthesis and Structure-Activity Relationship Study of Pyri-midine-Fused Diazepine Derivatives as L3MBTL3 Inhibitors', Chinese Journal of Organic Chemistry, vol. 36, no. 12, pp. 2948-2948.
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Histone methylation is one of epigenetic marks and its deregulation is linked to many diseases. Malignant brain tumor (MBT) domain protein is one of proteins that could read methylated lysine (Kme) of histones. L3MBTL1, a representative member of the MBT family, is related to transcriptional repression, hematopoietic function and tumor formation. Developing a potent and selective inhibitor of L3MBTL1 can help explain the regulatory mechanisms and validate its drugability. Active compound 1 for L3MBTL3 from a library of pyrimidine-fused diazepines was initially obtained. By incorporating the structural features of reported binders, the structure-activity relationship (SAR) studies were conducted, which led to four novel L3MBTL3 inhibitors with IC50 values under 1 μmol•L-1.
Zhou, H, Che, X, Bao, G, Wang, N, Peng, L, Barnash, KD, Frye, SV, James, LI & Bai, X 2016, 'Design, synthesis, and protein methyltransferase activity of a unique set of constrained amine containing compounds', Bioorganic & Medicinal Chemistry Letters, vol. 26, no. 18, pp. 4436-4440.
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Epigenetic alterations relate to various human diseases, and developing inhibitors of Kme regulatory proteins is considered to be a new frontier for drug discovery. We were inspired by the known multicyclic ligands, UNC669 and UNC926, which are the first reported small molecule ligands for a methyl-lysine binding domain. We hypothesized that reducing the conformational flexibility of the key amine moiety of UNC669 would result in a unique set of ligands. Twenty-five novel compounds containing a fused bi- or tricyclic amine or a spirocyclic amine were designed and synthesized. To gauge the potential of these amine-containing compounds to interact with Kme regulatory proteins, the compounds were screened against a panel of 24 protein methyltransferases. Compound 13 was discovered as a novel scaffold that interacts with SETD8 and could serve as a starting point for the future development of PKMT inhibitors.
Zhou, J, Gu, F, Liu, X & Qiu, J 2016, 'Enhanced Multiphoton Upconversion in Single Nanowires by Waveguiding Excitation', Advanced Optical Materials, vol. 4, no. 8, pp. 1174-1178.
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40-Fold enhancement of upconversion luminescence in a single NaGdF4–LiF hybrid nanowire is reported, along with a series of unique characteristics. These include four-photon upconversion from Er3+:2P3/2 excited state, a low excitation power threshold, and high optical-imaging resolution by waveguiding excitation compared to free-space spot excitation.
Zhu, Y, Kekalo, K, NDong, C, Huang, Y, Shubitidze, F, Griswold, KE, Baker, I & Zhang, JXJ 2016, 'Magnetic‐Nanoparticle‐Based Immunoassays‐on‐Chip: Materials Synthesis, Surface Functionalization, and Cancer Cell Screening', Advanced Functional Materials, vol. 26, no. 22, pp. 3953-3972.
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The unique properties of magnetic nanoparticles (MNPs), coupled with versatile surface engineering techniques, have led to a rising class of screening methods that enable separation of specific cell populations from complex biological samples. The growing sophistication and efficiency of these methods have far reaching implications for both fundamental research and clinical applications. In this study, the synthesis and surface engineering of MNPs is reviewed. Here, a model is introduced to illustrate how MNP morphology and particle–particle interactions influence magnetization, which is a key consideration in designing and selecting MNPs for efficient cell separations. Building upon these themes, immunomagnetic assays for capturing, isolating, and characterizing rare cell types from complex biological mixtures are reviewed. Although the focus of this study is on circulating tumor cells, these same techniques can be applied in screening for other rare cells of interest, such as various stem cell populations. In conclusion, current challenges and future directions for magnetic ‐nanomaterial‐based cell screening systems are discussed.
