Hong-Deng QIU

Name: 邱洪灯; Qiu, HongDeng

Organization: Chinese Academy of Sciences , China

Department: Lanzhou Institute of Chemical Physics

Title: (PhD)

Chemicals
References

A new route for synthesis of N-methylimidazolium-grafted silica stationary phase and reevaluation in hydrophilic interaction liquid chromatography

Co-reporter:Houmei Liu, Jia Chen, Zhan Li, Makoto Takafuji, Hirotaka Ihara, Hongdeng Qiu

Talanta 2017 Volume 164() pp:137-140

Publication Date(Web):1 March 2017

DOI:10.1016/j.talanta.2016.11.037

•A “solvent-free” and green method for preparation of stationary phase was proposed.•Stationary phase can be controllably and quantitatively synthesized.•N-Methylimidazolium-grafted silica column was evaluated in HILIC.•How the bonding amounts influence separation performances was investigated.In this work, a “solvent-free” and green method for controllable and quantitative preparation of chromatographic stationary phase has been proposed. About the method, the largely excess of functional monomer and strict control of the proportion between silane and silica are the two most important points. Due to the existence of excessive functional monomer, silane can be utilized at the maximum extent, thereby achieving quantitative and reproducible bonding. Meanwhile, the excessive monomer can also be well recycled. By this new method, we controllably synthesized three Sil-MIm columns with various bonding amounts to investigate how the bonding amounts influence separation performances. The experiment results stated in some cases the columns with appropriate bonding amounts rather than maximum, were the best to fulfil some specific tasks. Meanwhile, it also demonstrated how important it was to control the bonding amounts of stationary phase.A solvent-free and green method for controllable and quantitative synthesis of chromatographic stationary phase has been proposed.

Monodisperse core–shell melamine–formaldehyde polymer-modified silica microspheres prepared using a facile microwave-assisted method

Co-reporter:Houmei Liu;Tianhang Liu;Makoto Takafuji;Hongdeng Qiu;Hirotaka Ihara

New Journal of Chemistry (1998-Present) 2017 vol. 41(Issue 20) pp:11517-11520

Publication Date(Web):2017/10/09

DOI:10.1039/C7NJ02266B

A facile microwave-assisted synthesis method for the preparation of monodisperse core–shell melamine–formaldehyde (MF)-modified silica resin microspheres (SiO2@MF) was developed. Under the optimal conditions, uniform and monodisperse SiO2@MF microspheres with good thermal stability and clean surface were obtained.

Facile synthesis of enzyme functional metal-organic framework for colorimetric detecting H2O2 and ascorbic acid

Co-reporter:Cunji Gao, Hongmei Zhu, Jia Chen, Hongdeng Qiu

Chinese Chemical Letters 2017 Volume 28, Issue 5(Volume 28, Issue 5) pp:

Publication Date(Web):1 May 2017

DOI:10.1016/j.cclet.2017.02.011

In this work, a metal-organic frameworks material MIL-88 was prepared easily using solvent-thermal method, and was first found to have catalytic activities similar to those of biological enzymes such as catalase and peroxidase. The material was characterized by XRD, SEM, TEM, EDX, FT-IR techniques and an N2 adsorption method. It exhibited peroxidase-like activity through catalytic oxidation of the peroxidase substrate 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2, producing a blue-colored solution. Under optimal conditions, the absorbance at 652 nm is linearly correlated with the concentration of H2O2 from 2.0 × 10−6 mol/L to 2.03 × 10−5 mol/L (R2 = 0.981) with a detection limit of 5.62 × 10−7 mol/L (S/N = 3). More importantly, a sensitive and selective method for ascorbic acid detection was developed using this material as a catalyst. The analytical method for ascorbic acid detection was observed to have a linear range from 2.57 × 10−6 mol/L to 1.01 × 10−5 mol/L (R2 = 0.989) with a detection limit of 1.03 × 10−6 mol/L (S/N = 3). This work suggests MOFs have advantages of preparing biomimetic catalysts and extends applications of the functional MOFs in the field of biosensor.Download high-res image (129KB)Download full-size imageA material MIL-88 was firstly found possessing catalytic activities similar to peroxidase enzyme, which can be used as a catalyst to detect H2O2 and ascorbic acid.

Surface radical chain-transfer reaction in deep eutectic solvents for preparation of silica-grafted stationary phases in hydrophilic interaction chromatography

Co-reporter:Beibei Yang, Tianpei Cai, Zhan Li, Ming Guan, Hongdeng Qiu

Talanta 2017 Volume 175(Volume 175) pp:

Publication Date(Web):1 December 2017

DOI:10.1016/j.talanta.2017.07.038

•Surface radical chain-transfer reaction was investigated in DESs.•DESs were used as green media for preparation of polymer-grafted silica.•Poly(1-vinylimidazole-co-acrylic acid)-grafted silica stationary phase was prepared.In this paper, deep eutectic solvents (DESs) were firstly used as new and green solvents for the preparation of polymer-grafted silica stationary phases. 1-Vinylimidazole and acrylic acid were homopolymerized and copolymerized on silica via surface radical chain-transfer reaction in the DESs. Three stationary phases including poly(1-vinylimidazole)-, poly(acrylic acid)-, poly(1-vinylimidazole-co-acrylic acid)-grafted silica were obtained and characterized by elemental analysis and Fourier transform infrared spectroscopy. Their hydrophilic interaction chromatographic properties were investigated for separation of nucleosides, nucleobases, saccharides and amino acids. The retention changes of nucleosides and nucleobases on these columns were investigated under different chromatographic conditions including acetonitrile content, salt concentration, pH of mobile phase and column temperature. The repeatability of these columns was also investigated. The results demonstrate that DESs can be used as new media for the synthesis of silica-based stationary phases by homopolymerization and copolymerization on the surface of porous silica particles.DESs were firstly used as new and green solvents for the preparation of silica-grafted stationary phases for HILIC.Download high-res image (145KB)Download full-size image

Graphene Oxide/Ag Nanoparticles Cooperated with Simvastatin as a High Sensitive X-Ray Computed Tomography Imaging Agent for Diagnosis of Renal Dysfunctions

Co-reporter:Zhan Li;Longlong Tian;Jianli Liu;Wei Qi;Qiang Wu;Haijing Wang;Mohammad Ch Ali;Wangsuo Wu;Hongdeng Qiu

Advanced Healthcare Materials 2017 Volume 6(Issue 18) pp:

Publication Date(Web):2017/09/01

DOI:10.1002/adhm.201700413

Graphene oxides (GO) are attracting much attention in the diagnosis and therapy of the subcutaneous tumor as a novel biomaterial, but its diagnosis to tissue dysfunction is yet to be found. Here, a novel application of GO for diagnosis of renal dysfunction via contrast-enhanced computed tomography (CT) is proposed. In order to serve as contrast-enhanced agent, Ag nanoparticles (AgNPs) are composited on the surface of GO to promote its X-ray absorption, and then simvastatin is coinjected for eliminating in vivo toxicity induced by AgNPs. It is found that GO/AgNPs can enhance the imaging of CT into the lung, liver, and kidney of mice for a long circulation time (≈24 h) and a safety profile in vivo in the presence of simvastatin. Interestingly, the lower dose of GO/AgNPs (≈0.5 mg per kg bw) shows an excellent performance for CT imaging of renal perfusion, and visually exhibits the right renal dysfunction in model mice. Hence, this work suggests that graphene nanoparticles will play a vital role for the future medical translational development including drug carrier, biosensing, and disease therapy.

Preparation and characterization of carbon dot-decorated silica stationary phase in deep eutectic solvents for hydrophilic interaction chromatography

Co-reporter:Haijuan Zhang;Xin Qiao;Tianpei Cai;Jia Chen

Analytical and Bioanalytical Chemistry 2017 Volume 409( Issue 9) pp:2401-2410

Publication Date(Web):2017 March

DOI:10.1007/s00216-017-0187-z

In this paper, N-doped carbon dots (NCDs) were successfully decorated on the spherical porous silica surface in deep eutectic solvents (DESs) as a novel class of green solvents. The appropriate density and hydrophility of DESs guaranteed the fine dispersibility of silica particles and NCDs, resulting in a homogeneous and thin layer of NCDs immobilization. As compared with traditional organic solvents (DMF and THF), higher surface coverage was obtained in the medium of DES, proving its feasibility as a new kind of alternative solvent for hydrophilic nanomaterial-based surface modification of silica spheres. The resulting NCDs-decorated silica particles (Sil-NCDs) were characterized in detail and packed into chromatographic columns to study their initial feasibility as adsorbent material for liquid chromatography. The resultant packing materials demonstrate a selective behavior for polar compounds in hydrophilic interaction liquid chromatography (HILIC) mode. This work gives a typical example of using carbon dots as stationary phase component, and such material is hopeful to be used in other research fields such as solid absorbents, recycling catalysts, and solid-state electrochemistry etc.

A WS2 nanosheet-based nanosensor for the ultrasensitive detection of small molecule–protein interaction via terminal protection of small molecule-linked DNA and Nt.BstNBI-assisted recycling amplification

Co-reporter:Jia Chen, Cunji Gao, Abul K. Mallik and Hongdeng Qiu

Journal of Materials Chemistry A 2016 vol. 4(Issue 30) pp:5161-5166

Publication Date(Web):11 Jul 2016

DOI:10.1039/C6TB00881J

Small molecule–protein receptor interactions play vital regulatory roles in molecular diagnostics and therapeutics, chemical genetics, and drug development. However, the rapid, sensitive, low-cost, and selective detection of small molecule–protein receptor interaction remains a challenge. We report herein a new tungsten disulfide (WS2) nanosheet-based nanosensor for the ultrasensitive detection of small molecule–protein interaction via terminal protection of small molecule-linked DNA and Nt.BstNBI-assisted recycling amplification strategy. Taking the streptavidin (SA)–biotin system as a model, this assay exhibits high sensitivity with a detection limit of 5.3 pM. Besides a desirable sensitivity, the developed strategies also offer high selectivity, excellent reproducibility, low cost, and simplified operations, implying that these techniques may hold considerable potential for application in molecular diagnostics, biomedical research, genomic research as well as prediction of disease progression.

Selective Separation of Metal Ions via Monolayer Nanoporous Graphene with Carboxyl Groups

Co-reporter:Zhan Li, Yanqi Liu, Yang Zhao, Xin Zhang, Lijuan Qian, Longlong Tian, Jing Bai, Wei Qi, Huijun Yao, Bin Gao, Jie Liu, Wangsuo Wu, and Hongdeng Qiu

Analytical Chemistry 2016 Volume 88(Issue 20) pp:10002

Publication Date(Web):September 12, 2016

DOI:10.1021/acs.analchem.6b02175

Graphene-coated plastic substrates, such as polyethylene terephthalate (PET), are regularly used in flexible electronic devices. Here we demonstrate a new application of the graphene-coated nanoporous PET membrane for the selective separation of metal ions in an ion exchange manner. Irradiation with swift heavy ions is used to perforate graphene and PET substrate. This process could create graphene nanopores with carboxyl groups, thus forming conical holes in the PET after chemical etching to support graphene nanopores. Therefore, a monolayer nanoporous graphene membrane with a PET substrate is constructed successfully to investigate its ionic selective separation. We find that the permeation ratio of ions strongly depends on the temperature and H+ concentration in the driving solution. An electric field can increase the permeation ratio of ions through the graphene nanopores, but it inhibits the ion selective separation. Moreover, the structure of the graphene nanopore with carboxyl groups is resolved at the density functional theory level. The results show the asymmetric structure of the nanopore with carboxyl groups, and the analysis indicates that the ionic permeation can be attributed to the ion exchange between metal ions and protons on the two sides of graphene nanopores. These results would be beneficial to the design of membrane separation materials made from graphene with efficient online and offline bulk separation.

Solid-phase extraction of flavonoids in honey samples using carbamate-embedded triacontyl-modified silica sorbent

Co-reporter:Houmei Liu, Mingliang Zhang, Yong Guo, Hongdeng Qiu

Food Chemistry 2016 Volume 204() pp:56-61

Publication Date(Web):1 August 2016

DOI:10.1016/j.foodchem.2016.02.102

•Carbamate-embedded triacontyl-modified silica sorbent is prepared.•The sorbent is used for the solid-phase extraction for flavonoids.•The good extraction capacity is ascribed to the existence of multiple interactions.•The sorbent is successfully applied to honey samples analysis.In this study, carbamate-embedded triacontyl-modified silica (Sil-CBM-C30) is successfully prepared and used as an efficient sorbent for solid-phase extraction. The extraction performance of the resultant sorbent is evaluated with five flavonoids including myricetin, quercetin, luteolin, kaempferol and isorhamnetin. Main parameters, which affect extraction efficiencies, are carefully investigated and optimized. Comparative experiments between Sil-CBM-C30 and commercial C18 sorbents indicate that the extraction efficiencies of the former one surpass the latter one. The modification of carbamate-embedded triacontyl group on surface of silica causes analytes extracted by hydrophobic, hydrogen bonding and π–π interactions. Under optimal conditions, good linearities and satisfied LODs and LOQs are achieved. The SPE–HPLC–DAD method is successfully developed and applied for the honey sample analysis.

Preparation and evaluation of 2-methylimidazolium-functionalized silica as a mixed-mode stationary phase for hydrophilic interaction and anion-exchange chromatography

Co-reporter:Beibei Yang, Houmei Liu, Jia Chen, Ming Guan, Hongdeng Qiu

Journal of Chromatography A 2016 Volume 1468() pp:79-85

Publication Date(Web):14 October 2016

DOI:10.1016/j.chroma.2016.09.021

•A novel 2-methylimidazolium-functionalized silica stationary phase was prepared.•The column exhibited good selectivity in separating polar compounds.•The column showed excellent mixed-mode chromatographic performance.In this paper, a novel 2-methylimidazolium-functionalized silica stationary phase was prepared and further used for hydrophilic interaction and anion-exchange mixed-mode chromatography. The stationary phase was characterized by elemental analysis and Fourier transform infrared spectrometry. The chromatographic properties of this stationary phase were investigated by hydrophilic chromatography for the separation of nucleosides, nucleobases, water soluble vitamins, sulfonamides and saccharides, and ion chromatography for the separation of inorganic anions. The effect of acetonitrile content, salt concentration and pH values of the mobile phase on the retention of the stationary phases was also investigated. Compared with 1-methylimidazolium-functionalized silica stationary phase, this new stationary phase demonstrated similar or better separation selectivity. This new column demonstrated good performance and separation selectivity even better than a commercial hydrophilic column. Besides, 2-methylimidazolium-functionalized silica is possible to be modified again and used as a precursor to derivate some new stationary phases from the 3-position nitrogen.

A new nano-on-micro stationary phase based on nanodiamond bonded on silica for hydrophilic interaction chromatography

Co-reporter:Tianpei Cai, Haijuan Zhang, Zhan Li, A. F. M. Mustafizur Rahman and Hongdeng Qiu

RSC Advances 2016 vol. 6(Issue 39) pp:32757-32760

Publication Date(Web):24 Mar 2016

DOI:10.1039/C6RA04824B

Nanodiamond particles were covalently bonded on silica microparticles and the resulting material was nicely decorated with a thin layer of oxidized nanodiamonds. This new nano-on-micro hybrid material was packed into a column and successfully evaluated in hydrophilic interaction chromatography.

Deep eutectic solvent-based liquid-phase microextraction for detection of plant growth regulators in edible vegetable oils

Co-reporter:Ting Tan, Zhan Li, Xuejin Mao, Yiqun Wan and Hongdeng Qiu

Analytical Methods 2016 vol. 8(Issue 17) pp:3511-3516

Publication Date(Web):29 Mar 2016

DOI:10.1039/C6AY00053C

In this study, a series of tunable DESs were prepared and used for the liquid-phase microextraction of plant growth regulators, including indole-3-acetic acid, indole-3-butyric acid and 4-iodophenoxyacetic acid, from a multi-component edible vegetable oil matrix. Of the several types of DESs composed of different hydrogen acceptors and hydrogen bond donors, the DESs formed by tetramethylammonium chloride–ethylene glycol (in a 1:3 molar ratio) showed the best extraction efficiency, and 30 μL of the DESs yielded the highest efficiency of all volumes tested in the range of 10–50 μL. Extraction equilibrium was reached in only 7 min of ultrasonication under 50 °C. Under the optimum conditions, a good linearity was obtained for 3.0–50 μg mL−1 of indole-3-acetic acid, 1.2–58 μg mL−1 of indole-3-butyric acid and 7.5–75 μg mL−1 of 4-iodophenoxyacetic acid, with the correlation coefficients no less than 0.9980. Both the limits of detection (LODs) and limits of quantification (LOQs) were satisfied and could meet the requirements of the applications in oil samples. The study demonstrated that DESs could be used as efficient liquid-phase microextraction media for analysis of plant growth regulators in edible vegetable oil samples.

Silica-Based Phenyl and Octyl Bifunctional Imidazolium as a New Mixed-Mode Stationary Phase for Reversed-Phase and Anion-Exchange Chromatography

Co-reporter:Qiong Jiang;Wenjie Zhao;Hongdeng Qiu;Shusheng Zhang

Chromatographia 2016 Volume 79( Issue 21-22) pp:1437-1443

Publication Date(Web):2016 November

DOI:10.1007/s10337-016-3166-1

In this study, octylbenzimidazolium-modified silica (BeImC8-Sil) was prepared by covalent attachment of 1-octylbenzimidazole to γ-chloropropyl silica. The synthesized materials were characterized by the elemental analysis, IR spectrum, and thermogravimetric analysis. Due to the introduction of phenyl and octyl groups on the quaternary imidazolium, the developed BeImC8-Sil column can function via both reversed-phase and anion-exchange retention mechanisms. The chromatographic properties of the synthesized material were investigated by the separations of polycyclic aromatic hydrocarbons, mono-substituted derivatives of benzene, anilines, and phenols, revealing the existence of multiple interactions, including hydrogen bonding, π–π stacking, electrostatic forces, and hydrophobic interactions in reversed-phase mode; inorganic and organic anions were also separated mainly through anion-exchange interaction. The proposed BeImC8-Sil is a promising mixed-mode stationary phase for the separation of complex samples in high-performance liquid chromatography.

Utilization of deep eutectic solvents as novel mobile phase additives for improving the separation of bioactive quaternary alkaloids

Co-reporter:Ting Tan, Mingliang Zhang, Yiqun Wan, Hongdeng Qiu

Talanta 2016 Volume 149() pp:85-90

Publication Date(Web):1 March 2016

DOI:10.1016/j.talanta.2015.11.041

•The first time to use a series of environmentally benign and low-cost DES as mobile phase additives to separate quaternary alkaloids on C18.•The characteristics of the chromatographic peaks of quaternary alkaloids improved with respect to the mobile phase in the absence of DES.•Less amount of organic solvent is needed when addition of longer length-based DES in the mobile phase.•Separation mechanism of DESs as mobile phase additive was proposed.Deep eutectic solvents (DESs) were used as novel mobile phase additives to improve chromatographic separation of four quaternary alkaloids including coptisine chloride, sanguinarine, berberine chloride and chelerythrine on a C18 column. DESs as a new class of ionic liquids are renewably sourced, environmentally benign, low cost and easy to prepare. Seven DESs were obtained by mixing different hydrogen acceptors and hydrogen-bond donors. The effects of organic solvents, the concentration of DESs, the types of DESs and the pH values of the buffer solution on the separation of the analytes were investigated. The composition of acetonitrile and 1.0% deep eutectic solvents aqueous solution (pH 3.3, adjusted with hydrochloric acid) in a 32:68 (v/v) ratio was used as optimized mobile phase, with which four quaternary alkaloids were well separated. When a small amount of DESs was added in the mobile phase for the separation of alkaloids on the C18 column, noticeable improvements were distinctly observed such as decreasing peak tailing and improving resolution. The separation mechanism mediated by DESs as mobile phase additives can be attributed to combined effect of both hydrogen acceptors and hydrogen-bond donors. For example, choline chloride can effectively cover the residual silanols on silica surface and ethylene glycol can reduce the retention time of analytes. The proposed method has been applied to determine BerbC in Lanqin Chinese herbal oral solution and BerbC tablet. Utilization of DESs in mobile phase can efficiently improve separation and selectivity of analytes from complex samples.Deep eutectic solvents (DESs) were prepared and used as novel mobile phase additives to improve chromatographic separation of four quaternary alkaloids including coptisine chloride, sanguinarine, berberine chloride and chelerythrine.

Magnetic carbon nitride nanocomposites as enhanced peroxidase mimetics for use in colorimetric bioassays, and their application to the determination of H2O2 and glucose

Co-reporter:Jia Chen;Qiao Chen;Junying Chen;Hongdeng Qiu

Microchimica Acta 2016 Volume 183( Issue 12) pp:3191-3199

Publication Date(Web):2016 December

DOI:10.1007/s00604-016-1972-7

Graphite-like carbon nitride − Fe3O4 magnetic nanocomposites were synthesized by a chemical co-precipitation method. The nanocomposites were characterized by transmission electron microscopy, X-ray diffraction, FTIR spectroscopy, X-ray photoelectron spectroscopy and magnetization hysteresis loops. The nanocomposites exhibit enhanced peroxidase-like activity (compared to that of graphite-like carbon nitride or Fe3O4 NPs). More specifically, they are capable of catalyzing the oxidation of different peroxidase substrates (such as TMB, ABTS or OPD) by H2O2 to produce the typical color reactions (blue, green or orange). The nanocomposites retain their magnetic properties and can be separated by an external magnet. On the basis of these findings, a highly sensitive and selective method was applied to the determination of H2O2 and glucose (by using glucose oxidase). It was successfully applied to the determination of glucose in (spiked) human serum. Compared to other nanomaterial-based peroxidase mimetics, the one described here provides distinctly higher sensitivity for both H2O2 and glucose, with detection limits as low as 0.3 μM and 0.25 μM, respectively.

A SiO2 NP–DNA/silver nanocluster sandwich structure-enhanced fluorescence polarization biosensor for amplified detection of hepatitis B virus DNA

Co-reporter:Jia Chen, Qiao Chen, Cunji Gao, Mingliang Zhang, Bo Qin and Hongdeng Qiu

Journal of Materials Chemistry A 2015 vol. 3(Issue 6) pp:964-967

Publication Date(Web):09 Jan 2015

DOI:10.1039/C4TB01875C

A novel homogeneous biosensor based on the fluorescence polarization enhancement effect of the SiO2 NP–DNA/Ag nanocluster sandwich structure has been developed for sensitive and selective detection of hepatitis B virus DNA.

A novel green approach for the chemical modification of silica particles based on deep eutectic solvents

Co-reporter:Tongnian Gu, Mingliang Zhang, Jia Chen and Hongdeng Qiu

Chemical Communications 2015 vol. 51(Issue 48) pp:9825-9828

Publication Date(Web):08 May 2015

DOI:10.1039/C5CC02553B

Deep eutectic solvents (DESs), as a novel class of green solvents, were successfully applied as eco-friendly and sustainable reaction media for fast surface modification of spherical porous silica, resulting in stationary phases for high-performance liquid chromatography. The new reaction media were advantageous over organic solvents in many aspects, such as the high dispersibility of silica spheres and their non-volatility.

Versatile ligands for high-performance liquid chromatography: An overview of ionic liquid-functionalized stationary phases

Co-reporter:Mingliang Zhang, Abul K. Mallik, Makoto Takafuji, Hirotaka Ihara, Hongdeng Qiu

Analytica Chimica Acta 2015 Volume 887() pp:1-16

Publication Date(Web):5 August 2015

DOI:10.1016/j.aca.2015.04.022

•Ionic liquids (ILs) are amazing ligands for HPLC stationary phases.•IL-functionalized materials are classified according to HPLC modes.•We illustrate strategies for preparation of IL-functionalized stationary phases.•We describe characterizations and LC evaluations of IL-based stationary phases.•We put forward trends and perspectives on IL-based stationary phases.Ionic liquids (ILs), a class of unique substances composed purely by cation and anions, are renowned for their fascinating physical and chemical properties, such as negligible volatility, high dissolution power, high thermal stability, tunable structure and miscibility. They are enjoying ever-growing applications in a great diversity of disciplines.IL-modified silica, transforming the merits of ILs into chromatographic advantages, has endowed the development of high-performance liquid chromatography (HPLC) stationary phase with considerable vitality. In the last decade, IL-functionalized silica stationary phases have evolved into a series of branches to accommodate to different HPLC modes. An up-to-date overview of IL-immobilized stationary phases is presented in this review, and divided into five parts according to application mode, i.e., ion-exchange, normal-phase, reversed-phase, hydrophilic interaction and chiral recognition. Specific attention is channeled to synthetic strategies, chromatographic behavior and separation performance of IL-functionalized silica stationary phases.

Hemin-functionalized WS2 nanosheets as highly active peroxidase mimetics for label-free colorimetric detection of H2O2 and glucose

Co-reporter:Qiao Chen, Jia Chen, Cunji Gao, Mingliang Zhang, Junying Chen and Hongdeng Qiu

Analyst 2015 vol. 140(Issue 8) pp:2857-2863

Publication Date(Web):19 Feb 2015

DOI:10.1039/C5AN00031A

Hemin-functionalized WS2 nanosheets (hemin/WS2-NSs) were first obtained by hemin assembled on the surface of few-layered WS2 nanosheets (WS2-NSs) via van der Waals interactions. Significantly, this new material possessed the advantages of both hemin and WS2 nanosheets and exhibited some unique properties. Firstly, hemin/WS2-NSs had intrinsic peroxidase-like activity, which could effectively catalyze oxidation of the substrate 3,3′,5,5′-tetramethylbenzidine (TMB) by H2O2 to produce a typical blue colored reaction. Secondly, the activity of hemin/WS2-NSs was much higher than the activity of hemin or WS2-NSs alone. The catalytic activity followed the typical Michaelis–Menten kinetics and was dependent on the temperature, pH, H2O2 concentration, as well as reaction time. Based on this finding, a new highly sensitive and selective colorimetric method for H2O2 and glucose detection was developed. This method was simple and inexpensive for glucose detection using glucose oxidase (GOx) and hemin/WS2-NSs with a linear range of 0.5 × 10−5 to 2.0 × 10−4 mol L−1 with a detection limit of 1.5 × 10−6 mol L−1. The good catalytic activity and low-cost make the hemin/WS2-NSs a useful biocatalyst for a wide range of potential applications in environmental chemistry, biotechnology and clinical diagnostics.

Corrigendum to “A polar-embedded C30 stationary phase: Preparation and evaluation” [J. Chromatogr. A 1388 (2015) 133–140]

Co-reporter:Mingliang Zhang, Wenpeng Mai, Liang Zhao, Yong Guo, Hongdeng Qiu

Journal of Chromatography A 2015 Volume 1422() pp:351

Publication Date(Web):27 November 2015

DOI:10.1016/j.chroma.2015.10.042

A new highly Zn2+-selective and “off–on” fluorescent chemosensor based on the pyrene group

Co-reporter:Cunji Gao, Hongmei Zhu, Mingliang Zhang, Ting Tan, Jia Chen and Hongdeng Qiu

Analytical Methods 2015 vol. 7(Issue 19) pp:8172-8176

Publication Date(Web):07 Aug 2015

DOI:10.1039/C5AY01276G

In this work, an “off–on” type zinc ion fluorescent chemosensor H2L with pyrene as a fluorophore was investigated. The chemosensor H2L demonstrates a Zn2+-specific emission enhancement linearly with a 1:1 binding ratio even in the presence of a wide range of competing metal ions. This may be correlated with the efficient Zn2+ binding of H2L, which promotes a good chelation-enhanced fluorescence (CHEF) effect and prevents the photoinduced electron transfer (PET) effect, and CN isomerization is inhibited. Importantly, the fabricated chemosensor can selectively distinguish Zn2+ from Cd2+. And the recognition behaviour has been proved experimentally and computationally.

Sensitive and Selective DNA Detection Based on Lambda Exonuclease Assisted Signal Amplification

Co-reporter:Jia CHEN, Yun-Yun GUO, Qiao CHEN, Hong-Deng QIU

Chinese Journal of Analytical Chemistry 2015 Volume 43(Issue 10) pp:1513-1519

Publication Date(Web):October 2015

DOI:10.1016/S1872-2040(15)60871-4

A new versatile chemiluminescence biosensing platform with G-Quadruplexes/Hemin DNAzyme and lambda exonuclease (λexo) assisted signal amplification was designed for sensitive detection of DNA. The system involved target DNA, phosphate-DNA, auxiliary DNA and hairpin DNA. The selective digestion of λexo to 5′-phosphorylated strand of phosphate-DNA-auxiliary DNA-target DNA duplex sandwich structure resulted in the release of target DNA and auxiliary DNA. The released target DNA hybridized with another phosphate-DNA-auxiliary DNA duplex to trigger the target DNA recycling, while the released auxiliary DNA hybridized with hairpin DNA to activate DNAzyme segments. The activated DNAzyme segments interacted with hemin to form stable G-Quadruplexes/ Hemin DNAzymes that could catalyze H2O2-mediated oxidation luminol to produce chemiluminescence signals. In the presence of 10 units λexo, 1.0 × 10−3 M luminol, 3.0 × 10−2 M H2O2 and pH 9.0 buffer solution, the relative chemiluminescence intensity of luminol was linearly related with the concentrations of target DNA in the range of 2.0 × 10−12 M to 8.0 × 10−9 M. This unique analysis strategy provided a detection limit down to 7.0 × 10−14 M. The present method was successfully applied to the determination of target DNA in serum samples, which was also capable of discriminating mismatched DNA from perfectly matched target DNA with a high selectivity.A new strategy based on G-Quadruplexes/hemin DNAzyme and lambda exonuclease (λexo) assisted signal amplification for homogeneous chemiluminescence (CL) detection of sequence-specific DNA was designed and abricated. The established method was simple, cost-effective, specific and sensitive, and could be successfully applied in the analysis of real biological samples.

A polar-embedded C30 stationary phase: Preparation and evaluation

Co-reporter:Mingliang Zhang, Wenpeng Mai, Liang Zhao, Yong Guo, Hongdeng Qiu

Journal of Chromatography A 2015 1388() pp: 133-140

Publication Date(Web):

DOI:10.1016/j.chroma.2015.02.023

Hairpin assembly-triggered cyclic activation of a DNA machine for label-free and ultrasensitive chemiluminescence detection of DNA

Co-reporter:Jia Chen, Hongdeng Qiu, Mingliang Zhang, Tongnian Gu, Shijun Shao, Yong Huang, Shulin Zhao

Biosensors and Bioelectronics 2015 Volume 68() pp:550-555

Publication Date(Web):15 June 2015

DOI:10.1016/j.bios.2015.01.054

•A novel isothermal label-free, ultrasensitive and highly select chemiluminescence amplification platform for the detection of p53 DNA is proposed.•DNA used in this work does not require any chemical modification.•The method is capable of detecting p53 DNA in complex biological samples. It holds a great promise for further application in biomedical research and early clinical diagnosis.•The proposed assay strategy can be extended to other DNAs or RNAs detection by simply changing the sequences of the hairpin structures.•To the best of our knowledge, it is the first reported isothermal hairpin assembly-triggered cyclic activation of a DNA machine for the detection of p53 DNA.DNA plays important regulatory roles in many life activities. Here, we have developed a novel label-free, ultrasensitive and specific chemiluminescence (CL) assay protocol for DNA detection based on hairpin assembly-triggered cyclic activation of a DNA machine. The system involves two hairpin structures, H1 and H2. Firstly, a target DNA binds with and opens the hairpin structure of H1. Then, H2 hybridizes with H1 and displaces the target DNA, which is used to trigger another new hybridization cycle between H1 and H2, leading to the generation of numerous H1–H2 complexes. The generated H1–H2 complexes are further activated with the help of polymerase and nicking enzyme, continuously yielding a large amount of G-riched DNA fragments. The G-riched DNA fragment products interact with hemin to form the activated HRP-mimicking DNAzymes that can catalyze the oxidation of luminol by H2O2 to produce strong CL signal resulting in an amplified sensing process. Our newly proposed homogeneous assay enables the quantitative measurement of p53 DNA (as a model) with a detection limit of 0.85 fM, which is at least 5 orders of magnitude lower than that of traditional unamplified homogeneous optical approaches. Moreover, this assay exhibits high discrimination ability even against a single base mismatch. In addition, this strategy is also capable of detecting p53 DNA in complex biological samples. The proposed sensing approach might hold a great promise for further applications in biomedical research and early clinical diagnosis.

Progress in stationary phases modified with carbonaceous nanomaterials for high-performance liquid chromatography

Co-reporter:Mingliang Zhang, Hongdeng Qiu

TrAC Trends in Analytical Chemistry 2015 Volume 65() pp:107-121

Publication Date(Web):February 2015

DOI:10.1016/j.trac.2014.10.008

•Carbonaceous nanomaterials (CNMs) are useful for preparing HPLC stationary phases.•Carbonaceous nanomaterials are classified according to their structures.•We describe in detail processes for synthesizing carbonaceous nanomaterials.•We review characterization and LC evaluation of CNM-based stationary phases.•We set out trends and perspectives on CNM-based stationary phases.Carbonaceous nanomaterials (CNMs) are prevalent in many disciplines. In separation science, CNMs have made great contributions to the innovation of stationary phases for various chromatographic technologies. In this review article, we present an up-to-date overview of the development of stationary phases based on CNMs for high-performance liquid chromatography (HPLC). We devote a large part of this review to the accomplishments in the past five years with regard to retention and selectivity offered by new HPLC stationary phases modified with different types of CNMs, mainly including carbon nanotubes, fullerenes, nanographene and nanodiamonds. We pay specific attention to the approaches to chemical immobilization involving different types of CNM in synthesizing stationary phases.

Deep eutectic solvents as novel extraction media for phenolic compounds from model oil

Co-reporter:Tongnian Gu, Mingliang Zhang, Ting Tan, Jia Chen, Zhan Li, Qinghua Zhang and Hongdeng Qiu

Chemical Communications 2014 vol. 50(Issue 79) pp:11749-11752

Publication Date(Web):11 Aug 2014

DOI:10.1039/C4CC04661G

Deep eutectic solvents (DES) as a new kind of green solvent were used for the first time to excellently extract phenolic compounds from model oil. It was also proved that DES could be used to extract other polar compounds from non-polar or weakly-polar solvents by liquid-phase microextraction.

Preparation and chromatographic evaluation of new branch-type diamide-embedded octadecyl stationary phase with enhanced shape selectivity

Co-reporter:Mingliang Zhang, Jia Chen, Abul K. Mallik, Hongdeng Qiu, Shengxiang Jiang, Hirotaka Ihara

Analytica Chimica Acta 2014 Volume 833() pp:48-55

Publication Date(Web):23 June 2014

DOI:10.1016/j.aca.2014.05.011

•A new diamide-embedded octadecyl stationary phase was prepared.•Excellent hydrophobic and aromatic selectivity.•“Polymeric-C18” chromatographic behavior was found.•Superior shape and planarity selectivity over C18 towards isomeric PAHs.•Carbonyl group and adjacent double C18 chains impacted the retention substantially.A novel branch-type diamide-embedded octadecyl stationary phase was prepared by facile amidation. The preparation of this new phase involves the synthesis of new bifunctional silane ligand and surface modification of spherical silica via anchoring of silane coupling agent. The obtained diamide-embedded octadecyl stationary phase demonstrated excellent hydrophobic selectivity, as well as enhanced shape and planarity selectivity in comparison to commercial polymeric and monomeric C18 phases, respectively, as revealed by the systematic investigation into its liquid chromatographic retention of isomeric polycyclic aromatic hydrocarbons. The applicability of this new stationary phase was further testified by the effective separation of isomeric compounds belong to different chemical classes, including chain isomers of alkylbenzenes, and positional isomers of substituted aromatics. An in-depth analysis of the separation mechanisms other than molecular shape recognition involved in the new stationary phase was performed using a linear solvation energy relationships model and compared with its monoamide and pure C18 counterparts correspondingly. The performance of the new stationary phase in quantitative analysis of phenols from real-world samples was also evaluated.

A novel urea-functionalized surface-confined octadecylimidazolium ionic liquid silica stationary phase for reversed-phase liquid chromatography

Co-reporter:Mingliang Zhang, Ting Tan, Zhan Li, Tongnian Gu, Jia Chen, Hongdeng Qiu

Journal of Chromatography A 2014 Volume 1365() pp:148-155

Publication Date(Web):24 October 2014

DOI:10.1016/j.chroma.2014.09.018

•A new urea-functionalized octadecylimidazolium stationary phase was synthesized.•Superior aromatic selectivity over conventional C18.•High affinity for polar-substituted aromatics.•Enhanced hydrogen-bonding capacity and π–π stacking was observed.•The urea group facilitated the retention and selectivity considerably.One-pot synthesis of surface-confined ionic liquid functionalized silica spheres was proposed using N-(3-aminopropyl)imidazole, γ-isopropyltriethoxysilane and 1-bromooctadecane as starting materials. The surface modification of the silica spheres was successful with a high surface density of octadecylimidazolium, enabling the utilization of this new urea-functionalized ionic liquid-grafted silica material as stationary phase for high-performance liquid chromatography in reversed-phase mode. The long aliphatic chain combined with the multiple polar group embedded in the ligands imparted the new stationary phase fine selectivity towards PAH isomers and polar aromatics and higher affinity for phenolic compounds. The unique features of the new material, especially the effect of the urea group on the retention were elucidated by mathematic modeling.

Selective recognition and discrimination of water-soluble azo dyes by a seven-channel molecularly imprinted polymer sensor array

Co-reporter:Zerong Long;Yi Lu;Mingliang Zhang;Hongdeng Qiu

Journal of Separation Science 2014 Volume 37( Issue 19) pp:2764-2770

Publication Date(Web):

DOI:10.1002/jssc.201400684

A seven-channel molecularly imprinted polymer sensor array was prepared and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, UV-Vis spectroscopy, and nitrogen physisorption studies. The results revealed that the imprinted polymers have distinct-binding affinities from those of structurally similar azo dyes. Analysis of the UV-Vis spectral response patterns of the seven dye analytes against the imprinted polymer array suggested that the different selectivity patterns of the array were closely connected to the imprinting process. To evaluate the effectiveness of the array format, the binding of a series of analytes was individually measured for each of the seven polymers, made with different templates (including one control polymer synthesized without the use of a template). The response patterns of the array to the selected azo dyes were processed by canonical discriminant analysis. The results showed that the molecularly imprinted array was able to discriminate each analyte with 100% accuracy. Moreover, the azo dyes in two real samples, spiked chrysoidin in smoked bean curd extract and Fanta lime soda (containing tartrazine), were successfully classified by the array.

Homogenous formation and quaternization of urea-functionalized imidazolyl silane and its immobilization on silica for surface-confined ionic liquid stationary phases

Co-reporter:Mingliang Zhang, Jia Chen, Hongdeng Qiu, Abul K. Mallik, Makoto Takafuji and Hirotaka Ihara

RSC Advances 2014 vol. 4(Issue 65) pp:34654-34658

Publication Date(Web):01 Aug 2014

DOI:10.1039/C4RA04772A

A novel facile and efficient immobilization strategy was introduced on the basis of the reaction between isocyanate and amine and applied in surface modification of mesoporous silica spheres with a series of urea-functionalized imidazolium salts bearing aliphatic chains of different lengths and a large aromatic group. This resulted in an array of multifunctional silica materials as HPLC stationary phases with selectivity significantly influenced by the substituents and functional groups.

Anionic and cationic copolymerized ionic liquid-grafted silica as a multifunctional stationary phase for reversed-phase chromatography

Co-reporter:Hongdeng Qiu, Mingliang Zhang, Jia Chen, Tongnian Gu, Makoto Takafuji and Hirotaka Ihara

Analytical Methods 2014 vol. 6(Issue 2) pp:469-475

Publication Date(Web):29 Oct 2013

DOI:10.1039/C3AY41627E

Recently, we briefly reported a new method to prepare ionic liquid-modified silica via copolymerization of anionic and cationic monomer couples on mercaptyl-modified silica, which aimed to enhance the stability of the column during the use of buffer as a solvent. In this paper, the previously prepared copolymerized ionic liquid-grafted silica denoted Sil-P(ImC18-SS) was characterized via elemental analysis, thermogravimetric analysis, and diffuse reflectance infrared Fourier transform spectroscopy. The reversed-phase chromatographic properties were determined particularly by separation of Tanaka test mixture, polycyclic aromatic hydrocarbons and their isomers, disubstituted benzenes, flavonoids, bases and nucleosides. Compared with the conventional ODS column, Sil-P(ImC18-SS) exhibited enhanced shape selectivity for polycyclic aromatic hydrocarbons and better performance for the separation of some polar analytes such as bases and flavonoids. Moreover, compared with previously reported ionic liquid-modified silica stationary phases, the anionic and cationic copolymerized stationary phase offers the advantage of increased stability given that the anions and cations of the ionic liquids were concomitantly immobilized on the silica.

Preparation and applications of surface-confined ionic-liquid stationary phases for liquid chromatography

Co-reporter:Mingliang Zhang, Xiaojing Liang, Shengxiang Jiang, Hongdeng Qiu

TrAC Trends in Analytical Chemistry 2014 Volume 53() pp:60-72

Publication Date(Web):January 2014

DOI:10.1016/j.trac.2013.09.011

•Surface-confined ionic liquids (SCILs) are useful ligands for HPLC stationary phases.•SCILs exhibit outstanding multimodal operability.•The preparations and the applications of SCILs are reviewed.•Practicable new preparative strategies are proposed for SCILs.Ionic liquids (ILs) are a class of substances completely comprised of ions. Due to their unique properties (e.g., electric conductivity, low volatility, thermostability and tenability), their use has attracted considerable interest, including an increasing number of publications on their use in preparing stationary phases (SPs) of high-performance liquid chromatography. We highlight the existing pathways for making IL-based SPs, and we propose potential strategies for synthesis. We also give up-to-date information on their applications in different chromatographic modes.

Novel imidazolium-embedded and imidazolium-spaced octadecyl stationary phases for reversed phase liquid chromatography

Co-reporter:Mingliang Zhang, Jia Chen, Tongnian Gu, Hongdeng Qiu, Shengxiang Jiang

Talanta 2014 Volume 126() pp:177-184

Publication Date(Web):1 August 2014

DOI:10.1016/j.talanta.2014.03.057

•Two ionic liquid-modified stationary phases with octadecyl chains are prepared.•The stationary phases differ from each other in distribution patterns of the polar groups.•Study of stationary phases via a linear solvation energy relationship mode.•Hydrophobic and aromatic selectivities of these phases are investigated.•Insertion of polar imidazolium moieties into octadecyl groups remarkably impacts the chromatographic behavior.Two new stationary phases modified by alkylimidazoliums were prepared for the first time and characterized. One of the new phases was obtained via monomeric immobilization of octadecylimidazole to γ-chloropropyltrimethoxysilane modified silica to form polar-embedded phase; the other one was prepared by co-immobilization of two silane coupling agents (γ-chloropropyltrichlorosilane and octadecyltrichlorosilane) to silica, followed by quaternization of methylimidazole to form polar-spaced phase. This study was intended to compare the retention characteristics of these two stationary phases using linear solvation energy relationships model, as well as to examine the difference in selectivity by eluting alkylbenzenes, alkylnaphthalenes, condensed-ring and phenylene polynuclear aromatic hydrocarbons on both phases. Different effects of distributions of polar functional group and octadecyl chain were found to impact the chromatographic properties.Novel octadecyl stationary phases differ in distribution of imidazolium group have been prepared for the first time and comparatively evaluated via linear solvation energy relationships (LSER) model.

Preparation and characterization of dipyridine modified hybrid-silica monolithic column for mixed-mode capillary electrochromatography

Co-reporter:Sheng Tang, Licheng Wang, Haifeng Han, Hongdeng Qiu, Xia Liu and Shengxiang Jiang

RSC Advances 2013 vol. 3(Issue 21) pp:7894-7901

Publication Date(Web):15 Mar 2013

DOI:10.1039/C3RA40580J

A new mixed-mode organic–silica hybrid monolithic column for capillary electrochromatography was synthesized via a sol–gel process and a following post-modification with 4,4′-dipyridine. Characterization by SEM shows that the hybrid monolith has homogenous macroporous morphology and it is well attached to the inner wall of the capillary. A stable and reversed electroosmotic flow (EOF) was generated at acidic pH due to the pyridinium groups on the surface of the stationary phase. The column performance was evaluated by separating various kinds of compounds, such as polycyclic aromatic hydrocarbons (PAHs), alkylbenzenes, phenols, inorganic anions and organic acids. Multiple retention mechanisms including hydrophobic, π–π and anion-exchange interactions were exhibited at separation of the analytes. The monolithic stationary phase exhibited reversed-phase chromatographic behavior toward neutral solutes. Meanwhile, inorganic anions and organic acids can be separated by the mixed-mode mechanism comprising electrophoresis, hydrophobic and anion-exchange interactions. Good performance and repeatability showed that this new hybrid column can be used in the analysis of various compounds with great prospects.

A Sulfonic-Azobenzene-Grafted Silica Amphiphilic Material: A Versatile Stationary Phase for Mixed-Mode Chromatography

Co-reporter: Hongdeng Qiu;Mingliang Zhang;Tongnian Gu;Assoc. Makoto Takafuji; Hirotaka Ihara

Chemistry - A European Journal 2013 Volume 19( Issue 52) pp:18004-18010

Publication Date(Web):

DOI:10.1002/chem.201302746

Abstract

A novel sulfonic-azobenzene-functionalized amphiphilic silica material was synthesized through the preparation of a new sulfonic azobenzene monomer and its grafting on mercaptopropyl-modified silica by a surface-initiated radical chain-transfer reaction. The synthesis was confirmed by infrared spectra, elemental analysis, and thermogravimetric analysis. This new material was successfully applied as a new kind of mixed-mode stationary phase in liquid chromatography. This allows an exceptionally flexible adjustment of retention and selectivity by tuning the experimental conditions. The distinct separation mechanisms were outlined by selected examples of chromatographic separations in the different modes. In reversed-phase liquid chromatography, this new stationary phase presented specific chromatographic performance when evaluated using a Tanaka test mixture. Seven dinitro aromatic isomers, four steroids, and seven flavonoids were separated successfully in simple reversed-phase mode. This stationary phase can also be used in hydrophilic interaction chromatography because of the existing polar functional groups; for this, nucleosides and their bases were used as a test mixture. Interestingly, the same nucleosides and bases can also be separated in per aqueous liquid chromatography using the same stationary phase. Three ginsenosides including Rg1, Re, and Rb1 were successfully separated in hydrophilic mode. There is the potential for more applications to benefit from this useful column.

Octadecylimidazolium ionic liquid-modified magnetic materials: Preparation, adsorption evaluation and their excellent application for honey and cinnamon

Co-reporter:Houmei Liu, Zhan Li, Makoto Takafuji, Hirotaka Ihara, Hongdeng Qiu

Food Chemistry (15 August 2017) Volume 229() pp:

Publication Date(Web):15 August 2017

DOI:10.1016/j.foodchem.2017.02.080

•Octadecylimidazolium ionic liquid modified magnetic nanoparticles were synthesized.•Properties of the novel adsorbent were evaluated by four types of probe molecules.•Synergism and competition effects were existed during adsorption process.•The adsorbent was applied for real samples analysis of honey and cinnamon.A novel and versatile adsorbent based on 1-octadecylimidazolium ionic liquid modified magnetic nanoparticles (Fe3O4@SiO2@ImC18) possessing of both magnetic property and excellent adsorption ability was successfully synthesized. Twelve compounds from four kinds of substances (alkylbenzenes, PAHs, flavonoids and organic acids) were chosen as probe molecules to evaluate adsorption properties of the new adsorbent. A series of adsorption experiments were conducted and results indicated both synergism and competition effects were existed and multiple interactions took place during adsorption process. After considerable acquaintances with the adsorbent, it was successfully applied for real samples analysis of honey and cinnamon. Three flavonoid compounds of myricetin, quercetin and luteolin from honey and cinnamic acid from cinnamon were all detected and quantified. Meanwhile, it reached 280-fold concentration reduction of interferent during the extraction of cinnamic acid from cinnamon. The recoveries were in the range of 85.4–94.8% with relative standard deviations (n = 3) of 2.5–5.6%.The current study not only provided a strategy to evaluate new adsorbent, but also demonstrated the novel Fe3O4@SiO2@ImC18 material was reliable, accurate and suitable for sample pretreatment in pharmaceutical and food chemistry.

Deep eutectic solvents as novel extraction media for phenolic compounds from model oil

Co-reporter:Tongnian Gu, Mingliang Zhang, Ting Tan, Jia Chen, Zhan Li, Qinghua Zhang and Hongdeng Qiu

Chemical Communications 2014 - vol. 50(Issue 79) pp:NaN11752-11752

Publication Date(Web):2014/08/11

DOI:10.1039/C4CC04661G

A novel green approach for the chemical modification of silica particles based on deep eutectic solvents

Co-reporter:Tongnian Gu, Mingliang Zhang, Jia Chen and Hongdeng Qiu

Chemical Communications 2015 - vol. 51(Issue 48) pp:NaN9828-9828

Publication Date(Web):2015/05/08

DOI:10.1039/C5CC02553B

Co-reporter:Jia Chen, Cunji Gao, Abul K. Mallik and Hongdeng Qiu

Journal of Materials Chemistry A 2016 - vol. 4(Issue 30) pp:NaN5166-5166