沉淀聚合法制备1-脱氧野尻霉素分子印迹聚合物微球及其性能研究

本研究制备了1-脱氧野尻霉素分子印迹聚合物微球,考察溶剂、反应时间对分子印迹聚合物产率以及性能的影响。以1-脱氧野尻霉素为模板分子,α-甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EGDMA)为交联剂,采用沉淀聚合法合成分子印迹微球,采用静态吸附及扫描电镜(SEM)的方法对微球进行表征。结果表明,当反应时间为24 h、乙腈为溶剂时,所制得印迹聚合物微球的形貌和吸附性能较好,对1-脱氧野尻霉素与N-甲基-1-脱氧野尻霉素的选择性分离因子α为2.26,说明分子印迹聚合物微球对1-脱氧野尻霉素分子有特异性吸附和识别能力。     

分子印迹技术应用于血清中地高辛的快速检测

应用分子印迹的方法制备对地高辛有特异性吸附性能的印迹聚合物颗粒,再将颗粒与琼脂糖混合并固定于玻碳电极上制备成地高辛分子印迹聚合膜传感器,传感器可以特异性地结合模板分子地高辛且其电化学信号与模板浓度相关,再用它来检测血清中地高辛的含量。结果表明:分子印迹传感器具有制作简便、成本低、检测快速、特异性高、稳定性好等优点,检测下限为1.28 nmol/L,检测时间为5 min。     

浅谈菌丝体表面分子印迹吸附剂的选择性吸附

通过制备的方法获得菌丝体表面分子印迹吸附剂,本文系统的分析和探讨了针对模板金属离子菌丝体表面分子印迹吸附剂的吸附选择性。通过实验研究证明,菌丝体表面分子印迹吸附剂如果是以Ni2+为模板制备的,相对于非印迹吸附剂来讲,其对Cr3+、Cu2+、Ni2+的吸附容量以及吸附速率的提高幅度都是非常大的。而菌丝体表面分子印迹吸附剂相对于具有Ni2+金属离子混合溶液来讲,其对Ni2+的选择性以及吸附容量要比含有诸如Cu2+以及Cr3+的金属离子提高的都要明显很多;印迹吸附剂相对于非印迹吸附剂来讲,其在吸附非模板金属离子Cu2+以及Cr3+时具有明显降低的选择性。     

分子印迹聚合物对血浆中异丙酚吸附的研究

目的：合成异丙酚分子印迹聚合物,并用聚合物萃取人血浆中的异丙酚。方法：用热聚合法制备异丙酚分子印迹聚合物,考查聚合物的性能,并用它来萃取血浆中不同浓度的异丙酚。结果：模板分子和功能单体以氢键的方式结合;分子印迹聚合物选择性地吸附血浆中的异丙酚。结论：分子印迹聚合物可以从人血浆中吸附异丙酚,其吸附率受底物浓度的影响。     

空心磁性微球负载La掺杂TiO_2的制备和光催化性能

以自制的粒径均一分散P(St-AA)聚合物微球为模板,制备了P(St-AA)/Fe_2O_3纳米颗粒,热处理后获得的纳米磁性空心微球;在溶胶凝胶法制备La掺杂TiO_2方法的基础上,制备了以磁性空心微球为载体的空心磁性微球负载La掺杂TiO_2,通过紫外光催化实验表明,该产品降解亚甲基蓝的效率优于同等条件制备的La掺杂TiO_2。通过SEM、TEM对产物的形貌和微观结构进行了表征。     

PLGA人工抗原提呈细胞载体的制备

目的:目前常用的载体材料,在体内很难降解,限制了其在体内的应用,本文通过用PLGA微球制备人工抗原提呈细胞(AAPC)载体,对其功能进行验证.希望此方法能弥补传统方法的不足.方法:将软脂酸偶联到亲和素上,然后按照传统的复乳法来制备PLGA微球,并且通过使用荧光素(FITC)标记、生物素化的牛血清蛋白(BSA)对其功能进行验证.结果:通过该方法可以得到表面固定生物素的PLGA微球,并且证明软脂酸修饰并未影响到亲和素分子和生物素的结合,生物素化的BSA分子可以有效的结合到微球的表面.结论:PLGA微球表面很难引进合适的化学基团,导致其不能像聚苯乙烯微球那样通过化学反应来将亲和素分子固定在微球的表面上,通过将软脂酸偶联到亲和素分子上,可改变其表面很难引进合适的化学基团的不足,用其微球可用于制备AAPC载体.人工抗原提呈细胞是免疫学研究领域的新思路,可在基础免疫研究和临床治疗方面发挥较大的作用,但作为一门新兴技术,在制备、效果评价及应用方面需要逐渐完善和成熟,用PLGA微球为载体构建,弥补了磁珠、聚苯乙烯不能在体内降解的不足,且安全无毒,可供参考.     

心肌肌钙蛋白Ⅰ的分子印迹电化学生物传感器

应用分子印迹技术,以邻苯二胺和对苯二酚为功能单体,心肌肌钙蛋白Ⅰ(cTnI)为模板分子,在pH 7.0磷酸盐缓冲液中,利用循环伏安法在玻碳电极表面聚合形成了分子印迹膜.该分子膜对cTnI有特异性识别作用,在0.01～2.00 μg/mL的范围内,cTnI的浓度与氧化峰电流的变化呈线性关系,检测下限为2 ng/mL,响应时间为15 min.该分子印迹传感器具有制备简单、特异性及稳定性好等优点.     

硝酸铵水凝胶分子印迹聚合物的制备

目的:目前安全问题成为世界各国的首要问题,尤其是对炸药分子的检测。硝酸铵是硝铵炸药的主要成分。研究水凝胶分子印迹法对硝铵炸药分子的检测。方法:水凝胶分子印迹方法制备硝酸铵水凝胶分子印迹聚合物,运用静态结合实验对其结合率进行了测定。结果:聚合物对硝酸铵具有良好的识别和吸附性能。印迹聚合物的解离常数为4.08g/L,最大吸附量为3.51mg/g。结论:水凝胶分子印迹法可合成水溶性炸药分子印迹聚合物,并且识别及吸附性能良好。     

硝酸铵水凝胶分子印迹聚合物的制备

目的：目前安全问题成为世界各国的首要问题,尤其是对炸药分子的检测。硝酸铵是硝铵炸药的主要成分。研究水凝胶分子印迹法对硝铵炸药分子的检测。方法：水凝胶分子印迹方法制备硝酸铵水凝胶分子印迹聚合物,运用静态结合实验对其结合率进行了测定。结果：聚合物对硝酸铵具有良好的识别和吸附性能。印迹聚合物的解离常数为4.08g/L,最大吸附量为3.51mg/g。结论：水凝胶分子印迹法可合成水溶性炸药分子印迹聚合物,并且识别及吸附性能良好。     

普朗尼克F-127以及PLGA对多孔微球的影响

目的:考察致孔剂普朗尼克F-127以及不同型号聚乳酸-聚羟基乙酸共聚物(poly(lactic-co-glycolic acid),PLGA)配比对于PLGA多孔微球形态和孔洞形成的影响。方法:制备多种处方的PLGA多孔微球,添加不同量的致孔剂普朗尼克F-127,部分不添加任何致孔剂,并且利用PLGA型号为50501A和50502A的不同比例制备多种处方的多孔微球,进行SEM观察缓释多孔微球的整体形态和孔洞。结果:1)添加了不同量的致孔剂普朗尼克F-127的微球,表面的孔洞大小随F-127的添加量成正比关系。2)添加了致孔剂普朗尼克F-127的PLGA微球表面有较多的碎屑粘连,有大量的微球分子破裂,未有添加任何致孔剂的微球,微球的形态较好,球形规整。3)利用不同型号PLGA配比制备的微球SEM图表明,利用PLGA型号为50501A制备的微球表面孔洞清晰,孔洞均匀分布,而利用50502A制备的缓释多孔微球表面的孔洞很少。结论:1)致孔剂普朗尼克F-127会造成小分子的PLGA多孔微球的破裂,不宜作为小分子PLGA多孔微球时的致孔剂。2)不同型号PLGA的配比会对制备的PLGA多孔微球的孔径产生比较大的影响,形成的微球孔径与PLGA的特性粘度成反比。     

Synthesis and evaluation of uniformly sized nalidixic acid-imprinted nanospheres based on precipitation polymerization method for analytical and biomedical applications

For the first time in this work, uniform molecularly imprinted polymer (MIP) nanoparticles were prepared using nalidixic acid as a template. The MIP nanoparticles were successfully synthesized by precipitation polymerization applying methacrylic acid (MAA) as a functional monomer and trimethylolpropane trimethacrylate (TRIM) as a cross-linking monomer at different mole ratios. The morphology, binding, recognition, selectivity, and in vitro release behaviors of obtained particles were studied. The produced polymers were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetric. Furthermore, their morphology was analyzed accurately by scanning electron microscopy, photon correlation spectroscopy, and Brunauer-Emmett-Teller analysis. The nanospheres and microspheres with mean diameter values of 94 nm, 256 nm, and 1.2 μm were obtained using nalidixic acid-MAA-TRIM various mole ratios. Among the MIPs, the product with nalidixic acid-MAA-TRIM mole ratio of 1:12:12 established nanospheres with the lowest polydispersity index (0.003), an average pore diameter (12 nm), and the highest specific surface area (280 m(2) g(-1)) and selectivity factor (10.4). Results from binding experiments demonstrated that the imprinted nanospheres with a 94-nm mean diameter and a binding capacity of 28 mg of nalidixic acid per gram of polymer had higher specific affinity to nalidixic acid in contrast with the other imprinted nanospheres, microspheres, and nonimprinted particles. However, the binding performance of imprinted nanospheres in human serum was estimated using high-performance liquid chromatography analysis (binding approximately 98% of nalidixic acid). In addition, release experiments proved to be successful in the controlled release of nalidixic acid during a long period. The 20% of loaded nalidixic acid was released from the imprinted nanospheres within the first 20 h, whereas the remaining 80% was released in the after 120 h. The nalidixic acid release kinetics from the MIPs was highly affected by properties of the particles.     

Controlling size and uniformity of molecularly imprinted nanoparticles using auxiliary template

Molecularly imprinted nanomaterials are gaining substantial importance. As a simple and efficient synthetic method, precipitation polymerization has been used to prepare uniform molecularly imprinted microspheres for numerous template compounds. Despite of its general applicability, the difficulty of obtaining uniform particles for some difficult templates by precipitation polymerization has been reported. In this work, we attempted to produce uniform atrazine-imprinted nanoparticles using propranolol as an auxiliary template under standard precipitation polymerization condition. When propranolol was added in the prepolymerization mixture for atrazine imprinting, it displayed a significant effect on particle size and size distribution of atrazine-imprinted polymers. The molecular binding characteristics of the molecularly imprinted polymer (MIP) nanoparticles were found to be dependent on the relative ratios of the two templates. Under an optimal template propranolol-atrazine ratio of 1:3 mol/mol, very uniform imprinted nanoparticles (d(H) =?106?nm) with a polydispersity index of 0.07 were obtained. The loading of the auxiliary template (propranolol) could be reduced to as low as 5% without sacrificing the uniformity of the MIP nanoparticles. The uniform MIP nanoparticles could be easily encapsulated into polyethylene terephthalate nanofibers using a simple electrospinning technique. The composite nanofibers containing the MIP nanoparticles maintained specific molecular binding capability for both atrazine and propranolol.     

Room temperature synthesis and binding studies of solution‐processable histamine‐imprinted microspheres

Accurate quantification of histamine levels in food and in biological samples is important for monitoring the quality of food products and for the detection of pathophysiological conditions. In this study, solution processable histamine‐imprinted microspheres were synthesized at 30°C via dilute free radical phototochemical polymerization technique using ethylene glycol dimethacrylate (EGDMA) as the crosslinker and methacrylic acid (MAA) as the monomer. The processability of the resulting polymer is dictated by the monomer feed concentration (eg, 4 wt% 80:20 EGDMA:MAA formulation) and solvent (acetonitrile). Whereas, the particle size is influenced by the monomer feed concentration, the presence of template molecule, and independent of the crosslinker content. Evaluation of the binding performance of the photochemically imprinted polymers (PCP) with different crosslinker content (80 and 90 wt%) indicated that the selective binding capacity was notably higher in PCP‐80 (N= 16.0 μmol/g) compared to PCP‐90 (N= 10.1 μmol/g) when analyzed via frontal analysis capillary electrophoresis (FACE) using Freundlich isotherm. In addition, PCP‐80 microspheres are more selective toward histamine than conventional thermal polymers (CTP‐80) prepared at 60°C in the presence of structural analogs such as histidine, imidazole, and tryptamine under cross‐rebinding and competitive conditions. These results demonstrated that histamine‐selective imprinted polymers can be obtained readily using room temperature photochemical polymerization where these materials can be subsequently used as recognition element for optical‐based histamine sensing.     

Molecularly imprinted polymer microspheres for solid-phase extraction of chloramphenicol residues in foods

Preparation of molecularly imprinted polymer microspheres (MIPMs) for chloramphenicol (CAP) by aqueous suspension polymerization is reported for the first time in this study. The resulting MIPMs had the ability to specifically adsorb CAP, and the molecularly imprinted solid phase extraction (MISPE) based on the MIPMs was shown to be applicable for clean-up and preconcentration of trace CAP in milk and shrimp samples with high recoveries of 92.7% and 84.9%, respectively. Combined with MISPE, the conventional HPLC-UV analysis sensitivity for CAP in foods could be significantly increased.     

Binding site characteristics of 17beta-estradiol imprinted polymers

The variety of applications utilizing molecularly imprinted polymers (MIPs) requires synthetic strategies yielding different MIP formats including films, irregular particles, or spheres, along with precise knowledge on the specific material characteristics, such as binding capacity and binding efficiency of these materials. In response to this demand, MIPs are prepared in different formats by variation of the polymerization methodology. It is commonly agreed that micro- and sub-microspheres are particularly advantageous MIP formats, due to their monodispersity and facile synthesis procedures in contrast to conventional imprinted polymers prepared by bulk polymerization. However, the differences in actual rebinding characteristics of different MIP formats based on molecular interactions under a variety of binding/rebinding conditions have not been studied in detail to date. Consequently, the present work details an analytical strategy generically applicable to MIP systems for rebinding studies including equilibrium binding, non-equilibrium binding, and release experiments enabling more profound understanding on the molecular interactions between the imprinted materials and the template molecules. In this study, three MIP formats were considered for the same template molecule, 17beta-estradiol: irregularly shaped particulate polymers prepared by bulk polymerization and grinding, microspheres, and sub-microspheres. The latter two formats were synthesized via precipitation polymerization using different processing strategies. The morphologies and porosities of the resulting imprinted materials were characterized by scanning electron microscopy (SEM) and Brunauer-Emmett-Teller (BET) analysis, respectively. The obtained results indicate that microspheres prepared by precipitation polymerization provide superior rebinding properties during equilibrium binding in contrast to bulk polymers and sub-microspheres, and that the rebinding properties are different during equilibrium binding versus non-equilibrium binding. The median binding affinity constant determined during non-equilibrium rebinding is higher than the values obtained from equilibrium rebinding. Furthermore, the binding site distribution appears more homogeneous thief derived from non-equilibrium rebinding, as reflected in a heterogeneity index of m=0.725. Moreover, it is hypothesized that the specific interactions between template and monomers are related to the porosity of the imprinted polymers, which implies that the amount of binding sites and the pore sized distribution of the imprinted materials are a critical factor in achieving the desired MIP performance in various analytical applications. The BET results indicate that particles prepared with lower cross-linker-to-template ratio have a reduced surface area. Furthermore, it can be expected that there are less specific binding sites available at particles with reduced surface area and pore volume given similar distribution of the binding sites, as confirmed by the equilibrium binding isotherm studies. The pore size distribution results reveal that control of the pore size in the range of 100-180 A is essential to obtain the desired retention properties and Gaussian peak shape during HPLC analysis of small molecules.     

Molecularly imprinted microspheres as SPE sorbent for selective extraction of four Sudan dyes in catsup products

A highly selective molecularly imprinted solid-phase extraction (MISPE) coupled with high performance liquid chromatography (HPLC) ultraviolet-visible detection was developed for the simultaneous isolation and determination of four Sudan dyes (I, II, III and IV) in catsup products. The novel molecularly imprinted microspheres (MIM) were synthesized by aqueous suspension polymerization using phenylamine and naphthol as template, which showed high affinity to Sudan dyes in aqueous solution. In order to develop a selective extraction protocol for simultaneous determination the four Sudan dyes from catsup products, the molecular recognition properties of MIM as a SPE sorbent were evaluated. Under the optimized condition, good linearity was obtained from 0.01 to 2.5 μg g(-1) (r(2)≥ 0.9990) with the relative standard deviations of less than 3.4%. This proposed MISPE-HPLC procedure eliminated the effect of template leakage on quantitative analysis and could be applied to direct determination of four Sudan dyes in complicated food samples.     

Molecularly imprinted micro and nanospheres for the selective recognition of 17beta-estradiol

A one-step precipitation polymerization procedure for the synthesis of molecularly imprinted polymers selective for 17beta-estradiol yielding imprinted micro and nanospheres was developed in this study and compared to templated materials obtained by conventional bulk polymerization. The polymer particles prepared by precipitation polymerization exhibited a regular spherical shape at the micro and nanoscale with a high degree of monodispersity. Moreover, the influence of the polymerization temperature, and the ratio of functional monomer to cross-linker on the size of the obtained particles was investigated. The selectivity of the imprinted micro and nanospheres was evaluated by HPLC analysis and via radioligand binding assays. HPLC separation experiments revealed that the imprinted microspheres provide higher or similar affinity to the template in contrast to imprinted polymers prepared by conventional bulk polymerization or synthesized by multi-step swelling/polymerization methods. The dimensions of the imprinted nanospheres facilitate suspension in solution rendering them ideal for binding assay applications. Results from saturation and displacement assays prove that the imprinted nanospheres exhibit superior specific affinity to the target molecule in contrast to control materials. The binding properties of the nanospheres including binding isotherms and affinity distribution were studied via Freundlich isotherm affinity distribution (FIAD) analysis. Moreover, release experiments show that 70% of rebound 17beta-estradiol was released from the imprinted nanospheres within the first 2 h, while more intimately bound 17beta-estradiol molecules (approx. 16%) were released in the following 42 h. Fitting Brunnauer-Emmet-Teller (BET) multi-point adsorption isotherms to the obtained results indicated that the micro and nanospheres are characterized by a comparatively homogenous and narrow distribution of mesopores in contrast to the corresponding bulk polymers.     

Fabrication of a surface imprinted hydrogel shell over silica microspheres using bovine serum albumin as a model protein template

Surface imprinting is an effective approach to improve the template transfer efficiency in applications of molecularly imprinted polymers as biosensors and separation materials. In this paper, we tried to fabricate a surface imprinted hydrogel over silica microspheres for selective recognition of bovine serum albumin by covalent immobilization of a water-soluble UV sensitive initiator onto the surface of silica beads. The polymerization was initiated by UV radiation with N-[3-(dimethylamino)propyl]methacrylamide and N-isopropylacrylamide as the functional monomer and assistant monomer, respectively, and a thin coat of stimuli-responsive hydrogel yielded over the silica gels. The surface imprinted hydrogels exhibited specific affinity toward the template protein with an association constant (K_a) of 2.2 × 10⁵ L mol⁻¹ and a maximum binding capacity (Q_max) of 27.3 mg g⁻¹ in Tris–HCl buffer (pH 7.0). The rebinding and desorption kinetics of the surface imprinted hydrogels were determined and proven to be extremely fast (about 1 min compared to 3 h for the previously prepared bulk imprinted hydrogel). Besides, the hydrogel-silica core-shell particles inherit both the stimuli-responsive property of the hydrogel and the good mechanical strength of the silica beads based on the on-line evaluation with high-performance liquid chromatography. The above comprehensive merits of the obtained surface imprinted hydrogel suggest the presented approach an attractive and broadly applicable way of developing biosensors and high-performance protein separation materials.     

Direct detection of analyte binding to single molecularly imprinted polymer particles by confocal Raman spectroscopy

We describe the use of Raman spectroscopy to detect and quantify, for the first time, the presence of the imprinting template in single molecularly imprinted polymer microspheres. The polymers were imprinted with the β-blocking drugs propranolol and atenolol, and precipitation polymerization was used to obtain spherical particles of diameters of 200 nm and 1.5 μm. The size of the Raman laser spot being between 1 μm and a few μm, the nanoparticles were used for bulk detection whereas with micrometer-sized particles, quantitative measurements on single particles were possible. The laser power, and consequently the acquisition times, needed to be adapted as a function of the polymer and template used in order to avoid burning. Analyte quantification from Raman spectra is straightforward by determining the peak height of a typical Raman band of the analyte, and by using a typical polymer peak for normalization. Relatively low detection limits down to 1 μM have been reached for the detection of S-propranolol through bulk measurements on MIP nanoparticles.     

Monodispersed, molecularly imprinted polymers as affinity-based chromatography media

This review article deals with preparation methods for spherical and monodispersed molecularly imprinted polymers (MIPs) in micrometer sizes. Those methods include suspension polymerization in water, liquid perfluorocarbon and mineral oil, seed polymerization and dispersion/precipitation polymerization. The other methods are the use of beaded materials such as a spherical silica or organic polymer for grafting MIP phases onto the surfaces of porous materials or filling the pores of silica with MIPs followed by dissolution of the silica. Furthermore, applications of MIP microspheres as affinity-based chromatography media, HPLC stationary phases and solid-phase extraction media, will be discussed for pharmaceutical, biomedical and environmental analysis.