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[Tripeptide polymer-based cell-imprinted hydrogels for high-efficiency circulating tumor cell capture]. [高效循环肿瘤细胞捕获的三肽聚合物细胞印迹水凝胶]。
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.05002
Wenjing Sun, Zhiyuan Zhang, Xinmiao Zhao, Jinghua Chen, Guangyan Qing
<p><p>Circulating tumor cells (CTC) have emerged as crucial mediators in the metastatic cascade, offering invaluable insights as real-time liquid biomarkers for cancer progression, prognosis, and treatment response. Their exceptionally low concentration in peripheral blood, which typically ranges from a handful to a few dozen cells per milliliter amidst billions of background blood cells, poses formidable challenges for isolation and molecular characterization. Despite this, the efficient and specific capture of CTC holds tremendous potential for revolutionizing early cancer detection, dynamic monitoring of therapeutic efficacy, and guiding personalized treatment strategies. Currently, the primary technologies for CTC enrichment fall into two categories: immunoaffinity-based methods that employ antibodies targeting epithelial surface markers such as epithelial cell adhesion molecule (EpCAM), and label-free approaches that leverage physical properties including cell size, deformability, and density, exemplified by membrane filtration and centrifugal techniques. However, these conventional methods are hampered by several inherent limitations, including high operational costs, dependence on highly variable surface antigen expression, insufficient capture specificity leading to low purity, and significant interference from heterogeneous blood components such as leukocytes and platelets. Consequently, there is an urgent and growing need to develop novel functional materials and platforms that offer enhanced selectivity, robust stability in physiological conditions, excellent biocompatibility, and improved clinical applicability for the effective isolation and analysis of CTC. In this study, we innovatively integrate cell imprinting technology with a rational amino acid-based affinity strategy to develop a tryptophan-histidine-arginine (WHR) tripeptide-functionalized cell-imprinted hydrogel for highly efficient and selective capture of CTC. The design leverages the unique properties of mesoporous silica nanoparticles (MSN) as carriers, which are first synthesized and then surface-modified with epoxy groups via silane coupling agents. The WHR tripeptide is subsequently grafted onto the MSN surface through a ring-opening reaction, yielding the WHR@SiO₂ composite material. This material demonstrates strong and specific binding affinity toward sialic acid (Neu5Ac) and sialylated glycopeptides (SGP), which are overexpressed on the surface of many cancer cells. Building on this molecular recognition capability, a three-dimensional cell-imprinted hydrogel is fabricated using poly(ethylene glycol) dimethacrylate (PEGDMA) as the cross-linking backbone via free radical polymerization. The hydrogel is molded against SMMC-7721 template cells to create cavities that complement the target cells in size, shape, and surface topology, thereby enhancing capture efficiency through both physical and biochemical matching. Experimental results demonstrate that the WHR-modif
循环肿瘤细胞(CTC)已成为转移级联的关键介质,作为癌症进展、预后和治疗反应的实时液体生物标志物,提供了宝贵的见解。它们在外周血中的浓度极低,在数十亿的背景血细胞中,每毫升通常只有几到几十个细胞,这给分离和分子表征带来了巨大的挑战。尽管如此,CTC的高效和特异性捕获在革命性的早期癌症检测、治疗效果的动态监测和指导个性化治疗策略方面具有巨大的潜力。目前,CTC富集的主要技术分为两类:基于免疫亲和的方法,采用针对上皮细胞粘附分子(EpCAM)等上皮表面标记物的抗体,以及利用细胞大小、可变形性和密度等物理特性的无标记方法,例如膜过滤和离心技术。然而,这些传统方法受到一些固有限制的阻碍,包括高操作成本,依赖高度可变的表面抗原表达,捕获特异性不足导致低纯度,以及来自异质血液成分(如白细胞和血小板)的显著干扰。因此,迫切需要开发新的功能材料和平台,以提高CTC的选择性,在生理条件下具有强大的稳定性,出色的生物相容性,并提高临床适用性,从而有效地分离和分析CTC。在这项研究中,我们创新地将细胞印迹技术与合理的氨基酸亲和策略相结合,开发了一种色氨酸-组氨酸-精氨酸(WHR)三肽功能化的细胞印迹水凝胶,用于高效和选择性地捕获CTC。该设计利用了介孔二氧化硅纳米颗粒(MSN)作为载体的独特性能,首先将其合成,然后通过硅烷偶联剂对其进行环氧基表面改性。WHR三肽随后通过开环反应接枝到MSN表面,得到WHR@SiO 2复合材料。该材料对唾液酸(Neu5Ac)和唾液化糖肽(SGP)具有很强的特异性结合亲和力,这些物质在许多癌细胞表面过表达。基于这种分子识别能力,以聚乙二醇二甲基丙烯酸酯(PEGDMA)为交联骨架,通过自由基聚合制备了三维细胞印迹水凝胶。水凝胶在SMMC-7721模板细胞的基础上成型,形成与靶细胞在大小、形状和表面拓扑结构上互补的空腔,从而通过物理和生化匹配提高捕获效率。实验结果表明,whr修饰的水凝胶对SMMC-7721细胞的捕获效率高达94%,明显优于单独使用色氨酸、组氨酸或精氨酸等氨基酸修饰的水凝胶。该系统还表现出优异的血液相容性,对人血清白蛋白(HSA)的吸附最小,低于5%,表明在生物环境中具有优异的防污性能。体外细胞毒性评估证实了高生物相容性,共培养48小时后细胞存活率超过90%。通过扫描电子显微镜(SEM)和原子力显微镜(AFM)进一步表征,揭示了明确的表面印记,反映了模板细胞的形态,证实了地形线索的成功整合。印迹腔的物理结构与WHR三肽的生化亲和力之间的协同作用被认为是促进高捕获性能的关键因素,即使在低细胞浓度(低至100个细胞/mL)下也是如此。总之,这项工作提供了一个强大而有效的CTC捕获平台,该平台结合了细胞印迹形态学识别和whr介导的唾液化糖蛋白亲和力。该水凝胶具有高选择性、稳定性和生物相容性,为液体活检和早期癌症检测的临床应用提供了一个有前途的工具。该系统的模块化设计还允许通过改变肽序列或模板细胞来适应其他类型的癌症,突出了其在癌症研究和诊断中的广泛潜力。
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引用次数: 0
[Design of ZIF-L-based boronate affinity molecularly imprinted material and its application in the detection of ribavirin in environmental water]. [zif - l基硼酸亲和分子印迹材料的设计及其在环境水中利巴韦林检测中的应用]。
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.04033
Wanting Qi, Yukui Tong
<p><p>Ribavirin (RBV) is a broad-spectrum antiviral drug. It is widely used to treat various viral infections. However, its entry into water bodies can cause serious harm to both the ecological environment and human health. Thus, there is an urgent need for a simple and efficient method to detect RBV for detection purposes. In this study, a two-dimensional ZIF material (ZIF-L) served as the matrix, RBV as the template molecule, and 3-aminophenylboronic acid (APBA) as the functional monomer, using its self-polymerization ability to form a molecularly imprinted layer on the surface of ZIF-L. Imprinted cavities were created using a MeOH-HAc (1∶1, volume ratio) eluent to disrupt the interaction between RBV and APBA, yielding ZIF-L-based boronate affinity molecularly imprinted polymers (ZIF@B-MIPs). Non-imprinted materials (ZIF@B-NIPs) were prepared identically without RBV. ZIF@B-MIPs features dynamic recognition sites formed through pH-responsive boronate ester bonds. This enabled synergistic recognition based on the template molecule's "shape memory" and "chemical bonding". Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FT-IR) were employed to characterize the morphology and functional groups of the material. Notably, new FT-IR peaks emerged for ZIF@B-MIPs at 1 381 cm<sup>-1</sup> (B-O vibration) versus ZIF-L, confirming APBA polymerization. This indicates that the polymerization of APBA onto the surface of ZIF-L was successful. The synthesis and adsorption conditions were optimized. The results showed that, with a ZIF-L dosage of 100 mg, the optimal amount of the self-polymerizing reagent APBA was 100 mg. A self-polymerization time of 5 h was sufficient to form an appropriately thick imprinted layer. At pH 8.5, the stability of the polymer network was maintained while the imprinting effect and mass transfer efficiency were maximized. The post-elution re-adsorption capacity retention rate reached 96.8%, balancing elution efficiency with structural integrity. A RBV mass concentration of 60 mg/L was selected for the experimental requirements. After optimization, the saturation adsorption capacity of ZIF@B-MIPs for RBV reached 21.43 mg/g. The imprinting factor (IF) was 5.32. The material's performance was assessed through adsorption and reusability experiments. The results indicated that the material possesses good specificity and selective recognition ability. It also exhibits a rapid adsorption rate and good reusability. The adsorption experiment results showed that the adsorption kinetics followed the pseudo-second-order model (<i>R</i><sup>2</sup>=0.995 3). Adsorption equilibrium was achieved within 15 min. The adsorption process of RBV by the adsorbent involves chemisorption. The Langmuir isotherm adsorption model (<i>R</i><sup>2</sup>=0.982 5) fitted the experimental data better. This indicates that the adsorption of RBV by ZIF@B-MIPs likely involves monolayer adsorption. In mixed solutions of RBV and three interf
利巴韦林(RBV)是一种广谱抗病毒药物。它被广泛用于治疗各种病毒感染。然而,它进入水体会对生态环境和人体健康造成严重危害。因此,迫切需要一种简单有效的检测方法来检测RBV。本研究以二维ZIF材料(ZIF- l)为基体,RBV为模板分子,3-氨基苯基硼酸(APBA)为功能单体,利用其自聚合能力在ZIF- l表面形成分子印迹层。利用MeOH-HAc(体积比为1∶1)洗脱液破坏RBV与APBA之间的相互作用,形成印迹腔,得到基于zif - l的硼酸盐亲和分子印迹聚合物(ZIF@B-MIPs)。非印迹材料(ZIF@B-NIPs)的制备方法与RBV相同。ZIF@B-MIPs具有通过ph响应硼酸酯键形成的动态识别位点。这使得基于模板分子的“形状记忆”和“化学键”的协同识别成为可能。利用扫描电镜(SEM)和傅里叶变换红外光谱(FT-IR)对材料的形貌和官能团进行了表征。值得注意的是,与ZIF-L相比,ZIF@B-MIPs在1 381 cm-1 (B-O振动)处出现了新的FT-IR峰,证实了APBA聚合。这表明APBA在ZIF-L表面的聚合是成功的。优化了合成条件和吸附条件。结果表明,在ZIF-L用量为100 mg时,自聚合试剂APBA的最佳用量为100 mg。5 h的自聚合时间足以形成适当厚度的印迹层。在pH为8.5时,聚合物网络的稳定性得到了保证,印迹效果和传质效率得到了最大化。洗脱后的再吸附容量保持率达到96.8%,平衡了洗脱效率和结构完整性。选择RBV质量浓度为60 mg/L作为实验要求。优化后ZIF@B-MIPs对RBV的饱和吸附量达到21.43 mg/g。印迹因子(IF)为5.32。通过吸附实验和重复利用实验对材料的性能进行了评价。结果表明,该材料具有良好的特异性和选择性识别能力。吸附速度快,可重复使用性好。吸附实验结果表明,吸附动力学符合拟二阶模型(R2=0.995 3)。15 min内达到吸附平衡。吸附剂对RBV的吸附过程包括化学吸附。Langmuir等温吸附模型(R2= 0.9825)较好地拟合了实验数据。这表明ZIF@B-MIPs对RBV的吸附可能是单分子层吸附。在RBV与三种干扰物质(拉米夫定、尿苷、肌苷)质量浓度分别为1∶1和1∶10的混合溶液中,ZIF@B-MIPs对RBV的吸附量保持较高。干扰物质对吸附性能的影响最小。重复利用实验结果表明,经过6次吸附-解吸循环后,材料的吸附容量仍保持在初始吸附容量的93.6%。用6批吸附剂考察了ZIF@B-MIPs的重现性。对RBV的吸附量为19.41 ~ 20.73 mg/g。这表明该材料也具有良好的再现性。在实际环境水样的检测中,该方法表现出良好的适用性。在30、50、60 mg/L加标水平下,RBV在环境水样中的加标回收率为83.8% ~ 94.5% (RSDR2=0.991 6)。检出限为0.038 mg/L (S/N=3),定量限为0.081 mg/L (S/N=10)。ZIF@B-MIPs-HPLC技术成功应用于饮用水水源中RBV的高效吸附、富集和检测。它在人类健康和环境保护领域具有应用潜力。该技术为环境样品中微量抗病毒药物的快速检测提供了一种新的策略。
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引用次数: 0
[Preparation of superhydrophilic imprinted resin-graphene aerogel composite and its precise recognition of tumor biomarker in urine]. [超亲水性印迹树脂-石墨烯气凝胶复合材料的制备及其对尿液中肿瘤生物标志物的精确识别]。
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.05021
Mingwei Wang, Tao Tian, Ligai Bai, Dandan Han, Hongyuan Yan
<p><p>In recent years, molecularly imprinted polymers have shown considerable promise in analytical detection and early diagnosis of diseases due to their high selectivity and specificity. Nevertheless, the practical implementation of these methods is still restricted by several intrinsic limitations associated with traditional synthesis approaches, including a strong reliance on organic solvents, poor recognition efficiency in aqueous media, and low adsorption capacity. To overcome these challenges, this study presents an innovative strategy that integrates superhydrophilic resin with graphene aerogel (GA), resulting in successful fabrication of a superhydrophilic molecularly imprinted resin-GA composite (HMIR-GA) via surface in situ polymerization in water. The resulting HMIR-GA exhibited a significantly enhanced adsorption capacity and improved recognition performance in aqueous environments towards tumor biomarker. Characterization of the HMIR-GA was performed using Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), nitrogen adsorption-desorption analysis, and contact angle measurements. FT-IR spectra revealed that the broad peak at 3 400 cm<sup>-1</sup> can be ascribed to the formation of -OH associations. The absorption peak at 1 724 cm<sup>-1</sup> corresponds to the stretching vibration peak of C=O on the surface of graphene oxide (GO). The absorption peaks at 1 602 cm<sup>-1</sup> and 1 462 cm<sup>-1</sup> are assigned to the C=C stretching vibration peaks of resorcinol. During the reaction process, due to the reduction effect of ammonia water, the C=O on graphene oxide is reduced. The characteristic peak at 1 069 cm<sup>-1</sup> is induced by the stretching vibration of C-O-C, representing the formation by the reaction between resorcinol and hexamethylenetetramine. These characteristic peaks clearly demonstrate that the HMIR have been successfully incorporated into the graphene aerogel. The FT-IR results confirm the successful synthesis of HMIR-GA. SEM reveals that the surface of graphene oxide exhibits a wrinkled lamellar structure. In contrast, the fabricated HMIR-GA and superhydrophilic molecularly non-imprinted resin-GA composite (HNIR-GA) display a loose and porous architecture, indicating that the synthesized HMIR has been successfully grown onto the graphene aerogel. The porous structure is conducive to the rapid adsorption of 5-hydroxyindoleacetic acid (5-HIAA), which is beneficial for enhancing the performance of relevant applications. The Brunauer-Emmett-Teller (BET) specific surface areas of HMIR-GA and HNIR-GA are 95.1 m²/g and 44.5 m²/g, respectively. The pore volumes are 0.31 cm³/g and 0.20 cm³/g, respectively. In comparison with HNIR-GA, HMIR-GA possesses a larger specific surface area and pore volume, which is conducive to enhancing its adsorption capacity for 5-HIAA. To evaluate the hydrophilicity of HMIR-GA and HNIR-GA, contact angle measurements were performed. The results showed that
近年来,分子印迹聚合物由于其高选择性和特异性,在疾病的分析检测和早期诊断方面显示出相当大的前景。然而,这些方法的实际实施仍然受到与传统合成方法相关的几个固有局限性的限制,包括对有机溶剂的强烈依赖,在水介质中的识别效率差,以及低吸附能力。为了克服这些挑战,本研究提出了一种创新的策略,将超亲水树脂与石墨烯气凝胶(GA)相结合,通过在水中表面原位聚合成功制备了超亲水分子印迹树脂-GA复合材料(HMIR-GA)。由此得到的HMIR-GA在水环境中对肿瘤生物标志物的吸附能力和识别性能显著增强。利用傅里叶变换红外(FT-IR)光谱、扫描电镜(SEM)、氮吸附-解吸分析和接触角测量对HMIR-GA进行表征。FT-IR光谱显示,3 400 cm-1处的宽峰可归因于-OH缔合的形成。1 724 cm-1处的吸收峰对应于氧化石墨烯(GO)表面C=O的拉伸振动峰。在1 602 cm-1和1 462 cm-1处的吸收峰归属于间苯二酚的C=C伸缩振动峰。在反应过程中,由于氨水的还原作用,氧化石墨烯上的C=O被还原。在1 069 cm-1处的特征峰是由C-O-C的拉伸振动引起的,代表间苯二酚与六亚甲基四胺反应生成。这些特征峰清楚地表明,HMIR已成功地加入到石墨烯气凝胶中。FT-IR结果证实HMIR-GA的成功合成。扫描电镜显示,氧化石墨烯表面呈皱褶片状结构。相比之下,制备的HMIR- ga和超亲水分子非印迹树脂- ga复合材料(HNIR-GA)显示出松散的多孔结构,表明合成的HMIR已经成功生长在石墨烯气凝胶上。多孔结构有利于5-羟基吲哚乙酸(5-HIAA)的快速吸附,有利于提高相关应用的性能。HMIR-GA和HNIR-GA的比表面积分别为95.1 m²/g和44.5 m²/g。孔隙体积分别为0.31 cm³/g和0.20 cm³/g。与HNIR-GA相比,HMIR-GA具有更大的比表面积和孔容,有利于提高其对5-HIAA的吸附能力。为了评估HMIR-GA和HNIR-GA的亲水性,进行了接触角测量。结果表明,当水滴放置在这两种材料表面时,它们在0.07 s内迅速扩散并完全湿润表面,表明HMIR-GA和HNIR-GA具有优越的亲水性。这种增强的亲水性有助于从尿液样本中有效吸附和提取肿瘤生物标志物5-HIAA。静态和竞争吸附实验表明,HMIR-GA对5-HIAA具有较强的亲和力。采用拟一阶和拟二阶模型评价吸附动力学,拟二阶模型拟合较好(R²=0.999 3),表明化学吸附是主要吸附机理。此外,平衡吸附数据采用以下模型- langmuir, Freundlich, Temkin和Dubinin-Radushkevich (D-R)进行分析。Freundlich等温线模型拟合最佳(R²≥0.985 2),表明在非均质表面有多层吸附。以HMIR-GA为吸管尖固相萃取吸附剂,结合高效液相色谱法,建立了5-HIAA的高灵敏度精确测定方法。在0.02 ~ 40.0 μg/mL范围内线性良好(r=0.999 8)。基于3和10的信噪比,检测限和定量限分别为3.7 ng/mL和12.3 ng/mL。在加标质量浓度为0.1、1.0和10.0 μg/mL的条件下进行加标回收率试验,回收率在75.7% ~ 92.5%之间,相对标准偏差(rsd)小于3.4%。日间和日间试验的精密度评估的rsd分别为2.9%和4.1% (n=6)。最后,将该方法应用于实际尿样中5-HIAA水平的测定。 这项工作不仅为功能化分子印迹聚合物的制备提供了一种强大而环保的策略,而且在临床应用方面也有很大的前景,为胃肠胰腺神经内分泌肿瘤的早期诊断提供了关键的技术支持。
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引用次数: 0
[Applications of molecularly imprinted solid-phase microextraction coupled with chromatography/mass spectrometry for determination of drug residues]. [分子印迹固相微萃取-色谱/质谱联用技术在药物残留测定中的应用]。
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.06034
Jingyi Yan, Jingying Huang, Siyuan Peng, Mingsan Man, Dani Sun, Ping Liu, Lingxin Chen, Jinhua Li, Huaying Fan
<p><p>Drugs play an indispensable role in the fields of medicine, agriculture, and animal husbandry. However, their long-term and improper use may lead to drug residues in food, the environment and organisms, posing a potentially serious threat to human health and the ecological environment. For instance, antibiotic residues may induce bacterial resistance, pesticide residues may cause neurotoxicity, and hormone drugs may interfere with the endocrine system. Therefore, developing sensitive and accurate detection methods for drug residues has become an important prerequisite and current hot topic in drug research. Meanwhile, the complicated matrices and low contents of the residues make it necessary for the widely used chromatography/mass spectrometry (MS) determination technologies to be coupled with efficient sample pretreatment procedures. Molecularly imprinted solid-phase microextraction (MI-SPME) technology combines the rapidity, high efficiency and solvent-free characteristics of SPME, and the specific recognition and selective adsorption capabilities of molecularly imprinted polymers (MIPs), and shows significant advantages in the highly selective separation and enrichment of drug residues in complex samples. In recent years, the MI-SPME technology has become a research hotspot in the field of drug residue detection.This work systematically reviews the research progress since 2019 on the application of MI-SPME coupled with chromatography/MS in drug residue detection across food safety, environmental monitoring and biomedical fields. First, this work introduces in detail on the working principle and operation process of SPME technology. SPME achieves efficient enrichment of target analytes through the selective adsorption of the stationary phase-coated fibers, offering simplicity, speed, minimal solvent use, and compatibility with analytical instruments such as chromatography/MS.Next, the review focuses on elaborating the preparation methods and new technologies and strategies of MIPs. The traditional methods for preparing MIPs mainly include free radical polymerization, in-situ polymerization and sol-gel methods. However, traditional MIPs have defects such as template leakage risk, limited binding ability, and irregular material morphology, which restrict the application range. To this end, researchers have developed a series of novel preparation technologies and strategies, such as surface imprinting, nanoimprinting, dummy template imprinting, multi-template imprinting, multifunctional monomer imprinting and stimulus-response imprinting. These technologies and strategies have significantly enhanced the recognition and enrichment ability of MIPs for trace drug residues in complex samples by optimizing their structures and performances.To meet the requirements of different sample types and analytical instruments, MI-SPME media need to be designed into specific technical configurations through chemical or physical methods. This review summari
展望未来,随着绿色化学原理和即时检测技术的发展,MI-SPME有望在药物残留检测中发挥更大的作用。它将为食品安全、环境监测和生物医学研究提供更高效、更精确的技术支持。
{"title":"[Applications of molecularly imprinted solid-phase microextraction coupled with chromatography/mass spectrometry for determination of drug residues].","authors":"Jingyi Yan, Jingying Huang, Siyuan Peng, Mingsan Man, Dani Sun, Ping Liu, Lingxin Chen, Jinhua Li, Huaying Fan","doi":"10.3724/SP.J.1123.2025.06034","DOIUrl":"10.3724/SP.J.1123.2025.06034","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Drugs play an indispensable role in the fields of medicine, agriculture, and animal husbandry. However, their long-term and improper use may lead to drug residues in food, the environment and organisms, posing a potentially serious threat to human health and the ecological environment. For instance, antibiotic residues may induce bacterial resistance, pesticide residues may cause neurotoxicity, and hormone drugs may interfere with the endocrine system. Therefore, developing sensitive and accurate detection methods for drug residues has become an important prerequisite and current hot topic in drug research. Meanwhile, the complicated matrices and low contents of the residues make it necessary for the widely used chromatography/mass spectrometry (MS) determination technologies to be coupled with efficient sample pretreatment procedures. Molecularly imprinted solid-phase microextraction (MI-SPME) technology combines the rapidity, high efficiency and solvent-free characteristics of SPME, and the specific recognition and selective adsorption capabilities of molecularly imprinted polymers (MIPs), and shows significant advantages in the highly selective separation and enrichment of drug residues in complex samples. In recent years, the MI-SPME technology has become a research hotspot in the field of drug residue detection.This work systematically reviews the research progress since 2019 on the application of MI-SPME coupled with chromatography/MS in drug residue detection across food safety, environmental monitoring and biomedical fields. First, this work introduces in detail on the working principle and operation process of SPME technology. SPME achieves efficient enrichment of target analytes through the selective adsorption of the stationary phase-coated fibers, offering simplicity, speed, minimal solvent use, and compatibility with analytical instruments such as chromatography/MS.Next, the review focuses on elaborating the preparation methods and new technologies and strategies of MIPs. The traditional methods for preparing MIPs mainly include free radical polymerization, in-situ polymerization and sol-gel methods. However, traditional MIPs have defects such as template leakage risk, limited binding ability, and irregular material morphology, which restrict the application range. To this end, researchers have developed a series of novel preparation technologies and strategies, such as surface imprinting, nanoimprinting, dummy template imprinting, multi-template imprinting, multifunctional monomer imprinting and stimulus-response imprinting. These technologies and strategies have significantly enhanced the recognition and enrichment ability of MIPs for trace drug residues in complex samples by optimizing their structures and performances.To meet the requirements of different sample types and analytical instruments, MI-SPME media need to be designed into specific technical configurations through chemical or physical methods. This review summari","PeriodicalId":101336,"journal":{"name":"Se pu = Chinese journal of chromatography","volume":"44 2","pages":"151-168"},"PeriodicalIF":0.0,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12878571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Application of molecularly imprinted polymers-based sensors for determination of acute coronary syndrome biomarkers]. [分子印迹聚合物传感器在急性冠脉综合征生物标志物测定中的应用]。
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.08003
Yufan Zhang, Jingwen Xia, Jiayuan Zhu, Maosheng Zeng, Jingyi Bai, Qin Xu, Hang Gao
<p><p>Cardiovascular diseases (CVDs) are among the leading cause of global morbidity and mortality. Due to their high prevalence and often asymptomatic progression, there is a pressing need for diagnostic tools that enable the early, accurate, and accessible detection of them. Acute coronary syndrome (ACS), as a common and severe CVDs with high morbidity and mortality rates, has attracted considerable scientific interest. Various methods have been developed to detect ACS rapidly and accurately. Traditional diagnostic methods relying on antibody-based assays are effective. However, they face significant limitations, including high production costs, poor stability under varying environmental conditions, batch-to-batch variability, and cross-reactivity leading to false positives. These challenges have motivated the search for robust, cost-effective alternatives capable of detecting biomarkers with high sensitivity and specificity. Molecularly imprinted polymers (MIPs) have emerged as a promising alternative solution, offering antibody-like molecular recognition capabilities, superior stability, lower production costs, and resistance to harsh environmental conditions. This review systematically examines the latest advancements in MIP-based sensors for ACS biomarker detection in the last fifteen years, including imprinting strategies for key ACS biomarkers, sensor development and integration, and current challenges along with future perspectives. The first section focuses on the molecular imprinting techniques for essential ACS biomarkers, such as cardiac troponin (cTnI/cTnT), myoglobin (Myo), and creatine kinase (CK). It compares whole-protein imprinting with epitope imprinting, highlighting the advantages of the latter in reducing template costs and enhancing binding specificity. Epitope imprinting using short peptide sequences has demonstrated femtomolar detection limits while overcoming challenges associated with large protein templates, such as structural denaturation and difficult template removal. The review also explores innovative approaches like dummy template imprinting, where structurally similar but cheaper molecules are used to create MIPs for high-cost biomarkers, achieving comparable specificity and sensitivity. The second section discusses the integration of MIPs with advanced biosensing platforms. Electrochemical sensors, using MIP-modified electrodes, have achieved remarkable sensitivity and rapid response times, making them suitable for point-of-care testing (POCT). Optical sensors, particularly those based on surface-enhanced Raman spectroscopy and surface plasmon resonance, enable label-free, real-time detection with ultra-low detection limits. The review also addresses the integration of MIPs with microfluidic technology, where miniaturized devices facilitate automated, high-throughput biomarker analysis. Examples include paper-based microfluidic sensors that combine capillary action with MIP-SERs tags for multiplexed detection,
心血管疾病是全球发病率和死亡率的主要原因之一。由于它们的高患病率和通常无症状的进展,迫切需要能够早期、准确和容易发现它们的诊断工具。急性冠脉综合征(Acute coronary syndrome, ACS)作为一种发病率和死亡率高的常见重症心血管疾病,引起了科学界的广泛关注。为了快速准确地检测ACS,人们开发了各种方法。传统的基于抗体检测的诊断方法是有效的。然而,它们面临着显著的局限性,包括生产成本高、在不同环境条件下稳定性差、批次间的可变性以及导致误报的交叉反应性。这些挑战促使人们寻找强大的、具有成本效益的替代品,能够检测高灵敏度和特异性的生物标志物。分子印迹聚合物(MIPs)已经成为一种很有前途的替代解决方案,它具有类似抗体的分子识别能力,优越的稳定性,更低的生产成本,以及对恶劣环境条件的抵抗力。本文系统地回顾了近15年来基于mip的ACS生物标志物检测传感器的最新进展,包括关键ACS生物标志物的印迹策略、传感器的开发和集成、当前的挑战以及未来的展望。第一部分重点介绍了ACS基本生物标志物的分子印迹技术,如心肌肌钙蛋白(cTnI/cTnT)、肌红蛋白(Myo)和肌酸激酶(CK)。它比较了全蛋白印迹和表位印迹,突出了后者在降低模板成本和提高结合特异性方面的优势。使用短肽序列的表位印迹已经证明了飞摩尔检测限制,同时克服了与大蛋白质模板相关的挑战,如结构变性和难以去除模板。该综述还探讨了虚拟模板印迹等创新方法,其中使用结构相似但更便宜的分子为高成本生物标志物创建MIPs,获得类似的特异性和灵敏度。第二部分讨论了MIPs与先进生物传感平台的集成。使用mip修饰电极的电化学传感器具有显著的灵敏度和快速的响应时间,使其适用于即时检测(POCT)。光学传感器,特别是基于表面增强拉曼光谱和表面等离子体共振的光学传感器,可以实现无标签、实时的超低检测限检测。该综述还讨论了MIPs与微流控技术的集成,其中小型化的设备促进了自动化,高通量的生物标志物分析。示例包括基于纸张的微流体传感器,将毛细管作用与MIP-SERs标签相结合,用于多路检测,无需复杂的仪器即可实现低检测限。尽管取得了这些进展,但该综述指出了阻碍MIP基于ACS传感器广泛应用于临床的关键挑战。尽管MIPs的敏感性和特异性令人印象深刻,但在某些应用中,特别是在低丰度生物标志物方面,它们仍然落后于单克隆抗体。可重复性问题源于聚合条件和模板去除效率的变化。商业化障碍包括缺乏基于mip的诊断的标准化生产协议和监管框架。审查报告提出了几个战略方向来解决这些限制。计算建模和机器学习可以优化单体选择和聚合条件,以提高MIP的性能。结合MIPs和纳米材料的混合系统的发展可以进一步提高灵敏度和信号转导。化学家、工程师和临床医生之间的多学科合作对于将实验室创新转化为商业上可行的诊断工具至关重要。此外,MIPs与人工智能机器学习算法的集成可以支持个性化诊断和治疗策略的发展。这些未来的观点可能对心血管疾病的早期诊断和治疗产生重大影响。总之,基于mip的传感器代表了ACS诊断的一个有前途的方向,提供了独特的可负担性、稳定性和精度的组合。通过解决当前的技术和转化挑战,MIP技术有可能彻底改变疾病的早期检测,特别是在资源有限的地区。这篇综述不仅总结了十年来的研究进展,而且为未来的发展提供了一个计划,使个性化、分散的心血管诊断成为广泛的现实。
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引用次数: 0
[Molecularly imprinted polymers: novel green preparation methods and cutting-edge applications review]. 分子印迹聚合物:新型绿色制备方法与前沿应用综述
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.06010
Fei Li, Baolin Jia, Qiao Hu, Xiwen He, Langxing Chen, Yukui Zhang
<p><p>Molecular imprinting technology is an emerging technique that achieves specific recognition of imprinted molecules by simulating the interactions between antibody and antigen or between enzyme and substrate. The core of this technology lies in the preparation of molecularly imprinted polymers (MIPs). However, traditional preparation methods of MIPs face severe challenges due to drawbacks such as uneven morphology, limited conformational choices for molecular recognition, random and uncontrollable polymerization, and environmental safety hazards, making the innovation of synthesis methods urgent. In recent years, with the proposal of green chemistry concepts and the development of green synthesis methods, the preparation technology of MIPs has gradually transitioned towards resource-saving and environment-friendly directions. The preparation of green molecularly imprinted polymers (GMIPs) aims to replace traditional methods by reducing the use of solvents and the generation of waste liquids during the synthesis process, employing safe and non-toxic reagents and solvents, and developing efficient synthesis methods to improve energy efficiency. Green solvents such as water, supercritical carbon dioxide, deep eutectic solvents, and ionic liquids are used to replace organic solvents in the synthesis of traditional MIPs. Functional monomers with biocompatibility and environmental friendliness, including chitosan, cellulose, itaconic acid, dopamine, and cyclodextrin, have found increasing applications in the preparation of MIPs. In addition, the preparation technology of MIPs is gradually transitioning towards resource conservation and environmental friendliness. The development of novel synthesis methods such as green precipitation polymerization, microwave-assisted synthesis, supercritical fluid technology, ultrasound-assisted polymerization, and computer simulation-assisted design and characterization has promoted the popularity of GMIPs preparation methods. These novel preparation methods significantly improve the functionality and environmental compatibility of MIPs by precisely regulating reaction conditions, reducing energy consumption, and minimizing harmful by-products. They not only optimize the synthesis efficiency of MIPs, but also provide new ideas for solving the bottlenecks of traditional methods in morphology control and large-scale production. GMIPs, with their high selectivity, stability, and tunability, have shown breakthrough applications in multiple frontier fields. For example, in environmental monitoring, GMIPs are applied to detect heavy metal ions (such as lead and arsenic), organic pollutants (such as pesticides and antibiotics), and explosives in aqueous environments. In the field of food safety analysis, GMIPs enable efficient enrichment and detection of trace pollutants (such as pesticide residues, veterinary drugs, and mycotoxins) in food matrices, significantly outperforming traditional methods. In biomedical applica
分子印迹技术是一种通过模拟抗体与抗原或酶与底物之间的相互作用来实现对印迹分子特异性识别的新兴技术。该技术的核心在于分子印迹聚合物(MIPs)的制备。然而,传统的mip制备方法由于存在形态不均匀、分子识别构象选择有限、聚合随机不可控、环境安全隐患等缺点,面临严峻挑战,迫切需要创新合成方法。近年来,随着绿色化学概念的提出和绿色合成方法的发展,MIPs的制备技术逐渐向资源节约型和环境友好型方向转变。绿色分子印迹聚合物(GMIPs)的制备旨在通过减少合成过程中溶剂的使用和废液的产生,采用安全无毒的试剂和溶剂,开发高效的合成方法来提高能源效率,从而取代传统的合成方法。采用水、超临界二氧化碳、深共晶溶剂、离子液体等绿色溶剂代替有机溶剂合成传统的mip。壳聚糖、纤维素、衣康酸、多巴胺和环糊精等具有生物相容性和环境友好性的功能单体在mip的制备中得到了越来越多的应用。此外,MIPs的制备技术正逐步向资源节约型和环境友好型方向转变。绿色沉淀聚合、微波辅助合成、超临界流体技术、超声辅助聚合、计算机模拟辅助设计和表征等新型合成方法的发展促进了GMIPs制备方法的普及。这些新的制备方法通过精确调节反应条件、降低能耗和减少有害副产物,显著提高了MIPs的功能和环境相容性。它们不仅优化了MIPs的合成效率,而且为解决传统方法在形态控制和大规模生产方面的瓶颈提供了新的思路。GMIPs以其高选择性、稳定性和可调性在多个前沿领域取得了突破性的应用。例如,在环境监测中,gmip被用于检测水中环境中的重金属离子(如铅和砷)、有机污染物(如杀虫剂和抗生素)和爆炸物。在食品安全分析领域,gmip能够高效富集和检测食品基质中的微量污染物(如农药残留、兽药和真菌毒素),显著优于传统方法。在生物医学应用中,gmip被开发为药物控释系统、生物标志物检测平台和靶向治疗载体。此外,GMIPs在样品前处理(如固相萃取)中的高效性能进一步降低了分析成本并减少了对有机溶剂的依赖。本文综述了近年来GMIPs的新型制备方法及其在环境监测、食品安全、生物医学等方面的应用,并对GMIPs的发展进行了展望。
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引用次数: 0
[Design and synthesis of molecularly imprinted polymers and their applications in medical diagnosis and biocatalysis]. [分子印迹聚合物的设计与合成及其在医学诊断和生物催化中的应用]。
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.06013
Qingmei Song, Xinhao Li, Yongqin Lyu
<p><p>Molecularly imprinted technology (MIT) represents an advanced synthetic strategy that emulates biological recognition mechanisms, such as antigen-antibody or enzyme-substrate interactions, by creating three-dimensional cavity-like structures through the directional assembly of functional monomers around a template molecule. This process generates spatial and functional complementarity, enabling highly selective recognition of target species. Molecularly imprinted polymers (MIPs), often described as "synthetic antibodies", overcome the intrinsic limitations of natural biomolecules by offering superior selectivity, robustness, cost-effectiveness, and structural tunability. These features position MIPs as promising alternatives to natural antibodies in targeted sensing and drug delivery, with broad applications across biomedical, environmental, and pharmaceutical domains, including pollutant detection, and food safety monitoring. Despite substantial progress, key challenges remain, such as uneven imprinting layers, template residue, and limited aqueous compatibility in macromolecular imprinting. Furthermore, issues of industrial scalability, unclear recognition mechanisms, and insufficient integration with emerging fields such as microfluidics and artificial intelligence have hindered large-scale translation. In recent years, our research team has systematically advanced MIT through a tri-dimensional strategy encompassing high-throughput monomer screening, mechanistic elucidation of molecular recognition, and directional assembly of functional units. By establishing a standardized monomer library and integrating molecular dynamics simulations, we achieved precise material design under complex conditions. Through process optimization and material innovation, we developed a highly efficient solid-phase surface imprinting method that enables the fabrication of smart MIPs with stimuli-responsive properties (e.g., temperature and pH). These MIPs exhibit markedly enhanced binding affinity, with equilibrium dissociation constant (<i>K</i><sub>D</sub>) reaching 10<sup>-12</sup> mol/L, over four orders of magnitude higher than those of non-imprinted polymers (NIPs). Building on these advances, we established cross-disciplinary application platforms, including affinity-based protein separation and purification systems capable of efficient dual-enzyme cascade immobilization and inactivated enzyme renaturation. In the biomedical domain, we developed ultrasensitive biosensing methods achieving picogram-level detection of heart failure biomarkers and single-digit (≈5 cells/mL) detection of cancer cells in whole blood, extending these methods toward integrated tumor theranostics and microbial community regulation. This paper comprehensively summarizes our team's recent innovations in the rational design, functionalized fabrication, and cross-disciplinary applications of MIPs, spanning biosensing, biocatalysis, and biomedical diagnostics/therapeutics, while c
分子印迹技术(MIT)代表了一种先进的合成策略,它模拟了生物识别机制,如抗原抗体或酶-底物相互作用,通过在模板分子周围定向组装功能单体来创建三维腔状结构。这一过程产生了空间和功能上的互补性,使目标物种的高度选择性识别成为可能。分子印迹聚合物(MIPs),通常被描述为“合成抗体”,通过提供优越的选择性、稳健性、成本效益和结构可调性,克服了天然生物分子的内在局限性。这些特点使MIPs成为靶向传感和药物递送领域天然抗体的有希望的替代品,在生物医学,环境和制药领域具有广泛的应用,包括污染物检测和食品安全监测。尽管取得了实质性的进展,但关键的挑战仍然存在,如印迹层不均匀、模板残留和大分子印迹的水相容性有限。此外,工业可扩展性、不明确的识别机制以及与微流体和人工智能等新兴领域的整合不足等问题阻碍了大规模翻译。近年来,我们的研究团队通过高通量单体筛选、分子识别的机制阐明和功能单元的定向组装等三维策略,系统地推进了MIT的发展。通过建立标准化单体库,结合分子动力学模拟,实现了复杂条件下的精准材料设计。通过工艺优化和材料创新,我们开发了一种高效的固相表面印迹方法,可以制造具有刺激响应特性(例如温度和pH值)的智能MIPs。这些印迹聚合物表现出明显增强的结合亲和力,其平衡解离常数(KD)达到10-12 mol/L,比非印迹聚合物(NIPs)高出4个数量级以上。基于这些进展,我们建立了跨学科的应用平台,包括基于亲和的蛋白质分离和纯化系统,能够高效的双酶级联固定和失活酶复性。在生物医学领域,我们开发了超灵敏的生物传感方法,实现了皮图水平的心力衰竭生物标志物检测和全血中癌细胞的个位数(≈5个细胞/mL)检测,将这些方法扩展到综合肿瘤治疗和微生物群落调节。本文全面总结了我们团队在mip的合理设计,功能化制造和跨学科应用方面的最新创新,涵盖生物传感,生物催化和生物医学诊断/治疗,同时将这些创新与生物医学和催化的最新全球进展联系起来。展望未来,我们确定了下一代麻省理工学院的三个战略研究前沿。(i)智能响应材料系统:设计具有多刺激响应能力的mip(例如,磁、光热和pH信号),以实现可编程的药物释放、实时信号监测和动态反馈调节。(ii)动态识别的定量建模:建立多尺度理论框架,阐明空腔柔韧性与目标构象动力学之间的耦合关系,指导自适应MIPs的结构优化和功能导向设计。(三)集成智能治疗平台:将微流体和仿生识别模块集成到闭环系统中,能够进行生物标志物检测、靶向递送和实时治疗反馈,弥合了体外传感和体内精确干预之间的差距。沿着这些轨迹的协同发展将使麻省理工学院超越其作为“静态识别材料”的角色,并发展成为一个智能、自适应和系统的生物医学平台。这种进化将加速麻省理工学院的创新从实验室到临床和工业的转化,推动个性化医疗、即时诊断和合成生物学的进步,并产生深远的科学和社会影响。
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引用次数: 0
[Research progress on the application of molecularly imprinted nanozymes in the field of biosensing]. [分子印迹纳米酶在生物传感领域的应用研究进展]。
Pub Date : 2026-02-08 DOI: 10.3724/SP.J.1123.2025.06023
Xuan Zhang, Shucheng Liu, Jianming Pan
<p><p>Enzymes, as biological catalysts, have garnered significant interest due to their exceptional efficiency and specificity. However, the fragility of natural enzymes under varying temperature and pH conditions significantly restricts their broader utilization. In the past few years, noteworthy advancements have been achieved in creating biomimetic enzyme systems. Scientists have effectively designed artificial enzyme-mimicking systems that exhibit outstanding performance through the integration of various components, including small molecule compounds, deoxyribonucleic acid, and nanomaterials. These systems not only exhibit remarkable catalytic efficiency but also offer considerable benefits, such as adjustable activity, simplicity in modification, and enhanced stability and reusability. Nanomachines, as a new type of enzyme analogues, specifically refer to nanomaterials with enzyme-like catalytic functions. They have played a significant role in the development of biomimetic enzyme systems. Since the first report in 2007 that iron oxide nanoparticles have peroxidase (POD) mimicking activity, hundreds of nanomaterials have been confirmed to have catalytic activities similar to those of natural enzymes such as POD and oxidase (OXD). These novel enzyme analogues not only exhibit a wide range of enzyme-like activities and structural similarity to natural enzymes, but also possess unique nanomaterial characteristics, making their catalytic activities controllable and stable. As effective substitutes for natural enzymes, nanomachines have been widely applied in fields such as biosensing, medical treatment, and environmental remediation. While every cutting-edge technology presents certain limitations, nanozymes are not an exception. They encounter notable challenges, especially concerning substrate selectivity, which is essential for effective targeted catalysis and widespread applicability. To address the aforementioned imitation, researchers have been investigating effective approaches to improve the catalytic selectivity of nanozymes. Primarily, two methods are utilized to achieve selective bioanalysis based on nanozyme catalysis: the first method involves merging nanozymes with biological recognition factors (such as natural enzymes, antibodies, DNA strands, and aptamers), while the second focuses on developing nanozymes that possess intrinsic catalytic specificity through techniques like structure-mimetic design, surface modifications, or molecular imprinting. Incorporating external biological recognition elements can undermine both the stability and cost-effectiveness of nanozymes. Additionally, the methods available for the effective conjugation of nanozymes with biological components are still in their infancy. The creation of structure-mimetic nanozymes tends to be intricate and requires meticulous regulation. In contrast, a straightforward and accessible method for generating substrate recognition sites on nanozymes is the application of
酶作为生物催化剂,由于其特殊的效率和特异性而引起了人们极大的兴趣。然而,天然酶在不同温度和pH条件下的脆弱性极大地限制了它们的广泛利用。在过去的几年里,在创造仿生酶系统方面取得了显著的进展。科学家们已经有效地设计了人工酶模拟系统,通过整合各种成分,包括小分子化合物、脱氧核糖核酸和纳米材料,这些系统表现出出色的性能。这些系统不仅表现出卓越的催化效率,而且具有相当大的优势,如活性可调、修饰简单、稳定性和可重用性增强。纳米机器是一种新型的酶类似物,特指具有酶样催化功能的纳米材料。它们在仿生酶系统的发展中发挥了重要作用。自2007年首次报道氧化铁纳米颗粒具有模拟过氧化物酶(POD)活性以来,已有数百种纳米材料被证实具有类似于POD和氧化酶(OXD)等天然酶的催化活性。这些新型酶类似物不仅具有广泛的类酶活性和与天然酶的结构相似性,而且具有独特的纳米材料特性,使其催化活性可控且稳定。纳米机器作为天然酶的有效替代品,在生物传感、医疗、环境修复等领域得到了广泛的应用。虽然每一项尖端技术都有一定的局限性,纳米酶也不例外。它们面临着显著的挑战,特别是在底物选择性方面,这对于有效的靶向催化和广泛的适用性至关重要。为了解决上述模仿问题,研究人员一直在研究提高纳米酶催化选择性的有效方法。主要有两种方法用于实现基于纳米酶催化的选择性生物分析:第一种方法涉及将纳米酶与生物识别因子(如天然酶、抗体、DNA链和适体)合并,而第二种方法侧重于通过结构模拟设计、表面修饰或分子印迹等技术开发具有内在催化特异性的纳米酶。加入外部生物识别元素会破坏纳米酶的稳定性和成本效益。此外,纳米酶与生物组分有效结合的方法仍处于起步阶段。模拟结构的纳米酶的产生往往是复杂的,需要细致的管理。相比之下,在纳米酶上产生底物识别位点的一种简单易行的方法是应用分子印迹技术(MIT)。MIT复制酶底物或抗体-抗原对之间的相互作用,以制造精确形状和大小适合特定模板分子的空腔,从而促进准确的分子识别。由于其特殊的特异性、稳定性和可重复性,MIT被广泛应用于生物传感、医学诊断、药物评估、样品制备和荧光检测等各个领域。此外,分子印迹聚合物(MIPs)的固有优势,如其经济性,卓越的选择性,显著的热化学弹性,以及不需要生物衍生技术,使分子印迹成为模仿天然酶作用的可行策略。天然酶表现出底物特异性主要是由于其活性位点的三维结构。这些活性位点经过精心塑造,以确保与预期基板的空间配置完美匹配。根据这一概念,分子印迹纳米酶巧妙地将分子印迹技术与纳米酶的特性结合起来,使仿生催化剂在保持催化选择性的同时也表现出显著的底物特异性。本文首先概述了纳米酶的基本特性,然后阐述了分子印迹纳米酶的常规制备工艺,并深入探讨了分子印迹对纳米酶催化性能的影响。通过对典型案例的分析,介绍了分子印迹纳米酶生物传感领域的最新研究进展。最后,讨论了该领域面临的挑战和未来的发展方向,旨在为分子印迹和纳米酶在生物传感领域的应用提供理论参考和实践指导。
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引用次数: 0
[Research progress of molecular imprinting technology in the field of disease diagnosis and therapy]. 【分子印迹技术在疾病诊断与治疗领域的研究进展】。
Pub Date : 2026-01-01 DOI: 10.3724/SP.J.1123.2025.06036
Ran Zhu, Gan-Ping Cai, Hai-Jiao Zheng, Qiong Jia
<p><p>Disease biomarkers play important roles in modern medicine, enabling early disease diagnosis, precise subtyping, prognostic evaluation, and targeted therapy. Conventional biorecognition elements, such as antibodies and aptamers, offer high specificity but suffer from inherent limitations, including high production costs, instability in complex biological matrices, and significant batch-to-batch variation. Collectively, these constraints restrict their scalability and versatility for high-throughput, cost-effective, and multi-scenario clinical applications. Molecularly imprinted polymers (MIPs), prepared via molecular imprinting technology (MIT), have emerged as highly robust and promising synthetic receptors. During their formation, functional monomers assemble around a target molecule, and highly specific binding sites are formed after polymerization and template removal. MIPs exhibit a unique combination of advantages, ranging from cost-effectiveness to high selectivity, as well as high affinity comparable to natural counterparts, and outstanding physicochemical stability under harsh conditions. Driven by their highly flexible and customizable design capabilities, MIP development has witnessed remarkable advancements in recent years. These polymers are suitable for analyzing different types of disease biomarkers, ranging from proteins, peptides, and saccharides to complex biological entities such as whole cells and extracellular vesicles. Moreover, MIPs can be functionally engineered to integrate signal transduction or stimuli-responsive features, facilitating the creation of intelligent biomedical platforms. This review systematically summarizes the progress in applying MIT for disease diagnostics and therapeutics. It first elaborates on diverse imprinting techniques specifically tailored for different biomarker classes, including proteins, peptides, saccharides, cells, and extracellular vesicles. Subsequently, the article provides a comprehensive overview of their applications in diagnostics, encompassing biosensing, bioimaging, and bioseparation, as well as therapeutic applications, including drug delivery, photothermal and photodynamic therapy, biotoxin removal, and cell behavior regulation. Additionally, critical challenges hindering clinical translation are discussed, such as biocompatibility, long-term toxicity, high large-scale manufacturing costs, and the lack of standardized clinical validation protocols. Finally, promising future directions are outlined, emphasizing the development of biodegradable materials, integration with artificial intelligence, and adoption of green synthesis strategies. These synergistic approaches are expected to stimulate innovation, enabling the safe, reliable, and scalable translation of MIPs into real-world biomedical and clinical applications. In summary, MIPs represent a versatile, robust, and economically viable alternative to conventional biorecognition elements. Their customizable nature, combi
疾病生物标志物在现代医学中发挥着重要作用,可以实现疾病的早期诊断、精确分型、预后评估和靶向治疗。传统的生物识别元件,如抗体和适体,具有高特异性,但存在固有的局限性,包括高生产成本,复杂生物基质的不稳定性,以及批次间的显著差异。总的来说,这些限制限制了它们在高通量、低成本和多场景临床应用中的可扩展性和多功能性。分子印迹聚合物(MIPs)是通过分子印迹技术(MIT)制备的一种具有高度鲁棒性和前景的合成受体。在它们的形成过程中,功能单体聚集在目标分子周围,聚合和模板去除后形成高度特异性的结合位点。MIPs表现出独特的优势组合,从成本效益到高选择性,以及与天然相媲美的高亲和力,以及在恶劣条件下出色的物理化学稳定性。由于其高度灵活和可定制的设计能力,MIP的发展近年来取得了显着的进步。这些聚合物适用于分析不同类型的疾病生物标志物,范围从蛋白质、多肽和糖类到复杂的生物实体,如全细胞和细胞外囊泡。此外,mip可以在功能上进行设计,以整合信号转导或刺激响应特性,促进智能生物医学平台的创建。本文系统地综述了MIT在疾病诊断和治疗中的应用进展。它首先详细阐述了不同的印迹技术,专门针对不同的生物标志物类别,包括蛋白质,肽,糖类,细胞和细胞外囊泡。随后,文章全面概述了它们在诊断中的应用,包括生物传感、生物成像和生物分离,以及治疗应用,包括药物输送、光热和光动力治疗、生物毒素去除和细胞行为调节。此外,还讨论了阻碍临床转化的关键挑战,如生物相容性、长期毒性、大规模生产成本高以及缺乏标准化的临床验证方案。最后,展望了未来的发展方向,强调生物可降解材料的发展,与人工智能的融合,以及采用绿色合成策略。这些协同方法有望刺激创新,实现安全、可靠和可扩展的MIPs转化为现实世界的生物医学和临床应用。综上所述,MIPs是传统生物识别元件的一种多功能、稳健且经济可行的替代方案。它们的可定制性,加上功能工程能力,使MIPs成为疾病诊断和治疗领域的一项有前途的技术。未来专注于临床翻译、可持续性和智能平台集成的努力可能会加速它们在不同生物医学领域的采用。
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引用次数: 0
[Progress in electric field assisted molecular imprinting technology]. [电场辅助分子印迹技术进展]。
Pub Date : 2026-01-01 DOI: 10.3724/SP.J.1123.2025.05006
Jiang-Yi Wu, Xiao-Jia Huang
<p><p>Molecular imprinting technology (MIT) simulates the specific recognition mechanism between antibodies and antigens, and can construct separation media with specific recognition performance, demonstrating unique advantages in the fields of separation, purification, and trace detection in complex sample matrices. Molecularly imprinted polymers (MIPs), the core of MIT, form three-dimensional imprinting cavities matching the spatial structure and chemical properties of the target substance via three key steps: template self-assembly with functional monomer, cross-linking polymerization, and template elution. The prepared MIPs present highly selective extraction and recognition of the target substance. However, traditional MIT faces critical challenges in material preparation and application. During MIPs synthesis, due to the randomness of polymerization reactions, the resulting MIPs often have uneven distribution of imprinting sites and lack molecular orientation. This not only reduces the mechanical performance of MIPs, but also affects their specific recognition performance. In addition, incomplete removal of template molecules severely reduces the number of effective imprinting sites and may interfere with the accuracy of subsequent detection results. In the pre-treatment application of MIPs adsorbents, the mass transfer rate of the target substance in the sample solution is slow, which prolongs the adsorption equilibrium time of MIPs on it. In the sensor detection based on MIPs, there are inherent issues such as fluorescence quenching and insufficient signal amplification, which further limit the detection sensitivity. These challenges significantly limit the application of MIT in fields like environmental monitoring, biomedical diagnostics, and food safety analysis. In recent years, the cross fusion of electric field assisted technology and MIT has provided innovative strategies to solve the above-mentioned problems. During MIPs preparation, an external electric field can be applied to provide electrophoretic driving force to assist in regulating the directional self-assembly of functional monomers and template molecules. This can promote the ordered arrangement of imprinting sites at the micro level of MIPs prepared, achieving material uniformity of MIPs. For template molecule elution, applying an electric field can provide electrostatic repulsion between MIPs and template molecules. This can effectively weaken the inter-molecular forces between MIPs and template molecules, facilitate the diffusion of template molecules into the desorption solution, reduce the residual template molecules, and avoid the detection of "false positives". During the sample pretreatment process, electrophoretic force significantly enhances the mass transfer rate of the target substance, prompting it to aggregate around the MIPs adsorbent and achieve the purpose of pre-concentration. This can not only shorten the adsorption equilibrium time of MIPs for target su
分子印迹技术(Molecular imprinting technology, MIT)模拟了抗体与抗原之间的特异性识别机制,可以构建具有特异性识别性能的分离介质,在复杂样品基质的分离、纯化、痕量检测等领域显示出独特的优势。分子印迹聚合物(MIPs)是MIT的核心,通过三个关键步骤:模板自组装与功能单体,交联聚合和模板洗脱,形成与目标物质的空间结构和化学性质相匹配的三维印迹腔。所制备的MIPs对目标物质具有高度选择性的提取和识别。然而,传统的MIT在材料制备和应用方面面临着严峻的挑战。在MIPs合成过程中,由于聚合反应的随机性,所得的MIPs往往印迹位点分布不均匀,缺乏分子取向。这不仅降低了MIPs的机械性能,而且影响了它们的特定识别性能。此外,模板分子的不完全去除严重减少了有效印迹位点的数量,并可能干扰后续检测结果的准确性。在MIPs吸附剂的前处理应用中,目标物质在样品溶液中的传质速率较慢,延长了MIPs在其上的吸附平衡时间。在基于MIPs的传感器检测中,存在固有的荧光猝灭、信号放大不足等问题,进一步限制了检测灵敏度。这些挑战极大地限制了麻省理工学院在环境监测、生物医学诊断和食品安全分析等领域的应用。近年来,电场辅助技术与MIT的交叉融合为解决上述问题提供了创新策略。在mip制备过程中,可以利用外加电场提供电泳驱动力,帮助调控功能单体和模板分子的定向自组装。这可以促进所制备的MIPs在微观层面上印迹位点的有序排列,实现MIPs材料的均匀性。对于模板分子洗脱,施加电场可以在MIPs和模板分子之间提供静电斥力。这样可以有效削弱MIPs与模板分子之间的分子间作用力,有利于模板分子向解吸溶液中扩散,减少模板分子残留,避免检测出“假阳性”。在样品预处理过程中,电泳力显著提高了目标物质的传质速率,促使其聚集在MIPs吸附剂周围,达到预富集的目的。这不仅可以缩短MIPs对目标物质的吸附平衡时间,实现快速富集,而且可以有效地赶走电学性质相反的干扰物质,提高MIPs对目标物质的选择性萃取性能。在检测和分析阶段,电场诱导的信号增强效应可以显著提高传感器的响应灵敏度。结合电化学和荧光检测方法,可实现对目标物质的超灵敏检测。此外,基于mip的传感器可以与微流控技术相结合,实现痕量样品的快速检测和分析,极大地扩展了mip在现场检测和分析应用中的实用性。本文系统阐述了电场在MIPs制备、样品预处理和检测分析三个关键环节中的作用机理。同时,总结了电场辅助MIT在环境监测、生物医学、食品安全等领域的应用前景。最后,提出了电场辅助MITs的未来发展方向。
{"title":"[Progress in electric field assisted molecular imprinting technology].","authors":"Jiang-Yi Wu, Xiao-Jia Huang","doi":"10.3724/SP.J.1123.2025.05006","DOIUrl":"10.3724/SP.J.1123.2025.05006","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Molecular imprinting technology (MIT) simulates the specific recognition mechanism between antibodies and antigens, and can construct separation media with specific recognition performance, demonstrating unique advantages in the fields of separation, purification, and trace detection in complex sample matrices. Molecularly imprinted polymers (MIPs), the core of MIT, form three-dimensional imprinting cavities matching the spatial structure and chemical properties of the target substance via three key steps: template self-assembly with functional monomer, cross-linking polymerization, and template elution. The prepared MIPs present highly selective extraction and recognition of the target substance. However, traditional MIT faces critical challenges in material preparation and application. During MIPs synthesis, due to the randomness of polymerization reactions, the resulting MIPs often have uneven distribution of imprinting sites and lack molecular orientation. This not only reduces the mechanical performance of MIPs, but also affects their specific recognition performance. In addition, incomplete removal of template molecules severely reduces the number of effective imprinting sites and may interfere with the accuracy of subsequent detection results. In the pre-treatment application of MIPs adsorbents, the mass transfer rate of the target substance in the sample solution is slow, which prolongs the adsorption equilibrium time of MIPs on it. In the sensor detection based on MIPs, there are inherent issues such as fluorescence quenching and insufficient signal amplification, which further limit the detection sensitivity. These challenges significantly limit the application of MIT in fields like environmental monitoring, biomedical diagnostics, and food safety analysis. In recent years, the cross fusion of electric field assisted technology and MIT has provided innovative strategies to solve the above-mentioned problems. During MIPs preparation, an external electric field can be applied to provide electrophoretic driving force to assist in regulating the directional self-assembly of functional monomers and template molecules. This can promote the ordered arrangement of imprinting sites at the micro level of MIPs prepared, achieving material uniformity of MIPs. For template molecule elution, applying an electric field can provide electrostatic repulsion between MIPs and template molecules. This can effectively weaken the inter-molecular forces between MIPs and template molecules, facilitate the diffusion of template molecules into the desorption solution, reduce the residual template molecules, and avoid the detection of \"false positives\". During the sample pretreatment process, electrophoretic force significantly enhances the mass transfer rate of the target substance, prompting it to aggregate around the MIPs adsorbent and achieve the purpose of pre-concentration. This can not only shorten the adsorption equilibrium time of MIPs for target su","PeriodicalId":101336,"journal":{"name":"Se pu = Chinese journal of chromatography","volume":"44 1","pages":"43-52"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12801127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Se pu = Chinese journal of chromatography
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