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3D-printed electrochemical cells for multi-point aptamer-based drug measurements† 三维打印电化学电池用于基于多点色聚体的药物测量
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-08-08 DOI: 10.1039/D4SD00192C
John Mack, Raygan Murray, Kenedi Lynch and Netzahualcóyotl Arroyo-Currás

Electrochemical aptamer-based (E-AB) sensors achieve detection and quantitation of biomedically relevant targets such as small molecule drugs and protein biomarkers in biological samples. E-ABs are usually fabricated on commercially available macroelectrodes which, although functional for rapid sensor prototyping, can be costly and are not compatible with the microliter sample volumes typically available in biorepositories for clinical validation studies. Seeking to develop a multi-point sensing platform for sensor validation in sample volumes characteristic of clinical studies, we report a protocol for in-house assembly of 3D-printed E-ABs. We employed a commercially available 3D stereolithographic printer (FormLabs, $5k USD) for electrochemical cell fabrication and directly embedded electrodes within the 3D-printed cell structure. This approach offers a reproducible and reusable electrode fabrication process resulting in four independent and simultaneous measurements for statistically weighted results. We demonstrate compatibility with aptamer sequences binding antibiotics and antineoplastic agents. We also demonstrate a proof-of-concept validation of serum vancomycin measurements using clinical samples. Our results demonstrate that 3D-printing can be used in conjunction with E-ABs for accessible, rapid, and statistically meaningful validation of E-AB sensors in biological matrices.

基于电化学适配体(E-AB)的传感器可对生物样本中的小分子药物和蛋白质生物标记物等生物医学相关目标进行检测和定量。E-AB 通常是在市售的宏电极上制造的,这些宏电极虽然具有快速制作传感器原型的功能,但成本高昂,而且与临床验证研究中生物库中通常可用的微升样本容量不兼容。为了开发一种多点传感平台,以便在临床研究特有的样本容量下进行传感器验证,我们报告了一种内部组装三维打印 E-AB 的方案。我们使用市售的三维立体光刻打印机(FormLabs,价值 5,000 美元)制造电化学电池,并直接将电极嵌入三维打印的电池结构中。这种方法提供了可重复和可再用的电极制造工艺,可同时进行四次独立测量,从而获得统计加权结果。我们展示了与抗生素和抗肿瘤药物结合的aptamer序列的兼容性。我们还展示了使用临床样本测量血清万古霉素的概念验证。我们的研究结果表明,3D 打印技术可与 E-AB 结合使用,对生物基质中的 E-AB 传感器进行方便、快速和有统计意义的验证。
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引用次数: 0
A fast and highly selective ECL creatinine sensor for diagnosis of chronic kidney disease† 用于诊断慢性肾病的快速、高选择性 ECL 肌酐传感器
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-08-07 DOI: 10.1039/D4SD00165F
Hosein Afshary and Mandana Amiri

Monitoring of creatinine in human fluid has attracted considerable attention owing to the potential for diagnosis of chronic kidney disease. However, the detection of creatinine has been difficult owing to its electrochemical and optical inertness. In this approach, a highly selective and sensitive electrochemiluminescence (ECL) strategy based on homogeneous carbon quantum dots (CQDs) for the detection of creatinine was introduced. A copper(II) picrate complex was added at the surface of electrode to improve the selectivity of the sensor significantly by the formation of a Janovsky complex. A multi-pulse amperometric technique was applied as a very fast and reliable method for quantitative determination of creatinine. The calibration curve was acquired with a linear range from 1.0 × 10−8 to 1 × 10−5 M with a low detection limit of 8.7 × 10−9 M. The proposed creatinine sensing platform is experimentally very simple and shows high selectivity with a broad linear range of detection. Furthermore, the presented method can determine creatinine in real samples with excellent recoveries.

由于肌酐可用于诊断慢性肾脏疾病,因此对人体液中肌酐的监测备受关注。然而,由于肌酐具有电化学和光学惰性,其检测一直很困难。在这种方法中,引入了一种基于均质碳量子点(CQDs)的高选择性、高灵敏度电化学发光(ECL)策略来检测肌酐。在电极表面添加了吡啶甲酸铜 (II) 复合物,通过形成 Janovsky 复合物显著提高了传感器的选择性。多脉冲安培计技术是一种快速可靠的肌酐定量测定方法。所提出的肌酐传感平台在实验上非常简单,而且具有高选择性和较宽的线性检测范围。此外,所提出的方法还能测定真实样品中的肌酐,且回收率极高。
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引用次数: 0
Competitive Horseradish Peroxidase-Linked Aptamer Assay for Sensitive Detection of 17β-Estradiol with a New Aptamer 利用新型色聚体灵敏检测 17β 雌二醇的竞争性辣根过氧化物酶标记色聚体分析法
Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-08-07 DOI: 10.1039/d4sd00208c
Qiuyi Cheng, Qiang Zhao
17β-estradiol (E2) is one of typical endocrine disrupting compounds (EDCs), which plays a major role in facilitating the growth and regulating the balance of human endocrine system. E2 contamination can cause environment and health risks as E2 exposure can interfere endocrine system by binding to estrogen receptors. It is imperative to develop sensitive methods for E2 detection. Here we developed a competitive enzyme-linked aptamer assay for E2 detection by using a newly reported high-affinity DNA aptamer as affinity ligand. The complementary DNA (cDNA) of anti-E2 aptamer is conjugated on microplate. Horseradish peroxidase (HRP) is labeled on aptamer probe. In the absence of E2, HRP-labeled aptamer is captured by cDNA, and HRP catalyzes substrate into product, generating absorbance signal or chemiluminescence signal. In the presence of E2, E2 binds with aptamer, causing displacement of HRP-labeled aptamer from microplate and decrease of signals. In absorbance-analysis mode, the detection limit of E2 reached 0.2 nmol/L with a dynamic range from 0.2 nmol/L to 20 μmol/L. In chemiluminescence-analysis mode, this method enabled the quantification of E2 at 50 pmol/L, with a dynamic range from 50 pmol/L to 50 μmol/L. This method could also detect E2 spiked in lake water sample, showing promise in practical applications.
17β-雌二醇(E2)是典型的内分泌干扰化合物(EDCs)之一,在促进生长和调节人体内分泌系统平衡方面发挥着重要作用。由于暴露于 E2 会通过与雌激素受体结合干扰内分泌系统,因此 E2 污染会对环境和健康造成危害。开发灵敏的 E2 检测方法势在必行。在此,我们利用一种新报道的高亲和性 DNA 类似物作为亲和配体,开发了一种检测 E2 的竞争性酶联检测法。抗 E2 合体的互补 DNA(cDNA)被连接到微孔板上。适配体探针上标记有辣根过氧化物酶(HRP)。在没有 E2 的情况下,HRP 标记的适配体被 cDNA 捕获,HRP 将底物催化成产物,产生吸光度信号或化学发光信号。在 E2 存在的情况下,E2 与适配体结合,导致 HRP 标记的适配体从微孔板中移出,信号减弱。在吸光度分析模式下,E2 的检测限为 0.2 nmol/L,动态范围为 0.2 nmol/L 至 20 μmol/L。在化学发光分析模式下,该方法可定量检测 50 pmol/L 的 E2,动态范围为 50 pmol/L 至 50 μmol/L。该方法还能检测湖泊水样中添加的E2,显示了实际应用的前景。
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引用次数: 0
Paper integrated microfluidic contact lens for colorimetric glucose detection 用于比色葡萄糖检测的纸质集成微流体接触镜
Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-08-05 DOI: 10.1039/d4sd00135d
Pelin Kubra Isgor, Taher Abbasiasl, Ritu Das, Emin Istif, Umut Can Yener, Levent Beker
Contact lenses offer a simple, cost-effective, and noninvasive method for in-situ real-time analysis of various biomarkers. Electro-chemical sensors are integrated into contact lenses for analysis of various biomarkers. However, they suffer from rigid electronic components and connections, leading to eye irritation and biomarker concentration deviation. Here, a flexible, and microfluidic integrated paper-based contact lens for colorimetric analysis of glucose was implemented. Facilitating a three-dimensional (3D) printer for lens fabrication eliminates cumbersome cleanroom process and provides a simple, batch compatible process. Due to the capillary force of the filter paper, the sample was routed to detection chambers inside microchannels, and it allowed further colorimetric detection. Paper-embedded microfluidic contact lens successfully detects glucose down to 2 mM within ~10 sec. The small dimension of the microfluidic system enables detection of glucose levels as low as 5 µl. The results show the potential of the presented approach to analyze glucose concentration in a rapid manner. It is demonstrated that the fabricated contact lens can successfully detect glucose levels of diabetic patients.
隐形眼镜为原位实时分析各种生物标记物提供了一种简单、经济、无创的方法。电化学传感器被集成到隐形眼镜中,用于分析各种生物标志物。然而,这些传感器的电子元件和连接都比较僵硬,会对眼睛造成刺激,并导致生物标记物浓度偏差。在这里,我们实现了一种用于葡萄糖比色分析的柔性微流控集成纸基隐形眼镜。利用三维(3D)打印机制造镜片,省去了繁琐的洁净室流程,并提供了简单、批量兼容的工艺。由于滤纸的毛细力,样品被输送到微通道内的检测室,并可进一步进行比色检测。嵌入滤纸的微流控接触镜可在约 10 秒内成功检测出低至 2 mM 的葡萄糖。微流体系统尺寸小,可检测低至 5 µl 的葡萄糖水平。结果表明,所提出的方法具有快速分析葡萄糖浓度的潜力。结果表明,制作的隐形眼镜可以成功检测糖尿病患者的葡萄糖水平。
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引用次数: 0
A Dual State Emission Luminogen based on 1,3,3-trimethylindoline and chroman-2,4-dione Conjugate for Highly Selective Dual Channel Detection of Cyanide Ion 一种基于 1,3,3-三甲基吲哚啉和色烷-2,4-二酮共轭物的双态发射光源,用于高选择性双通道检测氰离子
Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-08-02 DOI: 10.1039/d4sd00155a
Snehadrinarayan Khatua, Sumit Kumar Patra, Monosh Rabha, Deikrisha Lyngdoh Lyngkhoi, Jogat Gogoi, Bhaskar Sen
Dual state emission luminogen (DSEgen) with strong fluorescence in both solution and solid states has extensive potential for numerous applications. Herein, a chroman-2,4-dione and indoline conjugate, 2 was synthesized for highly selective and sensitive turn-on fluorescent detection of cyanide ion. Compound 2 behaves as a molecular rotor and shows the dual state emission (DSE) phenomenon and multicolour emission. It displays bright fluorescence in both the concentrated solution and the solid-state. The compound is nonfluorescent in dilute solution, and with increasing concentration, it shows aggregation caused red-shifted emission. With increasing concentration, the emission colour changes from green to yellow to orange-red. The CC bond attached to the coumarin moiety is a compelling target for nucleophilic addition. Cyanide ions reacted with the probe and remarkably changed spectroscopic properties. With the gradual addition of cyanide, the colour of the probe solution was changed from yellow to colorless. The very weakly emissive probe 2 rapidly reacted with CN− and emitted strongly due to the inhibition of internal charge transfer (ICT) from indoline to chroman-2,4-dione. The DSEgen properties and CN sensing were thoroughly investigated and supported using spectroscopic studies, TDDFT, and single-crystal X-ray diffraction.
在溶液和固体状态下都具有强荧光的双态发射荧光剂(DSEgen)具有广泛的应用潜力。本文合成了一种铬-2,4-二酮和吲哚啉共轭物 2,用于高选择性和高灵敏度的氰离子荧光检测。化合物 2 表现为分子转子,具有双态发射(DSE)现象和多色发射。它在浓溶液和固态下都能显示出明亮的荧光。该化合物在稀溶液中无荧光,随着浓度的增加,会出现聚集引起的红移发射。随着浓度的增加,发射颜色从绿色变为黄色,再变为橙红色。香豆素分子上的 CC 键是亲核加成的一个重要目标。氰离子与探针发生反应,显著改变了光谱特性。随着氰化物的逐渐加入,探针溶液的颜色从黄色变为无色。由于抑制了从吲哚啉到色满-2,4-二酮的内部电荷转移(ICT),发射性很弱的探针 2 与 CN- 发生了快速反应,并发出强烈的光。利用光谱研究、TDDFT 和单晶 X 射线衍射对 DSEgen 性能和 CN 传感进行了深入研究和支持。
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引用次数: 0
Optimization of solvents, electrolytes, and mediators for polyindole-based electrochemical sensors 基于聚吲哚的电化学传感器
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-08-02 DOI: 10.1039/D4SD00175C
P. C. Pandey, Atul Kumar Tiwari and Roger J. Narayan

Surface-engineered conducting polymers (CPs) have enabled technological advances in chemistry and materials science. Heterocyclic conjugated organic molecules, specifically indole and its derivatives, have the potential to be polymerized under electrochemically controlled conditions in different types of compatible solvent media, including self-assembled nanofluids, for several applications. Polymer-based electrode materials are valuable for the detection of various targeted biomolecules and other analytes. This review outlines the evolution of the electropolymerization technique in recent years, along with developments in the field. With advances in nanoscience, several materials have been used to modify CPs for electrochemical sensing. Several biomedical applications and the role of antifouling agents in the properties of several electropolymerized thin films are highlighted.

表面工程导电聚合物(CP)推动了化学和材料科学的技术进步。杂环共轭有机分子,特别是吲哚及其衍生物,有可能在电化学控制条件下在不同的兼容溶剂介质中聚合,包括用于多种应用的自组装纳米流体。基于聚合物的电极材料对于检测各种目标生物分子或其他分析物具有重要价值。本综述概述了近年来电聚合技术的演变以及该领域的发展。随着纳米科学的发展,有多种材料被用于电化学传感方法的 CPs 改性。重点介绍了几种生物医学应用以及防污剂对几种电聚合薄膜特性的作用。
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引用次数: 0
Electrochemical detection of tumor cells based on proximity labelling-assisted multiple signal amplification† 基于近距离标记辅助多重信号放大技术的肿瘤细胞电化学检测技术
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-08-02 DOI: 10.1039/D4SD00217B
Guozhang Zhou, Fei Zhou, Xiaomeng Yu, Daiyuan Zhou, Jiaqi Wang, Bing Bo, Ya Cao and Jing Zhao

Malignant tumors are the second leading cause of human deaths worldwide, and early cancer screening and diagnosis can effectively reduce cancer mortality. Herein, we propose a new electrochemical method for the highly sensitive detection of MUC1-positive tumor cells based on proximity labelling-assisted multiple signal amplification. Specifically, a MUC1 aptamer-modified electrode was prepared for capturing MUC1-positive tumor cells, followed by binding of G4-DNA strands to the cells with the aid of a mild reduction reaction. A hemin/G4-DNA complex was then formed and acted as a mimic of horseradish peroxidase, catalysing the proximal labelling of tyramine-modified gold nanoparticles to induce silver-enhanced electrochemical signal amplification. Electrochemical results demonstrated that the method was able to specially identify MUC1-positive tumor cells and generate corresponding electrochemical responses in the range of 100 cells per mL to 1 × 106 cells per mL with a detection limit of 21 cells per mL. Furthermore, the method displayed good stability and anti-interference performance in complex serum environments. Therefore, our work may provide an effective tool to improve the accuracy of cell-based tissue examination and liquid biopsy for early diagnosis of cancers in the future.

恶性肿瘤是导致全球人类死亡的第二大原因,早期癌症筛查和诊断可有效降低癌症死亡率。在此,我们提出了一种基于近距离标记辅助多重信号放大的高灵敏度检测 MUC1 阳性肿瘤细胞的新型电化学方法。具体来说,我们制备了用于捕获 MUC1 阳性肿瘤细胞的 MUC1 合物修饰电极,然后借助温和的还原反应将 G4-DNA 链与细胞结合。然后形成血红素/G4-DNA 复合物,作为辣根过氧化物酶的模拟物,催化酪胺修饰金纳米粒子的近端标记,诱导银增强电化学信号放大。电化学结果表明,该方法能专门识别 MUC1 阳性肿瘤细胞,并在 100 个细胞/毫升至 1×106 个细胞/毫升的范围内产生相应的电化学反应,检测限为 21 个细胞/毫升。此外,该方法在复杂的血清环境中显示出良好的稳定性和抗干扰性能。因此,我们的工作可为提高基于细胞的组织检查和液体活检的准确性提供有效工具,从而在未来实现癌症的早期诊断。
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引用次数: 0
Direct writing of graphene electrodes for point-of-care electrochemical sensing applications 直接写入石墨烯电极用于护理点电化学传感应用
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-31 DOI: 10.1039/D4SD00140K
Lei Zhao, Andrew Piper, Giulio Rosati and Arben Merkoçi

Electrochemical sensors are increasingly garnering attention as valuable tools for point-of-care (POC) testing due to their low costs, high sensitivities, and ease of miniaturization. Graphene-based materials, renowned for their tunable electrical conductivity, high specific surface areas, versatile functionality, and biocompatibility; are highly suited for the fabrication of electrochemical sensors with heightened sensitivities. Non-contact, maskless, direct writing methods allow the rapid, large-scale production of graphene electrodes with high design flexibility. Researchers globally are advancing graphene electrode production, aiming for smaller, faster, and more efficient sensors. This review provides a comprehensive overview of recent advances on the direct writing of graphene electrodes for electrochemical sensing applications. It covers the basics of direct writing techniques, the advancements in graphene ink/precursor preparation, structural design, and device integration, with a focus on POC platforms.

电化学传感器因其低成本、高灵敏度和易于微型化等特点,正日益受到人们的关注,成为进行床旁(POC)检测的重要工具。石墨烯基材料以其可调导电性、高比表面积、多功能性和生物兼容性而闻名,非常适合制造灵敏度更高的电化学传感器。通过非接触、无掩模、直接写入的方法,可以快速、大规模地生产具有高度设计灵活性的石墨烯电极。全球的研究人员正在推进石墨烯电极的生产,目标是制造出更小、更快、更高效的传感器。本综述全面概述了直接写入石墨烯电极用于电化学传感应用的最新进展。它涵盖了直接写入技术的基础知识、石墨烯墨水/前驱体制备的进展、结构设计和器件集成,重点关注 POC 平台。
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引用次数: 0
Synthesis and characterization of La QDs: sensors for anions and H2O2† La QDs 的合成与表征:阴离子和 H2O2 传感器
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-26 DOI: 10.1039/D4SD00142G
Amit Sahoo and Achyuta N. Acharya

The development of sensitive and accurate fluorescence sensors for the detection of anions and reactive oxygen species (ROS, H2O2) is essential as they play significant roles in biological and chemical processes. In this work, semiconductor La QDs were synthesized. The synthesized La QDs were determined to be pure with 100% La element using EDS technique. La QDs were observed in both cubic and hexagonal lattice configurations through powder XRD analysis. The morphology of the La QDs was characterized using HRTEM and FESEM data as tiny, spherical, homogenous QDs with a diameter ranging from 2 to 6 nm. The fluorescence characteristics of the synthesized La QDs were examined by studying their sensing properties that increased with an increase in anion concentration and decreased with an increase in [H2O2]. The variation in emission intensity at 315 nm and 440.5 nm satisfied the Stern–Volmer equation. The LOD and LOQ of H2O2 and anion sensing with La QDs were studied in the μM range. The Langmuir binding plots and FTIR spectra supported the concept that the surface functionalization of La QDs occurred in the presence of anions. With two band gap energies of about 3.26 eV and 4.66 eV, the synthesized La QDs are a mixture of two (binary) semiconductors.

由于阴离子和活性氧(ROS、H2O2)在生物和化学过程中发挥着重要作用,因此开发用于检测阴离子和活性氧的灵敏而准确的荧光传感器至关重要。本研究合成了半导体 La QDs。利用 EDS 技术确定合成的 La QDs 纯度为 100%。通过粉末 XRD 分析,观察到 La QDs 具有立方和六方两种晶格构型。利用 HRTEM 和 FESEM 数据对 La QDs 的形态进行了表征,发现它们是微小、球形、均匀的 QDs,直径在 2 到 6 nm 之间。通过研究合成的 La QDs 的传感特性,考察了它们的荧光特性,即随着阴离子浓度的增加而增加,随着[H2O2]的增加而减少。在 315 nm 和 440.5 nm 处的发射强度变化符合 Stern-Volmer 方程。研究了 La QDs 在 μM 范围内传感 H2O2 和阴离子的 LOD 和 LOQ。朗缪尔结合图和傅立叶变换红外光谱支持了 La QDs 在阴离子存在时发生表面官能化的概念。合成的 La QDs 具有约 3.26 eV 和 4.66 eV 的两个带隙能,是两种(二元)半导体的混合物。
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引用次数: 0
Optimized gadolinium-DO3A loading in RAFT-polymerized copolymers for superior MR imaging of aging blood–brain barrier† 优化 RAFT 聚合共聚物中的钆-DOTA 负载,为老化血脑屏障提供优质磁共振成像
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-25 DOI: 10.1039/D4SD00063C
Hunter A. Miller, Aaron Priester, Evan T. Curtis, Krista Hilmas, Ashleigh Abbott, Forrest M. Kievit and Anthony J. Convertine

The development of gadolinium-based contrast agents (GBCAs) has been pivotal in advancing magnetic resonance imaging (MRI), offering enhanced soft tissue contrast without ionizing radiation exposure. Despite their widespread clinical use, the need for improved GBCAs has led to innovations in ligand chemistry and polymer science. We report a novel approach using methacrylate-functionalized DO3A ligands to synthesize a series of copolymers through direct reversible addition-fragmentation chain transfer (RAFT) polymerization. This technique enables precise control over the gadolinium content within the polymers, circumventing the need for subsequent conjugation and purification steps, and facilitates the addition of other components such as targeting ligands. The resulting copolymers were analysed for their relaxivity properties, indicating that specific gadolinium-DO3A loading contents between 12–30 mole percent yield optimal MRI contrast enhancement. Inductively coupled plasma (ICP) measurements corroborated these findings, revealing a non-linear relationship between gadolinium content and relaxivity. Optimized copolymers were synthesized with the claudin-1 targeting peptide, C1C2, to image BBB targeting in aged mice to show imaging utility. This study presents a promising pathway for the development of more efficient GBCA addition to copolymers for targeted drug delivery and bioimaging application.

钆基造影剂(GBCAs)的开发在推动磁共振成像(MRI)方面发挥了关键作用,它能在不暴露于电离辐射的情况下增强软组织造影效果。尽管钆基造影剂已广泛应用于临床,但对改进型钆基造影剂的需求促使配体化学和聚合物科学不断创新。我们报告了一种使用甲基丙烯酸酯功能化 DOTA 配体,通过直接可逆加成-碎片链转移(RAFT)聚合合成一系列共聚物的新方法。这种技术可以精确控制聚合物中的钆含量,省去了后续的共轭和纯化步骤,并有利于添加靶向配体等其他成分。对所得共聚物的弛豫特性进行了分析,结果表明,钆-DOTA 的具体装载量在 12-30 摩尔% 之间,能产生最佳的磁共振成像对比度增强效果。电感耦合等离子体 (ICP) 测量证实了这些发现,揭示了钆含量与弛豫性之间的非线性关系。优化后的共聚物与 claudin-1 靶向肽 C1C2 合成,在老龄小鼠的 BBB 靶向成像中显示出成像效用。这项研究为开发更高效的 GBCA 添加到共聚物中,用于靶向给药和生物成像应用提供了一条前景广阔的途径。
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引用次数: 0
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Sensors & diagnostics
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