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“Click” post-synthesis of chiral microporous organic network for chiral high-performance liquid chromatographic separation 用于手性高效液相色谱分离的手性微孔有机网络的 "点击 "后合成技术
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-29 DOI: 10.1016/j.aca.2024.343377
Han Li, Ke Li, Yuan-Yuan Cui, Cheng-Xiong Yang

Background

Chiral separation is of great significance but remains challenging in analytical chemistry. Chiral stationary phase based high-performance liquid chromatography (HPLC) is regarded as one of the most effective and widely used methods for chiral resolution. Microporous organic networks (MONs) are an emerging class of porous materials with designable topology, large surface area, abundant micropores, and excellent stabilities that have attracted tremendous interests in chromatographic separation. However, the usage of chiral MONs as chiral stationary phases for chiral HPLC separation has not been reported so far.

Results

Herein, we present the first example of chiral MON@SiO2-L-Cys as a novel stationary phase for chiral HPLC. MON@SiO2-L-Cys is post-synthesized with l-cysteine (L-Cys) via the specific thiol-yne click reaction. The packed MON@SiO2-L-Cys column is able to separate chiral aromatic alcohols, esters, and nitriles with good resolution (4.00 for 2-phenyl-2-pentanol) and high selectivity (3.56 for propranolol hydrochloride). Effects of sample dosage, mobile phase composition, and separation temperature are studied. The MON@SiO2-L-Cys packed column also exhibits chiral recognition complementarity with three commercial chiral columns. For example, 2-amino-2-phenylethanol and propranolol hydrochloride are able to achieve baseline separation on MON@SiO2-L-Cys packed column, but cannot be separated on commercial Chiralpak IA, IB, and IH columns. In addition, the MON@SiO2-L-Cys packed column gives comparable separation performance for 2-phenyl-2-pentanol even after 9 months’ utilization.

Significance

This work reports the first example of constructing chiral MON-based stationary phase for chiral HPLC separation via the facile click post-synthesis strategy. This study demonstrates the considerable prospect of chiral MONs as efficient chiral stationary phases for chiral HPLC and may open up a new area of MONs in chiral separation.
背景手性分离具有重要意义,但在分析化学中仍具有挑战性。基于手性固定相的高效液相色谱(HPLC)被认为是最有效、应用最广泛的手性分离方法之一。微孔有机网络(MONs)是一类新兴的多孔材料,具有可设计的拓扑结构、较大的比表面积、丰富的微孔和优异的稳定性,在色谱分离领域引起了极大的兴趣。结果我们首次将手性 MON@SiO2-L-Cys 作为新型固定相用于手性 HPLC。MON@SiO2-L-Cys是通过特定的硫醇-炔点击反应与L-半胱氨酸(L-Cys)进行后合成的。经填充的 MON@SiO2-L-Cys 色谱柱能够分离手性芳香醇、酯和腈,并具有良好的分辨率(2-苯基-2-戊醇为 4.00)和高选择性(盐酸普萘洛尔为 3.56)。研究了样品用量、流动相组成和分离温度的影响。MON@SiO2-L-Cys 填料色谱柱还与三种商用手性色谱柱具有手性识别互补性。例如,2-氨基-2-苯乙醇和盐酸普萘洛尔可在MON@SiO2-L-Cys填料柱上实现基线分离,但在商用Chiralpak IA、IB和IH柱上却无法分离。此外,MON@SiO2-L-Cys填料柱在使用9个月后仍能为2-苯基-2-戊醇提供相当的分离性能。 重要意义 本研究首次报道了通过简便的点击后合成策略构建手性MON基固定相用于手性高效液相色谱分离的实例。该研究表明,手性 MONs 作为高效手性固定相用于手性 HPLC 具有广阔的前景,并可能为 MONs 在手性分离领域的应用开辟一个新的领域。
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引用次数: 0
In situ growth of L012-reduced gold nanoparticles-loaded graphitic carbon nitride nanocomposite for potential-resolved ratiometric electrochemiluminescence analysis 原位生长 L012 还原金纳米粒子负载氮化石墨碳纳米复合材料,用于电位分辨比率电化学发光分析
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-29 DOI: 10.1016/j.aca.2024.343379
Wei Nie, Yisha Wang, Chao Hu, Xi Wei, Hua Cui

Background

Most electrochemiluminescence (ECL) analytical methods involve only changes in one single signal, which greatly limits their high sensitivity and stability for applied research. Potential-resolved electrochemiluminescence (PRECL), which provides calibrated analysis by self-correcting signal responses from dual channels, has attracted great interest in recent years. However, research on PRECL nanomaterials is still at an early stage. It is critical to develop a novel PRECL nanocomposite with high intensity in light emission, high resolution in potential separation, and reduced complexity in reaction systems for accurate detection.

Results

Here, a novel PRECL nanocomposite, L012-Au/g-C3N4, was synthesized by in situ growth of L012-reduced gold nanoparticles (L012-Au) on the surface of graphitic carbon nitride (g-C3N4) nanosheets. The g-C3N4 nanosheets served as effective carriers for L012 molecules and L012-Au, as well as efficient cathodic ECL emitters. With the addition of a single co-reactant (K2S2O8), two fully separated ECL peaks were observed around −1.3 V (ECL-1) and +0.6 V (ECL-2) at neutral conditions. The catalytic character of the incorporated gold nanoparticles accelerated the anodic ECL reaction and greatly enhanced the ECL intensity. Furthermore, an ECL mechanism based on the competitive relationship between K2S2O8 and dissolved oxygen was proposed. When dopamine (DA) was introduced into the PRECL reaction system, ECL-1 remained essentially unchanged, while ECL-2 intensity was significantly reduced. By analyzing the intensity ratio of ECL-2 to ECL-1 (I2/I1) to the detecting target, a ratiometric DA sensor with high sensitivity and stability was successfully constructed.

Significance

A nanocomposite L012-Au/g-C3N4 that can induce high-intensity ECL with two separated potentials in each polarity has been prepared by a simple synthetic method. The developed ratiometric sensor can eliminate systematic errors and improve accuracy. In addition, the multifunctionality of the nanocomposite and the necessity of only one co-reactant for neutral-condition ECL greatly reduced the reaction complexity. Our work offers new PRECL solutions to design highly sensitive and stable multi-response detection systems for in vitro diagnostics.
背景大多数电化学发光(ECL)分析方法只涉及单个信号的变化,这大大限制了其在应用研究中的高灵敏度和稳定性。电位分辨电化学发光(PRECL)通过双通道信号响应的自我校正来提供校准分析,近年来引起了人们的极大兴趣。然而,有关 PRECL 纳米材料的研究仍处于早期阶段。结果通过在氮化石墨碳(g-C3N4)纳米片表面原位生长 L012 还原金纳米粒子(L012-Au),合成了一种新型 PRECL 纳米复合材料 L012-Au/g-C3N4。g-C3N4 纳米片是 L012 分子和 L012-Au 的有效载体,也是高效的阴极 ECL 发光体。加入单一共反应物(K2S2O8)后,在中性条件下可观察到两个完全分离的 ECL 峰,分别在 -1.3 V(ECL-1)和 +0.6 V(ECL-2)左右。金纳米粒子的催化特性加速了阳极 ECL 反应,大大提高了 ECL 强度。此外,还提出了一种基于 K2S2O8 与溶解氧之间竞争关系的 ECL 机制。当在 PRECL 反应体系中引入多巴胺(DA)时,ECL-1 基本保持不变,而 ECL-2 的强度则显著降低。通过分析 ECL-2 与 ECL-1 的强度比(I2/I1)与检测目标的关系,成功构建了一种高灵敏度和高稳定性的 DA 比率传感器。所开发的比率传感器可消除系统误差并提高准确度。此外,纳米复合材料的多功能性以及中性条件 ECL 只需一种共反应物的特点大大降低了反应的复杂性。我们的工作为体外诊断设计高灵敏度和稳定的多反应检测系统提供了新的 PRECL 解决方案。
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引用次数: 0
Adhered-3D paper microfluidic analytical device based on oxidase-mimicking activity of Co-doped carbon dots nanozyme for point-of-care testing of alkaline phosphatase 基于共掺杂碳点纳米酶的氧化酶模拟活性的粘附-3D 纸微流体分析装置,用于碱性磷酸酶的床旁检测
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-29 DOI: 10.1016/j.aca.2024.343378
Jing Guo , Jing Zhang , Xia Tong
Paper-based microfluidic analytical devices (μPADs) have become promising alternatives to clinical laboratory-based methods for point-of-care testing (POCT) of biomarkers in family care and resource-limited communities. Here, Co-doped carbon dots (Co-CDs) nanozyme with outstanding oxidase-mimicking catalytic activity and red fluorescent emission were prepared, and combined adhered-3D μPAD (A-3D μPAD) to monitor facilely alkaline phosphatase (ALP) level in whole blood samples. Co-CDs catalyzed the oxidization of nonfluorescent o-phenylenediamine (OPD) into 2,3-diaminophenazine (oxOPD) with yellow fluorescent emission due to the generation of tremendous O2•- species. With addition of ALP, ALP hydrolyzed l-ascorbic acid 2-phosphate into ascorbic acid, and the latter was oxidized by Co-CDs, then reacted with OPD to form blue fluorescent emission 3-(dihydroxyethyl)furo [3,4-b]quinoxaline-1-one (DFQ). Both DFQ and oxOPD quenched the fluorescence intensity of Co-CDs via inner-filter effect. The cascade reaction of ALP/Co-CDs was incorporated into A-3D μPAD based on above sensing principles. A-3D μPAD enabled sample pretreatment, cascade reaction and signal output, and integrated portable minimized device and smartphone for visual ALP detection. The linear range and limit of detection for ALP were 0.5–150 U L−1 and 0.1 U L−1, respectively, and the color varied from red, yellow to blue. The detection results for whole blood samples were consistent with biochemical detector. The efficiency, disposability, practicality and low-cost of A-3D μPAD can be extended to determine various biomarkers, and provided technical support for nanozyme applications in POCT environments.
基于纸张的微流控分析装置(μPADs)已成为临床实验室方法的理想替代品,可用于家庭护理和资源有限社区的床旁生物标记物检测(POCT)。本文制备了具有出色的氧化酶模拟催化活性和红色荧光发射的掺钴碳点(Co-CDs)纳米酶,并将其与附着型三维μPAD(A-3D μPAD)相结合,以方便地监测全血样本中的碱性磷酸酶(ALP)水平。Co-CDs 催化无荧光的邻苯二胺(OPD)氧化成 2,3-二氨基吩嗪(oxOPD),由于生成了大量的 O2 物种,所以会发出黄色荧光。加入 ALP 后,ALP 将 L-抗坏血酸 2-磷酸水解为抗坏血酸,后者被 Co-CDs 氧化,然后与 OPD 反应生成发出蓝色荧光的 3-(二羟乙基)呋喃并[3,4-b]喹喔啉-1-酮(DFQ)。DFQ 和 oxOPD 都能通过内滤效应淬灭 Co-CD 的荧光强度。根据上述传感原理,ALP/Co-CDs 的级联反应被整合到了 A-3D μPAD 中。A-3D μPAD 实现了样品预处理、级联反应和信号输出,并集成了便携式微型装置和智能手机,可实现可视化 ALP 检测。ALP 的线性范围和检测限分别为 0.5-150 U L-1 和 0.1 U L-1,颜色从红色、黄色到蓝色不等。全血样本的检测结果与生化检测器一致。A-3D μPAD 的高效性、可抛弃性、实用性和低成本可扩展到多种生物标记物的检测,为纳米酶在 POCT 环境中的应用提供了技术支持。
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引用次数: 0
Rapid and accurate bacteria identification through deep-learning-based two-dimensional Raman spectroscopy 通过基于深度学习的二维拉曼光谱技术快速准确地识别细菌
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-29 DOI: 10.1016/j.aca.2024.343376
Yichen Liu , Yisheng Gao , Rui Niu , Zunyue Zhang , Guo-Wei Lu , Haofeng Hu , Tiegen Liu , Zhenzhou Cheng
Surface-enhanced Raman spectroscopy (SERS) offers a distinctive vibrational fingerprint of the molecules and has led to widespread applications in medical diagnosis, biochemistry, and virology. With the rapid development of artificial intelligence (AI) technology, AI-enabled Raman spectroscopic techniques, as a promising avenue for biosensing applications, have significantly boosted bacteria identification. By converting spectra into images, the dataset is enriched with more detailed information, allowing AI to identify bacterial isolates with enhanced precision. However, previous studies usually suffer from a trade-off between high-resolution spectrograms for high-accuracy identification and short training time for data processing. Here, we present an efficient bacteria identification strategy that combines deep learning models with a spectrogram encoding algorithm based on wavelet packet transform and Gramian angular field techniques. In contrast to the direct analysis of raw Raman spectra, our approach utilizes wavelet packet transform techniques to compress the spectra by a factor of 1/15, while concurrently maintaining state-of-the-art accuracy by amplifying the subtle differences via Gramian angular field techniques. The results demonstrate that our approach can achieve a 99.64 % and a 90.55 % identification accuracy for two types of bacterial isolates and thirty types of bacterial isolates, respectively, while a 90 % reduction in training time compared to the conventional methods. To verify the model's stability, Gaussian noises were superimposed on the testing dataset, showing a specific generalization ability and superior performance. This algorithm has the potential for integration into on-site testing protocols and is readily updatable with new bacterial isolates. This study provides profound insights and contributes to the current understanding of spectroscopy, paving the way for accurate and rapid bacteria identification in diverse applications of environment monitoring, food safety, microbiology, and public health.
表面增强拉曼光谱(SERS)提供了分子的独特振动指纹,在医学诊断、生物化学和病毒学领域得到了广泛应用。随着人工智能(AI)技术的快速发展,AI 支持的拉曼光谱技术作为生物传感应用的一个前景广阔的途径,极大地促进了细菌的识别。通过将光谱转换为图像,数据集可获得更多详细信息,从而使人工智能能够更精确地识别细菌分离物。然而,以往的研究通常会在高分辨率光谱图的高精度识别和数据处理的短训练时间之间进行权衡。在这里,我们提出了一种高效的细菌识别策略,它将深度学习模型与基于小波包变换和格拉米安角场技术的频谱图编码算法相结合。与直接分析原始拉曼光谱不同,我们的方法利用小波包变换技术将光谱压缩 1/15 倍,同时通过格拉米安角场技术放大细微差别,从而保持最先进的精度。结果表明,与传统方法相比,我们的方法对两种细菌分离物和 30 种细菌分离物的识别准确率分别达到了 99.64% 和 90.55%,同时减少了 90% 的训练时间。为了验证模型的稳定性,在测试数据集上叠加了高斯噪声,结果表明该模型具有特定的泛化能力和卓越的性能。该算法有望整合到现场测试协议中,并可根据新的细菌分离株随时更新。这项研究提供了深刻的见解,有助于当前对光谱学的理解,为环境监测、食品安全、微生物学和公共卫生等不同应用领域准确、快速地识别细菌铺平了道路。
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引用次数: 0
New solid phase microextraction fibers with green clay coating via radio frequency magnetron sputtering for detecting low-polar compounds in water samples 通过射频磁控溅射技术检测水样中低极性化合物的新型绿色粘土涂层固相微萃取纤维
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-28 DOI: 10.1016/j.aca.2024.343375
Jhon Fiscal-Ladino , Juan Jose Lozada-Castro , Jhon Jairo Rios-Acevedo , Diego Montaño-Montoya , Eduardo Carasek , Pablo Richter , Alvaro Pulzara-Mora , Liliana Moncayo Martínez , Milton Rosero-Moreano

Background

Developing highly sensitive and selective measurement techniques to detect trace compounds in diverse matrices is a significant challenge in analytical chemistry. These techniques must adhere to green chemistry principles by minimizing organic solvent use, simplifying sample preparation, and streamlining process steps. Additionally, there is a growing need for sustainable analytical methods due to increased environmental awareness. The problem addressed in this work is the need for an eco-friendly and efficient method for the extraction and detection of trace organochlorine pesticides in water samples.

Results

We employed SPME using a novel clay thin film sorbent, deposited on a nickel-titanium alloy wire via magnetron sputtering. Montmorillonite clay was chosen for its excellent adsorption properties and eco-friendly nature, aligning with green chemistry principles. The approach involved coating the SPME fiber with hydrophobic modified montmorillonite clay, followed by silylation. The method was tested for extracting 12 model organochlorine pesticides, including BHC, lindane, and DDT, demonstrating high isolation efficiency. The coated thin film and its silylation modification were characterized using standard spectroscopic techniques, confirming the successful creation of a new adsorbent phase. The direct immersion SPME approach achieved relative recoveries ranging from 65 % to 99 %, with reproducibility (RSD) below 6 %. This method provided low detection limits (10–15 ng L−1) and quantitation limits (32–50 ng L−1).

Significance

Our approach offers an eco-friendly, highly efficient solution for the extraction and detection of trace organochlorine pesticides. The significant improvement in recovery rates and reproducibility, combined with low detection and quantitation limits, underscores the potential of this method to enhance analytical practices in environmental monitoring and public health. Furthermore, the use of sustainable materials and processes aligns with global efforts to reduce environmental impact in analytical chemistry.
背景开发高灵敏度和高选择性的测量技术来检测各种基质中的痕量化合物是分析化学领域的一项重大挑战。这些技术必须遵守绿色化学原则,最大限度地减少有机溶剂的使用、简化样品制备和流程步骤。此外,由于环保意识的增强,对可持续分析方法的需求也在不断增长。本研究解决的问题是需要一种环保、高效的方法来萃取和检测水样中的痕量有机氯农药。之所以选择蒙脱石粘土,是因为它具有优异的吸附性能和环保特性,符合绿色化学原则。该方法包括在 SPME 纤维上涂覆疏水改性蒙脱石粘土,然后进行硅烷化处理。对该方法进行了测试,以提取包括 BHC、林丹和 DDT 在内的 12 种有机氯农药模型,结果表明该方法具有很高的分离效率。使用标准光谱技术对涂层薄膜及其硅烷化改性进行了表征,证实了新吸附相的成功创建。直接浸泡 SPME 方法的相对回收率为 65% 至 99%,重现性(RSD)低于 6%。我们的方法为痕量有机氯农药的萃取和检测提供了一种环保、高效的解决方案。我们的方法为痕量有机氯农药的萃取和检测提供了生态友好型的高效解决方案。回收率和重现性的显著提高,以及较低的检测和定量限,凸显了该方法在加强环境监测和公共卫生分析实践方面的潜力。此外,该方法使用可持续材料和工艺,符合全球在分析化学领域减少环境影响的努力。
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引用次数: 0
Deep eutectic solvent as stationary phase for flow analysis: Automated trace metal determination in food products 作为流动分析固定相的深共晶溶剂:食品中痕量金属的自动测定
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-26 DOI: 10.1016/j.aca.2024.343356
Andrey Shishov , Ulyana Markova , Valeriia Mulloyarova , Peter Tolstoy , Natalya Shkaeva , Dmitry Kosyakov , Nipu Kumar Das , Tamal Banerjee

Background

Deep eutectic solvents (DES) have emerged as effective solvents that address many challenges in analytical chemistry, particularly in microextraction. However, until now, their use has been primarily focused on extraction processes. This has significantly limited their application in analytical chemistry, especially in flow analysis, where the high viscosity of DES has made their use difficult.

Results

This paper presents a novel DES-based liquid-liquid microextraction approach for the separation and determination of trace metals in foods using an automated flow analysis system. In this study, a DES composed of thymol and thionalide was first prepared and thoroughly characterized by spectroscopic (IR, NMR) and differential scanning calorimetry techniques. The COSMO-SAC model was employed to predict the solubility of metal salts (Cu, Cd, Pb, and Hg) in the new DES. The solvent was applied to glass fiber as a stationary phase in an extraction column in a flow analysis. After microwave digestion of food samples, metals were extracted by this DES in an automated mode and subsequently eluted with an aqueous thiourea solution. The procedure demonstrated limits of detection (LOD) of 6 μg kg−1 for mercury, 4 μg kg−1 for copper, 6 μg kg−1 for lead and 0.6 μg kg−1 for cadmium.

Significance

This study represents the first application of a DES-based stationary phase in automated flow analysis, significantly enhancing extraction efficiency. The procedure enables precise and reliable determination of trace metals in food products, aligning with green chemistry principles by minimizing waste.
背景深共晶溶剂(DES)是一种有效的溶剂,可以解决分析化学中的许多难题,尤其是在微萃取方面。然而,到目前为止,它们的使用主要集中在萃取过程中。结果本文介绍了一种基于 DES 的新型液液微萃取方法,该方法利用自动流动分析系统对食品中的痕量金属进行分离和测定。在这项研究中,首先制备了由百里酚和亚硫酰基组成的 DES,并通过光谱(红外、核磁共振)和差示扫描量热技术对其进行了全面表征。利用 COSMO-SAC 模型预测了金属盐(铜、镉、铅和汞)在新 DES 中的溶解度。在流动分析中,将溶剂应用于玻璃纤维作为萃取柱中的固定相。微波消解食品样品后,用这种 DES 自动萃取金属,然后用硫脲水溶液洗脱。该方法的检测限(LOD)分别为:汞 6 μg kg-1、铜 4 μg kg-1、铅 6 μg kg-1、镉 0.6 μg kg-1。该程序可精确可靠地测定食品中的痕量金属,最大限度地减少浪费,符合绿色化学原则。
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引用次数: 0
In-situ synthesis of 2D nanozymes-coated cellulose nanofibers on paper-based chips for portable detection of biothiols 在纸质芯片上原位合成二维纳米酶涂层纤维素纳米纤维,用于便携式生物硫醇检测
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-25 DOI: 10.1016/j.aca.2024.343363
Chao Di , Yiwei Zhang , Lian Xue, Wenyi Zeng, Tengteng Wang, Yiwei Lin, Peng Chen, Xiaojun Feng, Wei Du, Bi-Feng Liu

Background

Simple, fast and low-cost paper-based analytical devices (PADs) have a good application prospect for point-of-care detection of GSH. However, effective immobilization of functional nanomaterials onto cellulose, as a critical factor in the construction of PADs, presents numerous difficulties and challenges.

Results

In this study, we have developed an exceptionally straightforward and environmentally friendly synthetic approach by using ovalbumin (OVA) as a bio-mineralization template for the preparation of MnO2 nanosheets. The MnO2 nanosheets produced in the solution phase exhibited excellent intrinsic nano-enzyme activity and biodegradability. The OVA-MnO2 nanosheets can effectively oxidize Amplex red in the absence of H2O2, enabling sensitive detection of GSH with a linear range of 5 nM–10 μM and a detection limit as low as 2.8 nM. Furthermore, we utilized this method to facilitate in situ synthesis of OVA-MnO2 nanosheets directly on paper substrates. This approach eliminates the need for conventional stirring and centrifugation steps, greatly simplifying the fabrication process while reducing material usage and time expenditure. Characterization of the chemical composition and morphology confirmed the intimate growth of the 2D nano-enzymes on the cellulose fibers. Utilizing smartphone capabilities, the OVA-MnO2 nanosheet-modified PAD enabled instrument-free detection of GSH, demonstrating high sensitivity (0.74 μM) and a wide linear response range (1–1000 μM).

Significance

The synthesis of MnO2 nanosheets directly on cellulose substrates substantially streamlines the modification workflow of PADs and reduces detection costs, offering new avenues for clinical diagnostics of relevant diseases.
背景简单、快速、低成本的纸基分析装置(PADs)在GSH的床旁检测方面具有良好的应用前景。结果在这项研究中,我们利用卵清蛋白(OVA)作为制备 MnO2 纳米片的生物矿化模板,开发了一种非常简单且环保的合成方法。在溶液相中制备的二氧化锰纳米片表现出优异的内在纳米酶活性和生物可降解性。OVA-MnO2纳米片能在无H2O2的情况下有效氧化安普莱斯红,从而实现了对GSH的灵敏检测,线性范围为5 nM-10 μM,检测限低至2.8 nM。此外,我们还利用这种方法直接在纸基底上原位合成了 OVA-MnO2 纳米片。这种方法无需传统的搅拌和离心步骤,大大简化了制备过程,同时减少了材料用量和时间消耗。对化学成分和形态的表征证实了二维纳米酶在纤维素纤维上的紧密生长。利用智能手机的功能,OVA-MnO2 纳米片修饰的 PAD 无需仪器即可实现 GSH 的检测,具有高灵敏度(0.74 μM)和宽线性响应范围(1-1000 μM)。
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引用次数: 0
A mitochondria-targeted nitric oxide probe with large Stokes shift for real-time imaging and evaluation of inflammatory bowel disease in situ 具有大斯托克斯位移的线粒体靶向一氧化氮探针,用于原位实时成像和评估炎症性肠病
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-24 DOI: 10.1016/j.aca.2024.343372
Jiatian Liu , Xueqian Chen , Andong Wang , Dongdong Su

Background

Inflammatory bowel disease (IBD) is a prevalent inflammatory disorder, and the abnormal expression of nitric oxide (NO) produced by biocatalysis of iNOS enzyme in mitochondria is directly associated with the occurrence and progression of IBD. Activatable fluorescent probes offer promising tools for early diagnosis of IBD, however, inadequate biodistribution and limited targeting properties of these probes in vivo severely impede accurate diagnosis of IBD and real-time evaluation of inflammatory levels in situ. Therefore, it is necessary to design a highly efficient fluorescent probe towards NO to overcome inadequate biodistribution and achieve accurate diagnosis and evaluation of IBD in situ.

Results

We designed a highly efficient mitochondria-targeted “turn-on” NIR fluorescent probe Cy-OMe which has excellent targeting properties and imaging ability. The response mechanism is probe Cy-OMe rapidly undergoes N-nitrosation reaction resulting in “turn-on” NIR fluorescence signal when exposed to NO. Cy-OMe exhibits high sensitivity and specificity in detecting NO content in vitro, owing to its large Stokes shift. Furthermore, the probe Cy-OMe not only efficiently targets mitochondria but also enables precise assessment of fluctuations in endogenous NO concertation across various cell types. Importantly, by virtue of large Stokes shift and excellent mitochondrial targeting ability, Cy-OMe has the capability to specifically evaluate dynamic fluctuations of NO in lipopolysaccharide (LPS)‐stimulated IBD mouse models in situ and Cy-OMe was achieved high-contrast imaging and precision diagnosis of intestinal inflammation diseases.

Significance

Cy-OMe can accurately assess fluctuations in NO levels and show high signal fidelity in the diseased intestine region, which has prospects in the non-invasive diagnosis of intestinal inflammation in vivo. At the same time, it is expected to serve as a potential diagnose platform for investigating the physiological processes underlying NO-related inflammatory diseases and promoting understanding of the pathological functions of NO across diverse inflammatory diseases.
背景炎症性肠病(IBD)是一种常见的炎症性疾病,线粒体中 iNOS 酶的生物催化产生的一氧化氮(NO)的异常表达与 IBD 的发生和发展直接相关。可激活的荧光探针为 IBD 的早期诊断提供了前景广阔的工具,然而,这些探针在体内的生物分布不足和靶向性有限,严重阻碍了 IBD 的准确诊断和原位炎症水平的实时评估。因此,有必要设计一种针对 NO 的高效荧光探针,以克服生物分布不足的问题,实现对 IBD 的原位准确诊断和评估。其反应机制是探针 Cy-OMe 在暴露于 NO 时会迅速发生 N-亚硝基化反应,从而产生开启的近红外荧光信号。由于 Cy-OMe 具有较大的斯托克斯位移,因此在体外检测 NO 含量时具有较高的灵敏度和特异性。此外,探针 Cy-OMe 不仅能有效靶向线粒体,还能精确评估不同类型细胞中内源性 NO 的协同波动。重要的是,凭借大斯托克斯位移和出色的线粒体靶向能力,Cy-OMe 能够在原位特异性评估脂多糖(LPS)刺激的 IBD 小鼠模型中 NO 的动态波动,Cy-OMe 实现了肠道炎症疾病的高对比度成像和精准诊断。意义Cy-OMe能准确评估NO水平的波动,并在病变肠道区域显示高信号保真度,在体内无创诊断肠道炎症方面具有广阔前景。同时,它有望成为一个潜在的诊断平台,用于研究 NO 相关炎症疾病的生理过程,并促进对 NO 在各种炎症疾病中的病理功能的了解。
{"title":"A mitochondria-targeted nitric oxide probe with large Stokes shift for real-time imaging and evaluation of inflammatory bowel disease in situ","authors":"Jiatian Liu ,&nbsp;Xueqian Chen ,&nbsp;Andong Wang ,&nbsp;Dongdong Su","doi":"10.1016/j.aca.2024.343372","DOIUrl":"10.1016/j.aca.2024.343372","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory bowel disease (IBD) is a prevalent inflammatory disorder, and the abnormal expression of nitric oxide (NO) produced by biocatalysis of iNOS enzyme in mitochondria is directly associated with the occurrence and progression of IBD. Activatable fluorescent probes offer promising tools for early diagnosis of IBD, however, inadequate biodistribution and limited targeting properties of these probes <em>in vivo</em> severely impede accurate diagnosis of IBD and real-time evaluation of inflammatory levels <em>in situ</em>. Therefore, it is necessary to design a highly efficient fluorescent probe towards NO to overcome inadequate biodistribution and achieve accurate diagnosis and evaluation of IBD <em>in situ</em>.</div></div><div><h3>Results</h3><div>We designed a highly efficient mitochondria-targeted “turn-on” NIR fluorescent probe <strong>Cy-OMe</strong> which has excellent targeting properties and imaging ability. The response mechanism is probe <strong>Cy-OMe</strong> rapidly undergoes N-nitrosation reaction resulting in “turn-on” NIR fluorescence signal when exposed to NO. <strong>Cy-OMe</strong> exhibits high sensitivity and specificity in detecting NO content <em>in vitro</em>, owing to its large Stokes shift. Furthermore, the probe <strong>Cy-OMe</strong> not only efficiently targets mitochondria but also enables precise assessment of fluctuations in endogenous NO concertation across various cell types. Importantly, by virtue of large Stokes shift and excellent mitochondrial targeting ability, <strong>Cy-OMe</strong> has the capability to specifically evaluate dynamic fluctuations of NO in lipopolysaccharide (LPS)‐stimulated IBD mouse models <em>in situ</em> and <strong>Cy-OMe</strong> was achieved high-contrast imaging and precision diagnosis of intestinal inflammation diseases.</div></div><div><h3>Significance</h3><div><strong>Cy-OMe</strong> can accurately assess fluctuations in NO levels and show high signal fidelity in the diseased intestine region, which has prospects in the non-invasive diagnosis of intestinal inflammation <em>in vivo</em>. At the same time, it is expected to serve as a potential diagnose platform for investigating the physiological processes underlying NO-related inflammatory diseases and promoting understanding of the pathological functions of NO across diverse inflammatory diseases.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1332 ","pages":"Article 343372"},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of chemosensitivity of tumor spheroids exposed to two-dimensional gradient of combination drugs in a hydrogel-based diffusion microfluidic platform 在基于水凝胶的扩散微流控平台上分析肿瘤球体对二维梯度复合药物的化疗敏感性
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-24 DOI: 10.1016/j.aca.2024.343371
Kin Fong Lei , Yu-Ting Lin , Sai Kiran Reddy Boreddy , Ping-Ching Pai

Background

Liver cancer stands as a leading cause of cancer-related deaths globally, challenging conventional treatments due to resistance to chemotherapy and targeted therapy. Although frontline medications show initial efficacy, prolonged use often leads to resistance and harm. Current clinical strategies rely on combination therapies, but evaluating their effectiveness remains challenging.

Results

To address this, we developed a hydrogel-based diffusion microfluidic platform for assessing chemosensitivity. This platform features a hydrogel-filled diffusion layer linked to liquid wells, allowing the creation of drug gradients. Tumor spheroids, cultured on the non-adhesive hydrogel surface, were exposed to single or combination drug gradients. Analysis revealed that drug efficacy, quantified by IC50 values, could be determined from responses to single drug gradients. A novel method was introduced to assess spheroid circularity as a time-invariant index of drug efficacy. Furthermore, exposing spheroids to 2D combination drug gradients allowed intuitive visualization of their responses via a color map. This analysis identified optimal drug combinations, exhibiting superior efficacy to monotherapy.

Significance

The microfluidic platform enables assessment of synergistic effects and replicates in vivo conditions, enhancing the relevance of test results. By offering a streamlined, fast, and efficient drug screening approach, this platform aims to provide insight into tumor spheroid responses to varying drug combinations, facilitating more effective clinical applications.
背景肝癌是全球癌症相关死亡的主要原因之一,由于对化疗和靶向治疗的耐药性,传统治疗方法面临挑战。虽然一线药物显示出初步疗效,但长期使用往往会导致耐药性和伤害。为了解决这个问题,我们开发了一种基于水凝胶的扩散微流控平台,用于评估化疗敏感性。该平台的特点是将充满水凝胶的扩散层与液孔相连,从而形成药物梯度。在非粘性水凝胶表面培养的肿瘤球体暴露于单一或组合药物梯度。分析表明,通过对单一药物梯度的反应,可以确定以 IC50 值量化的药物疗效。该研究采用了一种新方法来评估球体的圆度,以此作为药物疗效的时间不变指标。此外,将球体暴露于二维组合药物梯度可通过彩色图直观地显示球体的反应。这项分析确定了最佳药物组合,其疗效优于单一疗法。意义该微流体平台可评估协同效应,并复制体内条件,提高了测试结果的相关性。通过提供简化、快速和高效的药物筛选方法,该平台旨在深入了解肿瘤球体对不同药物组合的反应,从而促进更有效的临床应用。
{"title":"Analysis of chemosensitivity of tumor spheroids exposed to two-dimensional gradient of combination drugs in a hydrogel-based diffusion microfluidic platform","authors":"Kin Fong Lei ,&nbsp;Yu-Ting Lin ,&nbsp;Sai Kiran Reddy Boreddy ,&nbsp;Ping-Ching Pai","doi":"10.1016/j.aca.2024.343371","DOIUrl":"10.1016/j.aca.2024.343371","url":null,"abstract":"<div><h3>Background</h3><div>Liver cancer stands as a leading cause of cancer-related deaths globally, challenging conventional treatments due to resistance to chemotherapy and targeted therapy. Although frontline medications show initial efficacy, prolonged use often leads to resistance and harm. Current clinical strategies rely on combination therapies, but evaluating their effectiveness remains challenging.</div></div><div><h3>Results</h3><div>To address this, we developed a hydrogel-based diffusion microfluidic platform for assessing chemosensitivity. This platform features a hydrogel-filled diffusion layer linked to liquid wells, allowing the creation of drug gradients. Tumor spheroids, cultured on the non-adhesive hydrogel surface, were exposed to single or combination drug gradients. Analysis revealed that drug efficacy, quantified by IC<sub>50</sub> values, could be determined from responses to single drug gradients. A novel method was introduced to assess spheroid circularity as a time-invariant index of drug efficacy. Furthermore, exposing spheroids to 2D combination drug gradients allowed intuitive visualization of their responses via a color map. This analysis identified optimal drug combinations, exhibiting superior efficacy to monotherapy.</div></div><div><h3>Significance</h3><div>The microfluidic platform enables assessment of synergistic effects and replicates <em>in vivo</em> conditions, enhancing the relevance of test results. By offering a streamlined, fast, and efficient drug screening approach, this platform aims to provide insight into tumor spheroid responses to varying drug combinations, facilitating more effective clinical applications.</div></div>","PeriodicalId":240,"journal":{"name":"Analytica Chimica Acta","volume":"1332 ","pages":"Article 343371"},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative analysis of purity of human albumin preparations for clinical use 临床用人血白蛋白制剂纯度对比分析
IF 5.7 2区 化学 Q1 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-24 DOI: 10.1016/j.aca.2024.343364
Liye Maeyama, Stefanie Fas, Jörg Schüttrumpf, Selma Henrichsen

Background

Albumin is the most prevalent plasma protein and serves numerous physiological roles, both in body fluid management and in various other capacities. In many diseases, a deficiency of albumin has been observed, and in certain conditions, albumin substitution has been demonstrated to improve outcome in comparison to plasma expansion using crystalloid or other colloid solutions. The favourable effects of using albumin in patients with liver cirrhosis are likely associated with the non-oncotic functions of albumin. Albumin for clinical use is obtained through fractionation of pooled donor plasma. The production procedures are optimized to ensure pure, chemically uncompromised and native protein.

Results

We have extensively analysed commercial preparations of human albumin for clinical use from six different providers. Parameters that must correspond to the requirements of international pharmacopoeias were assessed (aluminium, ethanol, sodium, the presence of dimers and oligomers) and found to conform in all cases. In addition, we used for the first time nuclear magnetic resonance (NMR) as an additional analytical approach for investigating in greater depth the quality of a biological remedy gained from human plasma. We applied both 1H NMR and 13C-HSQC for confirming the identity of the albumin preparations, which also conformed in all cases. Moreover, we utilized T2-filtered 1H NMR and 13C-HSQC measurements to identify the presence of small molecules in the preparations. This demonstrated similar patterns of additional substances present, but also unveiled certain differences in purity in the products of the different providers.

Significance

Our analyses confirmed that albumin preparations in clinical use conform to the requirements. We furthermore demonstrate that NMR measurements can provide further depth in identity and purity measurements of biologicals. Despite largely standardized protocols in pharmaceutical albumin production, our in-depth analyses revealed differences in purity. Some samples exhibited lower levels of components other than albumin. We discuss possible causes of these observations and their potential implications for clinical therapy.
背景白蛋白是最常见的血浆蛋白,在体液管理和其他各种功能中发挥着多种生理作用。在许多疾病中都可观察到白蛋白缺乏,在某些情况下,白蛋白替代品与使用晶体液或其他胶体溶液进行血浆扩容相比,可改善预后。肝硬化患者使用白蛋白的良好效果可能与白蛋白的非抗凝血功能有关。临床使用的白蛋白是通过对集合供体血浆进行分馏获得的。我们广泛分析了六家不同供应商提供的临床用人血白蛋白商业制剂。对必须符合国际药典要求的参数(铝、乙醇、钠、二聚体和低聚物的存在)进行了评估,发现所有参数都符合要求。此外,我们还首次将核磁共振(NMR)作为一种额外的分析方法,用于更深入地研究从人体血浆中提取的生物药剂的质量。我们同时使用 1H-NMR 和 13C-HSQC 来确认白蛋白制剂的身份,结果也全部吻合。此外,我们还利用 T2 过滤 1H-NMR 和 13C-HSQC 测量来确定制剂中是否存在小分子物质。我们的分析证实,临床使用的白蛋白制剂符合要求。我们的分析证实了临床使用的白蛋白制剂符合要求,并进一步证明了 NMR 测量可进一步深入生物制品的特性和纯度测量。尽管药用白蛋白的生产规程基本标准化,但我们的深入分析发现了纯度方面的差异。一些样品中除白蛋白以外的其他成分含量较低。我们讨论了这些观察结果的可能原因及其对临床治疗的潜在影响。
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引用次数: 0
期刊
Analytica Chimica Acta
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