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An improved cancer diagnosis algorithm for protein mass spectrometry based on PCA and a one-dimensional neural network combining ResNet and SENet† 基于 PCA 以及结合 ResNet 和 SENet 的一维神经网络的改进型蛋白质质谱癌症诊断算法。
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-11-04 DOI: 10.1039/D4AN00784K
Liang Ma, Wenqing Gao, Xiangyang Hu, Dongdong Zhou, Chenlu Wang, Jiancheng Yu and Keqi Tang

Cancer is one of the most serious health problems worldwide. Because cancer has no specific symptoms in its early stages, it is often not diagnosed until it is in advanced stages, reducing the likelihood of successful treatment. Therefore, early diagnosis of cancer is a formidable challenge. Mass spectrometry-based proteomics offers a robust technical foundation for cancer diagnosis. However, mass spectrometry data are characterized by high dimensionality, large data volume, and noise interference, which can lead to diagnostic errors in clinical applications. To address this challenge, an improved algorithm combining principal component analysis (PCA) with a convolutional neural network (CNN) algorithm (denoted as PCA-1DSE-ResCNN) was proposed to assist in analyzing high-dimensional mass spectral data. The algorithm initially reduced the dimensionality of the data through the PCA technique. Subsequently, the convolutional neural network algorithm (1DSE-ResCNN) integrating residual blocks and squeeze-and-excitation blocks was used as a classifier. This approach can not only alleviate the issues of overfitting and gradient vanishing caused by deep network layers but also reduce redundant information, enabling the algorithm to effectively learn high-dimensional data features and deal with nonlinear relationships. To validate the effectiveness of the algorithm, the high-dimensional ovarian cancer mass spectrometry dataset was selected as an example to examine its application performance in early diagnosis of ovarian cancer. The experimental results demonstrated that the PCA-1DSE-ResCNN algorithm outperforms other methods in terms of accuracy, specificity, and sensitivity on three high-dimensional ovarian cancer datasets. This study will contribute to the rapid diagnosis and early detection of cancer.

癌症是全球最严重的健康问题之一。由于癌症在早期没有特异性症状,因此往往要到晚期才会被诊断出来,从而降低了成功治疗的可能性。因此,癌症的早期诊断是一项艰巨的挑战。基于质谱的蛋白质组学为癌症诊断提供了坚实的技术基础。然而,质谱数据具有维度高、数据量大、噪声干扰等特点,在临床应用中可能导致诊断错误。为应对这一挑战,研究人员提出了一种将主成分分析(PCA)与卷积神经网络(CNN)算法相结合的改进算法(称为 PCA-1DSE-ResCNN),以帮助分析高维质谱数据。该算法首先通过 PCA 技术降低数据维度。随后,使用卷积神经网络算法(1DSE-ResCNN)整合残差块和挤压-激发块作为分类器。这种方法不仅能缓解深度网络层带来的过拟合和梯度消失问题,还能减少冗余信息,使算法能有效学习高维数据特征并处理非线性关系。为了验证该算法的有效性,以高维卵巢癌质谱数据集为例,考察其在卵巢癌早期诊断中的应用性能。实验结果表明,PCA-1DSE-ResCNN 算法在三个高维卵巢癌数据集上的准确性、特异性和灵敏度均优于其他方法。这项研究将有助于癌症的快速诊断和早期检测。
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引用次数: 0
Phenoxy-1,2-dioxetane-Based Activatable Chemiluminescent Probes: Tuning of Photophysical Properties for Tracing Enzymatic Activities in Living Cells 基于苯氧基-1,2-二氧杂环丁烷的可活化化学发光探针:调节光物理特性以追踪活细胞中的酶活性
IF 4.2 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-11-01 DOI: 10.1039/d4an01082e
Jagpreet Singh Sidhu, Gurjot Kaur, Atharva Rajesh Chavan, Mandeep Chahal, Rajeev Taliyan
The use of chemiluminophores for tracing enzymatic activities in live-cell imaging has gained significant attention, making them valuable tools for diagnostic applications. Among various chemiluminophores, the phenoxy-1,2-dioxetane scaffold exhibits significant structural versatility and its activation is governed by the Chemically Initiated Electron Exchange Luminescence (CIEEL) mechanism. This mechanism can be initiated by enzymatic activity, changes in pH, or other chemical stimuli. The photophysical properties of phenoxy-1,2-dioxetanes can be fine-tuned through the incorporation of different substituents on the phenolic ring and by anchoring them with specific triggers. This review discusses the variations in physicochemical properties, including emission maxima, quantum yield, aqueous solubility, and pKa, as influenced by structural modifications, thereby establishing a comprehensive structure-activity relationship. Furthermore, it categorises the probes based on different enzyme classes, such as hydrolase-sensitive probes, oxidoreductase-responsive probes, and transferase-activatable phenoxy-1,2-dioxetanes, offering a promising platform technology for the early diagnosis of diseases and disorders. The summary section highlights key opportunities and limitations associated with applying phenoxy-1,2-dioxetanes in achieving precise and effective enzyme assays.
在活细胞成像中使用化学荧光团追踪酶的活动已受到广泛关注,使其成为诊断应用的重要工具。在各种化学荧光团中,苯氧基-1,2-二氧杂环丁烷支架具有显著的结构多样性,其活化受化学引发电子交换发光(CIEEL)机制控制。该机制可由酶活性、pH 值变化或其他化学刺激引发。苯氧基-1,2-二氧杂环丁烷的光物理特性可以通过在酚环上加入不同的取代基和使用特定的触发剂锚定来进行微调。本综述讨论了受结构修饰影响的物理化学特性变化,包括发射最大值、量子产率、水溶性和 pKa,从而建立了全面的结构-活性关系。此外,它还根据不同的酶类别对探针进行了分类,如水解酶敏感探针、氧化还原酶响应探针和可转移酶激活的苯氧基-1,2-二氧杂环丁烷,为疾病和失调的早期诊断提供了前景广阔的平台技术。摘要部分强调了应用苯氧基-1,2-二氧杂环丁烷实现精确有效的酶测定的主要机遇和局限性。
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引用次数: 0
Molecularly imprinted polymer sensors for biomarker detection in cardiovascular diseases 用于心血管疾病生物标记物检测的分子印迹聚合物传感器
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-30 DOI: 10.1039/D4AN01103A
Wenteng Tang, Junlei Han, Wenhong Zhang, Huimin Li, Jun Chen, Wei Song and Li Wang

Cardiovascular diseases (CVDs) are recognized as a significant threat to global health. The rapid, sensitive, and precise measurement of relevant biomarkers is essential for the timely diagnosis of CVDs. Molecularly imprinted polymers (MIPs), which act as artificial receptor recognition materials, have been extensively utilized in the detection of CVD biomarkers. Their widespread application is due to their cost-effectiveness, physical and chemical stability, straightforward preparation processes, and excellent compatibility with various sensor types. This review introduces the principles of MIP sensors in combination with electrochemical, optical, thermal transfer, and acoustic detection techniques for detecting CVD-related biomarkers. It then discusses methods developed over the past decade for detecting biomarkers of three major CVDs—coronary artery disease (CAD), acute myocardial infarction (AMI), and heart failure (HF)—using MIP sensors. Finally, the review summarizes the potential of MIP sensors in CVD biomarker detection and provides an outlook on future research directions.

心血管疾病(CVDs)被认为是对全球健康的重大威胁。快速、灵敏、精确地测量相关生物标记物对于及时诊断心血管疾病至关重要。作为人工受体识别材料的分子印迹聚合物(MIPs)已被广泛用于心血管疾病生物标志物的检测。分子印迹聚合物具有成本效益高、物理和化学性质稳定、制备过程简单以及与各种类型的传感器具有良好的兼容性等优点,因此得到了广泛的应用。本综述介绍了 MIP 传感器与电化学、光学、热传递和声学检测技术相结合用于检测气相沉积相关生物标记物的原理。然后讨论了过去十年中开发的利用 MIP 传感器检测三大心血管疾病(冠心病 (CAD)、急性心肌梗塞 (AMI) 和心力衰竭 (HF))生物标记物的方法。最后,综述总结了 MIP 传感器在心血管疾病生物标记物检测方面的潜力,并展望了未来的研究方向。
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引用次数: 0
Generation, manipulation, detection and biomedical applications of magnetic droplets in microfluidic chips 微流控芯片中磁性液滴的生成、操控、检测和生物医学应用
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-22 DOI: 10.1039/D4AN01175A
Chenyang Xu, Huanhuan Shi, Zhongjian Tan, Yun Zheng, Weizheng Xu, Zhengxian Dan, Jiacong Liao, Zhiying Dai and Yali Zhao

Microfluidic systems incorporating magnetic droplets have emerged as a focal point of significant interest within the biomedical domain. The allure of these systems lies in their capacity to offer precise control, enable contactless operation, and accommodate minimal sample concentration requirements. Such remarkable features serve to mitigate errors arising from human operation and other factors during cell or molecular detection. By providing innovative solutions for molecular diagnostics and immunoassay applications, magnetic droplet microfluidics enhance the accuracy and efficiency of these procedures. This review undertakes a comprehensive examination of the research progress in microfluidic systems centered around magnetic droplets. It adheres to a sequential presentation approach, commencing from the fundamental operation principles, specifically the generation of magnetic droplets on the microfluidic chip, and proceeding to their transmission and mixing within the microchannel via an array of operating techniques. Additionally, the relevant detection technologies associated with magnetic drop microfluidics and their numerous applications within the biomedical field are systematically classified and reviewed. The overarching objective of this review is to spotlight key advancements and offer valuable insights into the future trajectory of this burgeoning field.

包含磁性液滴的微流体系统已成为生物医学领域备受关注的焦点。这些系统的魅力在于它们能够提供精确的控制,实现非接触式操作,并满足最低的样品浓度要求。这些显著特点有助于减少细胞或分子检测过程中人为操作和其他因素造成的误差。通过为分子诊断和免疫测定应用提供创新解决方案,磁滴微流控技术提高了这些程序的准确性和效率。本综述全面考察了以磁滴为中心的微流控系统的研究进展。它采用顺序介绍的方法,从基本操作原理开始,特别是在微流控芯片上生成磁性液滴,然后通过一系列操作技术在微通道内传输和混合磁性液滴。此外,还对与磁滴微流控相关的检测技术及其在生物医学领域的众多应用进行了系统分类和综述。本综述的总体目标是突出关键进展,并为这一新兴领域的未来发展轨迹提供有价值的见解。
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引用次数: 0
Hyperpolarised [2-13C]-pyruvate by 13C SABRE in an acetone/water mixture† 丙酮/水混合物中的[2-13C] SABRE 对[2-13C]-丙酮酸的超极化作用
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-21 DOI: 10.1039/D4AN01005A
Oksana A. Bondar, Gamal A. I. Moustafa and Thomas B. R. Robertson

Signal Amplification By Reversible Exchange (SABRE) can provide strong signal enhancement (SE) to an array of molecules through reversible exchange of parahydrogen (pH2) derived hydrides and a suitable substrate coordinated to a transition metal. Among the substrates that can be used as a probe for hyperpolarised NMR and MRI, pyruvate has gained much attention. SABRE can hyperpolarise pyruvate in a low cost, fast, and reversible fashion that does not involve technologically demanding equipment. Most SABRE polarization studies have been done using methanol-d4 as a solvent, which is not suitable for in vivo application. The main goal of this work was to obtain hyperpolarized pyruvate in a solvent other than methanol which may open the door to further purification steps and enable a method to polarize pyruvate in water in future. This work demonstrates hyperpolarization of the [2-13C]pyruvate as well as [1-13C]pyruvate by SABRE in an acetone/water solvent system at room temperature as an alternative to methanol, which is commonly used. NMR signals are detected using a 1.1 T benchtop NMR spectrometer. In this work we have primarily focused on the study of [2-13C]pyruvate and investigated the effect of catalyst concentration, DMSO presence and water vs. acetone solvent concentration on the signal enhancement. The relaxation times for [2-13C]-pyruvate solutions are reported in the hope of informing the development of future purification methods.

通过可逆交换信号放大技术(SABRE),可以通过副氢(pH2)衍生氢化物与过渡金属配位的合适底物的可逆交换,为一系列分子提供强大的信号增强(SE)。在可用作超极化核磁共振和磁共振成像探针的底物中,丙酮酸盐备受关注。SABRE 能以低成本、快速、可逆的方式使丙酮酸盐超极化,而且不涉及技术要求高的设备。大多数 SABRE 极化研究都是以甲醇-d4 为溶剂进行的,这种溶剂不适合在体内应用。这项工作的主要目的是在甲醇以外的溶剂中获得超极化丙酮酸盐,这可能为进一步的纯化步骤打开大门,并使未来在水中极化丙酮酸盐的方法成为可能。这项工作展示了 SABRE 在丙酮/水溶剂系统中室温下对[2-13C]丙酮酸和[1-13C]丙酮酸的超极化,以替代常用的甲醇。使用 1.1 T 台式 NMR 光谱仪检测 NMR 信号。在这项工作中,我们主要侧重于研究 [2-13C]丙酮酸,并调查了催化剂浓度、DMSO 的存在以及水与丙酮溶剂浓度对信号增强的影响。报告了 [2-13C]- 丙酮酸溶液的弛豫时间,希望能为未来纯化方法的开发提供参考。
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引用次数: 0
Ti-based MOF nanosheets as a mass spectrometry imaging matrix for low molecular weight compounds to reveal the spatiotemporal content changes of hepatotoxic components during the processing of Polygonum multiflorum 钛基 MOF 纳米片作为低分子量化合物的质谱成像基质,揭示何首乌加工过程中肝毒性成分的时空含量变化
IF 4.2 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-21 DOI: 10.1039/d4an00964a
Feng-yan Kuang, De-jun Hu, Lu Wang, Fei Chen, Guang-Ping Lv
The selection of matrix is crucial for matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). This work successfully synthesized metal-organic frameworks (MOFs) matrices to address the limitations of the application of traditional organic matrices in the study of small molecule compositions, and Ti-based MOF nanosheets were screened as matrices for imaging the hepatotoxic components of Polygonum multiflorum. The comparison between six MOF materials and traditional organic matrices showed that Ti-based MOF nanosheets have less background interference, significant stability, and high salt resistance. The imaging results indicated that the main components of Polygonum multiflorum, free anthraquinone and stilbene glycoside, have unique spatial distribution characteristics. The successful application of the synthesized Ti-based MOF nanosheets in mass spectrometry imaging improved the detection ability of mass spectrometry imaging in the small molecule field, and the spatiotemporal content changes of hepatotoxic components in Polygonum multiflorum during the steaming process were observed, providing scientific basis for steaming.
基质的选择对于基质辅助激光解吸电离质谱成像(MALDI MSI)至关重要。针对传统有机基质在小分子成分研究中应用的局限性,本研究成功合成了金属有机框架(MOFs)基质,并筛选出Ti基MOF纳米片作为何首乌肝毒性成分成像的基质。六种 MOF 材料与传统有机基质的比较结果表明,钛基 MOF 纳米片背景干扰小、稳定性好、耐盐性高。成像结果表明,何首乌的主要成分游离蒽醌和二苯乙烯苷具有独特的空间分布特征。合成的 Ti 基 MOF 纳米片在质谱成像中的成功应用,提高了质谱成像在小分子领域的检测能力,并观察到蒸制过程中何首乌中肝毒成分的时空含量变化,为蒸制提供了科学依据。
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引用次数: 0
Liquid saliva-based Raman spectroscopy device with on-board machine learning detects COVID-19 infection in real-time† 基于液态唾液的拉曼光谱设备通过板载机器学习实时检测 COVID-19 感染情况
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-21 DOI: 10.1039/D4AN00729H
Katherine J. I. Ember, Nassim Ksantini, Frédérick Dallaire, Guillaume Sheehy, Trang Tran, Mathieu Dehaes, Madeleine Durand, Dominique Trudel and Frédéric Leblond

With greater population density, the likelihood of viral outbreaks achieving pandemic status is increasing. However, current viral screening techniques use specific reagents, and as viruses mutate, test accuracy decreases. Here, we present the first real-time, reagent-free, portable analysis platform for viral detection in liquid saliva, using COVID-19 as a proof-of-concept. We show that vibrational molecular spectroscopy and machine learning (ML) detect biomolecular changes consistent with the presence of viral infection. Saliva samples were collected from 470 individuals, including 65 that were infected with COVID-19 (28 from hospitalized patients and 37 from a walk-in testing clinic) and 251 that had a negative polymerase chain reaction (PCR) test. A further 154 were collected from healthy volunteers. Saliva measurements were achieved in 6 minutes or less and led to machine learning models predicting COVID-19 infection with sensitivity and specificity reaching 90%, depending on volunteer symptoms and disease severity. Machine learning models were based on linear support vector machines (SVM). This platform could be deployed to manage future pandemics using the same hardware but using a tunable machine learning model that could be rapidly updated as new viral strains emerge.

随着人口密度的增加,病毒爆发成为大流行病的可能性也在增加。然而,目前的病毒筛查技术使用特定的试剂,随着病毒的变异,检测的准确性也会降低。在这里,我们以 COVID-19 作为概念验证,展示了首个用于检测液态唾液中病毒的实时、无试剂、便携式分析平台。我们的研究表明,振动分子光谱和机器学习(ML)能检测出与病毒感染一致的生物分子变化。我们收集了 470 人的唾液样本,其中 65 人感染了 COVID-19(38 人来自住院病人,37 人来自免预约检测诊所),251 人的聚合酶链反应(PCR)检测呈阴性。另外 154 人来自健康志愿者。唾液测量在 6 分钟或更短时间内完成,根据志愿者的症状和疾病严重程度,机器学习模型预测 COVID-19 感染的灵敏度和特异性可达 90%。机器学习模型基于线性支持向量机(SVM)。该平台可用于管理未来的大流行病,使用相同的硬件,但使用可调整的机器学习模型,该模型可随着新病毒株的出现而快速更新。
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引用次数: 0
The development of a method to produce diagnostic reagents using LaNiO3 nanospheres and their application in nanozyme-linked immunosorbent assay for the colorimetric screening of C-reactive protein with high sensitivity† 开发一种利用 LaNiO3 纳米球生产诊断试剂的方法,并将其应用于纳米酶联免疫吸附测定法,以高灵敏度比色法筛查 C 反应蛋白
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-21 DOI: 10.1039/D4AN01160K
Maria Nikitina, Pavel Khramtsov, Stepan Devyatov, Rishat Valeev, Marina Eryomina, Andrey Chukavin and Mikhail Rayev

LaNiO3 perovskite nanoparticles, especially nanospheres (LNNS), show great promise in biomedical assays due to their peroxidase-like catalytic properties. However, LNNS-based diagnostic reagents have not been tested in nanozyme enzyme-linked immunosorbent assay (NLISA) or other enzyme-linked immunosorbent assays, and there is limited data on their synthesis. To fill this gap, it is necessary to develop a method for creating LNNS conjugates with monoclonal antibodies and to investigate the reproducibility, scalability, and applicability of these diagnostic reagents in NLISA. We have successfully developed a method for producing novel diagnostic reagents utilizing LaNiO3 nanospheres. Our research demonstrates the application of these nanospheres in a NLISA specifically designed for the detection of C-reactive protein (CRP) in real serum samples. This method is both reproducible and scalable, allowing for the efficient production of nanospheres that are functionalized with monoclonal antibodies targeting CRP, with a mean diameter of approximately 270 nm. Based on the promising results obtained from our experiments, we have developed and optimized a sandwich-format NLISA for CRP detection. This assay achieved a lower limit of detection at 0.178 μg L−1, with a dynamic range from 12.5 to 0.195 μg L−1 and a linear detection range extending from 0.195 to 6.25 μg L−1, showcasing its potential for clinical applications. The new NLISA method, utilizing LaNiO3 nanospheres in a sandwich format for the detection of CRP, significantly enhances sensitivity compared to similar use horseradish peroxidase-based ELISA. In this study for the first time, the functionalization of lanthanum nickelate nanospheres with recognition elements has been demonstrated. This advancement also sheds light on the technological challenges involved in synthesizing diagnostic reagents, identifying areas that need further exploration.

由于具有类似过氧化物酶的催化特性,LaNiO3 包晶纳米粒子,尤其是纳米球(LNNS),在生物医学检测中大有可为。然而,基于 LNNS 的诊断试剂尚未在纳米酶联免疫吸附测定(NLISA)或其他酶联免疫吸附测定中进行过测试,有关其合成的数据也很有限。为了填补这一空白,有必要开发一种方法来制造 LNNS 与单克隆抗体的共轭物,并研究这些诊断试剂在 NLISA 中的重现性、可扩展性和适用性。我们已成功开发出一种利用 LaNiO3 纳米球生产新型诊断试剂的方法。我们的研究展示了这些纳米球在 NLISA 中的应用,该 NLISA 专为检测真实血清样本中的 C 反应蛋白 (CRP) 而设计。这种方法具有可重复性和可扩展性,能高效生产出用针对 CRP 的单克隆抗体功能化的纳米球,其平均直径约为 270 nm。基于实验所取得的良好结果,我们开发并优化了一种用于检测 CRP 的夹心式 NLISA 方法。该检测方法的检测下限为 0.178 µg/L,动态范围为 12.5 至 0.195 µg/L,线性检测范围为 0.195 至 6.25 µg/L,展示了其临床应用的潜力。新的 NLISA 方法采用夹心形式的 LaNiO3 纳米球来检测 CRP,与类似的辣根过氧化物酶 -ELISA 相比,灵敏度显著提高。这项研究首次证明了镍酸镧纳米球与识别元素的功能化。这一进展还揭示了合成诊断试剂所面临的技术挑战,确定了需要进一步探索的领域。
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引用次数: 0
A gold nanomaterial-integrated distance-based analytical device for uric acid quantification in human urine samples† 用于人体尿样中尿酸定量的金纳米材料集成距离分析装置
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-18 DOI: 10.1039/D4AN01139B
Tapparath Leelasattarathkul, Thithawat Trakoolwilaiwan and Kawin Khachornsakkul

In this article, we present the first demonstration of a distance-based paper analytical device (dPAD) for uric acid quantification in human urine samples with instrument-free readout and user-friendliness for the rapid diagnosis and prognosis of various related diseases. By employing gold nanoparticles (AuNPs) as a peroxidase-like nanozyme, our proposed technique eliminates the utilization of horseradish peroxidase (HRP), making the device cost-effective and stable. In our dPAD, uric acid in the sample is oxidized by the uricase enzyme and subsequently catalysed with AuNPs in the sample zone, generating hydroxyl radicals (˙OH). Then, the produced ˙OH reacts with 3,3′-diaminobenzidine (DAB) to form poly DAB (oxDAB), resulting in a coloured distance signal in the detection zone of the dPAD. The variation of the distance of the observed red-brown colour is directly proportional to the uric acid concentration. Our sensor exhibited a linear range from 0.50 to 6.0 mmol L−1 (R2 = 0.9922) with a detection limit (LOD) of 0.25 mmol L−1, covering the clinical range of uric acid in urine. Hence, there is no need for additional sample preparation or dilution. Additionally, this assay is highly selective, with no interferences. We also found that this approach could accurately and precisely determine uric acid in human control samples with the recovery ranging from 99.37 to 100.35 with the highest RSD of 4.05%. Our method is comparable with the use of a commercially available uric acid sensor at a 95% confidence interval. Consequently, the developed dPAD offers numerous advantages such as cost-effectiveness, simplicity, and ease of operation with unskilled individuals. Furthermore, this concept can be applied for extensive biosensing applications in monitoring other biomarkers as an alternative analytical point-of-care (POC) device.

在这篇文章中,我们首次展示了一种基于距离的纸质分析装置(dPAD),用于人体尿液样本中尿酸的定量分析,该装置无需仪器读数,操作简便,可用于各种相关疾病的快速诊断和预后。通过采用金纳米粒子(AuNPs)作为过氧化物酶样纳米酶,我们提出的技术省去了辣根过氧化物酶(HRP)的使用,使该装置具有成本效益和稳定性。在我们的 dPAD 中,样品中的尿酸被尿酸酶氧化,然后与样品区中的 AuNPs 催化,产生羟基自由基(˙OH)。然后,产生的 ˙OH 与 3,3′-二氨基联苯胺(DAB)反应生成聚 DAB(oxDAB),从而在 dPAD 检测区产生彩色距离信号。观察到的红棕色距离变化与尿酸浓度成正比。我们的传感器的线性范围为 0.50 至 6.0 mmol L-1(R2 = 0.9922),检测限(LOD)为 0.25 mmol L-1,覆盖了尿液中尿酸的临床范围。因此,无需额外的样品制备或稀释。此外,这种检测方法选择性强,没有干扰。我们还发现,这种方法能准确测定人体对照样本中的尿酸,回收率在 99.37 至 100.35 之间,最高 RSD 为 4.05%。在 95% 的置信区间内,我们的方法可与使用市售尿酸传感器的方法相媲美。因此,所开发的 dPAD 具有成本效益高、操作简单、易于非熟练人员操作等众多优点。此外,这一概念还可广泛应用于监测其他生物标记物的生物传感,作为一种替代性的分析护理点(POC)设备。
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引用次数: 0
Acoustic levitation and manipulation of columns of droplets with integrated optical detection for parallelisation of reactions† 声悬浮和操纵液滴柱,集成光学检测功能,实现反应并行化
IF 3.6 3区 化学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-18 DOI: 10.1039/D4AN01096E
Ruchi Gupta and Nicholas J. Goddard

The most common methodology for performing multiple chemical and biological reactions in parallel is to use microtitre plates with either manual or robotic dispensing of reactants and wash solutions. We envision a paradigm shift where acoustically levitated droplets serve as wells of microtitre plates and are acoustically manipulated to perform chemical and biological reactions in a non-contact fashion. This in turn requires that lines of droplets can be levitated and manipulated simultaneously so that the same operations (merge, mix, and detect) can be performed on them in parallel. However, this has not been demonstrated until this work. Because of the nature of acoustic standing waves, a single focus has more than one trap, and can allow levitation of columns of droplets at the focal point and at half a wavelength above and below that point. Using this approach, we increased the number of acoustically levitated and merged droplets to 6 compared to 2 in the state-of-the-art. We showed that droplets in a column can be moved and merged with droplets in another column simultaneously and in a controlled manner to perform repeats and/or parallelisation of chemical and biological reactions. To demonstrate our approach experimentally, we built an acoustic levitator with top and bottom surfaces made of a 16 × 16 grid of 40 kHz phased array transducers and integrated optical detection system, studied two acoustic trap generation and movement algorithms, and performed an exemplar enzyme assay. This work has made significant steps towards acoustic levitation and manipulation of large numbers of droplets to eventually significantly reduce the use of the current state-of-the-art tools, microtitre plates and robots, for performing parallelised chemical and biological reactions.

并行进行多个化学和生物反应的最常见方法是使用微滴管板,手动或机器人分配反应物和洗涤液。我们设想进行模式转变,将声学悬浮液滴作为微滴管板的孔,通过声学操作以非接触方式进行化学和生物反应。这反过来又要求液滴线可以同时悬浮和操纵,以便对它们并行执行相同的操作(合并、混合和检测)。然而,在这项工作之前,这一点尚未得到证实。由于声驻波的性质,单个焦点具有一个以上的俘获器,可以悬浮焦点处以及该点上下半波长处的液滴柱。利用这种方法,我们将声学悬浮和合并液滴的数量增加到 6 个,而最先进的方法只有 2 个。我们的研究表明,一个液滴柱中的液滴可以与另一个液滴柱中的液滴同时移动和合并,并以可控的方式进行化学和生物反应的重复和/或并行化。为了在实验中展示我们的方法,我们建造了一个声学悬浮器,其上下表面由 16×16 个 40 kHz 相控阵传感器和集成光学检测系统组成,研究了两种声学阱的生成和移动算法,并进行了一次示例酶测定。这项工作在声学悬浮和操纵大量液滴方面迈出了重要的一步,最终将大大减少使用目前最先进的工具--微孔板和机器人来进行并行化学和生物反应。
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