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Stretchable and body-conformable physical sensors for emerging wearable technology 用于新兴可穿戴技术的可拉伸和人体适形物理传感器
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-24 DOI: 10.1039/D4SD00189C
Yong Lin, Weijie Qiu and Desheng Kong

Wearable physical sensors represent attractive devices for health monitoring and human–machine interfaces. Unlike traditional devices that prioritize increased sensitivity and selectivity, stretchability is crucial for wearable sensors to effectively adhere to the dynamic and curved contours of the human body. In addition to being stretchable, the conformal integration allows for durable skin–device interfaces, enabling long-term wearable detection. To track the latest progress, this perspective focuses on the rapidly advancing field of skin-attached physical sensors, analyzing their design approaches, critical applications, and desirable characteristics. The discussion begins with two primary strategies for creating stretchable electronic devices through structural designs and material innovations. We further discuss the significance of a conformal, seamless skin–device interface for wearable detection. We further elaborate on several critical physical sensors and their system integration. Finally, this article addresses current challenges and outlines future directions to translate knowledge in this evolving field into cutting-edge wearable technologies.

可穿戴物理传感器是健康监测和人机界面的理想设备。与优先考虑提高灵敏度和选择性的传统设备不同,可伸缩性对于可穿戴传感器有效贴合人体的动态和弯曲轮廓至关重要。除了可拉伸外,保形集成还可实现耐用的皮肤-设备接口,从而实现长期的可穿戴检测。为了跟踪最新进展,本视角将重点关注快速发展的皮肤附着物理传感器领域,分析其设计方法、关键应用和理想特性。讨论从通过结构设计和材料创新制造可拉伸电子设备的两种主要策略开始。我们进一步讨论了可穿戴式检测中皮肤与设备的保形和无缝接口的重要性。我们进一步阐述了几个关键的物理传感器及其系统集成。最后,本文探讨了当前面临的挑战,并概述了将这一不断发展的领域的知识转化为尖端可穿戴技术的未来方向。
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引用次数: 0
A nitroreductase-sensitive near-IR fluorescent biosensor for detecting tumor hypoxia in vivo† 用于检测体内肿瘤缺氧的对硝基还原酶敏感的近红外荧光生物传感器
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-23 DOI: 10.1039/D4SD00146J
Safiya Nisar and Binglin Sui

Tumor cells have high metabolic demands, leading to increased oxygen consumption and further exacerbating hypoxia, which has been regarded as a characteristic feature of solid tumors and plays a significant role in tumor growth, resistance to therapy, and overall treatment outcomes. Hypoxia-specific sensing probes are currently in urgent need to provide valuable information for tumor detection and monitoring. In this work, we developed a new near-IR fluorescence-emitting biosensor with a high fluorescence quantum yield for hypoxia detection in tumor tissues. In the presence of nitroreductase enzyme under tumor hypoxia, the nitro group of the biosensor molecule is converted into an amino group, and the resulting compound turns itself into a nonfluorescent dye through a self-immolating process, thus turning off the fluorescence emission of the biosensor. The fluorescence change of the biosensor in response to nitroreductase is sensitive and selective and is not influenced by the presence of other physiologically important species. In the in vitro and in vivo bioimaging experiments, the biosensor demonstrated high efficiency in detecting hypoxia and the capability of distinguishing solid tumors of different sizes, indicating its potential applications in tumor diagnosis and progression monitoring.

肿瘤细胞具有高代谢需求,导致耗氧量增加,进一步加剧了缺氧。缺氧一直被认为是实体瘤的一个特征,在肿瘤生长、抗药性和总体治疗效果方面起着重要作用。缺氧特异性传感探针目前急需为肿瘤检测和监测提供有价值的信息。在这项工作中,我们开发了一种具有高荧光量子产率的新型近红外荧光发射生物传感器,用于肿瘤组织中的缺氧检测。在肿瘤缺氧条件下,当硝基还原酶存在时,生物传感器分子中的硝基转化为氨基,由此产生的化合物通过自褪色过程变成无荧光染料,从而关闭了生物传感器的荧光发射。生物传感器对硝基还原酶的荧光变化具有灵敏性和选择性,不会受到其他重要生理物质的影响。在体外和体内生物成像实验中,该生物传感器在检测缺氧方面表现出很高的效率,并能区分不同大小的实体肿瘤,这表明它在肿瘤诊断和进展监测方面具有潜在的应用价值。
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引用次数: 0
Paper-based sensing of pancreatic-cancer biomarker α-chymotrypsin through turn-on lanthanide-luminescence† 基于纸张的胰腺癌生物标记物 α-Chymotrypsin 触发镧系元素发光传感技术
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-18 DOI: 10.1039/D4SD00124A
Ananya Biswas and Uday Maitra

We report the facile detection of a pancreatic cancer biomarker α-chymotrypsin (Chy) by turn-on, time-gated lanthanide luminescence for the first time. To the best of our knowledge, the non-peptide probe we designed is the simplest one currently available. The probe undergoes Chy-induced release of the sensitizing antenna (2,3-dihydroxynaphthalene), leading to enhanced lanthanide luminescence. The detection protocol was further modified to develop a paper-based sensor and was used to detect Chy in commercial tablets, and to rapidly screen Chy-inhibitors.

我们首次报道了利用开启的时间门控镧系元素发光法检测胰腺癌生物标志物α-糜蛋白酶(Chy)的简便方法。据我们所知,我们设计的非肽探针是目前最简单的探针。该探针会在 Chy 诱导下释放敏化天线(2,3-二羟基萘),从而导致镧系元素发光增强。该检测方案经进一步修改后被用于开发纸基传感器,并被用于检测商业药片中的糜蛋白酶和快速筛选糜蛋白酶抑制剂。
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引用次数: 0
An automated screening platform for improving the responsiveness of genetically encoded Ca2+ biosensors in mammalian cells† 提高哺乳动物细胞中基因编码 Ca2+ 生物传感器响应性的自动筛选平台
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-18 DOI: 10.1039/D4SD00138A
Yufeng Zhao, Yi Shen, Teodor Veres and Robert E. Campbell

Genetically-encoded, fluorescent protein (FP)-based biosensors are powerful tools for imaging dynamic cellular activities. Directed evolution is a highly effective method for developing enhanced versions of FP-based biosensors, but the screening process is laborious and time-consuming. Mammalian cell-based screening with electrical stimulation methods has been successful in accurately selecting variants of biosensors for imaging neuronal activities. We introduce an automated mammalian cell screening platform utilizing a fluorescence microscope and a liquid dispenser to enable the screening of biosensor responsiveness to chemical stimulation. We demonstrated the effectiveness of this platform in improving the response of a red fluorescent biosensor for Ca2+, K-GECO, for detection of histamine-induced changes in Ca2+ concentration. This method should be applicable to any FP-based biosensor that responds to pharmacological treatment or other exogenous chemical stimulation, simplifying efforts to develop biosensors tailored for specific applications in diverse biological contexts.

基于基因编码的荧光蛋白(FP)生物传感器是对动态细胞活动进行成像的强大工具。定向进化是开发基于 FP 的增强型生物传感器的高效方法,但筛选过程费时费力。利用电刺激方法进行基于哺乳动物细胞的筛选已成功地准确筛选出用于成像神经元活动的生物传感器变体。我们介绍了一种利用荧光显微镜和液体分配器的自动化哺乳动物细胞筛选平台,以筛选生物传感器对化学刺激的反应性。我们展示了该平台在改善 Ca2+ 红色荧光生物传感器 K-GECO 的响应方面的有效性,该传感器可用于检测组胺诱导的 Ca2+ 浓度变化。这种方法适用于任何能对药物治疗或其他外源化学刺激做出反应的基于 FP 的生物传感器,从而简化了为不同生物环境中的特定应用开发生物传感器的工作。
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引用次数: 0
Visually distinguishing between tumor tissue and healthy tissue within ten minutes using proteolytic probes† 利用蛋白水解探针在十分钟内目测区分肿瘤组织和健康组织
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-17 DOI: 10.1039/D4SD00047A
Debora Reinhardt, Björn ter Mors, Marc D. Driessen, Marcus Gutmann, Julian Faber, Lukas Haug, Anna-Maria Faber, Anna Herrmann, Prisca Hamm, Tessa Lühmann, Christian Linz and Lorenz Meinel

Accurately identifying tumor tissue is crucial during surgery, especially when removing head and neck squamous cell carcinomas (HNSCC). Our tumor-responsive probes are tailored for ex vivo diagnostics, streamlining today's complex surgical workflows and potentially enabling pathologists and surgeons to rapidly and objectively distinguish between healthy and tumor tissue. Designed based on insights from biological furin substrates and cleavage site screening, the probes detect HNSCC-associated protease activity. Within ten minutes of incubation, tumor tissue is differentiated from healthy tissue by visible fluorescence in biopsy supernatant.

在手术过程中,尤其是切除头颈部鳞状细胞癌 (HNSCC) 时,准确识别肿瘤组织至关重要。我们的肿瘤反应探针专为体内外诊断量身定制,可简化当今复杂的手术工作流程,使病理学家和外科医生能够快速、客观地区分健康组织和肿瘤组织。探针的设计基于对生物呋喃底物和裂解位点筛选的深入了解,可检测 HNSCC 相关蛋白酶的活性。在孵育十分钟内,肿瘤组织就能通过活检上清液中的可见荧光与健康组织区分开来。
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引用次数: 0
A CRISPR-amplified label-free electrochemical aptasensor for the sensitive detection of HbA1c† 用于灵敏检测 HbA1c 的 CRISPR 扩增无标记电化学适配传感器
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-16 DOI: 10.1039/D4SD00193A
Jianfeng Ma, Youwei Zheng, Yaoyao Xie, Dan Zhu, Lianhui Wang and Shao Su

Glycated hemoglobin (HbA1c) is a pivotal biomarker for the monitoring and early diagnosis of diabetes. The CRISPR-Cas system has fascinating application prospects in the next generation of biosensors due to its high specificity, efficiency, flexibility, and customization. Herein, a label-free electrochemical aptasensor was designed for the detection of HbA1c by combining the specific recognition ability of aptamers with the signal amplification effect of the CRISPR-Cas12a system. In the presence of HbA1c, the cistrans cleavage ability of Cas12a protein was activated, causing the pre-formed probe DNA to be heavily cleaved and the electrochemical signal to increase. With CRISPR-assisted signal amplification, the developed electrochemical aptasensor can detect as low as 0.84 ng mL−1 HbA1c. Moreover, this aptasensor can detect 10 ng mL−1 HbA1c in 50% human serum due to its high selectivity, reproducibility, and long-term stability, which is lower than its physiological level in human blood samples. All results proved that the proposed aptasensor has a promising application in the early diagnosis and long-term monitoring of diabetes.

糖化血红蛋白(HbA1c)是监测和早期诊断糖尿病的重要生物标志物。CRISPR-Cas 系统具有高特异性、高效性、灵活性和定制性等特点,在下一代生物传感器中具有广阔的应用前景。本文设计了一种无标记的电化学适配体传感器,将适配体的特异性识别能力与CRISPR-Cas12a系统的信号放大效应相结合,用于检测HbA1c。在 HbA1c 存在的情况下,Cas12a 蛋白的顺反裂解能力被激活,导致预先形成的探针 DNA 被大量裂解,电化学信号增加。通过 CRISPR 辅助信号放大,所开发的电化学适配传感器可以检测到低至 0.84 纳克/毫升的 HbA1c。此外,由于该传感器具有高选择性、可重复性和长期稳定性,它还能检测 50%人体血清中 10 ng/mL HbA1c 的含量,低于人体血样中的生理水平。所有结果都证明,该传感器在糖尿病的早期诊断和长期监测方面具有广阔的应用前景。
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引用次数: 0
Ultra-low dual detection of tetrahydrocannabinol and cannabidiol in saliva based on electrochemical sensing and machine learning: overcoming cross-interferences and saliva-to-saliva variations† 基于电化学传感和机器学习的唾液中四氢大麻酚和大麻二酚超低双检测:克服交叉干扰和唾液之间的差异
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-15 DOI: 10.1039/D4SD00102H
Greter A. Ortega, Herlys Viltres, Hoda Mozaffari, Syed Rahin Ahmed, Seshasai Srinivasan and Amin Reza Rajabzadeh

A novel alternative to cope with saliva-to-saliva variations and cross-interference while sensing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is reported here using two voltammetric sensors coupled with machine learning. The screen-printed electrodes modified with the same analyte molecules (m-Z-THC and m-Z-CBD) were employed for sensing ultra-low concentrations of THC and CBD in the 0 to 5 ng mL−1 range in real human saliva samples. Simultaneous detection of THC and CBD was carried out using m-Z-THC or m-Z-CBD to study the performance of each modified sensor. Also, CBD and THC have the same molecular structure; there is only a slight difference in how the atoms are arranged, and therefore both molecules will have similar electrochemical performance. Consequently, CBD can be a potential interference while detecting THC and THC can be an interference during CBD detection using electrochemical sensors. Therefore, machine learning was introduced to analyze the sensor analytical responses to overcome such issues. The data processing results provide suitable accuracies of 100% for training in the case of both sensors and 92 and 83% for m-Z-THC and m-Z-CBD, respectively, for dataset testing THC and CBD in saliva samples. Additionally, the saliva samples containing CBD and THC as cross-interference were accurately identified and classified.

本文报告了一种新颖的替代方法,即使用两种伏安法传感器并结合机器学习,在感测δ-9-四氢大麻酚(THC)和大麻二酚(CBD)时,可以应对唾液与唾液之间的差异和交叉干扰。用相同的分析分子(m-Z-THC 和 m-Z-CBD)修饰的丝网印刷电极可用于检测真实人体唾液样本中 0 至 5 纳克 mL-1 范围内的超低浓度四氢大麻酚和大麻二酚。使用 m-Z-THC 或 m-Z-CBD 同时检测了 THC 和 CBD,以研究每种改良传感器的性能。此外,CBD 和 THC 具有相同的分子结构;原子排列方式仅有细微差别,因此这两种分子具有相似的电化学性能。因此,在使用电化学传感器检测四氢大麻酚时,CBD 可能会产生潜在干扰,而在检测 CBD 时,四氢大麻酚也可能会产生干扰。因此,为了克服这些问题,我们引入了机器学习来分析传感器的分析响应。数据处理结果表明,在唾液样本中检测 THC 和 CBD 的数据集中,两种传感器的训练准确率均为 100%,m-Z-THC 和 m-Z-CBD 的准确率分别为 92% 和 83%。此外,含有 CBD 和 THC 作为交叉干扰的唾液样本也被准确识别和分类。
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引用次数: 0
CRISPR/Cas13a-assisted amplification-free miRNA biosensor via dark-field imaging and magnetic gold nanoparticles† 通过暗场成像和磁性金纳米粒子实现 CRISPR/Cas13a 辅助的无扩增 miRNA 生物传感器
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-11 DOI: 10.1039/D4SD00081A
Jae-Jun Kim, Jae-Sang Hong, Hyunho Kim, Moonhyun Choi, Ursula Winter, Hakho Lee and Hyungsoon Im

MicroRNAs (miRNAs) are short (about 18–24 nucleotides) non-coding RNAs and have emerged as potential biomarkers for various diseases, including cancers. Due to their short lengths, the specificity often becomes an issue in conventional amplification-based methods. Next-generation sequencing techniques could be an alternative, but the long analysis time and expensive costs make them less suitable for routine clinical diagnosis. Therefore, it is essential to develop a rapid, selective, and accurate miRNA detection assay using a simple, affordable system. In this work, we report a CRISPR/Cas13a-based miRNA biosensing using point-of-care dark-field (DF) imaging. We utilized magnetic-gold nanoparticle (MGNPs) complexes as signal probes, which consist of 200 nm-sized magnetic beads and 60 nm-sized gold nanoparticles (AuNPs) linked by DNA hybridization. Once the CRISPR/Cas13a system recognized the target miRNAs (miR-21-5p), the activated Cas13a cleaved the bridge linker containing RNA sequences, releasing 60 nm-AuNPs detected and quantified by a portable DF imaging system. The combination of CRISPR/Cas13a, MGNPs, and DF imaging demonstrated amplification-free detection of miR-21-5p within 30 min at a detection limit of 500 attomoles (25 pM) and with single-base specificity. The CRISPR/Cas13a-assisted MGNP-DF assay achieved rapid, selective, and accurate detection of miRNAs with simple equipment, thus providing a potential application for cancer diagnosis.

微RNA(miRNA)是一种短的(约18-24个核苷酸)非编码RNA,已成为包括癌症在内的各种疾病的潜在生物标记物。由于其长度较短,在传统的扩增方法中,特异性往往成为一个问题。下一代测序技术可以作为一种替代方法,但其分析时间长、成本高昂,不太适合常规临床诊断。因此,开发一种利用简单、经济的系统进行快速、选择性和准确 miRNA 检测的方法至关重要。在这项工作中,我们报告了一种基于 CRISPR/Cas13a 的 miRNA 生物传感技术,该技术采用了床旁暗场(DF)成像技术。我们利用磁性金纳米粒子(MGNPs)复合物作为信号探针,该复合物由 200 nm 大小的磁珠(MBs)和 60 nm 大小的金纳米粒子(AuNPs)通过 DNA 杂交连接而成。一旦 CRISPR/Cas13a 系统识别到目标 miRNA(miR-21-5p),激活的 Cas13a 就会裂解含有 RNA 序列的桥连接体,从而释放出 60 nm-AuNPs 并通过便携式 DF 成像系统进行检测和量化。将 CRISPR/Cas13a、MGNPs 和 DF 成像相结合,在 30 分钟内对 miR-21-5p 进行了无扩增检测,检测限为 500 阿托摩尔,具有单碱基特异性。CRISPR/Cas13a辅助的MGNP-DF检测方法利用简单的设备实现了对miRNA的快速、选择性和准确检测,从而为癌症诊断提供了潜在的应用前景。
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引用次数: 0
A holistic pathway to biosensor translation 生物传感器转化的整体途径
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-11 DOI: 10.1039/D4SD00088A
Laena D'Alton, Dênio Emanuel Pires Souto, Chamindie Punyadeera, Brian Abbey, Nicolas H. Voelcker, Conor Hogan and Saimon M. Silva

Point-of-care (POC) biosensors have enormous potential to help guide and inform clinical decisions at a patient's location. They are particularly relevant to underserved populations, and people living in remote locations where healthcare infrastructure and resources are often limited. The translation of effective POC biosensors into commercial products is rapidly growing across many research fields. A significant quantity of scientific articles focused on the fundamental, applied, and proof-of-concept aspects of biosensing are reported each year. However, this extensive body of work is not reflected in the comparatively small number of commercial biosensors available on the market. Here, we discuss key aspects of the biosensor translation process including the selection of analytical biomarkers in various body fluids, clinical trials, regulatory approval, consumer engagement, manufacturing and scale-up strategies, health economics, and legal and ethical considerations.

护理点(POC)生物传感器具有巨大的潜力,可在患者所在地帮助指导和告知临床决策。它们尤其适用于服务不足的人群和生活在偏远地区的人们,因为那里的医疗基础设施和资源往往有限。在许多研究领域,将有效的 POC 生物传感器转化为商业产品的工作正在迅速发展。每年都有大量关于生物传感的基础、应用和概念验证方面的科学文章被报道。然而,市场上商业生物传感器的数量相对较少,这并没有反映出大量的研究成果。在此,我们将讨论生物传感器转化过程中的关键环节,包括各种体液中分析生物标记物的选择、临床试验、监管审批、消费者参与、生产和扩大规模策略、卫生经济学以及法律和伦理方面的考虑。
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引用次数: 0
Cu2+-integrated carbon dots as an efficient bioprobe for the selective sensing of guanine nucleobase† Cu2+ 集成碳点作为选择性感知鸟嘌呤核碱基的高效生物探针
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-07-09 DOI: 10.1039/D4SD00137K
Monalisa Chowdhury, Debolina Basu and Prasanta Kumar Das

This present work aimed to craft copper (Cu2+)-doped carbon dots (CuCDs) for the selective and sensitive detection of a guanine nucleobase. By employing a hydrothermal method, we synthesized blue-emitting CuCDs having emission maxima at 423 nm. CuCDs were used as a fluorescence turn-on ratiometric probe to detect guanine, a critical purine base in DNA involved in energy transduction, cell signalling, and metabolic processes. In the presence of guanine, the fluorescence intensity of CuCDs significantly increased due to the stable non-covalent interaction between Cu2+ and guanine. CuCDs achieved a very low limit of detection (LOD) of 0.59 nM for guanine as a highly sensitive probe. CuCDs demonstrated selectivity for guanine with no interference from other nucleobases (adenine, thymine, and cytosine) and various biomolecules and metal ions commonly found in the cellular environment. In addition, CuCDs demonstrated a higher affinity for guanine-enriched oligonucleotide cMYC G 27-mer over dsDNA 26-mer devoid of a large guanine population. Furthermore, the fluorescence intensity of CuCDs increased in guanine-treated mammalian cells and G-quadruplex-enriched cancer cells compared with that in non-cancerous cells. Hence, we developed a highly sensitive ratiometric fluorescence probe, CuCDs, for the selective detection of guanine both in vitro and within mammalian cells via a “fluorescence turn-on mechanism”.

本研究旨在制作掺铜(Cu2+)碳点(CuCD),用于选择性灵敏检测鸟嘌呤核碱基。我们采用水热法合成了蓝色发光的 CuCD 碳点,其最大发射波长为 423 nm。CuCD 被用作荧光开启比率探针来检测鸟嘌呤,鸟嘌呤是 DNA 中的重要嘌呤碱基,参与能量转移、细胞信号传递和新陈代谢过程。在鸟嘌呤存在的情况下,由于 Cu2+ 与鸟嘌呤之间稳定的非共价作用,CuCD 的荧光强度显著增加。作为一种高灵敏度探针,CuCD 对鸟嘌呤的检测限(LOD)非常低,仅为 0.59 nM。CuCD 对鸟嘌呤具有选择性,而对其他核碱基(腺嘌呤、胸腺嘧啶、胞嘧啶)以及细胞环境中常见的各种生物大分子和金属离子没有干扰。此外,CuCD 对富含鸟嘌呤的寡核苷酸 cMYC G 27-mer 的亲和力高于缺乏大量鸟嘌呤的 dsDNA 26-mer。此外,与非癌细胞相比,CuCD 在经鸟嘌呤处理的哺乳动物细胞和富含 G-四叠体的癌细胞中的荧光强度会增加。因此,我们开发了一种高灵敏度的比率荧光探针 CuCD,通过 "荧光开启机制 "在体外和哺乳动物细胞内选择性地检测鸟嘌呤。
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引用次数: 0
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