Biosensors and Bioelectronics最新文献_第4页

A facile liquid biopsy assay for highly efficient CTCs capture and reagent-less monitoring of immune checkpoint PD-L1 expression on CTCs with non-small cell lung cancer patients

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-06 DOI: 10.1016/j.bios.2025.117236

Yuping Liu , Beibei Zhang , Xueyuan Wu , Fan Wang , Zhiyi Yang , Mengyi Li , Kaixuan Sheng , Yue Yan , Liang Zhu , Hui Jing , Yanmin Wu , Lili Hu , Yanyan Yu , Chenglin Li

Programmed cell death 1 ligand 1 (PD-L1) immunotherapy holds a pivotal role in lung cancer treatment. However, current methods for monitoring PD-L1 expression exhibit several limitations, including hysteresis and the invasive nature of tissue sampling. Circulating tumor cells (CTCs), the important biomarkers in liquid biopsy, are minimally invasive and facilitate continuous monitoring. Consequently, integrating CTC counting with PD-L1 expression analysis offers more comprehensive insights for the development of personalized treatment strategies development and efficacy evaluations. In this study, we presented a facile liquid biopsy assay designed for the dynamic monitoring of PD-L1 expression on CTCs captured from non-small cell lung cancer (NSCLC) patients. This assay was achieved by fabricating two high-performance probes: EpCAM and Vimentin dual-aptamer modified nitrogen-doped carbon quantum dots probe (E/V-apt-N-CQDs) and hairpin PD-L1 aptamer coupled with gold nanoparticles (PD-L1-apt-AuNPs). The E/V-apt-N-CQDs probe effectively captured two types of CTC models (H1299 and A549) exhibiting differential PD-L1 expression. Additionally, reagent-less detection of PD-L1 levels on CTCs was achieved using a portable magnetic electrochemical sensor with excellent specificity and sensitivity, which was capable of measuring PD-L1 concentrations as low as 2 ng/mL. Finally, this assay was applied in 41 NSCLC patients to investigate the correlation between CTC numbers or PD-L1 expression and disease progression and immunotherapy efficacy. The results indicated a significant association between elevated CTC counts or reduced PD-L1 levels and clinical progression. Moreover, this liquid assay successfully monitored dynamic changes in CTCs and PD-L1 expression in NSCLC patients receiving immunotherapy, indicating its potential for clinical application.

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引用次数: 0

Tidal microfluidic chip-based isolation and transcriptomic profiling of plasma extracellular vesicles for clinical monitoring of high-risk patients with hepatocellular carcinoma-associated precursors

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-06 DOI: 10.1016/j.bios.2025.117228

Kezhen Yi , Zhonglin Zhang , Peng Chen , Xiaodan Xi , Xudong Zhao , Yuan Rong , Fei Long , Qian Zhang , Ying Zhang , Menglu Gao , Weihuang Liu , Bi-Feng Liu , Zhenyu Zhu , Fubing Wang

Hepatocellular carcinoma (HCC) poses a significant global health burden, with escalating incidence rates and substantial mortality. The predominant etiological factors include liver cirrhosis (LC) and chronic hepatitis B infections (CHB). Surveillance primarily relies on ultrasound and Alpha-fetoprotein (AFP), yet their efficacy, particularly in early HCC detection, is limited. Hence, there is a critical need for accurate non-invasive biomarkers to enhance surveillance and early diagnosis.

Extracellular vesicles (EVs) hold promises as stable carriers of signaling molecules, offering potential in tumor diagnosis. Our study developed a novel tidal microfluidic chip for label-free EV isolation, enabling rapid and efficient enrichment from small plasma volumes. Through transcriptome sequencing and single-cell analysis, we identified HMMR and B4GALT2 as promising HCC-associated biomarkers in EVs.

In a comprehensive clinical evaluation, bi-mRNAs in EVs exhibited superior diagnostic performance over AFP, particularly in distinguishing early-stage HCC or AFP-negative cases from high-risk individuals (CHB/LC). Notably, our study demonstrated the potential of bi-mRNAs to complement imaging examinations, enabling early detection of HCC lesions.

In conclusion, the tidal microfluidic chip offers a practical solution for EV isolation, with the integration of EV-based biomarkers presenting opportunities for improved early detection and management of HCC in clinical practice.

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引用次数: 0

In situ pH-Controlled electrochemical sensors for glucose and pH detection in calf saliva

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-06 DOI: 10.1016/j.bios.2025.117234

Md Ridwan Adib , Colm Barrett , Shane O'Sullivan , Anna Flynn , Marie McFadden , Emer Kennedy , Alan O'Riordan

Electrochemical biosensors have been extensively researched and employed across diverse fields from environmental monitoring to clinical diagnostics. Detecting biomarkers like saliva pH and glucose are crucial indicators of the health and well-being of animals and opens the door for development of new non-invasive calf health measurements. Herein, we introduce a highly sensitive and stable electrochemical sensor for detection of pH and glucose in artificial and calf saliva. Pristine gold electrodes were employed for pH measurement using the voltage where the minimum of the gold oxide reduction peak occurred as a pH indicator. For glucose sensing, we utilized an effective in-situ pH control method enabled by interdigitated microelectrodes (IDEs) to optimize pH for accurate detection of glucose in artificial and calf saliva. Glucose oxidase (GOx) was first immobilized onto a platinum black modified gold IDE array through an electrodeposition process, which involved a mixture of o-phenylenediamine (o-PD) and β-cyclodextrin (β-CD). The enzymatic based glucose sensor showed an exceptional sensitivity of −0.46 nA mM⁻¹ in artificial saliva at a wide range of concentrations from 0.02 mM to 7 mM, with a LOD of 0.3 μM. Simultaneously, a sensitivity of −166 mV.pH⁻¹ was recorded for the pH sensor within the pH range of 5–9. These multiplexed sensors successfully detected glucose and pH levels in calf saliva noninvasively, which is particularly significant for meeting the frequent and continuous monitoring requirements of biomarkers (glucose, pH) associated with Bovine respiratory disease (BRD) and diarrhoetic calves.

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引用次数: 0

Catalytic boost in dual-active sites hierarchical hollow nanozymes: An enhanced robust and sensitive immunochromatographic assay for Aspergillus flavus.

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-05 DOI: 10.1016/j.bios.2025.117223

Meijuan Liang, Xiaofeng Hu, Du Wang, Xiaoqian Tang, Qi Zhang, Peiwu Li

The practical application of nanozyme-mediated Point-of-Care Testing (POCT) is always constrained by insufficient sensitivity, slow development time, and limited robustness. Here, we developed a dual-active site hierarchical hollow CuS@MIL-100(Fe) (CuS@MIL) nanozyme through an easy-to-operate process. The resultant CuS@MIL nanozyme exhibited a 5- and 3-fold increase in catalytic efficiency relative to CuS and MIL-100, while the color development time was shortened by more than 6-fold. Meanwhile, CuS@MIL retained 91.4% of its catalytic activity after six months of storage, indicating its robustness. Density functional theory (DFT) revealed that the improved catalytic activity of CuS@MIL nanozyme was associated with low energy barriers for •OH generation and efficient interfacial electron transfer at Cu-Fe dual-active sites. Leveraging their high and stable catalytic performance, a sensitive colorimetric lateral flow immunoassay (LFA) was applied for detection of Aspergillus flavus (A. flavus), achieving a 200- and 5.6-fold increase in sensitivity compared to conventional and nanozyme-based colorimetric methods. Attractively, the LFA effectively detected A. flavus in peanuts with results closely matching those of ELISA, demonstrating the potential for rapid, efficient, sensitive and robust colorimetric POCT.

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引用次数: 0

ViPER: A visual bipolar electrochemical biosensor based on isothermal addition of a universal tag for detection of SARS-CoV-2

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-04 DOI: 10.1016/j.bios.2025.117199

Seyedeh Malahat Shadman , Reyhaneh Tavakoli-Koopaei , Masoud A. Mehrgardi , Fatemeh Javadi-Zarnaghi

Emergence of recent pandemics/endemics e.g. COVID-19 and Dengue fever, demonstrated the necessity of development of strategies for swift adaptation of present biosensor for detection of the new emerging pathogens. However, development of a biosensor for a new target is time- and labor-consuming. In this study, we aimed to integrate the primer exchange reaction (PER), an isothermal technique that extends an initiator DNA with a user-defined single-stranded DNA tail, with bipolar electrochemistry. This integration led to the development of a universal biosensor, termed ViPER. We demonstrated the utility of the developed system to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic RNA as a model. The genomic RNA was reverse transcribed to a short cDNA and was tailed with a universal tag, consequently, the tagged cDNA was applied to an electrochemiluminescence integrated bipolar electrochemical biosensor (BPE-ECL). ECL signals were recorded using a digital camera and analyzed by ImageJ. The platform demonstrated a linear response over a wide dynamic range of 10⁻⁷-10⁻¹⁷ M for the target nucleic acid with a detection limit of 2.31 × 10⁻¹⁷ M for synthetic targets. The biosensor could also successfully discriminate between biological RNA samples from infected and non-infected individuals. This study introduces the potential of DNA-based visual biosensors for detecting single-stranded RNAs in low-equipped environments, and it holds promises for further development of an ultrasensitive method for various human RNA-based viral pathogens. Moreover, we can design a platform with a predetermined DNA probe sequence for a vast variety of different targets, simply by changing the PER input.

最近出现的大流行病/流行病（如 COVID-19 和登革热）表明，有必要制定战略，迅速调整现有的生物传感器，以检测新出现的病原体。然而，针对新目标开发生物传感器既费时又费力。在这项研究中，我们的目标是将引物交换反应（PER）与双极电化学技术相结合，引物交换反应是一种等温技术，可将启动子 DNA 与用户定义的单链 DNA 尾部进行延伸。通过这种整合，我们开发出了一种通用生物传感器，称为 ViPER。我们以检测严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）基因组 RNA 为模型，展示了所开发系统的实用性。将基因组 RNA 反转录为短 cDNA，并在其尾部加上通用标签，然后将标记的 cDNA 应用于电化学发光集成双极电化学生物传感器（BPE-ECL）。使用数码相机记录 ECL 信号，并用 ImageJ 进行分析。该平台在 10-7-10-17 M 的宽动态范围内对目标核酸呈线性响应，对合成目标的检测限为 2.31 × 10-17 M。该生物传感器还能成功区分感染者和非感染者的生物 RNA 样品。这项研究介绍了基于 DNA 的可视生物传感器在低装备环境中检测单链 RNA 的潜力，并有望进一步开发出针对各种基于人类 RNA 的病毒病原体的超灵敏方法。此外，我们只需改变 PER 输入，就能设计出具有预定 DNA 探针序列的平台，用于检测各种不同的目标。

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引用次数: 0

Upconversion nanoparticle-based optical biosensor for early diagnosis of stroke

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-03 DOI: 10.1016/j.bios.2025.117227

Pragati Kakkar , Tarun Kakkar , Padmaja Parameswaran Nampi , Gin Jose , Sikha Saha

Over 17 million people experience a stroke episode annually, with 5.9 million deaths. Stroke is diagnosed by physical tests and neuroimaging which need to be performed quickly to determine if the stroke is caused by ischaemia or haemorrhage. Neuroimaging can reliably confirm bleeding, but many patients with suspected ischaemic stroke (up to 40%) are subsequently confirmed to have alternative pathologies e.g., migraine or seizures (stroke mimics) delaying the transfer of stroke patients to an acute stroke unit for early intervention and treatment. Thus, a simple complimentary blood biomarker test to differentiate stroke patients from non-stroke patients with similar clinical symptoms is essential in prehospital and emergency settings for efficient stroke management and prompt treatment. The current 'Gold Standard' technique for detecting protein biomarkers is complex, time-consuming, and requires automated equipment. In this study, we have developed a proof-of-concept of lanthanide-doped upconversion nanoparticle (UCNP)-based optical biosensor platform for detecting glial fibrillary acidic protein (GFAP), a potential stroke biomarker, in human blood serum. The results show a linear response in photoluminescence quenching of UCNP conjugated GFAP antibody with the increasing concentration of GFAP biomarker in human blood serum. This approach can be used in the ambulance and Emergency Department to quickly diagnose a stroke. In the longer term, such techniques can be integrated into a self-assessment kit to monitor those patients who are at risk after strokes.

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引用次数: 0

Detection of brain metastases from blood using Brain nanoMET sensor: Extracellular vesicles as a dynamic marker for metastatic brain tumors 利用脑纳米MET传感器从血液中检测脑转移瘤：细胞外囊泡作为转移性脑肿瘤的动态标记物。

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-01 DOI: 10.1016/j.bios.2024.116968

Srilakshmi Premachandran , Ishita Shreshtha , Krishnan Venkatakrishnan , Sunit Das , Bo Tan

Brain metastases account for a significant number of cancer-related deaths with poor prognosis and limited treatment options. Current diagnostic methods have limitations in resolution, sensitivity, inability to differentiate between primary and metastatic brain tumors, and invasiveness. Liquid biopsy is a promising non-invasive alternative; however, current approaches have shown limited efficacy for diagnosing brain metastases due to biomarker instability and low levels of detectable tumor-specific biomarkers. This study introduces an innovative liquid biopsy technique using extracellular vesicles (EVs) as a biomarker for brain metastases, employing the Brain nanoMET sensor. The sensor was fabricated through an ultrashort femtosecond laser ablation process and provides excellent surface-enhanced Raman Scattering functionality. We developed an in vitro model of metastatic tumors to understand the tumor microenvironment and secretomes influencing brain metastases from breast and lung cancers. Molecular profiling of EVs derived from brain-seeking metastatic tumors revealed unique, brain-specific signatures, which were also validated in the peripheral circulation of brain metastasis patients. Compared to primary brain tumor EVs, we also observed an upregulation of PD-L1 marker in the metastatic EVs. A machine learning model trained on these EV molecular profiles achieved 97% sensitivity in differentiating metastatic brain cancer from primary brain cancer, with 94% accuracy in predicting the primary tissue of origin for breast metastasis and 100% accuracy for lung metastasis. The results from this pilot validation suggest that this technique holds significant potential for improving metastasis diagnosis and targeted treatment strategies for brain metastases, addressing a critical unmet need in neuro-oncology.

在与癌症相关的死亡病例中，脑转移瘤占了很大一部分，其预后较差，治疗方案有限。目前的诊断方法在分辨率、灵敏度、无法区分原发性和转移性脑肿瘤以及侵入性方面存在局限性。液体活检是一种很有前景的非侵入性替代方法；然而，由于生物标志物不稳定和可检测到的肿瘤特异性生物标志物水平较低，目前的方法对诊断脑转移瘤的疗效有限。本研究介绍了一种创新的液体活检技术，利用细胞外囊泡 (EV) 作为脑转移瘤的生物标记物，并采用了脑纳米MET 传感器。该传感器通过超短飞秒激光烧蚀工艺制作而成，具有出色的表面增强拉曼散射功能。我们开发了转移性肿瘤的体外模型，以了解肿瘤微环境和影响乳腺癌和肺癌脑转移的分泌物。从脑转移瘤中提取的EVs分子图谱揭示了独特的脑特异性特征，这些特征在脑转移患者的外周循环中也得到了验证。与原发性脑肿瘤EV相比，我们还观察到转移性EV中PD-L1标记物的上调。根据这些EV分子图谱训练的机器学习模型在区分转移性脑癌和原发性脑癌方面的灵敏度达到97%，在预测乳腺癌转移的原发组织方面的准确度达到94%，在预测肺转移方面的准确度达到100%。这项试验验证的结果表明，这项技术在改善脑转移瘤的转移诊断和靶向治疗策略方面具有巨大潜力，解决了神经肿瘤学领域尚未满足的关键需求。

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引用次数: 0

Stable liquid crystal-infiltrated photonic crystal sensing film for facile detection of streptomycin

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-01 DOI: 10.1016/j.bios.2025.117225

Anping Zhu, Wenting Gong, Deyan Bu, Jun Zhou, Zhaoyang Wu, Ruqin Yu

Liquid crystal (LC) biosensors have attracted interest due to their simplicity and ability to visualize results. However, their inherent instability including the fluidity of LCs and the complexity of operation, limits their potential as reliable and user-friendly detection tools. To enhance their practical applicability, a stable and facile LC-infiltrated photonic crystal (LCP) sensing film is developed through optimization of film substrate preparation and investigation of the response mechanism. The reflection peak of the LCP film, which is modulated by changes in LC orientation within the film, can be recorded using a fiber-optic spectrometer or observed visually. Molecular dynamics simulations, integrated with experimental data, were employed to improve LC induction efficiency and increase signal strength. This approach inherently improves the stability and sensitivity of LC biosensors, expanding their potential for use in compact devices. A triple-helix molecular conformational switch is introduced to establish a versatile and specific detection platform. When streptomycin was chosen as a model analyte, the LCP film exhibited a linear range from 5 nM to 10 μM, with a detection limit of 0.40 nM and a relative standard deviation of 2.19%, indicating high precision and reliability. Its practical application was further confirmed with food samples, highlighting its potential for at-home testing of antibiotic residues.

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引用次数: 0

Functionalized cascaded tapered optical fiber sensor for simultaneous detection of dengue II E and SARS-CoV-2 S proteins.

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-01 DOI: 10.1016/j.bios.2025.117200

Nurul Nadiah Zulkeflee, Yasmin Mustapha Kamil, Syamsiah Mashohor, Muhammad Hafiz Abu Bakar

This work demonstrates a label-free dual-sensing biosensor utilizing cascaded single-mode tapered fiber (SMTF) for the concurrent detection of Dengue II envelope (E) and SARS-CoV-2 spike (S) proteins. Two fiber tapers of different dimensions were employed in-line, with each taper functionalized with specific complementary antibodies to the targeted antigens. The cascaded interferometric effect yielded composite spectral output that exhibited discrete response toward localized refractive index changes due to binding of antigens and antibodies. Consistent red shifts were observed with increasing concentration of the targeted analyte, which led to sensitivity values of 6.91 nm/nM for SMTF1 and 9.96 nm/nM for SMTF2, with a detection limit of 0.1 pM. This dual-sensing platform demonstrates high sensitivity and specificity, rapid response times, and the potential for integration into portable diagnostic devices, presenting it as a promising tool for point-of-care diagnostics and simultaneous detection of multiple disease biomarkers.

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引用次数: 0

Bivariate tracking of NIR phototherapeutic probe that illuminates the deterioration process of NAFLD-HCC 对照亮非酒精性脂肪肝-肝癌恶化过程的近红外光疗探针进行双变量追踪。

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2025-02-01 DOI: 10.1016/j.bios.2024.116967

Jialu Yang , Huimin Xu , Yijun Zhao , Pengju Sun , Yuanyuan Li , Ting Chen , Yanmei Zhou

Non-alcoholic fatty liver disease (NAFLD) has evolved to become a major cause of hepatocellular carcinoma (HCC). Visualization of NAFLD-HCC deterioration process imaging is essential to understand the underlying pathophysiological processes. However, currently relevant probes with short emission wavelengths, univariate and the inability to achieve theranostics functionality have encountered obstacles in further evaluating the NAFLD-HCC process. Here, we present a carboxylesterase (CE)-activated NIR fluorescent probe (BODJ) which has lipid droplets (LDs)-targeting ability and emits at a wavelength of 858 nm with a fluorescence quantum yield of 19.06%. CE-activated BODJ was used as a visual tool to successfully visualize both NAFLD deterioration processes and HCC in situ based on changes in the average number of LDs and the associated fluorescence intensity fluctuations. Imaging results showed that changes associated with CE and LDs in the modelled cells varied during the transition from nonalcoholic fatty liver to nonalcoholic steatohepatitis and later progression to HCC, highlighting the close association between bivariate and disease. We also demonstrate that BODJ has photodynamic (PDT) and photothermal therapy (PTT) capabilities, allowing image-guided dual phototherapy to damage HCC in situ. This NIR probe, which takes advantage of bivariate to track the deterioration process that illuminates NAFLD-HCC and has dual phototherapy capabilities, provides new ideas for the design of probes related to the diagnosis and treatment of hepatic metabolic diseases.

非酒精性脂肪肝（NAFLD）已发展成为肝细胞癌（HCC）的主要诱因。非酒精性脂肪肝-肝癌恶化过程的可视化成像对于了解潜在的病理生理过程至关重要。然而，目前的相关探针发射波长短、单一，而且无法实现治疗功能，这些都为进一步评估非酒精性脂肪肝-肝癌的过程设置了障碍。在这里，我们提出了一种羧基酯酶（CE）激活的近红外荧光探针（BODJ），它具有脂滴（LDs）靶向能力，发射波长为858 nm，荧光量子产率为19.06%。CE 激活的 BODJ 被用作一种可视化工具，根据 LDs 平均数量的变化和相关的荧光强度波动，成功地对非酒精性脂肪肝恶化过程和原位 HCC 进行可视化。成像结果表明，在非酒精性脂肪肝向非酒精性脂肪性肝炎过渡以及随后向 HCC 发展的过程中，模型细胞中与 CE 和 LDs 相关的变化各不相同，这突出表明了双变量与疾病之间的密切联系。我们还证明了 BODJ 具有光动力疗法（PDT）和光热疗法（PTT）的能力，可在图像引导下进行双重光疗，对 HCC 造成原位损伤。这种近红外探针利用双变量的优势跟踪非酒精性脂肪肝-HCC的恶化过程，并具有双重光疗功能，为肝脏代谢疾病诊断和治疗相关探针的设计提供了新思路。

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引用次数: 0