Isolation and quantification of L1CAM-positive extracellular vesicles on a chip as a potential biomarker for Parkinson's Disease

IF 15.5 1区 医学 Q1 CELL BIOLOGY Journal of Extracellular Vesicles Pub Date : 2024-06-19 DOI:10.1002/jev2.12467
Danyu Li, Siyi Zou, Ziyang Huang, Congcong Sun, Guozhen Liu
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Abstract

Extracellular vesicles (EVs) carry disease-specific molecular profiles, demonstrating massive potential in biomarker discovery. In this study, we developed an integrated biochip platform, termed EVID-biochip (EVs identification and detection biochip), which integrates in situ electrochemical protein detection with on-chip antifouling-immunomagnetic beads modified with CD81 antibodies and zwitterion molecules, enabling efficient isolation and detection of neuronal EVs. The capability of the EVID-biochip to isolate common EVs and detect neuronal EVs associated with Parkinson's disease in human serum is successfully demonstrated, using the transmembrane protein L1-cell adhesion molecule (L1CAM) as a target biomarker. The EVID-biochip exhibited high efficiency and specificity for the detection of L1CAM with a sensitivity of 1 pg/mL. Based on the validation of 76 human serum samples, for the first time, this study discovered that the level of L1CAM/neuronal EV particles in serum could serve as a reliable indicator to distinguish Parkinson's disease from control groups with AUC = 0.973. EVID-biochip represents a reliable and rapid liquid biopsy platform for the analysis of complex biofluids offering EVs isolation and detection in a single chip, requiring a small sample volume (300 µL) and an assay time of 1.5 h. This approach has the potential to advance the diagnosis and biomarker discovery of various neurological disorders and other diseases.

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在芯片上分离和量化 L1CAM 阳性细胞外囊泡,作为帕金森病的潜在生物标记物。
细胞外囊泡(EVs)携带疾病特异性分子特征,在生物标记物发现方面具有巨大潜力。在这项研究中,我们开发了一种名为 EVID-生物芯片(EVs identification and detection biochip)的集成生物芯片平台,该平台将原位电化学蛋白检测与经 CD81 抗体和齐聚物分子修饰的芯片抗偶联免疫磁珠整合在一起,实现了对神经元 EVs 的高效分离和检测。以跨膜蛋白 L1-细胞粘附分子(L1CAM)为目标生物标记物,成功证明了 EVID 生物芯片分离普通 EV 和检测人类血清中与帕金森病相关的神经元 EV 的能力。EVID 生物芯片对 L1CAM 的检测具有高效性和特异性,灵敏度为 1 pg/mL。基于对76份人类血清样本的验证,该研究首次发现血清中L1CAM/神经元EV颗粒的水平可作为区分帕金森病和对照组的可靠指标,AUC = 0.973。EVID-生物芯片是一种可靠、快速的液体活检平台,可用于分析复杂的生物流体,在单个芯片中进行EVs分离和检测,只需少量样品(300微升),检测时间为1.5小时。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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