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TALANTA · 2024 · IF 5.6

Establishment of MS LOC platform and its pilot application in clinical lipidomics

Xiaoming Chen,Shuo Cao,Liye Tao,Runlan Yan,Sheng Cao,Jingwen Hao,Yuelin Yi,Chunyan Luan,Jianmin Wu,Yue Gao,Xiao Liang

Lipidomics has demonstrated significant potential for disease diagnosis and prediction. The development and optimization of a robust mass spectrometry (MS) platform for lipidome analysis is critically important, as it can facilitate biomarker discovery, cohort testing, and performance evaluation in clinical lipidomics studies. In this work, we developed a high-throughput and reliable platform, termed MS Lab on a Chip ( MS LOC ), which integrates the MetArray chip, an automated lipidomics pretreatment protocol, and the reflectron matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) instrument. The MetArray chip, produced through a mass production process, exhibited exceptional stability as an MS substrate. The integration of automated lipid pretreatment and MS detection processes ensures high throughput, stability and efficiency during sample preparation. The analysis of various lipid standards and different types of biological samples enabled comprehensive investigation of lipid features and annotation using the MS LOC . Furthermore, a small cohort study, consisting of hepatocellular carcinoma (HCC) and non-HCC groups, was conducted on this platform, providing preliminary validation of its performance and suggesting that this platform offers a comprehensive protocol for clinical lipidomics testing.

CAS / MDL: 25037-45-0
研究领域: 分析化学 · 临床研究 · 质谱技术 · 组学技术
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 43 ·8931-8944 · IF 7.571

A capillary-driven LoC-SERS device integrated with catalytic hairpin assembly amplification technology for NSCLC-related biomarkers detection

Shengjie Ge,Yujie Wang,Zhiyue Li,Bin Lu,Jinhua Zhu,Hongmei Lu,Xiaowei Cao,Yayun Qian

In this study, we apply catalytic hairpin assembly (CHA) as the signal amplification strategy for the quantification of carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA21-1) with a surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) as the carrier. Herein, antibody–DNA conjugates are designed to assist the application of CHA amplification in protein detection. In the presence of protein biomarkers, antibody–DNA conjugates can specifically bind to the target proteins, forming the antigen@antibody–DNA conjugates. The terminal free part of the DNA on the conjugates can trigger the CHA events to connect SERS nanotags to capture nanoprobes. Then, micro-magnet can gather the CHA products in a rectangular chamber, resulting in the aggregation of SERS nanotags, which can ultimately generate abundant “hot spots” for SERS signal enhancement. Using this strategy, CEA and CYFRA21-1 can be successfully determined with a limit of detection (LOD) as low as pg mL−1, much lower than recently reported methods. Meanwhile, a non-small cell lung cancer (NSCLC)-xenografted mouse model was established, and SERS was applied to analyze the expression level of CEA and CYFRA21-1 in tumorigenesis and development. The comparison between SERS results and those of the ELISA method demonstrated a high degree of consistency, suggesting that the proposed CHA-assisted LoC-SERS device has satisfying accuracy. Thus, introducing the CHA strategy via the design of antibody–DNA conjugates opens new gates to ultra-sensitive and specific SERS detection of protein biomarkers.

研究领域: 生物医学工程 · 分析化学 · 癌症研究 · 分子生物学
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TALANTA · 2023 · IF 6.1

LoC-SERS platform for rapid and sensitive detection of colorectal cancer protein biomarkers

Xiaowei Cao,Zhengqing Liu,Xiaogang Qin,Yuexing Gu,Yong Huang,Yayun Qian,Zhenguang Wang,Hongbo Li,Qunshan Zhu,Wei Wei

Colorectal cancer (CRC) remains a significant contributor to the global mortality rate, and a single biomarker cannot meet the specificity required for CRC screening. To this end, we developed a multiplexed, pump-free surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) using a one-step recognition release mechanism; the aptamer-functionalized novel Au nanocrown array (AuNCA) was used as the detection element embedded in the detection zone of the platform for rapid and specific detection of protein markers in multiple samples simultaneously. Here, the corresponding aptamer specifically captured the protein marker, causing the complementary strand of the aptamer carrying the Raman signal molecule to be shed, reducing the SERS signal. Based on this platform, sensitive and specific detection of the target can be accomplished within 15 min with detection limits of 0.031 pg/mL (hnRNP A1) and 0.057 pg/mL (S100P). Meanwhile, the platform was consistent with ELISA results when used to test clinical. By substituting different aptamers, this platform can provide a new solution for the rapid and sensitive detection of protein markers, which has promising applications in future disease detection.

研究领域: 生物医学工程 · 癌症研究 · 分析化学 · 分子生物学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

LoC-SERS Platform Integrated with the Signal Amplification Strategy toward Parkinson’s Disease Diagnosis

Xiaowei Cao,Shengjie Ge,Miao Chen,Haiyan Mao,Ying Wang

Multiplexed detection of Parkinson’s disease (PD) biomarkers is of great significance for early diagnosis and personalized treatment. In this study, we fabricated a robust surface-enhanced Raman scattering-enabled lab-on-a-chip (LoC-SERS) platform for simultaneous quantification of α-synuclein, phosphorylated tau protein 181, osteopontin, and osteocalcin. Herein, the antibody–DNA conjugate was designed to introduce the catalytic hairpin self-assembly (CHA) amplification into the protein detection. Au nano-stars (AuNSs) modified with Raman reporter molecules and hairpin-structure DNA 1 were applied as the SERS nanotags. Au-coated silicon nanocone array (Au/SiNCA) fabricated based on the maskless plasma etching-prepared high-density Si nanocone array (SiNCA) and surface ion sputtering was used as the capture substrate after the modification of hairpin-structure DNA 2. Benefitting from the antibody–DNA conjugate-induced CHA amplification, numerous AuNSs can be connected to the Au/SiNCA surface, which significantly amplify the plasmonic coupling effect for ultrasensitive SERS detection, and the limit of detection was less than the pg/mL level. The application of highly uniform Au/SiNCA and antibody–DNA conjugate endows the LoC-SERS platform excellent analytical performance, including superior reproducibility, satisfactory universality, and high sensitivity. In addition, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model was established, and satisfactory results were obtained in real sample analysis with the LoC-SERS platform, which may be enlightening for exploiting protein biomarkers in PD monitoring.

研究领域: 生物医学工程 · 分析化学 · 神经科学 · 疾病诊断
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MICROCHEMICAL JOURNAL · 2023 · IF 4.8

Aptamer-based LoC-SERS sensing system for rapid and highly sensitive detection of gastric cancer

Miao Chen,Shenghua Yao,Yongguo Yang,Fengjuan Jiang,Yan Yang,Yuexing Gu,Zhenguang Wang,Xiaowei Cao,Wei Wei

Multiplex detection of biomarkers is nontrivial for gastric cancer diagnosis. Herein, we presented a lab-on-a-chip surface-enhanced Raman scattering (LoC-SERS) sensing system for the detection of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-B (PDGF-B). The sensing system includes three parallel channels, each channel consists of two detection chambers, enabling the simultaneous analysis of multiple samples. The capillary structure provides self-driving power without the need of external pumps. The ordered gold nano-bipyramids (GNBPs) array in the detection chamber can form uniform and dense “hot spots”, due to the homogeneous double-tip structure and narrow gaps, resulting in better SERS performance. During the analysis process, VEGF and PDGF-B in the serum can lead to the change of aptamer conformation. Raman reporter-labeled complementary DNA is shed from the aptamer due to competition of the target. The entire process only requires 20 min, which is rapid. By monitoring the changes in Raman intensity and fitting it with the logarithm of concentration, the correlation between the intensity and concentration can be clearly reflected as a mathematical relationship. The LoC-SERS sensing system has been verified to have excellent selectivity and reproducibility. Via the sensing system, the limits of detection (LOD) of VEGF and PDGF-B are as low as 0.342 pg/mL and 0.265 pg/mL in serum, respectively. In addition, the accuracy was verified through enzyme-linked immunosorbent assay (ELISA). Therefore, the proposed LoC-SERS sensing system has great potential for clinical detection of gastric cancer.

研究领域: 生物医学工程 · 癌症诊断 · 纳米技术 · 分析化学
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ANALYTICA CHIMICA ACTA · 2023 · IF 6.2

Multiplex signal amplification strategy-based early-stage diagnosis of Parkinson's disease on a SERS-enabled LoC system

Shengjie Ge,Gaoyang Chen,Jialin Deng,Yuexing Gu,Yu Mao,Xinyu Zhou,Guang Li

In this paper, a multiplex signal amplification strategy was developed for the determination of miR-214 and miR-221 on a surface-enhanced Raman scattering (SERS)-enabled lab-on-a-chip (LoC) system to realize the early-stage diagnosis of Parkinson's disease (PD). The gold nanobipyramids (GNBPs) with great monodispersity were functionalized with Raman reporter molecules and hairpin DNA 1, serving as the SERS nanotags. The presence of targets can initial the strand displacement amplification (SDA) reaction and the numerous short-stranded trigger DNA (tDNA) can be released under the action of polymerase and nicking enzyme . Then, the tDNA can trigger the catalytic hairpin assembly (CHA) event between the SERS nanotags and the capture nanoprobes (Magnetic beads (MBs) modified with hairpin DNA 2), resulting in the aggregation of GNBPs on the MBs surface. The multiplex signal amplification contributed by the SDA-CHA strategy and the magnet-induced aggregation effect can ultimately lead to the significant improvement of the detection sensitivity and the limit of detection (LOD) was low to aM level with reproducibility and specificity meanwhile. Furthermore, a MPTP-induced PD mice model was established to verify the practicability and the expression level of miR-214 and miR-221 at different stages analyzed with the LoC system was confirmed by qRT-PCR.

研究领域: 医学诊断 · 生物化学 · 纳米技术
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IEEE SENSORS JOURNAL · 2025 · IF 4.5

Integration of An Open EWOD Structure and Printed Electrochemical Sensors on Common Digital Microfluidic Platform

Zhiwei Zhang,Yi Li,Lulu Liu,Peilin Mao,Lei Zhang,Jie Liang,Jianhua Zhang

Digital microfluidics (DMF) technology provides high-precision and flexible liquid manipulation capabilities for lab-on-a-chip (LOC) systems, enabling complex biochemical reactions and detection analyses within a compact space. Electrowetting-on-dielectric (EWOD), one of the most widely used actuation mechanisms in DMF devices, is favored for its simplicity, controllability, rapid response, and cost-effectiveness. However, due to challenges in fabricating sensors on hydrophobic surfaces, reports on EWOD chips integrated with biosensors remain limited. In this work, we successfully integrated electrochemical sensors into EWOD chips via plasma treatment for surface modification. The plasma-treated EWOD device maintained excellent droplet actuation performance (movement time <8 s) and achieved glucose detection in the 0-0.6 mM range using the embedded sensor. The limit of detection was determined to be 0.056 mM (S/N = 3). This EWOD chip with integrated printed electrochemical sensors represents a promising tool for diverse biochemical analyses.

研究领域: 微流控技术 · 生物分析化学 · 传感器 · 芯片实验室技术 · 电化学 · 生物医学工程
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AAPS PHARMSCITECH · 2023 ·Vol. 24 ·期 4 ·1-18 · IF 3.3

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy

Cao Xia,Liu Qi,Adu-Frimpong Michael,Shi Wenwan,liu Kai,Deng Tianwen,Yuan Hui,Weng Xuedi,Gao Yihong,Yu Qingtong,Deng Wenwen,Yu Jiangnan,Wang Qilong,Xiao Gao,Xu Ximing

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro . (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes. Graphical Abstract

研究领域: 肿瘤学 · 药学 · 生物医学工程 · 纳米技术
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