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ANALYTICAL CHEMISTRY · 2013 · IF 5.695

Surface-Enhanced Raman Scattering Chip for Femtomolar Detection of Mercuric Ion (II) by Ligand Exchange

Yuanxin Du,Renyong Liu,Bianhua Liu,Suhua Wang,Ming-Yong Han,Zhongping Zhang

The chemical sensing for the convenient detection of mercuric ion (II) (Hg2+) have been widely explored with the use of various sensing materials and techniques. It still remains a challenge to achieve ultrasensitive but simple, rapid, and inexpensive detection to metal ions. Here we report a surface-enhanced Raman scattering (SERS) chip for the femtomolar (fM) detection of Hg2+ by employing silver-coated gold nanoparticles (Au@Ag NPs) together with an organic ligand. 4,4′-Dipyridyl (Dpy) can control the aggregation of Au@Ag NPs via its dual interacting sites to Ag nanoshells to generate strong Raman hot spots and SERS readouts. However, the presence of Hg2+ can inhibit the aggregation of Au@Ag NPs by the coordination with Dpy, and as a result the SERS signals of Dpy are quenched. On the basis of these findings, a SERS chip has been fabricated by the assembly of Au@Ag NPs on a piece of silicon wafer and the further modification with Dpy. The exchange of Dpy from the chip into the aqueous Hg2+ droplet results in the quenching of Raman signals of Dpy, responding to 10 fM Hg2+ that is about 6 orders of magnitude lower than the limit defined by the U.S. Environmental Protection Agency in drinkable water. Each test using the SERS chip only needs a droplet of 20 μL sample and is accomplished within ∼4 min. The SERS chip has also been applied to the quantification of Hg2+ in milk, juice, and lake water.

CAS / MDL: 1148-79-4
研究领域: 分析化学 · 环境科学 · 材料科学
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BIOSENSORS & BIOELECTRONICS · 2020 · IF 10.257

Mass spectrometric biosensing: Quantitation of multiplex enzymes using single mass probe and fluorous affinity chip

Nan Feng,Junjie Hu,Qiulin Ma,Huangxian Ju

This work presents a concept of “mass spectrometric biosensing” by using a chip to recognize the targets and mass spectrometry to detect the signals switched by the recognition. The chip is prepared on an ITO slide with a hydrophobic fluorous-tag monolayer to self-assemble the mixture of mass probe and fluorous-tagged cysteine as a spacer through fluorous affinity interaction. The presence of spacer provides suitable conditions for recognition reactions on the chip. By designing a single mass probe as the peptide substrates of corresponding target enzymes , a novel quantitative strategy based on the ratio of signal intensities of different species on the chip is developed for MALDI-MS assay of multiplex enzyme activities . Using caspase-3 and protein kinase A as targets, the reactions with designed mass probe produce three mass shifts to act as two “fingerprint” patterns for obtaining the dual enzyme activities. The proposed biosensing method shows the detectable ranges from 0.05 to 50 μU μL −1 and 0.4–40 μU μL −1 with correlation coefficients of 0.990 and 0.989 for PKA and caspase-3, respectively. The biosensing application has been demonstrated by monitoring these enzymes in cell lysates upon anti-cancer drug treatment, indicating the prospect of the novel biosensing protocol in biomedical study.

CAS / MDL: 25316-40-9
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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

An ultrasensitive biosensing flexible chip using a novel silver@Prussian blue core-shell nanocube composite

Pengqi Yang,Jun Pang,Fuhao Hu,Jingmeng Peng,Danfeng Jiang,Zhenyu Chu,Wanqin Jin

A real-time, portable, ultrahigh sensitive and selective biosensing chip is desired to satisfy the urgent requirement of the practical application. In this study, a novel three-dimensional (3D) silver nanocubes@Prussian blue (AgNCs@PB) core-shell material has been designed to develop an ultrasensitive biosensing chip by a seed-mediated interfacial assembly approach. A Prussian blue (PB) shell with the 30.12 nm thickness was precisely controlled to in-situ grow on the whole surface of AgNCs through the electrostatic interaction. A flexible and portable biosensing chip was printed and functionalized by using this 3D AgNCs@PB biosensing material to integrate the superior conductivity from AgNCs and electrocatalytic activity from PB for the remarkable performance enhancement. This chip can realize about four times increase of the sensitivity compared with the other PB based screen-printing electrode (SPE), as well as a very wide linear response from 0.01 mM to 1.3 mM and an ultralow limit of detection (LOD) of 0.005 mM for the glucose detection with an excellent anti-interference ability. Especially, it also presented an ultra-accurate detection of the blood sugar in a real serum with a low deviation (3.37%).

CAS / MDL: 1313-84-4
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JOURNAL OF THE EUROPEAN CERAMIC SOCIETY · 2024 · IF 5.8

Reactive cold sintering of dense barium sulfate ceramics for high-reliability chip packaging in integrated circuits

Jia Peng Yuan,Bing Liu,Cheng Chao Hu,Kai Xin Song,Yu Hui Huang

Reactive cold sintering (RCS) is an innovative ceramic consolidation technique that combines a low-temperature reaction with the cold sintering process . In this work, equimolar (CH 3 COO) 2 Ba and (NH 4 ) 2 SO 4 were homogeneously mixed to obtain a reactive activator abbreviated as RA and then added to barium sulfate (BaSO 4 ) powder obtaining BaSO 4 – x wt%RA ( x = 5, 7.5, 10, 12.5, and 15). Dense (>96 % theoretical) BaSO 4 ceramics were successfully fabricated via RCS of BaSO 4 – x wt%RA at 200℃ with a constantly applied pressure of 250 MPa. The Woolfrey-Bannister method provided quantitative insights into the activation energy , indicating that RA effectively reduced the energy required for densification . The Vickers hardness (1.76 GPa) and coefficient of thermal expansion (CTE, 18.8 ppm/°C) of the RCSed BaSO 4 ceramics were comparable to the high-temperature (850 °C) sintered counterparts. Moreover, finite element analyses confirmed the high CTE value of the RCSed BaSO 4 ceramics holds great promise for high-reliability chip packaging applications.

研究领域: 材料科学 · 电子工程
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BIOSENSORS & BIOELECTRONICS · 2024 · IF 10.7

Antibody screening-assisted multichannel nanoplasmonic sensing chip based on SERS for viral screening and variants identification

Yi Liu,Huanjiao Weng,Zhiwei Chen,Ming Zong,Shubin Fang,Zili Wang,Shaohua He,Yangming Wu,Jizhen Lin,Shangyuan Feng,Duo Lin

The Omicron variants of SARS-CoV-2 have been spreading globally and has never disappeared from our sight, indicating that its coexistence with humans has become a fact, and monitoring its evolution and spread remains a current task. Although polymerase chain reaction (PCR) is the most commonly used virus detection method, it requires labor-intensive and time-consuming procedures in a laboratory setting. Herein, a multichannel nanoplasmonic sensing chip based on surface enhanced Raman spectroscopy (SERS) was developed for detecting N and S proteins, as well as IgG and IgM, related to SARS-CoV-2 Omicron variants. Through a self-screening process, specific antibodies for on-site and rapid identification of important variants of concerns (VoCs) were obtained, and their binding was confirmed by protein structure analysis. The use of these S protein specific antibodies can accurately identify Omicron VoCs (BA. 5, BF.7,XBB.1.5) with the detection limit (LoD) at 0.16 pg/mL. Then, the proposed SERS array chip was integrated with a hand-held Raman spectrometer to successfully detect the Omicron subvariants in real saliva samples within only 20 minutes, greatly reducing the detection time of PCR. This sensing technology will provide a powerful and rapid point-of-care testing (POCT) method for virus diagnosis, subtype identification, and post infection antibody level monitoring.

研究领域: 生物医学工程 · 分析化学 · 病毒学 · 医学诊断
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LAB ON A CHIP · 2025 · IF 5.4

Elevated interstitial flow in the cerebrospinal fluid microenvironment accelerates glioblastoma cell migration on a microfluidic chip

Wanting Hu,Hua Sun,Huibo Qi,Linkai Jiang,Kaining Zhang,Xiaomeng Jia,Yu Wang,Yu Xiang,Qionglin Liang

Glioblastoma is one of the most malignant tumors in the world, but the development of its therapies remains limited. Herein, a microfluidic chip that mimics the cerebrospinal fluid (CSF) circulation microenvironment is proposed to study the migration characteristics of glioblastoma U87-MG cells and U251 cells in complex environments where glioblastoma coexists with diseases that elevate CSF levels. In the presence of interstitial flow (IF), changing both cell densities and the cellular environment results in increased cell motility, including an increase in the number of migrating cells, the mean displacement of the top 30% fastest-moving cells, and the overall mean displacement. Then, through dynamic migration characterization analysis, it was found that IF enhances cell velocity and speed. Importantly, cells exposed to IF tend to migrate in directions with smaller angles of deviation from the opposite direction of IF. Finally, cytoskeleton inhibitors and decreased expressions of focal adhesion proteins, such as cytochalasin D, FAK inhibitors (VS-6063 and PF-573228), and FAK siRNA, were both proved to decrease the cells' response to IF. This work not only demonstrates the effect of IF on glioblastoma cell migration, but also indicates the reliability of microfluidic chips for modeling complex physiological environments, which is expected to be further developed for drug screening.

CAS / MDL: 518-47-8
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Digital microfluidic chip with photopatterned reactive sites for direct biomolecules immobilization and magnetic beads-free immunoassay

Qiudi Xu,Ke Liu,Yu He,Lan Wang,Zefan Lu,Zhongxuan Liu,Tao Zhang

Digital microfluidics (DMF), as an emerging liquid-handling technology, is widely recognized as an ideal platform for enzyme-linked immunosorbent assay (ELISA). However, current DMF-based ELISA methods are highly dependent on magnetic beads (MBs), which usually involves tedious modification of MBs, complex peripherals for MBs control, and impairs the parallel processing capability of DMF. To address these issues, we herein developed a photopatterned reactive sites-integrated DMF chip (PRS-DMF) for MBs-free immunoassay. By taking advantage of click chemistry between N-(allyloxycarbonyloxy) succinimide and thiol-ene substrate, the preparation of PRS is very simple, and leaves the reactive N-hydroxysuccinimide (NHS) ester groups on the surface. This enables direct biomolecules immobilization without any surface modification/activation processes. Moreover, the patterned micropillar array can notably increase the specific surface area, and promote the liquid mixing and immunoreaction. As a consequence, highly sensitive and MBs-free ELISA can be readily achieved on PRS-DMF, with a proof-of-concept H5N1 assay having been successfully demonstrated herein, which offers a low limit of detection (LOD) of 147 pg/mL. This also avoids the use of complex magnetic peripherals, and thus, contributing to the instrument miniaturization into a very compact form. It is therefore reasonably expected that the proposed PRS-DMF may serve as a promising platform for a variety of biological and biomedical applications, especially in the field of point-of-care testing (POCT).

研究领域: 生物技术 · 医学检验 · 微流控技术 · 免疫学
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LAB ON A CHIP · 2021 ·Vol. 21 ·期 6 ·1109-1117 · IF 6.799

Rapid nitrate determination with a portable lab-on-chip device based on double microstructured assisted reactors

Fang Wang,Jiaomeng Zhu,Xuejia Hu,Longfei Chen,Yunfeng Zuo,Yi Yang,Fenghua Jiang,Chengjun Sun,Weihong Zhao,Xiaotian Han

Determining the nitrate levels is critical for water quality monitoring, and traditional methods are limited by high toxicity and low detection efficiency. Here, rapid nitrate determination was realized using a portable device based on innovative three-dimensional double microstructured assisted reactors (DMARs). On-chip nitrate reduction and chromogenic reaction were conducted in the DMARs, and the reaction products then flowed into a PMMA optical detection chip for absorbance measurement. A significant enhancement of reaction rate and efficiency was observed in the DMARs due to their sizeable surface-area-to-volume ratios and hydrodynamics in the microchannels. The highest reduction ratio of 94.8% was realized by optimizing experimental parameters, which is greatly improved compared to conventional zinc–cadmium based approaches. Besides, modular optical detection improves the reliability of the portable device, and a smartphone was used to achieve a portable and convenient nitrate analysis. Different water samples were successfully analysed using the portable device based on DMARs. The results demonstrated that the device features fast detection (115 s per sample), low reagent consumptions (26.8 μL per sample), particularly low consumptions of toxic reagents (0.38 μL per sample), good reproducibility and low relative standard deviations (RSDs, 0.5–1.38%). Predictably, the portable lab-on-chip device based on microstructured assisted reactors will find more applications in the field of water quality monitoring in the near future.

研究领域: 环境科学 · 分析化学
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APPLIED OPTICS · 2019 ·Vol. 58 ·期 17 ·4720-4725 · IF 1.973

On-chip 3D SERS materials produced by self-assemble of copper microparticle and galvanic replacement reaction

Haiyan Zhang,Yuan Yuan,Sheng Yan,Kai Lou,Yibo Gao,Shuxia Wang,Yingzhou Huang

Surface-enhanced Raman scattering (SERS) has powerful capabilities in the field of environmental analysis and biological diagnostics because of its instinctive properties of high sensitivity and label-free detection. However, the fabrication of SERS substrate requires complicated processes and expensive equipment. This paper proposes a simple method approach to synthesize a 3D SERS substrate via electroless galvanic replacement reaction inside a microfluidic channel. Copper microparticles are assembled in a microfluidic channel, and silver nitrate solution is pumped into the channel to in situ produce the silver nanoparticles (Ag NPs) on the surface of copper microparticles. Because the copper particles occupy the channel by stack, the 3D Cu@AgNP SERS substrate can be obtained. The probing molecule (methylene blue) was utilized to investigate with the limit of detection (1×10−7  M). The biological molecules (urea and melamine) have been used to demonstrate its benefits in medical applications, and cancer cell detection has been implemented to demonstrate its benefits in cell biology. In addition, the device can filter and wash cells, forming a simple and fast filter. Our work on this simple fabrication method of active SERS substrate has great value for medical and biological applications.

研究领域: 分析化学 · 生物医学工程 · 环境科学
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ANALYTICAL CHEMISTRY · 2017 · IF 6.32

Integrated Smartphone-App-Chip System for On-Site Parts-Per-Billion-Level Colorimetric Quantitation of Aflatoxins

Xiaochun Li,Fan Yang,Jessica X. H. Wong,Hua-Zhong Yu

We demonstrate herein an integrated, smartphone-app-chip (SPAC) system for on-site quantitation of food toxins, as demonstrated with aflatoxin B1 (AFB1), at parts-per-billion (ppb) level in food products. The detection is based on an indirect competitive immunoassay fabricated on a transparent plastic chip with the assistance of a microfluidic channel plate. A 3D-printed optical accessory attached to a smartphone is adapted to align the assay chip and to provide uniform illumination for imaging, with which high-quality images of the assay chip are captured by the smartphone camera and directly processed using a custom-developed Android app. The performance of this smartphone-based detection system was tested using both spiked and moldy corn samples; consistent results with conventional enzyme-linked immunosorbent assay (ELISA) kits were obtained. The achieved detection limit (3 ± 1 ppb, equivalent to μg/kg) and dynamic response range (0.5–250 ppb) meet the requested testing standards set by authorities in China and North America. We envision that the integrated SPAC system promises to be a simple and accurate method of food toxin quantitation, bringing much benefit for rapid on-site screening.

研究领域: 食品安全 · 生物医学工程 · 分析化学
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Nanomaterials · 2022 ·Vol. 12 ·期 10 ·1711 · IF 5.719

One-Chip Isolation of Drug-Resistant Acute Myeloid Leukemia Cells with CXCR4-Targeted Magnetic Fluorescent Nanoprobes

Fan Wang,Yuqi Jiang,Luhai Wang,Yi Chen,Yu Zhang,Ming Ma

Drug resistance and relapse lead to high mortality in acute myeloid leukemia, and studies have shown that CXCR4 overexpression is highly correlated with poor prognosis and drug resistance in leukemia cells. Isolation and detection of AML cells with CXCR4 overexpression will be crucial to the treatment of AML. In this paper, magnetic nanoparticles were firstly prepared successfully by high-temperature thermal decomposition method, and then characterized by TEM, VSM and DLS. Subsequently CXCR4-targeted magnetic fluorescent nanoprobes conjugated with antibody 12G5 were constructed by stepwise coupling. In cell experiments, the obtained probes demonstrated excellent targeting efficacy to CXCR4 overexpressed AML cells HL-60. In addition, HL-60 cells labelled with the magnetic probes can be magnetic isolated successfully in one microfluidics chip, with efficiency of 82.92 ± 7.03%. Overall, this method utilizes the superiority of superparamagnetic nanomaterials and microfluidic technology to achieve the enrichment and capture of drug-resistant cells in a microfluidic chip, providing a new idea for the isolation and detective of drug-resistant acute myeloid leukemia cells.Keywords:acute myeloid leukemia;magnetic nanoparticles;nanoprobe;magnetic isolation;microfluidic chip

研究领域: 肿瘤学 · 纳米技术 · 血液学 · 分子生物学
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iScience · 2022 · IF 6.107

A human cornea-on-a-chip for the study of epithelial wound healing by extracellular vesicles

Zitong Yu,Rui Hao,Jing Du,Xiaoliang Wu,Xi Chen,Yi Zhang,Wei Li,Zhongze Gu,Hui Yang

Summary Organs-on-chips are microfluidic devices for cell culturing to simulate tissue-level or organ-level physiology and recapitulate their microenvironment, providing new and significant solutions other than traditional animal tests. In vitro testing platforms for ocular biological studies have been increasingly used in preclinical efficacy and toxicity prediction. Here, we developed a microfluidic platform consisting of human corneal cells and porous membrane, replicating the multi-scale structural organization and biological phenotype. We verified the fully integrated human cornea’s barrier effects on the chip. Moreover, we found that extracellular vesicles derived from bone marrow-derived mesenchymal stem cells can significantly accelerate the mild corneal epithelial wound healing, and the decreased expression of matrix metallopeptidase-2 protein indicated that this method effectively inhibits corneal inflammation and angiogenesis. This work improves our ability to simulate the interaction between the human cornea and the external world in vitro and contributes to the future development of new screening platforms for biopharmaceuticals.

研究领域: 生物医学工程 · 组织工程 · 药学 · 细胞生物学
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