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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Multiplexed microfluidic chip based flow injection analysis system for simultaneous determination of Fe(III), Mn(II) and Cu(II)

Fang Li,Nuotong Shen,Qingcheng Li,Chen Yang,Limin Zhang,Mingjin Wang

The development of microfluidic flow injection analysis (FIA) system for simultaneous and real-time detection of multiple metal ions is of great importance for environmental monitoring, food safety and industrial field. In this work, a multiplexed microfluidic chip based FIA system was fabricated for simultaneous determination of three metal ions, by using Fe(III), Mn(II) and Cu(II) as models. The multiplexed microfluidic chip based FIA system is composed of three parts, including a multi-channel FIA system for solution manipulation, a group of microfluidic chips for reagents mixing and reaction, and one fiber optic spectrometer for fast and real-time absorbance signal detection. The sample solution and chromogenic reagents were injected into the microfluidic chips to carry out specific colorimetric reactions. Fe(III), Mn(II) and Cu(II) reacts with 5-sulfosalicylic acid, formaldoxime, and bis(cyclohexanone) oxalyldihydrazone, respectively, to generate orange, ember and blue colored solution with peak absorbance at 420 nm, 450 nm, and 600 nm, respectively. The absorbance signal of the generated three channels of solution can be sequentially detected by using only one mini spectrometer. The linear detection range for Fe(III), Mn(II) and Cu(II) is 0.1–20 mg/L, 0.1–12 mg/L and 0.2–12 mg/L, respectively. The limit of detection for Fe(III), Mn(II) and Cu(II) is 0.07, 0.02 and 0.1 mg/L respectively. And the limit of quantification for Fe(III), Mn(II) and Cu(II) is 0.2, 0.07 and 0.3 mg/L, respectively. The recoveries of spiked Fe (III), Mn (II), and Cu (II) in real water samples are between 95.3 % to 106 %. Finally, the developed microfluidic chip based FIA system was successfully applied to simultaneous determination of three metal ions in environmental water samples and zinc smelting solution from zinc hydrometallurgy industry with satisfied results.

CAS / MDL: 370-81-0 5965-83-3
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2024 · IF 4.3

Smartphone-based colorimetric paper chip sensor using single-atom nanozyme for the detection of carbofuran pesticide residues in vegetables

Lifan Zhang,Ziyue Lang,Bozhi Lu,Tinglan Yang,Xinyi Zhang,Muxue Wang,Xiaomei Zhang,Hongmei Cao,Daixin Ye

Carbofuran (CBF), which exhibit high toxicity, persistent residues, ease of accumulation, and resistance to degradation, pose serious threats to human health and harm the ecological environment. Therefore, there is an urgent need to develop a rapid and accurate method for detecting CBF. In this work, a low-cost, portable, and easy-to-use paper chip biosensor was developed, integrating smartphones for the detection of CBF pesticide residues. This biosensor facilitates rapid on-site testing, meeting the needs for immediate analysis. CBF has the ability to inhibit acetylcholinesterase (AChE) activity. In the presence of AChE, acetylthiocholine (ATCh) is hydrolyzed to produce thiocholine (TCh). TCh, in turn, can inhibit the catalytic activity of Ni-N-C single-atom nanozymes (SAzyme) synthesized using Ni(OH) 2 nanochip as a metal precursor, which possess high peroxidase activity. Consequently, the concentration of CBF can be determined by observing the resultant color changes. The results showed that this sensor had a good linear response in the range of CBF concentration from 10 to 500 ng/mL, and the LOD was as low as 8.79 ng/mL. In testing three actual samples—Chinese cabbage, cabbage, and lettuce—the recoveries ranged from 81.09% to 125.27%. This demonstrated that the proposed smartphone-based colorimetric paper chip sensor, utilizing Ni-N-C SAzyme, offers an immediate, convenient, and rapid new strategy for detecting CBF.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2024 · IF 8.5

Nucleic acid aptamer based thermally oxidized porous silicon/zinc oxide microarray chip for detection of ochratoxin A in cereals

Jiayu Chen,Liyuan Zhang,Runzhong Yu

A nucleic acid aptamer based thermally oxidized porous silicon/zinc oxide microarray chip was constructed for the detection of ochratoxin A. The hybrid chains formed by aptamer and complementary chains labeled with fluorescent groups and fluorescent burst groups were used as recognition molecules, and the detection of toxins was accomplished on the chip by the principle of fluorescence signal burst and recovery. The modified QuEChERS method was used for sample pretreatment and the performance of the method was evaluated. The results showed that the linear range was 0.02 ∼ 200 ng/kg with the detection limit of 0.0196 ng/kg under the optimal detection conditions. The method was applied to different cereals with the recoveries of 90.30 ∼ 111.69 %. The developed microarray chip has the advantages of being cost-effective, easy to prepare, sensitive and specific, and can provide a new method for the detection of other toxins.

CAS / MDL: 141-43-5 5970-45-6
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ACS Nano · 2024 · IF 15.8

Unveiling the Heart’s Hidden Enemy: Dynamic Insights into Polystyrene Nanoplastic-Induced Cardiotoxicity Based on Cardiac Organoid-on-a-Chip

Tianyi Zhang,Sheng Yang,Yiling Ge,Lihong Yin,Yuepu Pu,Zhongze Gu,Zaozao Chen,Geyu Liang

Exposure to micro- and nanoplastics (MNPs) has been implicated in potential cardiotoxicity. However, in vitro models based on cardiomyocyte cell lines lack crucial cardiac characteristics, while interspecies differences in animal models compromise the reliability of the conclusions. In addition, current research has predominantly focused on single-time point exposures to MNPs, neglecting comparative analyses of cardiac injury across early and late stages. Moreover, there remains a large gap in understanding the susceptibility to MNPs under pathological conditions. To address these limitations, this study integrated cardiac organoids (COs) and organ-on-a-chip (OoC) technology to develop the cardiac organoid-on-a-chip (COoC), which was validated for cardiotoxicity evaluation through multiple dimensions. Based on COoC, we conducted a dynamic observation of the cardiac damage caused by short- and long-term exposure to polystyrene nanoplastics (PS-NPs). Oxidative stress, inflammation, disruption of calcium ion homeostasis, and mitochondrial dysfunction were confirmed as the potential mechanisms of PS-NP-induced cardiotoxicity and the crucial events in the early stages, while cardiac fibrosis emerged as a prominent feature in late stages. Notably, low-dose exposure exacerbated myocardial infarction symptoms under pathological states, despite no significant cardiotoxicity shown in healthy models. In conclusion, these findings further deepened our understanding of PS-NP-induced cardiotoxic effects and introduced a promising in vitro platform for assessing cardiotoxicity.

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MICROCHIMICA ACTA · 2024 ·Vol. 191 ·期 8 ·1-12 · IF 5.3

Unraveling the influence of CRISPR/Cas13a reaction components on enhancing trans-cleavage activity for ultrasensitive on-chip RNA detection

He Qian,Chen Qun,Lian Lijin,Qu Jiuxin,Yuan Xi,Wang Chuhui,Xu Lidan,Wei Jiazhang,Zeng Shaoling,Yu Dongmei,Dong Yuhan,Zhang Yongbing,Deng Lin,Du Ke,Zhang Canyang,Pandey Vijay,Gul Ijaz,Qin Peiwu

The CRISPR/Cas13 nucleases have been widely documented for nucleic acid detection. Understanding the intricacies of CRISPR/Cas13’s reaction components is pivotal for harnessing its full potential for biosensing applications. Herein, we report on the influence of CRISPR/Cas13a reaction components on its trans-cleavage activity and the development of an on-chip total internal reflection fluorescence microscopy (TIRFM)-powered RNA sensing system. We used SARS-CoV-2 synthetic RNA and pseudovirus as a model system. Our results show that optimizing Mg 2+ concentration, reporter length, and crRNA combination significantly improves the detection sensitivity. Under optimized conditions, we detected 100 fM unamplified SARS-CoV-2 synthetic RNA using a microtiter plate reader. To further improve sensitivity and provide a new amplification-free RNA sensing toolbox, we developed a TIRFM-based amplification-free RNA sensing system. We were able to detect RNA down to 100 aM. Furthermore, the TIRM-based detection system developed in this study is 1000-fold more sensitive than the off-coverslip assay. The possible clinical applicability of the system was demonstrated by detecting SARS-CoV-2 pseudovirus RNA. Our proposed sensing system has the potential to detect any target RNA with slight modifications to the existing setup, providing a universal RNA detection platform. Graphical Abstract

✓ 已验证 DOI PubMed 高影响因子
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TOXICOLOGY · 2024 · IF 4.8

Study on the mechanisms of defective spermatogenesis induced by TiO2 NPs based on 3D blood−testis barrier microfluidic chip

Ruoyun Dong,Li Li,Hongmei Chang,Guanling Song,Sixiu Liu

Titanium dioxide nanoparticles (TiO 2 NPs) can reduce sperm number, but the mechanisms of defective spermatogenesis induced by TiO 2 NPs have not been studied through cell-cell interactions at present. A kind of biomimetic three-dimensional blood−testis barrier microfluidic chip capable of intercellular communication was constructed with soft lithography techniques, including Sertoli cell (TM4), spermatogonia (GC-1) and vascular endothelial cell units, to study the mechanisms of TiO 2 NPs-induced defective spermatogenesis. TM4 and GC-1 cells cultured in TiO 2 NPs exposure and control chips were collected for transcriptomics and metabonomics analysis, and key proteins and metabolites in changed biological processes were validated. In TM4 cells, TiO 2 NPs suppressed glucose metabolism, especially lactate production, which reduced energy substrate supply for spermatogenesis. TiO 2 NPs also decreased the levels of key proteins and metabolites of lactate production. In GC-1 cells, TiO 2 NPs disturbed chemokine signaling pathways regulating cell proliferation and interfered with glutathione metabolism. The Cxcl13, Stat3 and p-Stat3 levels and cell proliferation rate were decreased, and the GSR, GPX4 and GSH contents were increased in GC-1 cells in chips under TiO 2 NPs treatment. The decrease in energy substrate supply for spermatogenesis and inhibition of spermatogonia proliferation could be the main mechanisms of defective spermatogenesis induced by TiO 2 NPs.

CAS / MDL: 13463-67-7
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ACS Sensors · 2025 · IF 9.1

Digital Profiling Subpopulations of Cancer Cell-Derived Exosomes via Aptamer-SERS Nanotags on a Wafer-Level Micropillar Array Chip

Chunyan Zhu,Xiaodong Lin,Ruyun Jin,Caini Long,Chunnan Zhu,Dongyun Zheng,Xiaofei Yang,Pan Zhang,Chao Liu

The clinical translation of exosome-based diagnostics and therapies is hindered by significant molecular heterogeneity. Current exosome phenotyping methods suffer from insufficient sensitivity, limited multiplexing capability, and poor scalability. To address these challenges, we developed a digital wafer-level micropillar array (WLM-Exo) platform. The chip features a high-surface-area micropillar array functionalized with a DSPE-PEG2000 lipid layer via Au–S bonding, enabling lipid-mediated membrane fusion for universal exosome enrichment and a uniform spatial distribution. Following capture, aptamer-based SERS nanotags bind specifically to target proteins on exosomes, generating distinct Raman signals upon laser excitation. Exosomal proteins are digitally quantified by measuring the activated area in the Raman images, exhibiting a log–log linear correlation with exosome concentration. The WLM-Exo platform demonstrates ultrasensitive detection (LOD: 2.11 particles/μL for CD63, 1.17 particles/μL for EpCAM, and 18.3 particles/μL for dual-biomarkers) and simultaneous tetra-color exosomal phenotyping capability. By enabling precise, scalable, and digital protein profiling, this technology offers significant potential for exosomes subtyping in personalized cancer diagnostics and therapeutics monitoring.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomicrofluidics · 2015 ·Vol. 9 ·期 2 · IF 3.357

Comparative toxicity of lead (Pb2+), copper (Cu2+), and mixtures of lead and copper to zebrafish embryos on a microfluidic chip

Li Yinbao,Yang Xiujuan,Chen Zuanguang,Zhang Beibei,Pan Jianbin,Li Xinchun,Yang Fan,Sun Duanping

Investigations were conducted to determine acute effects of Pb 2+ and Cu 2+ presented individually and collectively on zebrafish embryos. Aquatic safety testing requires a cheap, fast, and highly efficient platform for real-time evaluation of single and mixture of metal toxicity. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic effects of Pb 2+ and Cu 2+ using zebrafish ( Danio rerio ) embryos. The microfluidic chip is composed of a disc-shaped concentration gradient generator and 24 culture chambers, which can generate one blank solution, seven mixture concentrations, and eight single concentrations for each metal solution, thus enabling the assessment of zebrafish embryos. To test the accuracy of this new chip platform, we have examined the toxicity and teratogenicity of Pb 2+ and Cu 2+ on embryos. The individual and combined impact of Pb 2+ and Cu 2+ on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators, such as spontaneous motion at 22 hours post fertilization (hpf), mortality at 24 hpf, heartbeat and body length at 96 hpf, etc. It was found that Pb 2+ or Cu 2+ could induce deformity and cardiovascular toxicity in zebrafish embryos and the mixture could induce more severe toxicity. This chip is a multiplexed testing apparatus that allows for the examination of toxicity and teratogenicity for substances and it also can be used as a potentially cost-effective and rapid aquatic safety assessment tool.

研究领域: 毒理学 · 环境科学 · 生物医学工程
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Small · 2018 ·Vol. 14 ·期 20 ·1704433 · IF 9.598

Combining Multiplex SERS Nanovectors and Multivariate Analysis for In Situ Profiling of Circulating Tumor Cell Phenotype Using a Microfluidic Chip

Yizhi Zhang,Zhuyuan Wang,Lei Wu,Shenfei Zong,Binfeng Yun,Yiping Cui

Isolating and in situ profiling the heterogeneous molecular phenotype of circulating tumor cells are of great significance for clinical cancer diagnosis and personalized therapy. Herein, an on-chip strategy is proposed that combines size-based microfluidic cell isolation with multiple spectrally orthogonal surface-enhanced Raman spectroscopy (SERS) analysis for in situ profiling of cell membrane proteins and identification of cancer subpopulations. With the developed microfluidic chip, tumor cells are sieved from blood on the basis of size discrepancy. To enable multiplex phenotypic analysis, three kinds of spectrally orthogonal SERS aptamer nanovectors are designed, providing individual cells with composite spectral signatures in accordance with surface protein expression. Next, to statistically demultiplex the complex SERS signature and profile the cellular proteomic phenotype, a revised classic least square algorithm is employed to obtain the 3D phenotypic information at single-cell resolution. Combined with categorization algorithm partial least square discriminate analysis, cells from different human breast cancer subtypes can be reliably classified with high sensitivity and selectivity. The results demonstrate that this platform can identify cancer subtypes with the spectral information correlated to the clinically relevant surface receptors, which holds great potential for clinical cancer diagnosis and precision medicine.

研究领域: 生物医学工程 · 癌症研究 · 分析化学 · 微流控技术
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MICROCHEMICAL JOURNAL · 2017 · IF 3.034

On-chip single column transient isotachophoresis with free zone electrophoresis for preconcentration and separation of α-lactalbumin and β-lactoglobulin

Agustín G. Crevillén,Mercedes de Frutos,José Carlos Diez-Masa

Isotachophoresis (ITP) coupled to zone electrophoresis (ZE), either free zone electrophoresis (FZE) or gel electrophoresis (GE), carried out mainly in capillaries and, although less frequently, also in microchips, is a powerful preconcentration and separation technique which has been successfully used for the study of many low molecular-weight analytes. However, this analytical technique has been scarcely applied for proteins separation. In this work, an on-chip transient ITP coupled to free zone electrophoresis (t-ITP-MFZE) mode with LIF detection is developed for the preconcentration and separation of the proteins α-lactalbumin and β-lactoglobulin. Firstly, for LIF detection, the proteins were off-chip fluorescently labeled with the fluorogenic reagent Chromeo P503. Then, several separation parameters in t-ITP-MFZE mode such as leading electrolyte, terminating electrolyte, separation voltage, and injection time were optimized to achieve the maximum sensitivity while maintaining an adequate resolution between α-lactalbumin and β-lactoglobulin in a single column configuration t-ITP. Using the optimized electrolytes (50   mM imidazole/HCl pH   =   8 as leading electrolyte and 100   mM imidazole/12   mM HEPES pH   =   8 as terminating electrolyte) separation of both proteins was achieved in less than 4   min with peak resolution of 1.5. The LODs were 55   nM and 380   nM, for α-lactalbumin and β-lactoglobulin, respectively, which are adequate for some food allergenicity studies. Finally, comparison of the optimized t-ITP-MFZE method to the equivalent MFZE method, carried out also in microchips but without the isotachophoretic preconcentration step, provided preconcentration indexes for both proteins around 10.

研究领域: 分析化学 · 蛋白质组学 · 生物技术
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ACS Measurement Science Au · 2026 · IF 14.7

Rotational Microfluidic Paper-Based Chip Platform Integrating Nucleic Acid Sequence-Based Amplification for Visual and Sensitive Detection of Viable Pathogens

Liu Ping,Jin Mingzhu,Li Bowei,Sun Dani,Sun Hongxiao,Zhang Zhiyang,Wang Xiaoyan,Chen Lingxin

Sensitive, simple, and rapid detection of pathogens is essential in preventing the transmission of related diseases and protecting human health. In this study, a rotational microfluidic paper-based analytical device integrating nucleic acid sequence-based amplification (NASBA) and colorimetric analysis was developed for the detection of viable pathogens. Biotin- and HRP (horseradish peroxidase)-labeled DNA single strands were used as the capture probe and detection probe, respectively. The capture probe was anchored on the surface of the paper chip based on the interaction between biotin and streptavidin. The target mRNA of the pathogen could be exponentially amplified through NASBA isothermal amplification, and then the product of amplification was combined with the capture probe and detection probe according to nucleic acid hybridization. With a simple and rapid RNA extraction method, isothermal amplification, and colorimetric analysis, this rotational microfluidic paper-based analytical platform could accomplish the whole process of pathogen detection within 110 min using simple equipment. The limit of detection for E. coli was as few as 10 CFU/mL (with a 95% positive detection rate in 20 replicate samples). The quantitative analysis of pathogens could be carried out by detecting the gray value on the paper chip with a smartphone. This portable platform has great potential for the on-site, rapid, and visual detection of viable pathogens such as bacteria and viruses.

CAS / MDL: 54827-17-7
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SENSORS AND ACTUATORS B-CHEMICAL · 2026 · IF 8.3

A double-spiral microelectrode chip for reagent-free detection of mercury(II) in seawater based on in-situ pH modulation

Nan Qiu,Zeqian Wei,Jiayi Li,Yang Li,Chao Bian

A double-spiral microelectrode sensor chip was developed for reagent-free detection of mercury ions (Hg(II)) in seawater via in-situ pH modulation. This sensor chip, fabricated with thin-film technology, employs double-spiral microelectrodes configuration where one spiral functions as the working electrode for Hg(II) detection, while the other serves as the pH-modulating electrode. By applying a constant voltage of 1.2 V to the pH-modulating electrode, water electrolysis was induced and a localized acidic microenvironment was established at the working electrode-solution interface. This approach effectively eliminated the need for the external strong acid reagents used in conventional detection methods. The experimental results demonstrate that the sensor achieved a linear detection range of 0.3–350 μg/L for reagent-free Hg(II) determination in simulated seawater samples, with a detection limit of 0.14 μg/L. The sensor also exhibited excellent repeatability, selectivity, and anti-interference capability. The recovery rates for Hg(II) detection in real seawater samples ranged between 93% and 109%. The integration of in-situ pH modulation into the double-spiral electrode paves the way for environmentally friendly, reagent-free sensors to monitor heavy metals in seawater.

CAS / MDL: 1415-93-6
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