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ANALYTICAL CHEMISTRY · 2026 · IF 7.3

Electrokinetic Enrichment and Purification of Proteins and Anions from High-salt Samples on Liquid Plasticine-Based Open Chip

Niu Jicheng,Fu Wenxuan,Su Bin,Wang Zhen

Microfluidic chips are promising for on-site analysis in medical diagnostics and food safety because they enable miniaturized, integrated sample processing. However, the analysis of complex, salt-rich matrices of biological and food samples remain challenging for conventional closed chips and electrokinetic pretreatment methods. Here, we developed an open, reconfigurable electrophoresis chip based on liquid plasticine, in which a moving neutralization reaction electrophoresis system (MNRES) was implemented for high-salt sample pretreatment. Liquid plasticine enabled facile construction of pump-free, valve-free, optically transparent, and cuttable open reservoirs and channels. In the MNRES, OH – and H + generated by water electrolysis reacted with NH 4 + and CH 3 COO – , producing moving neutralization reaction boundaries accompanied by dynamic electric field and pH gradients. These two coupled gradients enabled salt removal, field amplified stacking, and meanwhile the pH gradient induced protein focusing, thereby allowing simultaneous enrichment and purification of proteins and anionic species. It is demonstrated that proteins and anionic species in 0.9% NaCl solution can be effectively separated and enriched by approximately 10-fold. Moreover, the MNRES-pretreated analyte zones can be directly monitored by smartphone-based online colorimetry or transferred to liquid-plasticine microreactors for offline chromogenic assays. This work provides a flexible open-fluidic strategy for integrated electrokinetic pretreatment and visual detection of complex high-salt samples.

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LAB ON A CHIP · 2025 · IF 5.4

Engineering Spatially Defined Extracellular Matrix Gradients to Govern Self-Organized Multicellular Aggregates in a Glioblastoma-on-a-Chip

Jianing Li,Xinghua Gao,Xiaoling Yang,Hongcai Wang,Xindi Sun,Chang Xue,Jingyun Ma

The spatial heterogeneity of biochemical cues within the tumor microenvironment (TME) critically influences cancer progression and therapeutic resistance. However, existing models often lack the capacity to generate stable, quantitative concentration gradients in a high-throughput and biomimetic manner. Here, we present a glioblastoma-on-a-chip platform featuring a 48-microwell array that enables spontaneous formation of spatially defined extracellular matrix (ECM) gradients through a structure-guided solution replacement process. This integrated strategy combines gradient generation, sample arraying, and gel solidification into a single step, allowing one-step fabrication of gelatin methacryloyl (GelMA) microgel arrays with 48 discrete concentration conditions. We successfully generated continuous fibronectin (FN) gradients, quantitatively validated with a linear standard curve (R2 = 0.9899) and categorized into five statistically distinct groups (**p < 0.01). Computational fluid dynamics simulations confirmed physiological flow perfusion in the microchannels, providing essential biophysical TME cues. When applied to 3D dynamic co-culture of U87 glioblastoma and vascular endothelial cells (HUVECs), the FN gradient critically regulated the formation of self-organized multicellular aggregates, showing strong concentration dependence in their probability, number, and size. These aggregates exhibited significant upregulation of cancer stem cell markers (CD133, Vimentin, α-SMA), with CD133 expression increased by over 559-fold compared to the control group. Compared to conventional 96-well plate MTT assays, the multicellular aggregates demonstrated enhanced resistance to temozolomide, highlighting its utility for drug response studies in a physiologically relevant context. This work establishes a robust platform for constructing quantitative ECM gradients and serves as a potential tool for investigating cell-ECM interactions and high-throughput drug screening within biomimetic TMEs.

CAS / MDL: 106797-53-9 60842-46-8
研究领域: 肿瘤学 · 生物医学工程 · 组织工程 · 微流控技术 · 转化医学 · 药物筛选 · 细胞生物学 · 肿瘤微环境
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Nanomaterials · 2019 ·Vol. 9 ·期 10 ·1451 · IF 4.034

3D-Printed Concentration-Controlled Microfluidic Chip with Diffusion Mixing Pattern for the Synthesis of Alginate Drug Delivery Microgels

Shixuan Cai,Hongyan Shi,Guoqian Li,Qilu Xue,Lei Zhao,Fu Wang,Bo Hu

Alginate as a good drug delivery vehicle has excellent biocompatibility and biodegradability. In the ionic gelation process between alginate and Ca2+, the violent reaction is the absence of a well-controlled strategy in the synthesizing calcium alginate (CaA) microgels. In this study, a concentration-controlled microfluidic chip with central buffer flow was designed and 3D-printed to well-control the synthesis process of CaA microgels by the diffusion mixing pattern. The diffusion mixing pattern in the microfluidic chip can slow down the ionic gelation process in the central stream. The particle size can be influenced by channel length and flow rate ratio, which can be regulated to 448 nm in length and 235 nm in diameter. The delivery ratio of Doxorubicin (Dox) in CaA microgels are up to 90% based on the central stream strategy.[email protected]microgels with pH-dependent release property significantly enhances the cell killing rate against human breast cancer cells (MCF-7). The diffusion mixing pattern gives rise to well-controlled synthesis of CaA microgels, serving as a continuous and controllable production process for advanced drug delivery systems.Keywords:3D-printing;microfluidic chips;concentration controlled;diffusion mixing pattern;calcium alginate microgels

研究领域: 生物医学工程 · 药物递送系统
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TALANTA · 2019 · IF 4.916

Study on uptake of gold nanoparticles by single cells using droplet microfluidic chip-inductively coupled plasma mass spectrometry

Han Wang,Beibei Chen,Man He,Xiaoting Li,Pengyu Chen,Bin Hu

Cellular uptake of Au NPs is the premise for their application in drug delivery, cell/tissue imaging and quantitation analysis of biomarkers in the cells. However, conventional methods for cell analysis may lead to the loss of important information from abnormal or atypical cells in the cell population. In this work, with 15, 30 and 60 nm Au [email protected] acid and Au [email protected] as model materials, the cellular uptake of Au NPs in single HeLa cells is studied by using an on-line droplet chip inductively coupled plasma mass spectrometry hyphenated technique. It is found that the average amount of Au uptake for Au [email protected] acid is higher than that for Au [email protected] at high incubation concentrations. The distribution of the number of uptaken Au NPs in single HeLa cells shows a great difference when HeLa cells are incubated with different Au NPs. The percentage of cells uptaking Au NPs in the cell population also reveals a difference in cellular uptake between Au [email protected] acid and Au [email protected] at the single-cell level. To explain the abovementioned phenomenon, the endocytosis mechanisms of Au NPs are investigated. Clathrin-mediated endocytosis is found to be the major internalization pathway for 15 and 30 nm Au [email protected]

研究领域: 分析化学 · 纳米技术 · 细胞生物学
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Metallomics · 2023 ·Vol. 15 ·期 4 · IF 3.4

Droplet microfluidic chip-ICP–MS-based single-cell analysis for study of cellular behavior of macrophages to thimerosal

Ma Junrong,He Man,Chen Beibei,Hu Bin

Thimerosal (THI) is widely used as an antimicrobial preservative, but can hydrolyze to ethylmercury, causing potentially neurotoxicity. In this work, a THP-1 cell line was used to investigate the biological behavior of THI. An on-line droplet microfluidic chip system combined with time-resolved inductively coupled plasma mass spectrometry was used to quantify Hg in single THP-1 cells. The cellular uptake and elimination behaviors of THI were studied, and the toxicity of THI in terms of redox balance was discussed. The results showed that a small number of cells (<5%) exhibited a high uptake content (>200 fg/cell) for THI, and most of the cells (68.8–85.8% for different exposure groups at 25 h) exhibited a relatively low uptake content (<20 fg/cell). After stopping exposure to THI, the cells showed an elimination process for Hg, which was rapid in the first several hours and gradually slowed down. When the elimination time was 25 h, 7.4–26.3% of the cells in different exposure groups still contained a detectable amount of Hg (>2 fg/cell), indicating Hg could not be eliminated completely, which may cause cumulative toxicity to macrophages. Moreover, it was found that exposure to THI even at 50 ng/mL can cause cellular oxidative stress behavior, leading to an increase in reactive oxygen species level and a decrease in glutathione level. This trend would continue for a period of time after stopping THI exposure. With the elimination of Hg, the redox balance of cells showed a tendency to stabilize and restore, but cannot be restored to normal status, indicating a long-term chronic toxicity of THI to THP-1 cells.

CAS / MDL: 111-27-3 1338-43-8
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Chemosensors · 2023 ·Vol. 11 ·期 4 ·232 · IF 4.2

Rapid Fabrication of Homogeneous Submicron Silver Particles via a Microfluidic Chip and Use as a SERS Detection Substrate

Junjie Chen,Suyang Li,Fuqi Yao,Wanbing Xu,Yunfeng Li,Qiang Chen,Pei Liang

Silver particles have been widely used in SERS detection as an enhancement substrate. The large-scale synthesis of Ag particles with controllable size and shape is still a challenge. We demonstrate a high-throughput method for the preparation of monodisperse submicron silver particles using S-shaped microfluidic chips. Submicron silver particles were prepared by a simplified reduction method. By adjusting the concentration of the reducing agent ascorbic acid and the stabilizer PVP, the particle size and morphology could be controlled, obtaining a size distribution of 1–1.2 μm for flower-like silver particles and a size distribution of 0.5–0.7 μm for quasi-spherical silver particles. This microfluidic system can be used to fabricate submicron silver particles on a large scale, continuously and stably, with a production efficiency of around 1.73 mg/min. The synthesized submicron silver particles could realize ultra-sensitive SERS detection, and the lowest concentration of rhodamine 6G (R6G) that could be detected was 10−9M.Keywords:submicron silver particles;microfluidic chip;SERS detection

CAS / MDL: 50-81-7 7761-88-8
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Analytical Methods · 2023 ·Vol. 15 ·期 24 ·2971-2978 · IF 3.1

Point of care testing (POCT) of cholesterol in blood serum via a moving reaction boundary electrophoresis titration chip

Muhammad Idrees Khan,Qiang Zhang,Youli Tian,Shah Saud,Yiren Cao,Jicun Ren,Weiwen Liu,Chengxi Cao

Cholesterol (CHO) in human blood is one of the most frequently and crucially quantified substances in diagnostic laboratories. However, visual and portable point of care testing (POCT) methods have been rarely developed for the bioassay of CHO in blood samples. Here, we developed an electrophoresis titration (ET) model, a chip device of ∼60 grams, and a quantification method for the POCT of CHO in blood serum based on a moving reaction boundary (MRB). In this model, the selective enzymatic reaction is integrated with an ET chip for visual and portable quantification. At first, CHO reacted with cholesterol oxidase (CHOx) in the anode well, producing H2O2 and cholest-4-en-3-one in the solution. H2O2 further oxidized the colorless and chargeless leucocrystal violet (LCV) dye into violet colored positively charged crystal violet (CV+) and, under the influence of the electric field, the CV+ migrates in the ET channels and is titrated by the alkali of sodium hydroxide immobilized in the ET channels. The length covered by the MRB was measured as a function of the CHO content. The relevant experiments validated the feasibility of the model and method. Furthermore, the experiments revealed the high selectivity, portability, and visuality of the ET-MRB model, device, and method. Finally, the experiments showed a fair sensitivity of LOD of 5 μM, good linearity of 10–1000 μM (r2 = 0.9919), fair stability (intra-day RSD of less than 5.09% and an inter-day RSD of less than 6.36%), and high recovery (99.4–105%). All the data and results indicate the potential of the ET-MRB model, chip device, and method for POCT of CHO in human blood samples.

CAS / MDL: 57-88-5
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JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION · 2023 ·Vol. 37 ·期 6 ·1271-1278 · IF 1.6

Integrated Organ-on-a-chip with Human-induced Pluripotent Stem Cells Directional Differentiation for 3D Skin Model Generation

Luo Zhang,Gong Chaihong,Mao Xiaowei,Wang Zhe,Liu Zhifan,Ben Yali,Zhang Weiying

Keratinocytes and fibroblasts, derived from hiPSCs, were used to construct the human epidermal model by a culture patch made by monolayer poly-(lactic-co-glycolic acid) (PLGA) nanofibers and a human skin-on-a-chip device. Unlike the conventional culture dish method, two different epidermal cells are successfully adhered to the front and back sides of the patch, which produces a three-dimensional nanofibrous scaffold similar to a natural extracellular matrix before the patch was cultured in the skin-on-a-chip device to mimic the physiological conditions of human skin. As expected, the differentiated hiPSCs show the expression of keratinocyte- and fibroblast- specific proteins on the patch, and the layering is found between these two kinds of cells, indicating that this approach creates a powerful in vitro system for modeling skin development and diseases.

CAS / MDL: 24650-42-8
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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY · 2022 ·Vol. 195 ·期 5 ·3109-3121 · IF 3.094

Nickel-Doped Microfluidic Chip for Rapid and Efficient Immunomagnetic Separation and Detection of Breast Cancer Cell-Derived Exosomes

Fang Huiying,Liu Mei,Jiang Wei

Breast cancer cell-derived exosomes have high potential as biomarkers for continuous biopsies and longitudinal monitoring in breast cancer. However, it is extremely difficult to separate exosomes with high recovery and high purity from complex media, such as urine, plasma, saliva and cell culture supernatants. Here, we designed a flexible and simple microfluidic chip for exosome separation. The capture zone of the chip is a three-dimensional structure of interlaced cylinders doped with nickel powder. Exosomes were separated from cell culture supernatant by the immunomagnetic separation method in continuous flow mode and were detected by fluorescence imaging with high sensitivity. The chip achieved a high exosome recovery rate (> 74%) and purity (> 67%) at an injection rate of 3.6 mL/h. Thus, this chip was demonstrated to be a cutting-edge platform for the separation and detection of exosomes. It could also be applied to separate and detect other types of exosomes, microbubbles and cells.

CAS / MDL: 7440-02-0 70131-67-8
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Study on pre-concentration of trace heavy metal ions in water quality detection using FO-electroosmotic integrated chip

Zhao Cui,Meng Zhang,Yang Yuan,Hui Jia,Huu Hao Ngo,Jie Wang

The focus of this study is on the enhanced concentration effect of the pump effect in forward osmosis (FO) and electroosmotic integrated chip. The study investigates the strengthening effect of the FO process, driven by the pump effect, on the electroosmotic flow process under the same energy consumption, using low-concentration heavy metal ions (Cr 3+ ) as the target enrichment. In the chip system, the pump effect, caused by capillary pressure difference, successfully replaces the osmotic pressure of the draw solution as a new driving force for the FO process. By adjusting the size and number of channels and avoiding errors, the study achieves the highest efficiency of the FO process in the chip, concentrating Cr 3+ from 1.26 × 10 −4 mol/L to 8.01 × 10 −4 mol/L (6.4 times) within 32 min. Excluding the influence of the electrokinetic (EK) limit of low-concentration samples, the concentration efficiency of an individual electroosmotic chip in this study is positively correlated with cross-nanochannel voltage (V cn ). The integrated FO and electroosmosis chip reduce the duration required to concentrate 50 mL Cr 3+ sample to the limit from 90 min to 16 min (5.6 times) compared to the single electroosmotic process. Furthermore, a series of Cr 3+ samples with concentrations below the detection limit of the UV–vis spectrophotometer were concentrated and detected by the integrated chip. The results indicate that the concentration limit of the FO-electroosmotic integrated chip for samples can increase the detection limit of Cr 3+ from 1.37 × 10 −4 mol/L to 3.67 × 10 −6 mol/L.

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Nature Communications · 2022 ·Vol. 13 ·期 1 ·1-12 · IF 17.694

Critical role of hydrogen sorption kinetics in electrocatalytic CO2 reduction revealed by on-chip in situ transport investigations

Mu Zhangyan,Han Na,Xu Dan,Tian Bailin,Wang Fangyuan,Wang Yiqi,Sun Yamei,Liu Cheng,Zhang Panke,Wu Xuejun,Li Yanguang,Ding Mengning

Precise understanding of interfacial metal−hydrogen interactions, especially under in operando conditions, is crucial to advancing the application of metal catalysts in clean energy technologies. To this end, while Pd-based catalysts are widely utilized for electrochemical hydrogen production and hydrogenation, the interaction of Pd with hydrogen during active electrochemical processes is complex, distinct from most other metals, and yet to be clarified. In this report, the hydrogen surface adsorption and sub-surface absorption (phase transition) features of Pd and its alloy nanocatalysts are identified and quantified under operando electrocatalytic conditions via on-chip electrical transport measurements, and the competitive relationship between electrochemical carbon dioxide reduction (CO 2 RR) and hydrogen sorption kinetics is investigated. Systematic dynamic and steady-state evaluations reveal the key impacts of local electrolyte environment (such as proton donors with different p K a ) on the hydrogen sorption kinetics during CO 2 RR, which offer additional insights into the electrochemical interfaces and optimization of the catalytic systems.

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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

A colorimetric and ratiometric fluorescent paper chip for biogenic amine monitoring based on a simple pH-sensitive AIEgen

Xirui Chen,Yujie Tu,Song Cheng,Xujing Guo,Tianying Lu,Yuqian Guo,Xiaolin Huang,Yonghua Xiong,Ben Zhong Tang

Existing single-signal-response fluorescent materials for biogenic amine detection have unsatisfactory detection performance. Herein, we developed a simple pH-sensitive aggregation-induced emission-active fluorogen (AIEgen) and demonstrated its potential for ratiometric monitoring of biogenic amines. This AIEgen, namely 4-(dimethylamino)styryl)quinoxalin-2(1 H )-one (ASQ), shows a typical donor (D)-acceptor (A) structure with nonmonotonic color and fluorescence responses to pH stimulation by its protonation/deprotonation on the D/A moieties. Subsequently, the H + ASQ-labeled paper chips were successfully prepared by physically depositing ASQ on qualitative filter paper, followed by the acidification by hydrochloric acid. Upon the exposure to ammonia vapour, the obtained H + ASQ-labeled paper chips exhibited obvious color and ratiometric fluorescence responses owing to the deprotonation of H + ASQ indicators, indicating that the proposed paper chips can be used for the detection of biological amines by bimodal colorimetry and ratiometric fluorescence. Under the optimal conditions, H + ASQ-labeled paper chip achieved the real-time, non-destructive, and visual monitoring of meat and seafood freshness by simultaneously quantify the biogenic amine index with high performance liquid chromatography (HPLC). The results of this work suggest that ratiometric AIEgen can serve as a promising alternative strategy to ensure accurate monitoring of biogenic amines and food freshness.

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