LAB ON A CHIP
·
2024
·Vol. 24
·期 24
·5384-5397
·
IF 6.1
Siyue Xiong,Chushu Zhu,Chengxuan Wang,Peitao Dong,Xuezhong Wu
Cortisol, known as the “stress hormone”, is secreted by the adrenal cortex. Measuring cortisol levels in body fluids is essential for evaluating stress levels, adrenal function, hormone imbalance, and psychological well-being. Early diagnosis and management of related conditions depend on this measurement. A rapid detection method that combines immunoassay and surface-enhanced Raman scattering (SERS) technology has become widely used in bioanalysis, offering benefits such as fast detection, high throughput, integrated microsystems, and high specificity. This study introduces a pump-free microfluidic chip integrating a solid-state SERS substrate to detect trace amounts of cortisol in bodily fluids through immunoassay. The method relies on a competitive reaction between cortisol and SERS tags with cortisol antigens immobilized on gold nanostructured substrates in a microfluidic environment. Two detection channels are used to provide controls and enhance measurement efficiency and accuracy. Solid-state gold nanostructured substrates offer a larger surface area for antibody capture and act as SERS-active substrates, which significantly enhance the Raman signal and improve the microsystem's sensitivity and applicability. Driven by a capillary pump, the sample can be loaded within 60 seconds, with the entire detection process taking less than 10 min, significantly reducing the detection time. Results indicate that the detection limit for cortisol is 10 pg mL−1, meeting clinical biomarker thresholds. The integrated SERS microfluidic chip shows great promise as an analytical tool for the rapid and sensitive diagnosis of cortisol in bodily fluids.
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高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Yun Zheng,Xuanhao Jia,Huanhuan Shi,Weizheng Xu,Zhongjian Tan,Yu Cao,Zhengxian Dan,Zhiying Dai
The real-time detection of biomarkers in saliva is of great significance for early non-invasive diagnostic of related diseases. In this work, molecular imprinting technology was used to prepare a lactic acid monolithic column, which could realize specific adsorption and elution of lactic acid, achieving solid phase microextraction (SPME) of lactic acid in samples, and purify the analytes. Lactic acid monolithic column was then embedded into the microfluidic channel, and passive microfluidic structures such as stop valve, retention valve, trigger valve and capillary pump were utilized to construct the SPME self-driven microfluidic chip. A series of complex operations such as lactic acid adsorption, rinse and elution on the monolithic column could be realized automatically without external power. Since the purification of the analytes was achieved by the monolithic column, the low-cost nano copper oxide modified electrode was used to achieve the specific electrochemical analysis of lactic acid. The screen-printed electrode was designed and fabricated, and the integrated electrochemical detection circuit was used to realize the portable analysis of Na + , K + and lactic acid simultaneously. The microfluidic chip, screen-printed electrode and miniaturized detection circuit are integrated into a Point-of-care testing (POCT) device, which realizes the automatically real-time detection of saliva. By adjusting the template molecule in monolithic column polymerization, the application of this physiological fluid POCT device can be extended, and may provide some implications for the development of portable non-invasive health monitoring devices.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Sen Zhang,Xingdong Yang,Feng Zhang,Jun-qin Qiao,Wei-juan Zheng,Hong-zhen Lian
Both MXenes and metal-organic frameworks (MOFs) have been attracting lots of attention since being found and have been applied in various fields. Furthermore, MXene-MOF composites have been recently studied to combine the advantages of MXenes and MOFs. However, the synthesis of MXene-MOF composites still suffers from questions such as low-efficiency of exfoliation of MXenes to layered nanosheets, uneven distribution of MOF nanoparticles on MXene nanosheets and extra modification process before the growth of MOF nanoparticles. To resolve these problems, herein, a sonication-assisted minimally intensive layer delamination (SA-MILD) method was proposed to achieve high yield of thin-layer Ti 3 C 2 T x MXene nanosheets. Then, a stirring in-situ growth method (SISG) was carried out to uniformly grow UiO-66–NH 2 nanoparticles on Ti 3 C 2 T x nanosheets to form two-dimensional potato-chip-like Ti 3 C 2 –UiO-66–NH 2 nanocomposites instead of conventional solvothermal method for the first time. Finally, MXene-MOF composites were calcined to increase the chemical stability and endowed with magnetism by the in-situ oxidation growth of Fe 3 O 4 nanoparticles. Thanks to the massively exposed Ti O, Zr O and Fe O sites, the well-characterized magnetic trimetallic oxides (MTMOs) could enrich phosphopeptides by easy magnetic separation through metal oxide affinity chromatography mechanism in a short time. High sensitivity (0.5 nmol∙L −1 of α −/ β -casein) and great anti-interference ability (1:1:2000 of the molar ratio of α −/ β -casein to bovine serum albumin) were realized for the efficient enrichment of phosphopeptides with MTMOs. Non-fat milk and traditional Chinese medicine injections were used as the examples to explore the biomedical applicability of the as-prepared MTMOs with excellent results.
研究领域:
材料科学
·
纳米技术
·
分析化学
·
蛋白质组学
·
生物医学工程
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高影响因子
LAB ON A CHIP
·
2025
·
IF 5.4
Liyang Wu,Bingcheng Lin,Huadong Fan,Yihong Li
Glioblastoma (GB), the most common primary malignant brain tumor, faces limited treatment efficacy due to Blood-Brain-Barrier (BBB) restricting drug delivery. Sonodynamic therapy (SDT) presents a promising non-invasive alternative, using ultrasound for deep tissue penetration to transiently open the BBB and activate sonosensitizers for localized GB destruction. However, mechanistic understanding and optimization of SDT are hindered by the lack of integrated platforms capable of quantitatively elucidating the relationships between ultrasound-controlled BBB dynamics, drug delivery kinetics, and SDT efficacy. To address this, we developed a physiologically relevant BBB-GB organ-on-a-chip model integrating human cerebral microvascular endothelial cells (HCMECs), primary astrocytes (ACs), and U87-MG cells within a Matrigel-embedded microfluidic chip. This model recapitulated key BBB features, confirmed by continuous ZO-1 tight junction expression and size-selective permeability (FITC-dextran assay). Crucially, the ultrasound-opened barrier retained selective permeability, favoring nanocarriers like our tumor-targeting SFN@RB@SPM nanomicelles while effectively excluding free small molecules (Rose Bengal) and other nanoparticle types (Exo-RB), thereby mimicking the discriminative function of the biological BBB. low-intensity ultrasound (1 MHz, 1 W/cm2, 30 seconds) induced transient, reversible BBB opening, with full functional and structural recovery within 24 hours. Utilizing this controlled opening, our self-assembled tumor-targeting nanomicelles (SFN@RB@SPM) exhibited significantly enhanced BBB permeability. Real-time monitoring revealed efficient, selective uptake of SFN@RB@SPM by U87-MG cells. Sequential ultrasound application—first to open the BBB for nanomicelles delivery and second to activate SDT—synergistically amplified intracellular reactive oxygen species (ROS) generation and induced near-complete U87-MG cell death. These effects were unachievable with either ultrasound or nanomicelles alone. This integrated BBB-GB organ-on-a-chip platform enables simultaneous quantification of ultrasound-regulated BBB permeability, multi-cellular interactions, tumor-targeted nanodrug delivery dynamics, and SDT therapeutic efficacy. It thus provides a powerful in vitro tool for elucidating SDT mechanisms and accelerating the development of novel glioma therapies.
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高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Lin Wu,Guohua Wu,Di Wu,Wenqi Hu,Qijun Du,Qinrui Lu,Jiashu Wang,Ao Xie,Youlong Yang,Jie Liu,Wenlong Zhang,Chengwei Sun,Bangchuan Hu,Zipeng Yao,Hongbin Deng,Mengjiao Xia,Haijie Hu,Shuqi Wang
Cholangiocarcinoma (CCA), particularly intrahepatic cholangiocarcinoma (ICC), is a highly aggressive malignancy with extensive stromal fibrosis and frequent pulmonary metastasis. Existing in vitro models, including 2D cultures, animal systems, and Matrigel-based organoids with fixed stiffness, fail to replicate physiologically relevant cell–matrix interactions. Here, we developed a stiffness-tunable microfluidic chip integrating sodium alginate–decellularized ECM (SA–dECM) hydrogels, enabling dynamic modulation of stiffness (2.90–13.31 kPa) to mimic clinical tumor conditions (∼7.94 kPa). Increased stiffness promotes chemoresistance, with gemcitabine IC 50 rising from 0.139 to 0.282 µ m and cisplatin from 2.49 to 4.23 µ m , alongside epithelial-mesenchymal transition (EMT), as evidenced by a 64% reduction in E-cadherin and a 6.35 fold increase in MMP2 expression. Co-culture of ICC organoids and lung fibroblasts on-chip further reveals that stiff matrices activate fibroblasts via TGF-β signaling, increasing α-SMA and collagen deposition by 7.5 and 5.4 fold, respectively. These changes contribute to a pre-metastatic niche, as confirmed by a 4.11 fold increase in invasive cell counts in PET membrane invasion assays. This dynamic stiffness-tunable platform provides a robust in vitro model for studying stiffness-driven invasion and pre-metastatic niche formation in ICC and offers a valuable tool for personalized screening of anti-fibrotic and chemosensitizing therapies.
研究领域:
癌症研究
·
生物医学工程
·
微流控技术
·
肿瘤微环境
·
转移机制
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PubMed
高影响因子
LAB ON A CHIP
·
2025
·
IF 5.4
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.
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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Analytical Methods
·
2015
·Vol. 7
·期 21
·9190-9197
·
IF 1.821
Hao Wan,Qiyong Sun,Haibo Li,Fei Sun,Ning Hu,Ping Wang
Herein, we present a novel miniaturized multisensor chip integrated with a nanoband electrode array (NEA) for lead and copper detection and a light addressable potentiometric sensor (LAPS) for pH sensing. By this means, pH information could be provided before electrochemical analysis to ensure high performance in heavy metal quantification due to the significant effects of solution acidity on electrochemical analyses. The fabrication processes of the multisensor chip are described in detail and the electrochemical behaviour of NEA was characterized using cyclic voltammetry in sulfuric acid and acetate buffer. For the detection of lead and copper qualitatively and quantitatively, square wave anodic stripping voltammetry (SWASV) was applied with the standard addition method. Deposition potential and deposition time were optimized to be −0.6 V and 120 s, respectively. NEA exhibited a sensitivity of 0.510 μA pbb−1 and 0.678 μA ppb−1 towards lead and copper, respectively, with high correlation coefficients. The repetitive and long-term experiments also demonstrated the good reproducibility and stability of NEA in heavy metal detection. Moreover, the silicon nitride modified LAPS showed a pH sensitivity of 56.49 mV pH−1 with a high correlation coefficient of 0.9999. The reproducibility of LAPS was also investigated and a deviation of less than 2 mV was obtained in both the samples. These results indicate that the miniaturized multisensor chip demonstrates good electrochemical performance in heavy metal and pH sensing.
研究领域:
分析化学
·
环境科学
·
材料科学
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Animal Nutrition
·
2022
·
IF 5.285
Chizhu Ding,Xiang Chen,Xiaoyu Chen,Yue Liu,Menglin Xia,Ziyi He,Qinshu Kang,Xianghua Yan
Lysine is one of the essential amino acids and plays a vital role in the growth, development and health of pigs. Blood lysine concentration is a direct indication of lysine status; however, current methods can not satisfy the demands for rapid and on-site lysine concentration measurement of swine serum. Here, we developed blue-emissive nitrogen-doped carbon dots as a fluorescence probe for the determination of lysine with high fluorescence quantum yield, stability, sensitivity and specificity. The carbon dots were entrapped within hydrogel microstructures to fabricate microfluidic chips for rapid assay for lysine quantification. We further developed an imaging attachment to integrate the microfluidic chip and a smartphone into a portable point-of-care testing platform. This platform requires only 3 μL sample and has a linear detection range of 25 to 300 μmol/L with a limit of detection less than 16 μmol/L, which covers the normal range of lysine concentration in swine serum. We tested lysine concentration in swine serum using this platform with high accuracy, low sample consumption, and within 3 min. Together, these results may provide a rapid and portable platform for dynamic monitoring of swine lysine status and contribute to precise feed formula modulation with low-protein diet strategy.
研究领域:
生物化学
·
分析化学
·
畜牧学
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高影响因子
Micromachines
·
2019
·Vol. 10
·期 12
·884
·
IF 2.426
Zhao Xi Song,Hui Hui Chai,Feng Chen,Ling Yu,Can Fang
Seed germination and seedling root development are important indicators of plant development. This work designed and fabricated a foldable microfluidic chip array for conducting nondestructive and continuous evaluation of seed germination and subsequent seedling development in situ. Each plant chamber has two functional units: seed germination part and root-growth part. The root-growth parts are themselves connected to a single channel designed to provide a uniform culture medium for plant growth. The individual chips are connected into an array using elastic hinges that facilitate the folding and unfolding of the array to accommodate different viewing purposes. In the folded state, the seed germination chambers form a closely spaced array platform to facilitate the comparison of seed germination and plant development characteristics. Unfolding the array facilitates a clear examination of root development within the root-growth parts. The observation window of an individual chip facilitates either the direct examination of the developing seedling (e.g., stems and leaves) or the use of a microscope for examining microscale features (e.g., root tips and root hairs). The potential of the proposed foldable chip array as a new cultivation platform for botanic studies is demonstrated by examining the seed germination and seedling development of tobacco (Nicotiana tabacum) under different cultivation conditions.Keywords:seed germination;root development;plant cultivation;microfluidic;foldable
研究领域:
植物学
·
生物工程
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PubMed
高影响因子
Nanomaterials
·
2019
·Vol. 9
·期 10
·1451
·
IF 4.034
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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PubMed
高影响因子
TALANTA
·
2019
·
IF 4.916
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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PubMed
高影响因子
ANALYST
·
2022
·Vol. 148
·期 3
·516-524
·
IF 5.227
Jinlong Liu,Wenjie Zhao,Meiyan Qin,Xiaofeng Luan,Yuang Li,Yang Zhao,Chengjun Huang,Lingqian Zhang,Mingxiao Li
The trans-epithelial electrical resistance (TEER) is widely used to quantitatively evaluate cellular barrier function at the organ level in vitro. The measurement of the TEER in organ-on-chips (organ chips) plays a significant role in medical and pharmacological research. However, due to the limitation of the electrical equivalent model for organ chips, the existing TEER measurements usually neglect the changes of the TEER during cell proliferation, resulting in the low accuracy of the measurements. Here, we proposed a new whole-region model of the TEER and developed a real-time TEER measurement system that contains an organ chip with a plate electrode. A whole region circuit model considering the impedance of the non-cell covered region was also established, which enables TEER measurements to be independent of the changes in the cell covered region. The impedance of the non-cell covered region is here attributed to the resistance of the porous membrane. By combining the real-time measurement system and the whole region model, subtle changes in cellular activity during the proliferation stage were measured continuously every 6 minutes and a more sensitive TEER response was obtained. Furthermore, the TEER measurement accuracy was also verified by the real-time measurement of the TEER with stimulation using the permeability enhancer ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA). The obtained results indicated that the new proposed whole region model and the real-time measurement system have higher accuracy and greater sensitivity than the traditional model.
研究领域:
生物医学工程
·
药理学
·
细胞生物学
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PubMed
高影响因子
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