CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Jiuhong Zhao,Wenjing Zhu,Yuxuan Mao,Guixia Ling,Peng Zhang
The increased uric acid (UA) level is closely related to many diseases. However, the detection of UA remains great challenges due to the pain of blood testing and the complexity of common methods. Therefore, the detection of UA is of great significance for public health. In this paper, a new method for UA detection is proposed. The swellable hydrogel microneedles (hydrogel MNs) can be used for minimally invasive extraction of skin interstitial fluid (ISF). The colorimetric detection of trace UA in ISF can be successfully achieved by virtue of DNAzyme@MOFs with enhanced peroxidase activity. This study provides a powerful tool for minimally invasive, painless, rapid and convenient detection of UA in clinical applications. This study not only avoids the use of expensive and unstable natural enzymes but also expands the applications of DNAzyme@MOFs in biomedical detection.
研究领域:
医学检测
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生物化学
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材料科学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
·
IF 5.2
Lujie Zhang,Qinghua Song,Peijing Yang,Zhanqiang Liu
Microneedle (MN) technology is a promising minimally invasive tool for interstitial skin fluid (ISF) extraction. Hydrogel MN patches enable efficient ISF extraction. However, the traditional polydimethylsiloxane (PDMS) photopolymerization method has limitations in morphology control, accuracy, and susceptibility to process parameter interference, affecting MN strength and functional consistency. To address these challenges, we propose a composite hydrogel MN patch based on Digital Light Processing (DLP) 3D bioprinting of hyaluronic acid methacryloyl (HAMA)/gelatin methacryloyl (GelMA) for high-efficiency ISF transdermal extraction. The structure and performance of the MNs were improved by optimizing the bio-ink ratio and printing parameters. Adjusting the ratio of GelMA and HAMA improved the cross-linking structure, optimizing the mechanical properties and swelling performance of the composite hydrogel. Optimizing the light intensity and exposure time ensured consistent MN morphology, resulting in well-defined and evenly distributed needle tips. Controlled UV exposure avoided defects such as uneven cross-linking or brittleness. The results showed that when the HAMA-to-GelMA ratio was 8:2, the light intensity was 9 mW/cm 2 , and the exposure time was 6 s, the MN patches demonstrated excellent microstructures and mechanical properties, with each MN enduring over 1.28 N and achieving a swelling rate above 1200 %. In vitro experiments verified effective penetration and ISF extraction, obtaining 8.5 mg of PBS in 1 min and successfully quantifying glucose concentration. In summary, this study establishes a robust MN patch with superior swelling performance and enhanced ISF extraction efficiency and provides a promising platform for minimally invasive diagnosis and real-time health monitoring.
研究领域:
生物医学工程
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材料科学
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药学
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DOI
PubMed
高影响因子
Biosensors-Basel
·
2023
·Vol. 13
·期 5
·537
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IF 5.4
Qingya Zeng,Mengxin Xu,Weilun Hu,Wenyu Cao,Yujie Zhan,Yuxin Zhang,Qingqing Wang,Tao Ma
Though monitoring blood glucose (BG) is indispensable for regulating diabetes, the frequent pricking of the finger by the commonly used fingertip blood collection causes discomfort and poses an infection risk. Since glucose levels in skin interstitial fluid (ISF) correlate with blood glucose levels, monitoring glucose in the skin ISF can be a viable alternative. With this rationale, the present study developed a biocompatible porous microneedle capable of rapid sampling, sensing, and glucose analysis in ISF in a minimally invasive manner, which can improve patient compliance and detection efficiency. The microneedles contain glucose oxidase (GOx) and horseradish peroxidase (HRP), and a colorimetric sensing layer containing 3,3′,5,5′-tetramethylbenzidine (TMB) is on the back of the microneedles. After penetrating rat skin, porous microneedles harvest ISF rapidly and smoothly via capillary action, triggering the production of hydrogen peroxide (H2O2) from glucose. In the presence of H2O2, HRP reacts with TMB contained in the filter paper on the back of microneedles, causing an easily visible color shift. Further, a smartphone analysis of the images quickly quantifies glucose levels in the 50–400 mg/dL range using the correlation between color intensity and glucose concentration. The developed microneedle-based sensing technique with minimally invasive sampling will have great implications for point-of-care clinical diagnosis and diabetic health management.Keywords:porous microneedle;interstitial fluid;glucose;colorimetric detection;diabetes
研究领域:
生物医学工程
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糖尿病管理
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即时诊断
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DOI
PubMed
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Rongrong Huang,Peipei Wan,Shengjie Hu,Chenyang Zhang,Wenjun Miao
MicroRNAs (miRNAs) in dermal interstitial fluid (ISF) have recently been recognized as clinically promising biomarkers for the diagnosis and prognosis of cancer. However, the detection poses significant challenges, primarily due to the low abundance of miRNAs and the limitations of current sampling techniques. To address this issue, we develop novel porous microneedles (PMNs) array-based sensor composed of poly(vinyl alcohol) porous hydrogel and DNA-templated silver nanoclusters (AgNCs) to facilitate the enrichment and highly sensitive detection of ISF miRNA. Leveraging the capillary action facilitated by its unique porous structure and the swelling properties of the hydrogel, the PMNs array can efficiently extract 2.7 ± 0.3 mg of ISF within 5 min. Additionally, the interconnected pores within the PMNs array contribute to an increased specific surface area, thereby offering a convenient platform for the decoration of DNA-templated AgNCs. The immobilized large amount of AgNCs effectively capture the target miRNA from the extracted ISF, resulting in miRNA-induced fluorescence quenching of AgNCs. Subsequently, the introduction of the duplex-specific nuclease leads to the cleavage of DNA in DNA-RNA heteroduplexes, which release miRNA to interact with other AgNCs. This process of target recycling triggers a further reduction in fluorescence intensity, thereby enabling sensitive detection of the low-abundant miRNA down to 1.6 pM. Both in vitro and in vivo experiments validate the efficacy of the AgNCs immobilized PMNs array for the detection of miRNA biomarkers in ISF within minutes. These results indicate that the proposed PMNs array-based sensor holds great potential for the development of noninvasive personalized diagnostic strategies.
研究领域:
生物医学工程
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分子诊断
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2022
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IF 10.684
Mengjia Zheng,Yuyue Zhang,Tianli Hu,Chenjie Xu
Microneedle (MN)-based diagnostic devices can efficiently access skin interstitial fluid (ISF) for accurate and minimally invasive detection of health-related biomarkers. This work reports a biomarker (i.e., glucose or alcohol) monitoring MN device that is composed of swellable MNs and electrochemical test strip. This device is constructed by adhering MN patch on the electrochemical strips using the chitosan as the connecting layer. The MNs penetrate the skin for extraction of ISF that flows to the backing layer of MNs and is analyzed by the test strip. In the in vitro skin models, this device accurately detects the glucose from 0 mM to 12 mM and alcohol from 0 mM to 20 mM. In vivo experiment shows this MN device is capable of minimally invasive sampling of ISF and analysis of glucose levels to determine the glycemic status of mice.
研究领域:
生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2025
·
IF 10.5
Jiuhong Zhao,Jinnan Zhao,Xiaoyu Zhang,Guixia Ling,Peng Zhang
The level of dopamine (DA) in the human body has a certain correlation with neurological diseases. However, most detection methods of DA are complex and expensive. In this study, laccase-like DNAzyme@MOF with improved pH stability was successfully prepared. DNAzyme@MOF could catalyze the chromogenic substrate to change the color of the solution for the detection of DA in ISF. The addition of DNAzyme made DNAzyme@MOF possess higher stability and enzyme-like activity. The operation process was simple, rapid, and intuitive. In addition, the in vivo DA content in skin interstitial fluid (ISF) was analyzed by an off-line method. The swelling hydrogel microneedles (MNs) were prepared to extract skin ISF. DA in skin ISF was recovered and detected by laccase-like DNAzyme@MOF. This study realized the minimally invasive detection of DA. The proposed detection method of biomarkers in ISF based on DNAzyme@MOF would provide a new dimension towards the future development for the detection of other biomarkers in ISF.
研究领域:
生物化学
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医学检测
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纳米材料科学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 6
·1730
·
IF 5.4
Jianmin Chen,Xiaozhen Cai,Wenqin Zhang,Danhong Zhu,Zhipeng Ruan,Nan Jin
Microneedles (MNs) have recently garnered extensive interest concerning direct interstitial fluid (ISF) extraction or their integration into medical devices for continuous biomarker monitoring, owing to their advantages of painlessness, minimal invasiveness, and ease of use. However, micropores created by MN insertion may provide pathways for bacterial infiltration into the skin, causing local or systemic infection, especially with long-term in situ monitoring. To address this, we developed a novel antibacterial sponge MNs (SMNs@PDA-AgNPs) by depositing silver nanoparticles (AgNPs) on polydopamine (PDA)-coated SMNs. The physicochemical properties of SMNs@PDA-AgNPs were characterized regarding morphology, composition, mechanical strength, and liquid absorption capacity. The antibacterial effects were evaluated and optimized through agar diffusion assays in vitro. Wound healing and bacterial inhibition were further examined in vivo during MN application. Finally, the ISF sampling ability and biosafety of SMNs@PDA-AgNPs were assessed in vivo. The results demonstrate that antibacterial SMNs enable direct ISF extraction while preventing infection risks. SMNs@PDA-AgNPs could potentially be used for direct sampling or combined with medical devices for real-time diagnosis and management of chronic diseases.Keywords:microneedles;antibacterial activity;silver nanoparticles;ISF sampling;medical devices
研究领域:
生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Lin He,Yan Zhou,Min Zhang,Mingjian Chen,Yuchen Wu,Lanlin Qi,Lamei Liu,Bin Zhang,Xiaohai Yang,Xiaoxiao He,Kemin Wang
Detection of slight pH changes in skin interstitial fluid (ISF) is crucial yet challenging for studying pathological processes and understanding personal health conditions. In this work, we construct an i-motif DNA based fluorescent ratiometric microneedle sensing patch (IFR-pH MN patch) strategy that enables minimally invasive, high-resolution, and sensitive transdermal monitoring of small pH variations in ISF. The IFR-pH MN patch with advanced integration of both ISF sampling and pH sensing was fabricated from the cross-linking of gelatin methacryloyl and methacrylated hyaluronic acid, wrapping with pH-sensitive hairpin-containing i-motif DNA based fluorescent ratiometric probes in the matrix. Because it is mechanically robust for skin penetration and has high swelling ability, the IFR-pH MN patch could be quickly extracted as sufficient liquid from agarose gel (∼56.4 μL in 10 min). Benefiting from conformation changes of the hairpin-containing i-motif DNA under pH variation and ratiometric fluorescence signal readout, the IFR-pH MN patch could quantitate pH over a small range between pH 6.2 and 6.9 with an accuracy of 0.2 pH units in the mimic skin model. Furthermore, in vivo testing on wound and tumor mouse models indicated the ability of the biocompatible IFR-pH MN patch to penetrate the skin for obtaining transdermal pH values, demonstrating the potential applications in monitoring and intervention of pathological states.
研究领域:
生物医学工程
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分子生物学
·
传感技术
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DOI
PubMed
高影响因子
BIOMEDICAL MICRODEVICES
·
2019
·Vol. 21
·期 3
·1-10
·
IF 2.327
Chen Jianmin,Wang Meixia,Ye Yaling,Yang Zhouyan,Ruan Zhipeng,Jin Nan
Microneedle (MN) patch has been used for collecting dermal interstitial fluid (ISF) containing biomarkers from patients with safety, pain-free and easy-to-use manner. However, long sampling time for biomarkers analysis still poses a significant challenge. Here, we describe a new sponge-forming MN patch consisting of polyvinyl formal (PVF) for rapidly extracting ISF from skin. Owing to the supreme water affinity of PVF, this MN patch can extract 1.6 mg ISF in 1 min without the assistance of extra devices, which remarkably facilitates timely analysis. The MN patch had preserved structural integrity in the swelling hydrated state without leaving residues in skin after usage, and the treated skin recovered within 8 h. More importantly, the extracted ISF can be efficiently recovered from the MN patch by simple centrifugation for the subsequent offline analysis of biomarkers such as glucose and cholesterol. Our results reveal that the new sponge-forming MN patch holds considerable promise for minimally invasive sampling ISF for biomarkers detection in real-life situations.
研究领域:
生物医学工程
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分析化学
·
药学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Jiachen Zhu,Weiliang Wang,Gang Chen,Tian Gao,Zhiyong Gao,Liang Peng,Luwen Wang,Wei Cai
Uric acid (UA) and dopamine (DA) are crucial biomarkers in the human body. However, there is limited research on detecting UA or DA in subcutaneous interstitial fluid (SISF), and no studies on their simultaneous detection in SISF. Here, we developed an electrochemical microneedle sensor based on the carboxylated carbon nanotubes/multiwalled carbon nanotubes (CCNT/CNT) composite electrode for the simultaneous detection of UA and DA. Highly carboxylated CCNT was prepared and mixed with CNT and organosilicon-modified acrylic resin to form the CCNT/CNT composite. The carboxyl functional groups of CCNT enhance the electrode’s adsorption of UA and DA, while CNT improves electron conduction. The sensor achieves a wide linear detection range for UA (5–600 μM) with high sensitivity (7.13 μA μM −1 cm −2 ) and linearity (R 2 = 0.994), as well as a wide linear range for DA (2–200 μM) with high sensitivity (13.31 μA μM −1 cm −2 ) and linearity (R 2 = 0.994). The sensor achieved simultaneous detection of DA and UA in artificial interstitial fluid (ISF), with sensitivity and linearity remaining nearly unchanged compared to that in PBS, and is not affected by high levels of ascorbic acid (AA). Finally, the sensor successfully detected changes in UA levels in ISF of subjects before and after alcohol consumption in vivo , demonstrating its practical application capabilities. This study presents a practical strategy for detecting human biomarkers characterized by low cost, easy fabrication and excellent performance of electrode materials, and a well-designed microneedle sensor preparation scheme, making it highly promising for further research extension.
研究领域:
生物医学工程
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分析化学
·
材料科学
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产品关联
DOI
高影响因子
JOURNAL OF DRUG TARGETING
·
2024
·
IF 4.3
Yangcheng He,Yuyi Feng,Danxai Qiu,MinHua Lin,Hai Jin,Zhiwen Hu,Xue Huang,Suihong Ma,Yan He,Meiqi Lai,Wenhui Jin,Jianhua Liu
Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.
研究领域:
肿瘤学
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纳米医学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Haifeng Zhang,Zhaoxin Li,Shengtian Sang,Liang Yin
As the number of people with diabetes continues to increase, the use of high-performing blood glucose testing devices for blood glucose management is critical. Therefore, a flexible micronedle sensor (MNs sensor) based on flexible micronedle array structure (MNs array) is proposed in this study, inspired by the ultra-fast water absorption characteristics of straw, which can be used to quickly, conveniently and noninvasculatively detect glucose concentration in human interstitium fluid (ISF). The MNs sensor is the composite of flexible MNs array and highly sensitive detection electrode. The MNs sensor has excellent mechanical properties, the maximum pressure is 69.2 N (4 times the average), the compressive strength is 88.13 MPa (1.88 times the average), and the fracture compression ratio is 194.7 %(3.36 times the average). These properties enable MN sensors to penetrate the stratum corneum in complete form while extracting ISF quickly and consistently. Meanwhile, the MN sensor has the highly sensitivity (1826.75nA mM −1 cm −2 , 4.72 times the average value). It has a wider detection range (1 mM-30 mM) and faster detection (30 s) than existing MN glucose detectors. In addition, the MN sensor has excellent anti-interference performance and can accurately detect glucose concentration in the case of multiple disturbances. This work lays a foundation for the development of a new painless, real-time monitoring and high accuracy blood glucose detection system.
研究领域:
生物医学工程
·
糖尿病研究
·
传感器技术
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）