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Biosensors-Basel · 2023 ·Vol. 13 ·期 5 ·537 · IF 5.4

Porous Colorimetric Microneedles for Minimally Invasive Rapid Glucose Sampling and Sensing in Skin Interstitial Fluid

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 · 糖尿病管理 · 即时诊断
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ACS Sensors · 2024 · IF 8.2

Silver Nanoclusters-Decorated Porous Microneedles Coupling Duplex-Specific Nuclease-Assisted Signal Amplification for Sampling and Detection of MicroRNA in Interstitial Fluid

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 · 分子诊断 · 纳米技术
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2025 · IF 5.2

Iontophoresis-driven transdermal drug delivery system based on porous microneedles for hyperuricemia treatment

Rui Wang,Han Wang,Rui Yao,Yan Li,Sedrati Manar,Lei Nie,Khaydar E. Yunusov,Jianwei Pan,Guohua Jiang

An iontophoresis-driven porous microneedles (IPMNs) system has been developed for hyperuricemia management, which can be effectively prolong the anti-hyperuricemia effect. Porous microneedles (PMNs) with good biocompatibility, high porous volume, and excellent substance exchange capacity were firstly prepared for drug transdermal delivery and active iontophoresis.   In vitro experiments showed that the transdermal delivery efficiency of anti-hyperuricemia drug (Allopurinol, AP) could be controlled using the iontophoresis current of IPMNs system. The AP release amount could be increased to 1.54 mg with iontophoresis under constant voltage of 1.5 V for 30 min. In vivo transdermal delivery of AP on mice models using IPMNs system exhibited an effective anti-hyperuricemia response. The serum uric acid (SUA) level could be dropped to ∼ 158.2 μmol/L within 2 h, and maintaining for 7 h under the normal level, leading a long-term therapeutic effect. This IPMNs system exhibits a low cost, user-friendly, and active delivery, showing great potential for hyperuricemia self-administration.

研究领域: 药物递送 · 生物医学工程 · 皮肤病学
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PLoS One · 2017 ·Vol. 12 ·期 2 ·e0172043 · IF 2.806

Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery

Jiyu Li,Bin Liu,Yingying Zhou,Zhipeng Chen,Lelun Jiang,Wei Yuan,Liang Liang

Microneedle arrays (MA) have been extensively investigated in recent decades for transdermal drug delivery due to their pain-free delivery, minimal skin trauma, and reduced risk of infection. However, porous MA received relatively less attention due to their complex fabrication process and ease of fracturing. Here, we present a titanium porous microneedle array (TPMA) fabricated by modified metal injection molding (MIM) technology. The sintering process is simple and suitable for mass production. TPMA was sintered at a sintering temperature of 1250°C for 2 h. The porosity of TPMA was approximately 30.1% and its average pore diameter was about 1.3 μm. The elements distributed on the surface of TPMA were only Ti and O, which may guarantee the biocompatibility of TPMA. TPMA could easily penetrate the skin of a human forearm without fracture. TPMA could diffuse dry Rhodamine B stored in micropores into rabbit skin. The cumulative permeated flux of calcein across TPMA with punctured skin was 27 times greater than that across intact skin. Thus, TPMA can continually and efficiently deliver a liquid drug through open micropores in skin.

研究领域: 材料科学 · 医学工程 · 药物递送
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IEEE TRANSACTIONS ON ELECTRON DEVICES · 2025 · IF 3.2

Porous Microneedle Array Electrode Using Interstitial Fluid as Conductive Fillers for Biosafe and Long-Term Biopotential Monitoring

Zifan Xue,Yunfan Zhang,Yuting Zheng,Shengnan Shen,Hui Li

The microneedle array electrodes (MNAEs) can record high-quality biopotentials comparable to wet electrodes while effectively addressing durability and comfort issues caused by electrolytic gel. However, current MNAEs rely on the use of conductive materials, such as metals, which typically exhibit insufficient biosafety and raise concerns due to the risk of functional coating shedding or microneedles (MNs) fracturing and remaining in the body. Here, a biosafe porous-MNAE using interstitial fluid (ISF) as conductive fillers is proposed. Its porous-MNs can penetrate the high-impedance stratum corneum (SC) and automatically absorb ISF through capillary action for electric conduction. This allows the preparation of porous-MNs using totally biodegradable and biocompatible materials, such as polyglycolic acid (PGA) and polylactic acid (PLA) used in this work, without compromising electrode impedance. The results show that the proposed porous-MNAE possesses adequate mechanical property, hygroscopicity, biodegradability, and wearability for practical applications. Meanwhile, it demonstrates a competitive normalized electrode–skin interface impedance (EII) of 1.94 ± 0.09 kΩ⋅cm2 at 10 Hz on pig ear skin and exhibits priority in continuous 6-h EII measurement. In brief, these results reveal the promising potential of porous-MNAE for biosafe and long-term biopotential monitoring.

研究领域: 生物医学工程 · 材料科学
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ANALYTICA CHIMICA ACTA · 2024 · IF 5.7

Thylakoid-based green preparation of porous microneedles for antibiotic residues detection in food samples

Rongrong Huang,Yue Xu,Peipei Wan,Tong Zhu,Weili Heng,Wenjun Miao

Background Antibiotic residues in food chain have raised concerns regarding their toxicity and involvement in antimicrobial resistance. However, most existing antibiotic biosensors are primarily applicable to liquid food samples. Given the complex matrix characteristics of foods, there is an urgent need for the development of effective antibiotic detection platforms that exhibit high universality and flexibility. Porous microneedles (PMN) are microdevice structures with needle-like shapes and microscale pores throughout their composition, which facilitate rapid sampling. Consequently, the integration of PMN with biosensors holds significant promise for the detection of antibiotic residues in complex food samples. Results In this study, hydrogel-forming PMN are fabricated by leveraging the oxygen-production capacity of thylakoid to generate bubbles and form porous structures. These PMN are then integrated with a fluorescence aptasensor for the quantification of the antibiotic netilmicin. The aptasensor consists of a netilmicin (NET) aptamer with stem loop and hairpin structure, which facilitated the binding of SYBR Green I to produce a fluorescent signal. In the presence of NET, the complete binding between NET and the aptamer results in a reduction of fluorescence intensity, thereby generating a detectable signal change for the detection of NET. Utilizing capillary action accelerate fluid extraction (2.9 times faster than nonporous microneedles) and a large specific surface area (5.1072 m 2 /g) conducive to aptasensor adsorb, the PMN achieve efficient capture and quantification of antibiotic with limits of detection and quantitation of 5.99 nM and 19.8 nM, respectively. Significance Porous microneedles with tunable porosity and desirable mechanical properties are successfully fabricated. The integration of PMN with aptasensor enable the efficient detection of netilmicin in fish, milk and river water samples, demonstrating high recovery rates. The PMN represent potential tools for the convenient and rapid detection of antibiotic residues within complex food matrices, thereby enhancing food safety monitoring.

研究领域: 生物技术 · 分析化学 · 食品科学 · 材料科学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2025 · IF 5.6

Porous microneedle-mediated continuous glucose monitoring based on reverse iontophoresis

Rui Yao,Olanrewaju Yaasir Olatunji,Rui Wang,Zhenyu Wu,Guohua Jiang

Measuring blood glucose concentrations via continuous glucose monitoring is an important aspect of management for patients with diabetes. In this study, a continuous glucose monitoring device has been developed by integration of porous microneedles, reverse iontophoresis and biosensor technologies. An enzyme-based glucose biosensor as working electrode was firstly fabricated by electrodepositing polydopamine (PDA) onto screen-printed electrodes, and following depositing glucose oxidase (GOx) by linking of glutaric dialdehyde. The interstitial fluid (ISF) extraction could be accelerated with assistance of reverse iontophoresis. The glucose in the ISF could react with GOx on the electrode to generate a current response of blood glucose concentration. The minimally measurement results for blood glucose showed an enhanced sensitivity of 0.934 μA/mM with a high correlation (R 2 >0.99), low limit of detection (LOD ≈ 19.3 μM), broad linear detection range (LDR = 2–18 mM) that satisfices glucose detection application.

研究领域: 生物医学工程 · 生物传感器 · 糖尿病管理 · 药物传递 · 分析化学
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Analytical Methods · 2025 · IF 2.6

Porous microneedle-based electrochemical sensor for potassium and glucose in skin interstitial fluid

Dake Ai,Xin Tang,Zhenlong Meng,Yang Yu,Xiuxiu Guo,Yuanpeng Wang

The monitoring of biomarkers in interstitial fluid (ISF) holds significant promise for non-invasive, real-time health assessment. In this study, we present a novel porous microneedle-based electrochemical sensor (PMES) designed for the extraction and detection of key electrolytes and metabolites in ISF. The system integrates porous microneedles (PMNs) with screen-printed electrodes (SPEs) and polyethylene glycol (PEG)-loaded filter paper to facilitate efficient ISF collection and enable electrochemical detection. Both in vitro and in vivo experiments demonstrated the PMES's high biocompatibility and ability to detect potassium and glucose with reproducible, clinically relevant performance. For context, we also fabricated MN-electrode sensors (potentiometric Na+; amperometric glucose) and performed head-to-head comparisons, in which PMES exhibited superior long-term stability under identical insertion conditions. Compared with these directly functionalized MN electrodes prepared in this work, PMES maintained signal stability by decoupling ISF extraction (PMNs with PEG-assisted collection) from electrochemical transduction (external SPEs), thereby mitigating abrasion-induced coating delamination and biofouling; this comparison pertains to the architectures tested here and demonstrates the potential of PMES for minimally invasive, time-resolved health monitoring.

研究领域: 生物传感器 · 微加工技术 · 电化学 · 生物医学工程 · 即时诊断 · 可穿戴设备
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

Fabrication of controlled porous and ultrafast dissolution porous microneedles by organic-solvent-free ice templating method

Qinying Yan,Shulin Shen,Linxiao Liu,Jiaqi Weng,Gensuo Zheng,Xu Dong,Jing Yang,Qingliang Yang,Jing Xie

Porous Microneedles (PMNs) have been widely used in drug delivery and medical diagnosis owing to their abundant interconnected pores. However, the mechanical strength, the use of organic solvent, and drug loading capacity have long been challenging. Herein, a novel strategy of PMNs fabrication based on the Ice Templating Method is proposed that is suitable for insoluble, soluble, and nanosystem drug loading. The preparation process simplifies the traditional microneedle preparation process with a shorter preparation time. It endows the highly tunable porous morphology, enhanced mechanical strength, and rapid dissolution performance. Micro-CT three-dimensional reconstruction was used to better quantify the internal structures of PMNs, and we further established the equivalent pore network model to statistically analyze the internal pore structure parameters of PMNs. In particular, the mechanical strength is mainly negatively correlated with the surface porosity, while the dissolution velocity is mainly positively correlated with the permeability coefficient by the correlation heatmap. The poorly water-soluble Asiatic acid was encapsulated in PMNs in nanostructured lipid carriers, showing prominent hypertrophic scar healing trends. This work offers a quick and easy way of preparation that may be used to expand PMNs function and be introduced in industrial manufacturing development.

研究领域: 药学 · 生物医学工程 · 材料科学 · 药物递送系统
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