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ACS Sensors · 2023 · IF 8.9

Fast and Sensitive Detection of Protein Markers Using an All-Printing Photonic Crystal Microarray via Fingertip Blood

Jimei Chi,Meng Su,Bingjie Xue,Lijun Cheng,Zewei Lian,Yang Yun,Xu Yang,Xue Wang,Hongfei Xie,Huadong Wang,Yuan Wang,Jie Du,Yanlin Song

With the demand for point-of-care testing (POCT) in cardiovascular diseases, the detection of biomarkers in trace blood samples is of great significance in emergency medicine settings. Here, we demonstrated an all-printed photonic crystal microarray for POCT of protein markers (named “P4 microarray”). The paired nanobodies were printed as probes to target the soluble suppression of tumorigenicity 2 (sST2) as a certified cardiovascular protein marker. Benefiting from photonic crystal-enhanced fluorescence and integrated microarrays, quantitative detection of sST2 is 2 orders of magnitude lower than that of a traditional fluorescent immunoassay. The limit of detection is down to 10 pg/mL with the coefficient of variation being less than 8%. Detection of sST2 via fingertip blood is achieved in 10 min. Moreover, the P4 microarray after 180 days of storage at room temperature showed excellent stability for detection. This P4 microarray, as a convenient and reliable immunoassay for rapid and quantitative detection of protein markers in trace blood samples, has high sensitivity and strong storage stability, which hold great potential to advance cardiovascular precision medicine.

CAS / MDL: 99-20-7
研究领域: 生物医学工程 · 临床化学 · 心脏病学 · 即时检测
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ANALYTICAL CHEMISTRY · 2024 · IF 6.7

Afterglow Nanoprobe-Enabled Quantitative Lateral Flow Immunoassay by a Palm-Size Device for Household Healthcare

Jiuchuan Guo,Yudong Zhou,Jie Cheng,Fuli Chen,Jiahui Xu,Lirong Yang,Huifang Shi,Zhongfu An,Jinhong Guo,Xing Ma

Lateral flow immunoassay (LFIA), a classical point-of-care testing (POCT) technique, plays an important role in disease screening and healthcare monitoring. However, traditional LFIA is either designed for qualitative analysis or requires expensive equipment for quantification, limiting its use in household diagnosis. In this study, we proposed a new generation of LFIA for household health monitoring by using ultralong organic phosphorescence (UOP) nanomaterials as afterglow nanoprobes with a self-developed palm-size sensing device. The UOP nanoprobes exhibit a phosphorescence signal with a second-level lifetime, which completely avoids the interference from excitation light and biological background fluorescence. Therefore, an ultraminiaturized and low-cost UOP nanosensor was successfully designed by eliminating the complex optical path and filtering systems. We chose an inflammatory factor, C-reactive protein (CRP), for household POCT validation. The whole analysis was completed within 9 min. A limit of detection (LOD) of 0.54 ng/mL of CRP antigen was achieved with high stability and good specificity, which is comparable to laboratory instruments and fully satisfying the clinical diagnosis requirement.

CAS / MDL: 9004-32-4
研究领域: 生物医学工程 · 分析化学 · 医学诊断 · 纳米技术 · 即时检测设备
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Journal of Materials Chemistry C · 2021 ·Vol. 9 ·期 41 ·14938-14945 · IF 7.393

Flexible, self-healable, adhesive and wearable hydrogel patch for colorimetric sweat detection

Lirong Wang,Tailin Xu,Xuecheng He,Xueji Zhang

Recent advances in wearable sweat sensors with noninvasive health monitoring capabilities have provided enormous potential for point-of-care testing (POCT) diagnostics and personalized medicine. In this paper, we present a flexible, self-healable, adhesive and wearable hydrogel patch for on-demand sweat colorimetric detection. Such a user-specific wearable hydrogel patch is simply prepared by the solvent displacement method, and can directly attach to human skin for in situ sweat sampling and colorimetric analysis without any complicated preparation steps. This wearable hydrogel patch shows excellent reliability and stability for measuring pH (4–9), glucose (0–2 mM), Cl− (0–100 mM) and Ca2+ (0–16 mM) in human sweat through integration with smartphones. The analysis and detection of multiple sweat biomarkers of 15 healthy volunteers have been successfully realized by effectively converting the analyte concentration into RGB digital signals through the wearable hydrogel patch. Such a wearable hydrogel patch with flexible, self-healable, adhesive properties can achieve on-demand in situ sweat colorimetric detection, holding great potential in point-of-care devices.

研究领域: 生物材料 · 可穿戴技术 · 生物医学工程 · 即时诊断 · 健康监测
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ANALYTICAL CHEMISTRY · 2018 · IF 6.042

Portable and Label-Free Detection of Blood Bilirubin with Graphene-Isolated-Au-Nanocrystals Paper Strip

Yuxiu Zou,Yinling Zhang,Yiting Xu,Yiqin Chen,Siqi Huang,Yifan Lyu,Huigao Duan,Zhuo Chen,Weihong Tan

Point-of-care testing (POCT) devices represent a growing field that aims to develop low-cost, rapid, sensitive diagnostic testing platforms that are portable and self-contained. Surface-enhanced Raman spectroscopy (SERS) is an approach has shown high potential in POCT technology. However, the specificity or ability to uniquely detect a desired biomarker in complex biological samples is a key factor for translating SERS technologies to POCT. Herein, we fabricated cellulose SERS strips (CS) decorated with novel plasmonic nanoparticles, termed graphene-isolated-Au-nanocrystals (GIANs), for the portable detection of complex biological samples. This CS@GIANs SERS strip was used to detect free bilirubin (BR) in the blood of newborns, a biomarker of jaundice, without sample labeling or prepreparation. CS@GIANs showed superior affinity to hydrophobic BR molecules compared to typical SERS substrate, which reduced the steric hindrance effect from the nonspecific binding of BR with serum albumin in blood and improved sensitivity. Meanwhile, with the separation property of cellulose chromatography papers, CS@GIANs showed superior anti-interference to other biomolecules that had been previously adsorbed on the SERS strip. Moreover, the SERS signal from the graphitic shell of GIANs could be used as a stable internal calibration standard, which improved the reproducibility and accuracy of Raman analysis. Such a cellulose SERS strip holds high potential for enhancing current efforts in the development of rapid and low-cost point-of-care diagnostic testing.

研究领域: 医学诊断 · 纳米技术 · 生物医学工程 · 分析化学
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

Paper-based fluorometric sensing of malachite green using synergistic recognition of aptamer-molecularly imprinted polymers and luminescent metal–organic frameworks

Nuo Duan,Xiaowan Chen,Xianfeng Lin,Dichen Ying,Zhouping Wang,Wenbo Yuan,Shijia Wu

Herein, a paper-based fluorescence sensor based on the metal-organic frameworks capped with aptamer and molecular imprinted polymer ( [email protected] ) was designed for malachite green (MG) and realized sensitive detection by using digital image colorimetry with the aid of smartphone. The green fluorescence terbium MOF-76 was prepared and used as a carrier to conjugate with MG specific aptamer. MG, as template molecule, was subsequently added into MOF-Apt to generate MIP layer under the action of co-polymerization process. With the addition of MG, the fluorescence of [email protected] was quenched because MG was synergistically bound with aptamer and MIP and induced photo-induced electron transfer (PET) effect. Then, the obtained [email protected] probe was applied to a circle pattern paper and measured by a smartphone, in which color recognition software was installed to read out the RGB values of the acquired images. The detection limit for paper-based detection was 0.1 ng/mL. This point of care testing (POCT) method was applied to detect MG in fish and water samples with recoveries in 94.0–105.6 %. This method endows synergistic binding effect of aptamer and MIP, enhancing the detection sensitivity and specificity, and the paper-based detection with smartphone facilitate the on-site monitoring. It is expected that this sensor will be of great significance for the detection and monitoring of illegal additive in food stuffs.

研究领域: 分析化学 · 环境科学 · 食品安全 · 材料科学
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JOURNAL OF MATERIALS SCIENCE · 2023 ·Vol. 58 ·期 31 ·12747-12763 · IF 4.5

Borocarbonitride tubulous nanozymes for bacterial colorimetric point-of-care testing and in situ enzymatic/photothermal synergistic inactivation

Cui Yong,Bao Zhihong,Zhang Jinghai,Wang Chao

As a typical mimic of natural enzymes, carbon-based peroxidase-like nanozymes have developed vigorously recent years, which are widely used in biomedical research. In this paper, borocarbonitride nanotubes (BCNNTs) were synthesized via assembly and pyrolysis of small organic molecules achieving boron (B) and nitrogen (N) co-doping in carbon nanotubes. As non-metallic nanozymes, BCNNTs exhibited high peroxidase-like activity and photothermal conversion capability, which were applied to bacterial colorimetric point-of-care testing (POCT) and in situ synergistic inactivation. By BCNNTs functionalized with specific antibody of Staphylococcus aureus , sensitive visible and rapid POCT of Staphylococcus aureus was accomplished. Right after the bacterial assay, the bacterial inactivation proceeded efficiently owing to both the catalytic decomposition of H 2 O 2 and photothermal disinfection induced by BCNNT nanozymes, that eliminated bacterial contamination and further transmission without delay. The multifunctional BCNNT nanozymes possessed high peroxidase-like activity, photothermal property, good biocompatibility and stability, which had great potentials in food safety testing, environmental monitoring, and microbial control and therapy.

研究领域: 生物医学工程 · 纳米技术 · 分析化学 · 微生物学
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ADVANCED MATERIALS · 2024 · IF 27.4

Quantitative Assessment of Fungal Biomarkers in Clinical Samples via an Interface-Modulated Optical Fiber Biosensor

Pengwei Chen,Haotian Wu,Yajing Zhao,Lv Zhong,Yujiao Zhang,Xundi Zhan,Aoxiang Xiao,Yunyun Huang,Hong Zhang,Bai-Ou Guan

Invasive fungal infections pose a significant public health threat. The lack of precise and timely diagnosis is a primary factor contributing to the significant increase in patient mortality rates. Here, an interface-modulated biosensor utilizing an optical fiber for quantitative analysis of fungal biomarkers at the early stage of point-of-care testing (POCT), is reported. By integrating surface refractive index (RI) modulation and plasmon enhancement, the sensor to achieve high sensitivity in a directional response to the target analytes, is successfully optimized. As a result, a compact fiber-optic sensor with rapid response time, cost-effectiveness, exceptional sensitivity, stability, and specificity, is developed. This sensor can successfully identify the biomarkers of specific pathogens from blood or other tissue specimens in animal models. It quantifies clinical blood samples with precision and effectively discriminates between negative and positive cases, thereby providing timely alerts to potential patients. It significantly reduces the detection time of fungal infection to only 30 min. Additionally, this approach exhibits remarkable stability and achieves a limit of detection (LOD) three orders of magnitude lower than existing methods. It overcomes the limitations of existing detection methods, including a high rate of misdiagnosis, prolonged detection time, elevated costs, and the requirement for stringent laboratory conditions.

CAS / MDL: 9036-88-8
研究领域: 医学诊断 · 光学传感 · 生物医学工程 · 临床微生物学
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ANALYTICAL CHEMISTRY · 2020 · IF 6.785

Abnormal Liquid Chasing Effect in Paper Capillary Enables Versatile Gradient Generation on Microfluidic Paper Analytical Devices

Yu Liu,Jin-Wen Shangguan,Bi-Yi Xu,Xiao-Dong Yu,Jing-Juan Xu,Hong-Yuan Chen

Microfluidic paper analytical devices (μPADs) are smart and accessible substituents to traditional counterparts in point-of-care tests (POCT), which exploited delicate control over passive fluid in microscale for rich functions. In this work, we are extending such control by introducing novel ways to generate 1D and 2D gradients on μPADs. It is achieved by using paper-capillary-based serial sampling. The paper capillary is composed of a concaved paper channel sealed with tape, with test pads properly distributed aside. In such a structure, the liquid can not only quickly and automatically flow along the capillary but also be continuously consumed by the peripheral test pads. Thus, when we do serial sampling, an abnormal liquid chasing effect can be observed, where the later liquid sample chases and surpasses the earlier parts in the paper capillary, leading to reversely ordered sample distribution compared with that in a typical glass capillary. This specialty allows for fast, ordered, and tunable sequential sampling and enables efficient generation of 1D and 2D concentration gradient with one, two, and even three components on μPADs. Besides, we verified the applicability of this technique for arrayed assays, including 1D serial dilution-based metal ion colorimetry and a 2D bacterial antibiotic susceptibility test for synergic effect evaluations, which paves the way for high-throughput sample analysis and information-rich condition screening on μPADs.

CAS / MDL: 9003-01-4 5144-89-8
研究领域: 微流控 · 分析化学 · 生物医学工程 · 即时诊断
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ANALYTICAL CHEMISTRY · 2023 · IF 7.4

Flexible Point-of-Care Electrodes for Ultrasensitive Detection of Bladder Tumor-Relevant miRNA in Urine

Duo Chen,Na Chen,Fangning Liu,Yiming Wang,Huageng Liang,Yanbing Yang,Quan Yuan

Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I–III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.

研究领域: 生物医学工程 · 纳米技术 · 癌症诊断 · 电化学 · 即时检测设备
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BIOSENSORS & BIOELECTRONICS · 2022 · IF 12.545

Nanozyme-strip for rapid and ultrasensitive nucleic acid detection of SARS-CoV-2

Xiangqin Meng,Sijia Zou,Dandan Li,Jiuyang He,Ling Fang,Haojue Wang,Xiyun Yan,Demin Duan,Lizeng Gao

The coronavirus disease 2019 (COVID-19) pandemic has created a huge demand for sensitive and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current gold standard for SARS-CoV-2 detection is reverse transcription-polymerase chain reaction (RT-PCR)-based nucleic acid amplification. However, RT-PCR is time consuming and requires specialists and large instruments that are unattainable for point-of-care testing (POCT). To develop POCT for SARS-CoV-2, we combined recombinase polymerase amplification (RPA) and FeS 2 nanozyme strips to achieve facile nucleic acid amplification and subsequent colorimetric signal enhancement based on the high peroxidase-like activity of the FeS 2 nanozymes. This method showed a nucleic acid limit of detection (LOD) for SARS-CoV-2 of 200 copies/mL, close to that of RT-PCR. The unique catalytic properties of the FeS 2 nanozymes enabled the nanozyme-strip to amplify colorimetric signals via the nontoxic 3,3′,5,5′-tetramethylbenzidine (TMB) substrate. Importantly, the detection of clinical samples of human papilloma virus type 16 (HPV-16) showed 100% agreement with previous RT-PCR results, highlighting the versatility and reliability of this method. Our findings suggest that nanozyme-based nucleic acid detection has great potential in the development of POCT diagnosis for COVID-19 and other viral infections.

研究领域: 分子生物学 · 病毒学 · 即时诊断 · 纳米技术
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Solid-Phase microextraction on Self-Driven microfluidic chip using capillary micropump and microvalves for saliva electrochemical analysis

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.

CAS / MDL: 13746-66-2
研究领域: 微流控 · 电化学分析 · 即时检测 · 生物标志物检测 · 无创诊断
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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Dual-functional ultrathin wearable 3D particle-in-cavity SF-AAO-Au SERS sensors for effective sweat glucose and lab-on-glove pesticide detection

Dan Wang,Guanchen Xu,Xingshuang Zhang,Hongyu Gong,Li Jiang,Guanliang Sun,Yu Li,Guoran Liu,Yong Li,Shikuan Yang,Xiu Liang

A novel approach is developed to fabricate an ultra-thin layered flexible wearable Surface-Enhanced Raman Scattering (SERS) substrate named silk fibroin-anodic aluminum oxide-Au nanoparticles (SF-AAO-Au), which consists of biocompatible SF film as flexible support, ultrathin cavity AAO as template, and plasmonic Au NPs. The SF-AAO-Au sensor exhibits excellent SERS mechanical flexibility, homogeneity and sensitivity for its effective enhancement ability and highly ordered 3D periodic porous particle-in-cavity (PIC) arrays structure. The humidity-driven interface structure of biocompatible SF film provides good skin adhesion under various fitness tests and excellent mechanical flexibility as a wearable SERS sensor on natural skin (deformation within 5%). The flexible SF-AAO-Au can be developed as quantitative sweat glucose sensor in the concentration range of 10 − 7 10−7 to 10 − 3 10−3 M with a limit of detection (LOD) of 1.68 × 10 − 7 1.68×10−7 M and qualitative human sweat glucose detection ability. This SF-AAO-Au substrate can be further designed as lab-on-glove SERS sensing platform for ultrasensitive (LOD ~5.7 ppt) quantitative on-site detection of agricultural residues in a wide range. The effective dual-functional SERS wearable sensor realized for the first time paves a new way to develop smart wearable and non-destructive devices in environmental safety, forensic identification and point-of-care testing (POCT) diagnosis of physiological disease.

研究领域: 材料科学 · 纳米技术 · 可穿戴技术 · 分析化学 · 生物医学工程 · 环境科学
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