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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Self-powered bio-chip for ultra-sensitive dual MiRNAs detection: A portable platform for cancer biomarker analysis

Hui Li,Zongshan Zhang,Wantong Hao,Huixin Shi,Ruiyang Yin,Jing Xu

MicroRNAs (miRNAs) are key regulators of gene expression and play a crucial role in various biological processes. However, existing methods for miRNA detection face challenges in terms of sensitivity, specificity and ease of use. These limitations highlight the need for innovative and highly sensitive detection platforms capable of accurately quantifying miRNAs. In this work, an integrated biochip based on a self-powered sensor system developed for the ultra-sensitive detection of miRNAs-21 and miRNA-20a. The system uses a bilirubin oxidase (BOD)-supported bio-cathode and a glucose oxidase (GOD)-supported bio-anode to form a closed loop that converts chemical energy into electrical energy. The complementary chains of target miRNAs are modified on the bio-anode using a bio-conjugate amplification strategy, enabling the system to generate an electrical signal proportional to the concentration of miRNAs. The sensor has a wide linear range of 5 fmol/L to 10 nmol/L for miRNA-20a and 1 fmol/L to 10 fmol/L for miRNA-21, with low detection limits of 0.176 fmol/L and 0.138 fmol/L, respectively. These detection limits are significantly lower than those achieved by existing technologies, making our biosensor a significant advancement in the field. In addition, the sensor system is integrated into a portable chip that transmits electrical signals in real time via Bluetooth to a mobile phone interface, enabling convenient and rapid analysis.

CAS / MDL: 9001-37-0 92921-24-9
研究领域: 生物医学工程 · 分子生物学 · 分析化学
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ANALYST · 2024 · IF 3.6

Identification of new AAV vectors with enhanced blood-brain barrier penetration efficiency via organ-on-a-chip

Mengmeng Li,Yujian Zhong,Mingyang Zhu,Chunjin Pang,Lu Xiao,Ye Bu,Huapeng Li,Yong Diao,Chaoyong Yang,Dan Liu

To overcome limitations in generalizability and efficiency of current AAV vectors, in this current study, we constructed an AAV variant library by insertion of random heptapeptide sequences in the receptor-binding domain of the AAV9 capsid gene. We then applied a recently developed organ-on-a-chip in vitro model of human blood-brain barrier (BBB) to iteratively enrich for variants that efficiently cross the BBB and transduce astrocyte cells. Through multiple rounds of screening, we obtained two candidate AAV variants, AAV-M6 and AAV-M8, that showed significantly higher BBB penetration efficiency than AAV9 or AAV-PHP.eB. Quantitative PCR (qPCR) assay showed that AAV-M6 could accumulate to 5 times higher titer, while AAV-M8 reached 3 times higher titer, than AAV-PHP.eB in the neural chamber of the model. Transduction assay further verified that the AAV-M6 candidate vector was able to infect HA-1800 cells after crossing the BBB, suggesting it could potentially transduce brain parenchymal cells after crossing the hCMEC/D3 layer at higher efficiency than AAV-PHP.eB. Molecular simulations suggested that the human receptor proteins, LY6D and M6PR, could bind the AAV-M6 heptapeptide insertion with high affinity. This study provides two promising candidate AAV vectors and demonstrates the use of this in vitro BBB model for scalable, high throughput screening of gene therapies. These tools can drive investigations of the mechanisms underlying BBB permeability and the cell type specificity of virus vectors.

研究领域: 神经科学 · 基因治疗 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2013 · IF 5.437

Handy, rapid and multiplex detection of tumor markers based on encoded silica–hydrogel hybrid beads array chip

Zi-Xue Yang,Bao-An Chen,Heng Wang,Guo-Hua Xia,Jian Cheng,Xiao-Ping Pei,Fei Wang,Wen Bao

Malignant tumor has become the leading cause of death worldwide; however, multiplex detection technology could provide great assistance in large-scale population screening of diseases which could effectively reduce the mortality of malignant tumors. Here a microbeads array chip, which could be a perfect alternative method for the early screening, was developed. Silica–hydrogel hybrid bead (SHHB) with photonic encoding, which consists of both silica and hydrogel materials, was manufactured as the carrier of microbeads array for the first time. The SHHB has the advantages of the beads made of silica or hydrogel, but does not have their limitations. Reaction conditions of SHHBs array were optimized and then the fluorescent concentration curves of two widely-used tumor markers, human alpha fetoprotein and carcinoembryonic antigen, were constructed. The accuracy of SHHBs array has been proven according to the comparison between the results obtained by detecting 50 clinical samples with SHHBs array and chemiluminescence immunoassay . A cassette like chip device has also been developed to standardize operational processes and benefit automization in the next work. Hence it is concluded that SHHBs array chip is a handy, rapid and multiplex immunoassay technology, which could imply its practical application in clinical immunoassay in the near future.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物医学工程 · 免疫学 · 临床检验
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Journal of Materiomics · 2025 · IF 9.6

Room-temperature densified Al2O3-H3BO3 ceramics with excellent microwave dielectric properties and thermal conductivity for chip packaging

Zhan Zeng,Jin Cheng,Xinwei Xu,Hongye Wang,Yani Lu,Liang Sun,Naichao Chen,Xiaoyu Li,Boshen Zhang,Hong Wang

As electronic devices become increasingly miniaturized and demand greater integration, traditional packaging technologies face substantial challenges in meeting the needs for high-frequency performance and system reliability. Ceramic materials, known for their excellent dielectric properties and thermal stability, are promising candidates for advanced packaging applications. However, conventional high-temperature densification processes, which often exceed 1000 °C, restrict their compatibility with temperature-sensitive components in modern electronic systems. To overcome this limitation, we propose a novel approach to densify Al 2 O 3 -H 3 BO 3 ceramic at room temperature under low uniaxial stress. It is found that a H 3 BO 3 facilitates plastic deformation in the medium of deionized water, enhancing the densification of Al 2 O 3 -H 3 BO 3 ceramics even at minimal uniaxial stress. The resulting material exhibits a high relative density of over 96% and possesses excellent microwave dielectric properties (relative permittivity : 2.84–5.37; values: 12,924–69,000 GHz; resonant frequency values: −156.94 10 –6 ·°C –1 to −73.42 10 –6 ·°C –1 ) and thermal conductivity ( values: 1.96–5.96 W·m –1 ·K –1 ). After co-firing with a silicon wafer, the ceramic maintains its structural integrity, with no observable atomic diffusion at the ceramic-silicon interface, rendering it a potential candidate for advanced packaging and integration technologies.

CAS / MDL: 10043-35-3
研究领域: 材料科学 · 电子工程
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ANALYST · 2022 ·Vol. 147 ·期 16 ·3756-3763 · IF 5.227

An ion imprinting technology-assisted rotational microfluidic hybrid chip for the fluorescence detection of hexavalent chromium ions

Liyan Wang,Bowei Li,Jinhua Li,Ji Qi,Zhiyang Zhang,Lingxin Chen

Ion imprinting technology was integrated on a rotational microfluidic paper- and cloth-based hybrid chip for the sensitive and selective detection of hexavalent chromium (Cr(VI)) ions. The rotational microfluidic hybrid chip consisted of CdTe quantum dot based ion imprinting fluorescence sensing cloth and three layers of paper. Users can collect fluorescence signals conveniently via rotating the paper layer to expose the corresponding cloth-based sensing component. One microfluidic hybrid chip can realize the four-set multiplexed detection of Cr(VI) ions, with each set providing three parallel measurements. Furthermore, the quantitative determination of Cr(VI) ions can be achieved via substituting the calculated fluorescence quenching value into the linear calibration curve. The ion imprinting fluorescence sensing microfluidic hybrid chip provides a simple, efficient, and user-friendly device for Cr(VI) ion detection. Moreover, it might be further adapted for other sensing systems and the point-of-care testing of pollutants in combination with portable instruments or smartphones.

研究领域: 分析化学 · 环境科学 · 生物医学工程
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Advanced Healthcare Materials · 2025 · IF 9.6

An Integrated Microfluidic Biomimetic Tumor-on-a-Chip for Wide-Range Screening of Chemotherapy and Photodynamic Therapy

Jinwei Zhang,Meilin Sun,Fen Zhang,Tingting Xuanyuan,Xufang Liu,Danyang Yu,Wenming Liu

Microengineered cancer model is exceedingly practical in preclinical screening, while establishing a highly tumor-biomimetic pathophysiological microsystem with multi-function integration remains challenging. Here, an integrated microfluidic biomimetic tumor-on-a-chip (IMBTC) platform is established to reinforce at once the spatiotemporal control of fluid/cell samples and wide-range gradient (WRG), as well as the in vitro multi-feature reconstruction of native tumors for supporting diverse preclinical therapy evaluations. The active pneumatic manipulators enable precise cell capture and array-like organization with high positioning efficiency. The WRG generator can unprecedentedly create a wide range of chemical gradients with up to 8 orders of magnitude, affording efficient therapy screening evaluation in a single chip capable of producing hundreds of tumors with size-uniformity via coculturing under a physiological flow condition. Multiple high-biomimetic characteristics in the engineered tumors, including complex multilayer organization, various phenotypic/biochemical gradients involving proliferation, viability, metabolism, hypoxia, and molecular penetration, and heterogeneous cell and stroma compositions, are validated. The IMBTC system is applied to successively evaluate individual drug chemotherapy, combinatorial chemotherapy, and photosensitive drug-dominant photodynamic therapy, thereby identifying the effective lethal doses from wide-range antitumor concentration screenings. The verified IMBTC system offers considerable benefits for advancing the development of next-generation tumor-on-a-chip and an innovative preclinical screening paradigm.

CAS / MDL: 5451-09-2
研究领域: 生物工程 · 微流控技术 · 癌症研究 · 药理学 · 生物医学工程 · 细胞生物学
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OPTICS EXPRESS · 2025 ·Vol. 33 ·期 19 ·40647-40660 · IF 3.3

Ultrasensitive on-chip biosensing of MUC1 enabled by LSPR-enhanced two-channel optofluidic lab-in-fiber platform

Hongtao Li,Hongtao Li,Hongtao Li,Hongtao Li,Jiaoyan Dai,Jiaoyan Dai,Jiaoyan Dai,Weisheng Wang,Weisheng Wang,Weisheng Wang,Yuxuan Liu,Yuxuan Liu,Yuxuan Liu,Lei Huang,Lei Huang,Liang Lu,Liang Lu,Liang Lu,Jialiang Lv,Jialiang Lv,Jiping Lin,Jiping Lin,Jiping Lin,Lili Liang,Lili Liang,Benli Yu,Benli Yu,Benli Yu

For efficiently diagnosing early-stage breast cancer, current existing MUC1 biomarker detection methods suffer from common issues of low sensing sensitivities. In this study, a single-core two-channel optical fiber optofluidic on-chip sensor is employed to high-sensitivity detect breast cancer biomarker MUC1 protein, where a Mach-Zehnder interferometer (MZI) waveguide and a fiber Bragg grating (FBG) inscribed into the device by using a femtosecond laser direct writing technique. To improve the device’s sensitivity, two microfluidic channels are etched using hydrofluoric (HF) solution, and Au nanobipyramids (Au NBPs) material on an optical fiber is used to excite and realize the localized surface plasmon resonance (LSPR) enhancement. Thus, the device’s refractive index (RI) sensitivity increases from 25.07 to 580.22 nm/RIU. FBG compensates the device’s temperature sensitivity, achieving at -0.139 nm/℃. On the basis of the advanced LSPR enhancement strategy, the sensor can not only specifically sense MUC1 protein with an ultra-low limit of detection (LOD) of 20.74 aM, it can also detect MUC1 protein in real serum background with a LOD of 42.07 aM. The obtained ultra-low LOD is lower than most existing state-of-the-art MUC1 detection technologies. This study paves what we believe to be a new universal way for developing advanced high-sensitivity lab-in-fiber optofluidic sensing strategy.

CAS / MDL: 57-13-6 919-30-2
研究领域: 肿瘤学 · 生物医学工程 · 分子诊断 · 光学传感 · 转化医学 · 纳米生物技术 · 液体活检
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Bioactive Materials · 2023 · IF 18.9

Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury

Jinjian Huang,Ziyan Xu,Jiao Jiao,Zongan Li,Sicheng Li,Ye Liu,Ze Li,Guiwen Qu,Jie Wu,Yun Zhao,Kang Chen,Jieshou Li,Yichang Pan,Xiuwen Wu,Jianan Ren

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 ( Olfm4 ) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo , and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury.

研究领域: 生物医学工程 · 分子生物学 · 组织工程
✓ 已验证 DOI PubMed 高影响因子
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Advanced Electronic Materials · 2025 · IF 5.3

Novel Porous Gold Microspheres Anisotropic Conductive Film (PGMS-ACF) with High Compression Ratio for Flip Chip Packaging

Li Zhang,Zhaomeng Wang,Geng Wei,Puyue Xia,Sining Fan,Wenhao Zhang,Shaolong Tang

The preparation of conductive filler is a key technology in anisotropic conductive films preparation. In recent decades, research on the preparation of novel conductive particles has reached a bottleneck. Porous gold materials exhibit high compressibility, low density, and excellent conductivity. It is believed that using porous gold microspheres (PGMS) to supersede polymer composite conductive microspheres has the potential to prepare anisotropic conductive film (ACF) with better performance. However, preparing ultrafine (1–10 µm) PGMS remains challenging. Herein, the study presents a novel method for preparing PGMS with controllable particle size and high sphericity. Results show that porous gold microspheres ACF (PGMS-ACF), containing only 5 wt.% particles (size range 4.5–10.5 µm), achieves good conductivity when held at a pressure range of 0.05–0.6 MPa. Its compression ratio is between 33% and 71% at 0.3 MPa. The 4-point probe measurement shows a contact resistance as low as 10 mΩ in 2 mm 2 . Moreover, PGMS-ACF also exhibits a good linear relationship within 3.3 A. Compared to commercial polymer composite conductive microspheres ACF, PGMS-ACF offers a significant advantage in achieving a large compression ratio, which in turn leads to improved conductivity and reduces the need for precise sorting. The research provides a new approach for the preparation of novel ACF.

研究领域: 材料科学 · 电子工程
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Micromachines · 2022 ·Vol. 13 ·期 9 ·1394 · IF 3.523

Nucleic Acid Detection with Ion Concentration Polarization Microfluidic Chip for Reduced Cycle Numbers of Polymerase Chain Reaction

Chengzhuang Yu,Shijie Dai,Shanshan Li,Junwei Li,Hezhi Hu,Jiyu Meng,Chunyang Wei,Jie Jayne Wu

Nucleic acid detection is widely used in disease diagnosis, food safety, environmental monitoring and many other research fields. The continuous development of rapid and sensitive new methods to detective nucleic acid is very important for practical application. In this study, we developed a rapid nucleic-acid detection method using polymerase chain reaction (PCR) combined with electrokinetic preconcentration based on ion concentration polarization (ICP). Using a Nafion film, the proposed ICP microfluidic chip is utilized to enrich the nucleic acid molecules amplified by PCR thermal cycles. To demonstrate the capability of the microfluidic device and the hybrid nucleic-acid detection method, we present an animal-derived component detection experiment for meat product identification applications. With the reduced cycle numbers of 24 cycles, the detection can be completed in about 35 min. The experimental results show that this work can provide a microfluidic device and straightforward method for rapid detection of nucleic acids with reduced cycle numbers.Keywords:microfluidic;nucleic acid detection;polymerase chain reaction;electrokinetic preconcentration;ion concentration polarization

研究领域: 生物工程 · 分子生物学
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ANALYST · 2021 ·Vol. 146 ·期 22 ·6960-6969 · IF 4.616

A digitalized isothermal nucleic acid testing platform based on a pump-free open droplet array microfluidic chip

Ping Mao,Lei Cao,Zedong Li,Minli You,Bin Gao,Xianghong Xie,Zhenrui Xue,Ping Peng,Chunyan Yao,Feng Xu

Digital PCR has shown great potential for quantitative nucleic acid testing (NAT), but most existing platforms are dependent on large auxiliary equipment (e.g., vacuum pump, amplification instrument, fluorescence microscope) to achieve target dispersion, amplification, signal capture and result analysis. Such complex, expensive and bulky NAT platforms have limited their applications in resource-limited areas, especially for point-of-care testing (POCT). In this work, we designed a digital isothermal NAT platform based on a pump-free open droplet array microfluidic chip. A pump-free microfluidic chip was developed based on an open microdroplet array in the form of thousands of independent microdroplets for spontaneous sample dispersion, without the need for external power. Combined with a handheld fluorescent signal reader based on a smartphone, this digital NAT platform can accurately quantify as low as 1 copy per μL of λDNA. Therefore, our integrated NAT platform, as a potable, robust and low-cost tool for highly accurate NA quantitative analysis, holds great potential for POCT applications.

研究领域: 分子生物学 · 生物医学工程 · 医学诊断
✓ 已验证 DOI PubMed 高影响因子
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PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY · 2021 · IF 2.162

Study on covalent coupling process and flow characteristics of antibody on the surface of immunoassay microfluidic chip

Hao Zhong,Yong Li,Guodong Liu,Tao Xu,Yiping Suo,Zhiqiang Wang

The immune response system of immunoassay microfluidic chips is a dynamic reaction process that continuously sends reactants to the surface of a solid carrier. Signal acquisition results from the heterogeneous immune reactions and reactant transport. Antibody immobilization is the most important part of heterogeneous immune reactions, and reactant transport is reflected in the form of fluid velocity. Here, we reported several surface modification processes on polystyrene substrates that are employed to study the relationship between the antibody immobilization and flow behavior in heterogeneous immune response processes. The antibody was immobilized using covalent grafting. Based on the mechanism of sandwich enzyme linked immunosorbent assay, a fluorescence quantitative detection method was used to evaluate the immune response process. The effects of different surface modification processes on immune response and flow behavior were studied. We identified an optimal flow velocity in the dynamic immune response system in the microfluidic chip. The immune response signal was the strongest when the average flow velocity was approximately 0.2 mm/s in the procalcitonin detection system. Compared with the amino and aldehyde group substrates, the epoxy group substrate has the highest antibody immobilization efficiency; compared with the surface modified by small molecular groups, the introduction of Poly-L-Lysine can increase the amount of antibody immobilization.

研究领域: 生物化学 · 微流控技术 · 免疫学 · 分析化学
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