Publications by authors named "Hongju Mao"

Extracellular vesicles (EVs) and EV-derived microRNAs (EV-miRNAs) are emerging as promising circulating biomarkers for early detection of malignant tumors such as non-small cell lung cancer (NSCLC). However, utilization of the gold standard method of RNA detection, the reverse transcription - quantitative polymerase chain reaction (RT-qPCR), on EV-miRNAs is hindered by laborious sample purification requirements and time-consuming multi-step procedures. Herein, we propose and demonstrate a miniaturized digital microfluidic (DMF) workstation for all-in-one EV-miRNA detection based on RT-qPCR.

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In the realm of wearable technology, strategically placing sensors at various body locations enhances the detection of diverse physiological indicators crucial for remote medical care. However, current devices often focus on a single body part for specific physical parameters, which hinders the seamless integration of sensors across multiple body parts and necessitates redesign for new detection capabilities. Here, we propose a modular, reconfigurable circuit assembly method that can be adaptable for multiple body locations to construct the body net.

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Droplet microarrays (DMAs) leveraging wettability differences are instrumental in digital immunoassays, single-cell analysis, and high-throughput screening. This study introduces an enhanced Teflon lift-off process to fabricate hydrophilic-hydrophobic patterns on a digital microfluidic (DMF) chip, thereby integrating DMAs with DMF technology. By employing DMF for droplet manipulation and utilizing wettability differences, the automated generation of high-throughput DMAs was achieved.

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As a prerequisite for extracellular vesicle (EV) -based studies and diagnosis, effective isolation, enrichment and retrieval of EV biomarkers are crucial to subsequent analyses, such as miRNA-based liquid biopsy for non-small-cell lung cancer (NSCLC). However, most conventional approaches for EV isolation suffer from lengthy procedure, high cost, and intense labor. Herein, we introduce the digital microfluidic (DMF) technology to EV pretreatment protocols and demonstrate a rapid and fully automated sample preparation platform for clinical tumor liquid biopsy.

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Magnetic biomolecule-based bionic magnetic field sensors are anticipated to open up novel pathways for magnetic field detection. The detection range and accuracy of current bionic magnetic field sensors are limited, and little work is based on the capacitive response principle. We successfully developed a biochemical interface with an extralarge target-receptor size ratio, which can be manufactured in a single step for weak magnetic field detection across a wide frequency range, and we used electrochemical capacitance as a magnetic field change conduction strategy.

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In recent years, wearable sensors have revolutionized health monitoring by enabling continuous, real-time tracking of human health and performance. These noninvasive devices are usually designed to monitor human physical state and biochemical markers. However, enhancing their functionalities often demands intricate customization by designers and additional expenses for users.

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Cell models are one of the most widely used basic models in biological research, and a variety of in vitro cell culture techniques and models have been developed recently to simulate the physiological microenvironment in vivo. However, regardless of the technique or model, cell culture is the most fundamental but crucial component. As a result, we have developed a cell culture monitoring system to assess the functional status of cells within a biochip.

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Signal transduction mediated by epidermal growth factor receptor (EGFR) gene affects the proliferation, invasion, metastasis, and angiogenesis of tumor cells. In particular, non-small cell lung cancer (NSCLC) patients with increased in copy number of EGFR gene are often sensitive to tyrosine kinase inhibitors. Despite being the standard for detecting EGFR amplification in the clinic, fluorescence in situ hybridization (FISH) traditionally involves repetitive and complex benchtop procedures that are not only time consuming but also require well-trained personnel.

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The World Health Organization (WHO) has stated that countless cancer patients could be saved if early detection and treatment were available. However, current clinical evaluation of tumors still relies primarily on imaging examinations and tissue biopsies. These methods not only require sophisticated equipment, but also have high false positive rates or invasive problems.

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Cancer cell spheroids have been shown to mimic in vivo tumour microenvironment and are therefore suitable for in vitro drug screening. Microfluidic technology can provide conveniences for spheroid assays such as high-throughput, simplifying manual operation and saving reagent. Here, we propose a concentration gradient generator based on microfluidic technology for cell spheroid culture and assay.

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Organ-on-a-Chip is a microfluidic cell culture device manufactured via microchip fabrication methods [...

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The concept of digital microfluidics (DMF) enables highly flexible and precise droplet manipulation at a picoliter scale, making DMF a promising approach to realize integrated, miniaturized "lab-on-a-chip" (LOC) systems for research and clinical purposes. Owing to its simplicity and effectiveness, electrowetting-on-dielectric (EWOD) is one of the most commonly studied and applied effects to implement DMF. However, complex biomedical assays usually require more sophisticated sample handling and detection capabilities than basic EWOD manipulation.

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Magnetic-sensitive proteins are regarded as key factors in animals' precise perception of the geomagnetic field. Accurate feedback on the response of these tiny proteins to magnetic fields remains a challenge. Here, we first propose a real-time accurate magnetic sensor based on the MagR/Cry4 complex-configured graphene transistor with an integrated on-chip gate.

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Macrophages and fibroblasts are two types of important cells in wound healing. The development of novel platforms for studying the interrelationship between these two cells is crucial for the exploration of wound-healing mechanisms and drug development. In this study, a microfluidic chip composed of two layers was designed for the co-culturing of these two cells.

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Senescence is an inevitable natural life process that involves structural and functional degeneration of tissues and organs. Recently, the process of skin aging has attracted much attention. Determining a means to delay or even reverse skin aging has become a research hotspot in medical cosmetology and anti-aging.

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An organ-on-a-chip is a device that combines micro-manufacturing and tissue engineering to replicate the critical physiological environment and functions of the human organs. Therefore, it can be used to predict drug responses and environmental effects on organs. Microfluidic technology can control micro-scale reagents with high precision.

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The gingival epithelium-capillary interface is a unique feature of periodontal soft tissue, preserving periodontal tissue homeostasis and preventing microorganism and toxic substances from entering the subepithelial tissue. However, the function of the interface is disturbed in periodontitis, and mechanisms of the breakdown of the interface are incompletely understood. To address these limitations, we developed a microfluidic epithelium-capillary barrier with a thin culture membrane (10 μm) that closely mimics the in vivo gingival epithelial barrier with an immune micro-environment.

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When dealing with infectious pathogens, the point-of-care screening and diagnosis strategy should be low-cost, simple, rapid and accurate. Here, we report a multifunctional rapid PCR platform allowing both simultaneous screening of suspected cases and accurate identification and quantification of the virus. Based on the platform, samples suspected of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are screened first, after which subsequent precise quantification of the virus (SARS-CoV-2) can be performed if necessary.

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Exosomes are lipid-bilayered nanovesicles secreted by cells to mediate intercellular communication. Various kinds of biomolecules involved in exosomes offer non-invasive approaches for detecting or monitoring disease and developing targeted therapeutics. Here, we present an integrated microfluidic exosome isolation and detection system (EXID system) to analyze the abundance of the exosomal PD-L1 protein marker, which is a transmembrane protein expressed by tumors to suppress immune activation of T cells.

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A microfluidic chip has been integrated with a capacitive biosensor based on mass-producible three-dimensional (3D) interdigital electrode arrays. To achieve the monitoring of biosensor preparation and cardiac- and periodontitis-related biomarkers, all the processes were detected in a continuously on-site way. Fabrication steps for the microfluidic chip-bonded 3D interdigital capacitor biosensor include gold thiol modification, the activation of EDC/sulfo-NHS, and the bioconjugation of antibodies.

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In recent years, nanopore technology has become increasingly important in the field of life science and biomedical research. By embedding a nano-scale hole in a thin membrane and measuring the electrochemical signal, nanopore technology can be used to investigate the nucleic acids and other biomacromolecules. One of the most successful applications of nanopore technology, the Oxford Nanopore Technology, marks the beginning of the fourth generation of gene sequencing technology.

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We report the first combination of droplet digital and rapid PCR techniques for efficient, accurate, and quantitative detection of SARS-CoV-2 RNA. The presented rapid digital PCR system simultaneously detects two specific targets (ORF1ab and N genes) and one reference gene (RNase P) with a single PCR thermal cycling period around 7 s and the total running time less than 5 min. A clear positive signal could be identified within 115 s via the rapid digital RT-PCR, suggesting its efficiency for the end-point detection.

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SARS-Cov-2 has erupted across the globe, and confirmed cases of COVID-19 pose a high infection risk. Infected patients typically receive their treatment in specific isolation wards, where they are confined for at least 14 days. The virus may contaminate any surface of the room, especially frequently touched surfaces.

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Emerging evidence indicates that extracellular vesicle (EV) long non-coding ribonucleic acids (lncRNAs) in lung cancer may be clinically useful biomarkers for early diagnosis using liquid biopsy. However, the extremely low quantities of EV-lncRNAs in peripheral blood are a major challenge for multi-target detection. In this study, we developed a new multi-colour fluorescence digital PCR EV-lncRNA (miDER) analysis chip, and then demonstrated its ability to quickly and accurately analyse the levels of two target genes and one reference gene from peripheral blood.

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Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy. Because of their nanoscale size, complex biogenesis, and methodological limitations related to exosome isolation and detection, advancements in their analysis remain slow. Microfluidic technology offers a better analytic approach compared with conventional methods.

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