Biomedical Microdevices最新文献

Nucleic acid-based molecular diagnostics are essential for the prevention, early detection, and treatment of cancer and infectious diseases. In this study, we developed a 3D-printed, electricity-free detection system for CRISPR-based nucleic acid detection. To eliminate the need for costly electrical heaters, we developed a reusable heating platform powered by a sodium acetate-based handwarmer. To maintain optimal temperatures for the CRISPR reaction, we designed and fabricated a 3D-printed heatsink filled with docosane wax to regulate the temperature. The fully 3D-printed microfluidic chip integrates finger-activated fluid transport via a 3D-printed flexible blister, a CRISPR reaction chamber, and a lateral flow strip for visual readout. We demonstrated the system’s analytical performance by detecting HPV-16 DNA with a sensitivity as low as 1 femtomolar. Additionally, we validated its clinical pilot feasibility using clinical cervical samples, achieving results consistent with standard PCR assays. Overall, this low-cost, reusable, and electricity-free detection system offers a practical solution for point-of-care molecular testing, particularly in resource-limited settings.

The manipulation of fragile biological tissues such as engineered cell sheets remains a major challenge for regenerative medicine and tissue engineering. Manual handling with tools like tweezers often induces wrinkling or tearing, compromising tissue integrity. Here, we present an automated cell sheet manipulator that integrates a thermoresponsive microchanneled poly(N-isopropylacrylamide) (PNIPAAm) hydrogel with an embedded microheater, mounted on a programmable three-axis motorized stage. Upon localized heating and cooling, the hydrogel undergoes rapid, reversible volumetric transitions that enable suction-based gripping and release of cell sheets within a few seconds. The custom LabVIEW interface synchronizes stage movement and thermal cycling, allowing reproducible, hands-free operation. A compliance-based Z-axis apparatus ensured uniform low-magnitude contact forces, preventing mechanical damage during transfer. Using this system, human iPSC-derived neural sheets were reliably transferred onto human brain microvascular endothelial cell (hBMEC) monolayers. Compared to manual transfer, the automated manipulator preserved cell sheet flatness and minimized micro-wrinkling, resulting in safe retention of intercellular architecture and structural integrity. This work demonstrates a robust, user-friendly platform for automated and gentle handling of delicate biological sheets. By enabling the precise stacking of engineered tissues while preserving their morphology, this system provides a promising tool for advanced biofabrication workflows, supporting defect-free 3D tissue assembly and implantation.

For application in the fabrication of artificial blood vessels, we developed a method for non-contact culturing of vascular endothelial cells following a process of non-contact retention. Utilizing the propulsive force acting on cells under ultrasound exposure when the cells were surrounded by lipid bubbles, the conditions of the acoustic field were investigated. First, cells were cultured in the presence of lipids without ultrasound to derive the optimal concentration of lipids. Next, cells were retained on the inner surface of the flow path using various acoustic fields, which include single-focal, multifocal, and bar-shaped fields. After culturing the cells in the path without flow for 24 h, the cultured area of cells was measured to evaluate the series of performance. In the experiment of cell culturing without ultrasound, the cultured area decreased inversely proportional to the lipid concentration, thus deriving the optimal concentration of bubbles. When the bar-shaped fields were used for the retention process, significant cell engraftment was observed compared to other fields, even though the acoustic intensity of SATA (Spatial average temporal average) and the retained area of the cells were similar. Those results suggest that conditions of acoustic field, including the distribution and magnitude of sound pressure according to the flow direction, are dominant for non-contact culturing of cells following retention. We succeeded in culturing cells at desired position on inner wall of the path, regardless of the direction of gravity.

The Lateral flow immunoassay (LFIA) has been widely used in environmental monitoring and disease diagnosis due to its advantages of low cost, simple operation, and convenience. However, its accuracy and sensitivity remain major challenges to be addressed. D-dimer is an important biomarker for thrombotic diseases. In this work, we show for the first time a core–shell Au@Ag nanoparticle (NP) labeled colorimetrically enhanced LFIA for D-dimer detection. The superior performance of Au@Ag LFIA stems from the silver shell's enhancement of plasmon resonance, which boosts optical signals to yield brighter scattering and superior visual contrast. Compared with conventional AuNPs, Au@AgNPs significantly improve sensitivity, leading to more accurate results. The detection limit for D-dimer was improved by approximately tenfold, reaching 1 ng/mL, due to the improved cross-coupling efficiency of Au@AgNPs compared with AuNPs. We anticipate that, with further development and validation, this enhanced LFIA could become a valuable tool in a wide range of clinical diagnostic applications.

The facile and large-scale construction of in vitro biomimetic three-dimensional (3D) tumor models has been pursued for cancer exploration, clinical/preclinical drug screening and discovery, as well as personalized therapy. The utilization of microengineering technologies in in vitro tumor fabrication and modeling is one of the most promising approaches and allows to create innovative outcomes being impractical or impossible to reach using conventional methods. Herein, an overview of technological and methodological development of microengineered systems for 3D tumor production and modeling is presented. The typical features of microengineering technologies are emphasized. The recent progress in the establishment of the miniaturized platforms based on multiple microfluidic and microarray methods for 3D tumor preparation and biomimetic construction are summarized. Their key advantages, achievements, and limitations with respect to cell manipulation and tumor formation are described and discussed. Finally, the challenges that need to be overcome to strengthen the functional performance of microengineered platforms are highlighted.

This study evaluates the mucoadhesive properties of Opuntia-carrageenan superporous hydrogel (OPM-CRG SPH) in vitro and in vivo, assessing its potential as a biomaterial for gastrointestinal (GI) mucoadhesive drug delivery systems. Mucoadhesive polymers are critical for anchoring drug delivery devices to specific mucosal sites, enabling localized and sustained drug presence. By prolonging residence time at the site of application, such biomaterials hold the potential to improve drug bioavailability and therapeutic outcomes, particularly in GI delivery platforms. This research explores the mucoadhesive performance of OPM-CRG SPH, which could advance the development of effective GI mucoadhesive drug delivery systems. In vitro mucoadhesion was tested using goat GI mucosa and a texture analyzer, measuring key parameters such as work of adhesion (W_ad) and maximum detachment force (F_max) under varying instrumental conditions. In vivo GI-retention studies were conducted on New Zealand rabbits, using X-ray radiography to monitor the formulation’s retention in the GI tract (GIT). Mucoadhesion increased with contact time and force but exhibited minimal change by withdrawal speed. Distinct mucoadhesive behaviors were observed across different GIT segments, with the highest F_max and W_ad values recorded in large intestinal tissues. In vivo studies confirmed maximum adherence at higher pH levels, consistent with in vitro findings. X-ray imaging demonstrated successful 8 to 10-h mucoadhesion in rabbits. The hydrogel exhibits promising mucoadhesive properties, making it a viable candidate for GI drug delivery systems. Its ability to adhere effectively across various GI segments and sustain prolonged retention highlights its potential for enhancing drug delivery efficiency.

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Localized surface plasmon resonance (LSPR) sensors have good potential for label-free non-invasive detection of biomolecules, healthcare diagnosis, disease monitoring, gas sensing, and food safety. For detection of low concentration small-sized bioanalytes (e.g., viruses, proteins, etc) the plasmonic field needs to be localized on a larger device surface area. Our study focuses on the optimization and fabrication of leaky Au nanoresonators based sensing platform for SARS-CoV-2 detection with uniform sensitivity over a 100 (mu)m (times) 100 (mu)m active sensing area. The Au nanoresonator array was optimized to detect 100 nm sized bioanalytes as it matches the size of SARS-CoV-2. The performance of the optimized design was tested with 100 nm sized polystyrene beads which demonstrated a sensitivity of 17.05 ± 3.25 nm/decade. The Au nanoresonators were functionalized with anti-SARS-CoV-2 antibody to detect SARS-CoV-2. Our experimental results demonstrate the best detection sensitivity of 1.32 ± 0.08 nm/decade and limit of detection of 1 VLP (mu)L(^{-1}).

Traditional two-dimensional cultures and patient-derived xenografts fail to fully mimic the complexity of the tumor microenvironment, limiting their utility in drug discovery and personalized medicine. Recent breakthroughs in three-dimensional tumor modeling have led to the development of brain tumor organoids, patient-derived organoids, and bioengineered tumor-on-chip systems that offer more physiologically relevant platforms for studying glioblastoma biology and therapeutic response. One of the key advancements in these models is the incorporation of vascular networks to mimic the neurovascular unit and the blood-brain barrier (BBB). Various strategies such as co-culturing with endothelial cells, bio-printing vascularized scaffolds, and utilizing microfluidic platforms have been explored to enhance vascularization within glioblastoma organoids. These models have demonstrated improved nutrient and oxygen exchange, reduced hypoxia, and better maintenance of tumor heterogeneity. However, challenges remain in achieving fully functional capillary networks, BBB integrity, and immune cell integration. This review provides a comprehensive analysis of the latest advancements in brain tumor organoid research, focusing on vascularization strategies, their impact on tumor modeling, and their potential applications in drug screening and personalized therapy. We discussed the strengths and limitations of glioblastoma models, highlighted advanced bioengineering techniques for enhancing organoid complexity, and explored future directions for clinically relevant tumor organoids.

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In this study, a novel immunosensor for carcinoembryonic antigen (CEA) determination was designed, and the synergistic effect of zero-dimensional gold nanoparticles and two-dimensional nanomaterials TiS₂ was investigated. In this regard, gold nanoparticles were electrochemically deposited on the surface of the screen-printed electrode (SPE), with MAU employed as a surface activation agent following the insertion of TiS₂ nanosheets. The anti-CEA was attached to the surface through EDC/NHS chemistry, utilizing the carboxy end of MUA attached to AuNPs and TiS₂ nanosheets. The resulting structure was subsequently protected by Nafion, and non-specific binding to the surface was prevented by the addition of bovine serum albumin (BSA). In a similar manner, an immunosensor was formulated that did not contain TiS₂. CEA quantification was executed via an impedimetric approach. A comprehensive evaluation of the impedimetric outcomes indicated that the immunosensor comprising AuNPs alone was inadequate in achieving an accurate measurement range. Nevertheless, an immunosensor with a very low concentration range (1-100 pg/mL) and a low limit of detection (LOD, 0.21 pg/mL) value could be prepared through the synergistic effect of TiS₂. The AuNPs-TiS₂-based immunosensor exhibits both high selectivity and reproducibility. Furthermore, the immunosensor exhibits noteworthy storage stability, thus making it well-suited for the quantification of CEA in biological specimens, such as blood. The properties described herein serve to substantiate the hypothesis that the Au-TiS₂-based immunosensor is a promising candidate for clinical applications.

Breast cancer (BC) continues to be the most frequently diagnosed malignancy and the primary cause of cancer-related deaths among women globally. The traditional treatment modalities, such as chemotherapy, surgery, and radiotherapy, are often associated with significant toxicity to healthy tissues and systemic side effects, highlighting the pressing need for safer and more targeted therapeutic strategies. Recently, microneedle innovation has become an evident alternative for delivering anti-neoplastic agents, offering minimally invasive, transdermal administration that can bypass hepatic metabolism and reduce systemic toxicity. Microneedle (MNs) arrays hold potential not only for drug delivery but also for vaccination, diagnostic sampling, and targeted therapy in BC management. However, despite these promising attributes, there exists a notable gap in the scientific literature specifically addressing the application of microneedles in breast cancer therapy, with relatively few comprehensive studies in this domain. This review aims to bridge that gap by summarizing recent advancements in MN-based strategies for breast cancer treatment. It highlights the ability of MNs to enable simultaneous drug loading, controlled release, and improved patient compliance through non-invasive administration. Furthermore, the review discusses MN properties, mechanisms of action, therapeutic benefits, relevant clinical trials, patents, and future challenges, thereby providing a valuable resource for researchers and promoting the translation of MN technology into clinical practice for breast cancer management.

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