Biomedical Microdevices最新文献

This review focuses on the recent progress in electrochemical biosensors, which are emerging as innovative, sensitive, and cost-efficient platforms for identifying and monitoring biomarkers associated with neurodegeneration. We examine the basic principles behind the operation of electrochemical biosensors, emphasizing the significance of bioreceptors and transducers, as well as the influence of electrode materials such as metals, carbon-based nanomaterials, and conducting polymers (CPs) on the sensors’ performance. The role of nanotechnology is highlighted for its capacity to improve signal transduction, bioreceptor immobilization, and the detection of multiple targets, all while ensuring miniaturization and portability. Additionally, we outline recent approaches for enhancing signal amplification and optimizing performance across various biosensor generations. The use of these biosensors in detecting protein aggregates, genetic mutations, and exosomal biomarkers is reviewed in the context of early diagnosis and tracking disease progression. Finally, the paper discusses current challenges and suggests future directions to aid the clinical application of electrochemical biosensors in diagnosing neurodegenerative diseases. Major barriers impeding the transition of these technologies to clinical approach are discussed along with the variability in performance with real patient samples, lack of reproducibility, scaling up the synthesis of nanomaterials, and the requirement for changes in standardized validation and regulation.

The expression levels of miRNAs in cells or biological fluids are closely associated with the onset and progression of many diseases, making the detection of miRNAs in serum and plasma increasingly important. However, due to the low levels of miRNAs in biological fluids and the complexity of their surrounding environment, their analysis faces challenges related to accuracy and reproducibility. We developed a duplex-specific nuclease (DSN)-mediated detection method for the direct detection of miRNA-21 in real samples. This method eliminates the need for total RNA extraction from real samples using commercial kits, a key advantage over traditional methods requiring pre-treatment. As verified by performance evaluation, this method exhibits a linear range of 5.00 fmol·L^− 1 to 500 pmol·L^− 1 and a limit of detection (LOD) of 2.66 fmol·L^− 1 for miRNA-21. Direct detection of miRNA-21 in real samples yielded favorable results. These findings confirm that the method holds great application potential for the direct detection of miRNA-21 in real biological samples and exhibits promising prospects in clinical cancer diagnosis and drug screening.

Once implanted, biodegradable devices gradually deteriorate, potentially compromising clinical performance. Consequently, evaluating the alterations in physicochemical characteristics after implantation is crucial. Nonetheless, there is currently no established methodology for precisely assessing these alterations. This study sought to develop accurately simulated cranial defect physiological conditions (SCDPC) and examine the physicochemical modifications in biodegradable cranioplasty plates (BCP) to anticipate their performance changes following implantation in humans. We analyzed the physicochemical property alterations of BCP following 24 weeks of exposure to SCDPC. Following 24 weeks under SCDPC, the BCP showed a notable reduction in mass (− 0.79%) and tensile strength (− 69.30%). A decrease in molecular weight was noted after 12 weeks of implantation in rabbits (− 9.67%) and following 12 weeks of exposure to SCDPC (− 4.73%). The physicochemical alterations identified under simulated in vitro cranial defect conditions closely mirrored those found in the in vivo setting. In summary, assessing BCP under SCDPC offers an innovative and dependable approach for precisely forecasting performance shifts after implantation. This strategy could provide meaningful guidance for the advancement of BCP and various other biodegradable medical devices.

Roughly 5% of the population is affected by hearing loss. In case of a functional middle ear impairment with decreased transmission, different types of active middle ear implants may restore hearing. To drive the round window membrane (RWM) for example, bone anchored actuators or floating mass transducer (FMT) have been used in clinics. Bone anchored devices are usually too big for the round window niche and FMTs display low displacement and force at low frequencies. This paper focuses on the stimulation of the RWM by a stator-based actuator that combines small size and bone anchoring. The design features a rotational-symmetric balanced armature core with flexible membrane parts manufactured micro technologically. Membranes and assembled prototypes were evaluated on the bench in the range of 0.1 kHz – 10 kHz and prototypes tested in human temporal bones. We demonstrate the feasibility of a balanced armature actuator of appropriate size for RW placement. With 1.4 mm outer diameter and 4.9 mm length, the actuator fits the anatomical constraints. Acoustic stimulation of the RWM resulted in a maximum output of approximately 80 eq. dB SPL at 300 Hz increasing to > 100 eq. dB SPL above 5 kHz. The measured output is comparable to clinically used devices. The design lacked sufficient robustness leading to a low yield in manufacturing and failures in experiments, although the output level was insensitive to static force loading up to 30 mN. Future developments require an increased maximum output level and improved robustness.

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Radiotherapy (RT) is widely used for malignant tumors ablation in the clinic. However, redundant doses of X-rays might cause irreversible side effects in the periphery of tumor sites. To address this, the convergence of low-dose RT with a novel therapeutic method is promising. Here, a hydrogel system was created that combines nanozymes with NIR-II photothermal therapy and RT sensitization. Meteor hammer-like nanozyme Au-MnOx and agarose hydrogel were mixed to form multifunctional nanozyme hydrogel (MNH). The system experienced a reduction in MNH hardness when exposed to 1064 nm laser irradiation, allowing the release of Au-MnOx to react with H₂O₂ in the tumor microenvironment, resulting in the production of ·OH, which destroys bioactive substances and increases oxidative stress. This process also improves the effectiveness of hyperthermia in photothermal therapy (PTT). In addition, MNH-baed PTT enhances the RT sensitivity. Additionally, Au, with a high atomic number emits X-rays, leading to the generation of reactive oxygen species (ROS) through preexisting processes, which enhances radiation-induced DNA damage. Notably, the in vivo results indicated that MNH + NIR + RT could achieve a potent tumor inhibition rate with negligible side effects to normal tissues. This work paves a new avenue for novel nanozyme-based radiosensitization.

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.