Biomedical Microdevices最新文献

Optogenetics is a widely used tool to dissect neural circuits with optical stimulation, but it requires that light is delivered to photosensitive neurons inside the brain. Implantable neural probes with microscale LEDs (µLEDs) are an emerging approach to delivering light to the brain with superior light output control. However, approaches to integrate µLEDs in neural probes depend on complex fabrication processes. Here, we developed an implantable small form factor neural probe that integrates highly efficient commercial flip chip µLEDs using only standard lithography processes in silicon and a custom automated LED mounting approach with custom 3D-printed tools on a pick-and-place machine. The probe has a cross-sectional area under 0.013 mm² but can output up to 2.5 mW of optical power with an irradiance of 175 mW/mm². Due to the high plug efficiency of the LED, the neural probe can perform stimulation protocols up to 20 Hz and 80% duty cycles without surpassing estimated hotspot temperature elevations above 1 ºC. The neural probes were validated in vivo, with brain activity in the motor cortex of transgenic mice being reliably modulated by pulsed light emitted from the probe.

Osteoarthritis (OA) is the common form of chronic joint disease. The disease progression can affect all joints of the body, seriously affecting patients’ quality of life. The most effective clinical treatment for OA at the moment is the oral or intravenous administration of non-steroidal anti-inflammatory drugs, such as meloxicam (MX). However, certain challenges associated with the conventional use of those drugs include long dosing cycles, poor patient compliance, and systemic toxic side effects, primarily gastrointestinal reactions. Joint synovial fluid mainly consists of sodium hyaluronate (HA). In recent years, HA has been developed and used to treat OA with local injections. However, it also faces the limitations of short injection cycle, frequent administration, and increases the risk of exogenous infection. In this study, a microsphere gel formulation containing PL407, HA and meloxicam microspheres was prepared and the MX-MS-Gel system showed good performance, syringeability and stability. The results of in vitro release studies showed that the MX-MS-Gel released 8.6% in vitro at 72 h and 28.0% at 480 h, with a more moderate drug release. By injecting iodoacetic acid into the knee joint of rats to establish an OA model, MX-MS-Gel significantly improved the inflammatory response of OA, while the safety of MX-MS-Gel was superior and evaluated in this study, which was safe. The results showed that MX-MS-Gel could realize the purpose of delaying the drug release rate and reducing the frequency of administration, thus improving patient compliance and medication safety.

Extracorporeal Membrane Oxygenation (ECMO) serves as a crucial intervention for patients with severe pulmonary dysfunction by facilitating oxygenation and carbon dioxide removal. While traditional ECMO systems are effective, their large priming volumes and significant blood-contacting surface areas can lead to complications, particularly in neonates and pediatric patients. Microfluidic ECMO systems offer a promising alternative by miniaturizing the ECMO technology, reducing blood volume requirements, and minimizing device surface area to improve safety and efficiency. This study investigates the oxygen transport performance of three membrane types— polydimethylsiloxane (PDMS), polypropylene, and a novel nanoporous silicon nitride (NPSiN) membrane—in a microfluidic ECMO platform. While nanoporous membranes rely on pore-mediated diffusion and PDMS on polymer lattice diffusion, results show no significant differences in device oxygenation efficiency (p > 0.05). Blood-side factors, including the diffusion rate of oxygen through the red blood cell (RBC) membrane, RBC residence time, and hemoglobin binding kinetics, were identified as primary bottlenecks. Even computational models of a hypothetical infinitely permeable membrane corroborate the limited impact of membrane material. These findings suggest a shift in ECMO design priorities from membrane material to blood-side enhancements. This research provides a foundation for optimizing ECMO systems.

Microneedles with porous internal structures can provide pathways for transdermal ionic current and drug delivery by penetrating the stratum corneum of the skin. However, conventional porous microneedle arrays are typically monolithic and rigid, limiting their flexibility and adaptability to curved skin surfaces. To address the issue, a method to directly integrate an array of porous microneedles to a flexible substrate is proposed, preserving their skin penetration capability while enhancing flexibility. The resulting array conforms to curved skin surfaces while effectively reducing transdermal ionic resistance. Numerical and analytical modeling demonstrates that the limited number of needles on a flexible array is sufficient to reduce transdermal resistance. Further, an enzymatic battery is combined to create a fully organic, porous microneedle-based bioelectric skin patch that can generate stable transdermal current suitable for stimulation and drug delivery applications.

This study demonstrates cyanocobalamin-loaded dissolving microneedles (CNBL-MNs) as a minimally invasive transdermal solution for managing cyanocobalamin (CNBL) deficiency, offering an alternative to intramuscular injections and oral supplements. The CNBL-MNs were developed using biodegradable, water-soluble polymers such as polyvinylpyrrolidone K25, Dextran K40, and chitosan to ensure controlled and gradual release of the CNBL. The formulation’s stability and integrity were assessed through FTIR and XRD analyses. SEM imaging revealed well-formed microneedles with a height of 800 μm, a 200 μm base diameter, and a 500 μm pitch. EDS confirmed the successful incorporation of CNBL in the microneedle array. The Parafilm^® membrane insertion test revealed that the microneedles had strong mechanical properties and achieved 100% penetration efficiency. The microneedle array also demonstrated excellent (P > 0.05) flexibility and structural stability. Ex-vivo release studies showed that 88.51% of the CNBL was released over 48 h, following a first-order kinetic model. The n value of 0.51 for Korsmeyer-Peppas model indicate an anomalous transport mechanism, suggesting a combination of diffusion and erosion. The in-vivo pharmacokinetic evaluation in Wistar rats demonstrates that CNBL-MNs-2 exhibited a larger area under the curve (AUC₀–t) (61.57 ± 4.23 ng·h/mL) than the IP injection (37.04 ± 5.83 ng·h/mL), indicating significant (p > 0.05) increase in systemic availability and sustained release. The Cmax of CNBL-MNs-2 (6.10 ± 0.533 ng/mL) was comparable to that of the IP injection (6.20 ± 1.5 ng/mL), confirming efficient systemic absorption via the microneedle system. Additionally, Tmax was significantly (p > 0.05) prolonged with CNBL-MNs-2 (8 h) compared to the IP injection (2 h), suggesting a slower, more controlled CNBL release.

Glaucoma is a leading cause of irreversible blindness worldwide, affecting millions of individuals due to its progressive damage to the optic nerve, often caused by elevated intraocular pressure (IOP). Conventional methods of IOP monitoring, such as tonometry, provide sporadic and often inaccurate readings due to fluctuations throughout the day, leaving significant gaps in diagnosis and treatment. This review explores the transformative potential of smart contact lenses equipped with continuous IOP monitoring and therapeutic capabilities. These lenses integrate advanced materials such as graphene, nanogels, and magnetic oxide nanosheets alongside sophisticated biosensing and wireless communication systems. By offering continuous, real-time data, these lenses can detect subtle IOP fluctuations and provide immediate feedback to patients and clinicians. Moreover, drug-eluting capabilities embedded in these lenses present a groundbreaking approach to glaucoma therapy by improving medication adherence and providing controlled drug release directly to the eye. Beyond IOP management, these innovations also pave the way for monitoring biochemical markers and other ocular diseases. Challenges such as biocompatibility, long-term wearability, and affordability remain, but the integration of cutting-edge technologies in smart contact lenses signifies a paradigm shift in glaucoma care. These developments hold immense promise for advancing personalized medicine, improving patient outcomes, and mitigating the global burden of blindness.

This study focuses on the design and simulation of a biosensor based on HEMT technology, with a focus on a GaN/AlGaN MOSHEMT architecture with a cavity and a boron-doped GaN cap layer, for identifying label-free biological molecules. The inclusion of a boron-doped GaN cap layer in the AlGaN/GaN heterostructure facilitates E-mode operation. We examined the influence of neutral or label-free biomolecules on the electron concentration and device sensitivity. The Sentaurus TCAD device simulation tool was used to analyze the MOSHEMT structure. Our findings suggest that low dielectric biomolecules increase the drain current, whereas higher dielectric values decrease the drain current. We also evaluated the device performance across various cavity lengths (100 nm, 200 nm, 300 nm, and 400 nm). The AlGaN/GaN MOSHEMT provides excellent sensitivity and precision in biological detection. The proposed GaN cap layer MOSHEMT biosensor is designed to detect biomolecules such as Keratin, Zein, ChOx, Biotin, Streptavidin, and Urease. The addition of these biomolecules to the nanocavity significantly enhances the drain current, transconductance (g_m), output conductance (g_d), and sensitivity. The device demonstrates high sensitivity (~ 73%) under optimized parameters, making it suitable for precise label-free biosensing applications.

Unbound cortisol in saliva, detectable through non-invasive sampling, is widely recognized as a validated biomarker for the biochemical evaluation of common mental disorders such as chronic stress, depression, anxiety, and post-traumatic stress disorder (PTSD). In this work, we report a novel polymer lab-on-a-chip (LOC) for microfluidic lateral flow assay (mLFA) with on-chip dried reagents for the detection of unbound cortisol in saliva using a competitive immunoassay protocol. The new polymer microchannel lateral flow assay on lab-on-a-chip (mLFA-LOC), replicated using injection molding technology, are composed of sequentially connected microchannels for sample loading, detection antibody immobilization, flow delay, sensing spirals for test and control, and a capillary pump at the end. The competitive immunoassay of cortisol can be autonomously performed through the microchannels after sample loading of the filtered saliva, and the fluorescence signals emitted from the sensing spirals are detected and quantified by a custom-designed, portable fluorescence analyzer developed in this work. For the evaluation of cortisol assay, artificial saliva samples spiked with unbound cortisol were analyzed using mLFA-LOC and the portable analyzer. The performed competitive assay of unbound cortisol showed a limit of detection (LoD) of 1.8 ng/mL and an inter-chip coefficient of variation (CV) of 4.0%, which covers the clinical range for on-site unbound salivary cortisol analysis. The newly developed mLFA-LOC platform certainly works successfully for the rapid on-site sampling and analysis of salivary biomarkers.

Graphical Abstract

Lateral flow immunoassays typically rely on optical tests conducted on paper strips. However, the 3D matrix of paper embedded with optical nanoparticles often limits detection sensitivity and the ability of detection instruments to capture signals. This study introduces a novel approach using a glass chip-based lateral flow immunoassay, with albumin as a typical biomarker for detection, enabling the presence of the signal on a flat surface. Compared with traditional paper-based immunoassay, glass-based lateral flow immunoassay has achieved a uniform distribution pattern for albumin detection, lowered the limit of detection from 100 ng/mL to 1 ng/mL, and reduced detection time through an improved liquid mobility system. The glass-based method also shortens the detection time by 28.5% to 147.8 s compared to the traditional method. This research presents a new methodology for lateral flow immunoassays that can be applied to a wide range of biomarkers, with potential benefits for various medical and environmental applications.

Multiplex polymerase chain reaction (PCR) tests multiple biomarkers or pathogens that cause overlapping symptoms, making it an essential tool in syndromic testing. To achieve a multiplex PCR on chip, a design based on capillary-driven fluidic actuation is proposed. Our silicon chip features 22 reaction chambers and allows primers and probes to be pre-spotted in the reaction chambers prior to use. The design facilitates rapid sample loading through a common inlet channel, delivering reagents to all reaction chambers in less than 10 s. A custom clamping mechanism combined with a double depth cavity design ensures proper sealing during temperature cycling without the need for extra reagents like oil. Temperature cycling and fluorescence imaging were performed using custom-made hardware. As a proof of concept, two single nucleotide polymorphisms (SNPs), CyP2C19*2 and PCSK9 were detected. These results demonstrate the feasibility of on-chip multiplex PCR, compatible with different assays in parallel and requiring only a single pipetting step for reagent loading, without active fluidic actuation like pumping.