Biomedical Microdevices最新文献

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.

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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.

This study demonstrates the development of polymeric PLGA (50:50) nanoparticles containing dexamethasone acetate, which are dispersed in a PVA film and added to hydrophobic intraocular lenses (IOL) exclusively designed for this application. The resulting IOL-drug delivery system (IOL-DDS) can be introduced into the eye with syringe-type injectors and standard surgical techniques. The obtained results showed that the lens design does not compromise stability within the eye or weaken the loops, preserves its optical zone, and maintains injector’s functionality during surgery. The IOL-DDS releases the drug in vivo for 7 days within the therapeutic concentration range. Short-term assessment confirms the safety of the developed device for ocular structures, which is supported by slit lamp observations, intraocular pressure measurements, optical coherence tomography, and histological analysis. Minor changes in specular microscopy parameters are observed and may be related to the use of IOL and surgical instruments designed for human eyes in smaller rabbit eyes.

GPR120 is a free fatty acid receptor capable of signalling excess fatty acids. GPR120 can be activated by various types of free fatty acids, causing intracellular signal transduction and exerting energy regulation, immune homeostasis, and neuronal functions. It has been suggested that Trp198 may be an important residue in the recognition and activation of GPR120 by fatty acid ligands, but direct experimental evidence is lacking. In this study, a GPR120-based bilayer gold nanoparticle biosensor (Trp198→Pro) was constructed by genetically manipulating Trp198 on GPR120 by replacing it with proline for the determination of linkage variability between 14 naturally occurring fatty acid ligands and mutant receptors. The results showed that both before and after amino acid substitution the GPR120 bilayer nanogold receptor sensor responded to all 14 natural fatty acid ligands. And the linkage transformation constants of crotonic acid, dodecanoic acid, oleic acid, linoleic acid, α-linolenic acid, and DHA decreased after Trp198 was replaced by Pro. To further reveal its molecular recognition mechanism, molecular simulation docking experiments were performed on GPR120 and 14 fatty acid ligand compounds before and after amino acid substitutions, respectively. The results showed that before and after the amino acid substitutions, the binding conformational affinity values of GPR120 docked with the ligands were negative, implying that these fatty acid ligands can spontaneously bind to the active pocket of GPR120 without absorbing external energy. Upon replacement of Trp198 by Pro, the active pocket of GPR120 at the optimal docking site with the fatty acid ligand is altered, leading to changes in the amino acid residues that exert the interaction. The above results demonstrate that Trp198 indeed plays an important role in the recognition of fatty acid ligands on GPR120. The present study provides direct quantitative evidence for the roles played by different amino acid residues in receptor-ligand recognition and interaction. At the same time, it provides new ideas for the study of other receptor-ligand-linked metastable mechanisms and kinetic laws.

Microfluidic chips have emerged as versatile and powerful tools that enable the precise manipulation of fluids and bioparticles at the microscale. Their impact on detection applications is profound, offering advantages such as miniaturization, enhanced sensitivity, multiplexing capability, and integrated functions. These chips can be customized for specific techniques, such as DNA analysis, immunoassays, chemical sensing, and cell-based assays. With a wide range of types available, including Lab-on-a-Chip, droplet-based, paper-based, electrochemical, optical, and magnetic chips, they find applications in diverse fields such as medical diagnostics, DNA analysis, cell analysis, food safety testing, environmental monitoring, and industrial processes. This powerful technology replicates laboratory capabilities on miniature chip-scale devices, resulting in time and cost savings while enabling portability and field-use capability. Its impact spans genetic analysis, proteomic analysis, cell culture, biosensors, pathogen detection, and point-of-care diagnostics, playing a pivotal role in advancing chemical and biological analysis. The overall aim of this review is to provide an overview of the development of microfluidic biochips for biological detection and discuss their various applications.