Biomicrofluidics最新文献

Filters with high throughput, minimal dead volume, and greater sensitivity to particle size are needed, which traditional benchtop filtration cannot provide. Leveraging microfabrication techniques developed by the electronics and optics industries, the filters presented here feature a unique serpentine "NanoRidge" structure, offering a continuous filtration gap spanning over three meters on a compact 4 × 14.5 mm² footprint. This design provides more precise size filtration cut-offs and consistent flow paths compared to traditional membrane filtration systems. Despite challenges associated with glass substrate deformation impacting uniform filter gap sizes, the study provides valuable insights into the development of NanoRidge filters (NRFs) for enhancing filtration efficiency in preparatory techniques and sample analysis. This study describes the fabrication and testing of these new filter types and directly compares the performance to traditional membrane filters using the metrics of particle size cut-off (the smallest difference in particle size which can be filtered vs passed) and particle loss. The NanoRidge filters were characterized using imaging (during fabrication, post-fabrication and use, fluorescent particles captured and small molecule dye), pressure and flow measurements, and a series of particle sizes "filter or pass" studies. Particle capacity (100-250 nm) ranged from 5 × 10⁸ to 7 × 10⁹ in 1 ml samples at a flow rate of 100 μl/min with backpressure in the range of 1-3 Bar. The optimized fabrication procedure for the 150 nm NRF yielded a small particle recovery of 95% while also achieving a large particle filtration of 73%. High filtration efficiency was also proven in the final 60 and 80 nm NRF fabrication procedures at 96% and 91%, respectively.

Environmental pollution remains a major societal problem, leading to serious impacts on living organisms including humans. Human activities such as civilization, urbanization, and industrialization are major causes of pollution. Imposing stricter rules helps control environmental pollutant levels, creating a need for reliable pollutant monitoring in air, water, and soil. The application of traditional analytical techniques is limited in low-resource areas because they are sophisticated, expensive, and bulky. With the development of biosensors and microfluidics technology, environmental monitoring has significantly improved the analysis time, low cost, portability, and ease of use. This review discusses the fundamentals of portable devices, including microfluidics and biosensors, for environmental control. Recently, publications reviewing microfluidics and biosensor device applications have increased more than tenfold, showing the potential of emerging novel approaches for environmental monitoring. Strategies for enzyme-, immunoassay-, and molecular-based analyte sensing are discussed based on their mechanisms and applications. Microfluidic and biosensor platforms for detecting major pollutants, including metal ions, pathogens, pesticides, and antibiotic residues, are reviewed based on their working principles, advantages, and disadvantages. Challenges and future trends for the device design and fabrication process to improve performance are discussed. Miniaturization, low cost, selectivity, sensitivity, high automation, and savings in samples and reagents make the devices ideal alternatives for in-field detection, especially in low-resource areas. However, their operation with complicated environmental samples requires further research to improve the specificity and sensitivity. Although there is a wide range of devices available for environmental applications, their implementation in real-world situations is limited. This study provides insights into existing issues that can be used as references and a comparative analysis for future studies and applications.

High-quality-factor (Q) optical microcavities have attracted extensive interest due to their unique ability to confine light for resonant circulation at the micrometer scale. Particular attention has been paid to optical whispering-gallery mode (WGM) microcavities to harness their strong light-matter interactions for biological applications. Remarkably, the combination of high-Q optical WGM microcavities with microfluidic technologies can achieve a synergistic effect in the development of high-sensitivity optofluidic sensors for many emerging biological analysis applications, such as the detection of proteins, nucleic acids, viruses, and exosomes. They can also be utilized to investigate the behavior of living cells in human organisms, which may provide new technical solutions for studies in cell biology and biophysics. In this paper, we briefly review recent progress in high-Q microcavity-based optofluidic sensor technologies and their applications in biological analysis.

This research aims to tackle the limitations faced in surgical education nowadays, particularly in the complex field of spinal cord tumor removal surgery. An innovative flexible piezoresistive sensor designed to mimic a motor nerve was developed and integrated into a bionic spine surgery simulation system, allowing for the intraoperative nerve monitoring possible during simulated tumor removal surgeries. The motor nerve, fabricated using a combination of carbon nanotubes and silicone rubber, exhibited a strong correlation between applied force and resultant changes in resistance, as confirmed by experimental results. This creative system can play an important role in providing valuable feedback for training doctors, facilitating the assessment of surgical precision and success, and enabling doctors to take necessary precautions to minimize the risk of nerve damage in real surgical scenarios. Ultimately, this proposed system has the potential to elevate the standard of surgical education, foster skill development among doctors, and significantly contribute to enhanced patient care and recovery.

Microfluidic systems have enormous potential for enabling point-of-care diagnostics due to a number of advantages, such as low sample volumes, small footprint, low energy requirements, uncomplicated setup, high surface-to-volume ratios, cost-effectiveness, etc. However, fluid mixing operations are constrained by molecular diffusion since the flow is usually in the laminar regime. The slow nature of molecular diffusion is a technological barrier to implementing fluid transformations in a reasonable time. In this context, magnetically actuated micro-mixers of different sizes, shapes, materials, and actuation techniques provide a way to enhance fluid mixing in microfluidic devices. In this paper, we review the currently existing micro-mixing technologies. From a fundamental perspective, the different magnetization models for permanent and induced dipoles are discussed. The single-particle dynamics in steady and oscillating magnetic fields is studied in order to determine the flow generated and the torque exerted on the fluid due to the magnetic particles. The effect of particle interactions, both magnetic and hydrodynamic, is examined.

The study unveils a simple, non-invasive method to perform micromixing with the help of spatiotemporal variation in the Lorentz force inside a microchannel decorated with chemically heterogeneous walls. Computational fluid dynamics simulations have been utilized to investigate micromixing under the coupled influence of electric and magnetic fields, namely, electromagnetohydrodynamics, to alter the direction of the Lorentz force at the specific locations by creating the reverse flow zones where the pressure gradient, $\nabla p=0$ . The study explores the impact of periodicity, distribution, and size of electrodes alongside the magnitude of applied field intensity, the flow rate of the fluid, and the nature of the electric field on the generation of the mixing vortices and their strength inside the microchannels. The results illustrate that the wall heterogeneities can indeed enforce the formation of localized on-demand vortices when the strength of the localized reverse flow overcomes the inertia of the mainstream flow. In such a scenario, while the vortex size and strength are found to increase with the size of the heterogeneous electrodes and field intensities, the number of vortices increases with the number of heterogeneous electrodes decorated on the channel wall. The presence of a non-zero pressure-driven inflow velocity is found to subdue the strength of the vortices to restrict the mixing facilitated by the localized variation of the Lorentz force. Interestingly, the usage of an alternating current (AC) electric field is found to provide an additional non-invasive control on the mixing vortices by enabling periodic changes in their direction of rotation. A case study in this regard discloses the possibility of rapid mixing with the usage of an AC electric field for a pair of miscible fluids inside a microchannel.

Microfluidic concentration gradient generators (μ-CGGs) are critical in various biochemical assays, including cell migration, drug screening, and antimicrobial susceptibility testing. However, current μ-CGGs rely on integration with flow systems, limiting their scalability and widespread adoption owing to limited infrastructure and technical expertise. Hence, there is a need for flowless diffusional gradient generators capable of standalone operation, thereby improving throughput and usability. In this study, we model such a diffusional μ-CGG as an infinite source-sink system to capture two characteristic timescales: (i) gradient generation dictated by the diffusion timescale and (ii) stability determined by the rate of change in reservoir concentrations. Through finite-element simulations, we explored the influence of various geometric parameters such as the channel length, cross-sectional area, node and reservoir volumes, and the solute diffusivity on these timescales, along with experimental confirmation using fluorescent tracer diffusion. Our results show that while the gradient stability strongly depends on the reservoir volumes, diffusion length, and solute diffusion coefficient, they are independent of the node shape or the shape of the channel cross section. However, gradient profiles were found to be the strong functions of the diffusion length, solute diffusivity, and the geometric pattern of the microfluidic grid. Additionally, we showcased the versatility of the design by generating discrete gradient profiles and combinatorial gradients of two and three solutes, thus improving throughput in a wide range of on-chip biological assays. These findings underscore the potential of our microfluidic device as an easy-to-use, inexpensive, efficient, and high-throughput platform for various on-chip biological assays.

Electric fields are used in biology to address a broad range of questions and through a variety of techniques, including electroporation, gene electrotransfer (GET), electrostimulation (ES), and electrochemotherapy. Each of these modalities requires specific conditions and has drastically different target outcomes on the cell. ES has demonstrated that non-pore forming electric fields alter cell cycle progression. However, pore forming electric fields such as with GET have not been as widely explored despite major clinical advancements. Additionally, the real-time visual analysis of electrical field effects on mammalian cell culture is currently lacking among most commercial systems. To facilitate investigations into these research areas, an electroporation cytometry system was developed including a custom chamber compatible with live cell imaging and exponential decay pulse generator for live cell analysis. The functionality of the system was demonstrated using a recombinant cell line using U-2 OS cells and FUCCI(CA)5 cell cycle reporter. The exposure of the cells to a 180 V pulse in both unsynchronized and synchronized populations revealed an effect on the cell cycle.

The physiological origins and functions of extracellular vesicles (EVs) and lipoproteins (LPs) propel advancements in precision medicine by offering non-invasive diagnostic and therapeutic prospects for cancers, cardiovascular, and neurodegenerative diseases. However, EV/LP diagnostics (ExoLP-Dx) face considerable challenges. Their intrinsic heterogeneity, spanning biogenesis pathways, surface protein composition, and concentration metrics complicate traditional diagnostic approaches. Commonly used methods such as nanoparticle tracking analysis, enzyme-linked immunosorbent assay, and nuclear magnetic resonance do not provide any information about their proteomic subfractions, including active proteins/enzymes involved in essential pathways/functions. Size constraints limit the efficacy of flow cytometry for small EVs and LPs, while ultracentrifugation isolation is hampered by co-elution with non-target entities. In this perspective, we propose a charge-based electrokinetic membrane sensor, with silica nanoparticle reporters providing salient features, that can overcome the interference, long incubation time, sensitivity, and normalization issues of ExoLP-Dx from raw plasma without needing sample pretreatment/isolation. A universal EV/LP standard curve is obtained despite their heterogeneities.