Biomicrofluidics

Point-of-care (POC) diagnostic devices have been developing rapidly in recent years, but they are mainly using saliva instead of blood as a test sample. A highly efficient self-separation during the self-driven flow without power systems is desired for expanding the point-of-care diagnostic devices. Microfiltration stands out as a promising technique for blood plasma separation but faces limitations due to blood cell clogging, resulting in reduced separation speed and efficiency. These limitations are mainly caused by the high viscosity and hematocrit in the blood flow...

Mixing within micro- and millichannels is a pivotal element across various applications, ranging from chemical synthesis to biomedical diagnostics and environmental monitoring. The inherent low Reynolds number flow in these channels often results in a parabolic velocity profile, leading to a broad residence time distribution. Achieving efficient mixing at such small scales presents unique challenges and opportunities. This review encompasses various techniques and strategies to evaluate and enhance mixing efficiency in these confined environments...

Chronic myelogenous/myeloid leukemia (CML) is a type of cancer of bone marrow that arises from hematopoietic stem cells and affects millions of people worldwide. Eighty-five percent of the CML cases are diagnosed during chronic phase, most of which are detected through routine tests. Leukocytes, micro-Ribonucleic Acids, and myeloid markers are the primary biomarkers for CML diagnosis and are mainly detected using real-time reverse transcription polymerase chain reaction, flow cytometry, and genetic testing...

Mitosis is a crucial biological process where a parental cell undergoes precisely controlled functional phases and divides into two daughter cells. Some drugs can inhibit cell mitosis, for instance, the anti-cancer drugs interacting with the tumor cell proliferation and leading to mitosis arrest at a specific phase or cell death eventually. Combining machine learning with microfluidic impedance flow cytometry (IFC) offers a concise way for label-free and high-throughput classification of drug-treated cells at single-cell level...

In recent years, cell-based therapies have transformed medical treatment. These therapies present a multitude of challenges associated with identifying the mechanism of action, developing accurate safety and potency assays, and achieving low-cost product manufacturing at scale. The complexity of the problem can be attributed to the intricate composition of the therapeutic products: living cells with complex biochemical compositions. Identifying and measuring critical quality attributes (CQAs) that impact therapy success is crucial for both the therapy development and its manufacturing...

96-well microtiter plates, widely used in immunoassays, face challenges such as prolonged assay time and limited sensitivity due to the lack of analyte transport control. Orbital shakers, commonly employed to facilitate mass transport, offer limited improvements and can introduce assay inconsistencies. While microfluidic devices offer performance enhancements, their complexity and incompatibility with existing platforms limit their wide adoption. This study introduces a novel microfluidic 96-well cover designed to convert a standard 96-well plate to a mass-transport-controlled surface bioreactor...

Computer vision has become a powerful tool in the field of biosensing, aiding in the development of innovative and precise systems for the analysis and interpretation of biological data. This interdisciplinary approach harnesses the capabilities of computer vision algorithms and techniques to extract valuable information from various biosensing applications, including medical diagnostics, environmental monitoring, and food health. Despite years of development, there is still significant room for improvement in this area...

Cancer spatial and temporal heterogeneity fuels resistance to therapies. To realize the routine assessment of cancer prognosis and treatment, we demonstrate the development of an Intelligent Disease Detection Tool (IDDT), a microfluidic-based tumor model integrated with deep learning-assisted algorithmic analysis. IDDT was clinically validated with liquid blood biopsy samples (n = 71) from patients with various types of cancers (e.g., breast, gastric, and lung cancer) and healthy donors, requiring low sample volume (∼200  μ l) and a high-throughput 3D tumor culturing system (∼300 tumor clusters)...

Microphysiological systems (MPSs), also known as organ-on-chip or disease-on-chip, have recently emerged to reconstitute the in vivo cellular microenvironment of various organs and diseases on in vitro platforms. These microfluidics-based platforms are developed to provide reliable drug discovery and regulatory evaluation testbeds. Despite recent emergences and advances of various MPS platforms, their adoption of drug discovery and evaluation processes still lags. This delay is mainly due to a lack of rigorous standards with reproducibility and reliability, and practical difficulties to be adopted in pharmaceutical research and industry settings...

This study presented a platform of multiplex fluorescence detection of single-cell droplet microfluidics with demonstrative applications in quantifying protein expression levels. The platform of multiplex fluorescence detection mainly included optical paths adopted from conventional microscopy enabling the generation of three optical spots from three laser sources for multiple fluorescence excitation and capture of multiple fluorescence signals by four photomultiplier tubes. As to platform characterization, microscopic images of three optical spots were obtained where clear Gaussian distributions of intensities without skewness confirmed the functionality of the scanning lens, while the controllable distances among three optical spots validated the functionality of fiber collimators and the reflector lens...

Acoustic manipulation of particles in microchannels has recently gained much attention. Ultrasonic standing wave (USW) separation of oil droplets or particles is an established technology for microscale applications. Acoustofluidic devices are normally operated at optimized conditions, namely, resonant frequency, to minimize power consumption. It has been recently shown that symmetry breaking is needed to obtain efficient conditions for acoustic particle trapping. In this work, we study the acoustophoretic behavior of monodisperse oil droplets (silicone oil and hexadecane) in water in the microfluidic chip operating at a non-resonant frequency and an off-center placement of the transducer...

The development of physiologically relevant in vitro systems for simulating disease onset and progression and predicting drug metabolism holds tremendous value in reducing drug discovery time and cost. However, many of these platforms lack accuracy in replicating the tissue architecture and multicellular interactions. By leveraging three-dimensional cell culture, biomimetic soft hydrogels, and engineered stimuli, in vitro models have continued to progress. Nonetheless, the incorporation of the microvasculature has been met with many challenges, specifically with the addition of parenchymal cell types...

As one of the hot spots in the field of microfluidic chip research, micromixers have been widely used in chemistry, biology, and medicine due to their small size, fast response time, and low reagent consumption. However, at low Reynolds numbers, the fluid motion relies mainly on the diffusive motion of molecules under laminar flow conditions. The detrimental effect of laminar flow leads to difficulties in achieving rapid and efficient mixing of fluids in microchannels. Therefore, it is necessary to enhance fluid mixing by employing some external means...

Here, results are presented on the focusing of <mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mn>1</mml:mn><mml:mspace/><mml:mi>μ</mml:mi></mml:math>m polystyrene particle suspensions using a synchronous oscillatory pressure-driven flow and oscillatory electric field in a microfluidic device. The effect of the phase difference between the oscillatory fields on the focusing position and focusing efficiency was investigated. The focusing position of negatively charged polystyrene particles could be tuned anywhere between the channel centerline to the channel walls...

Large-scale and controllable fabrication is an indispensable step for the industrialization and commercialization of halide perovskite nanocrystals, which are new-generation semiconductor materials for optoelectronic applications. Microfluidics, which provides continuous and precise synthesis, has been considered as a promising technique to fulfill this aspect. The research studies over the past decades have witnessed the advancement of microfluidics as a powerful tool in the fabrication of halide perovskite nanocrystals...

Organ-on-a-chip devices are powerful modeling systems that allow researchers to recapitulate the in vivo structures of organs as well as the physiological conditions those tissues are subject to. These devices are useful tools in modeling not only the behavior of a healthy organ but also in modeling disease pathology or the effects of specific drugs. The incorporation of fluidic flow is of great significance in these devices due to the important roles of physiological fluid flows in vivo . Recent developments in the field have led to the production of vascularized organ-on-a-chip devices, which can more accurately reproduce the conditions observed in vivo by recapitulating the vasculature of the organ concerned...

Digital bioanalysis places great emphasis on the highly sensitive and rapid detection of biomolecules at the single-molecule level. Rooted in single-molecule biophysics, this innovative approach offers numerous insights into biomolecular mechanisms with an unprecedented level of sensitivity and precision. Moreover, this method has significant potential to contribute to disease diagnostics, enabling the highly sensitive detection of biomarkers or pathogens for early disease diagnosis and continuous disease monitoring...

The efficient breakage of one cell or a concentration of cells for releasing intracellular material such as DNA, without damaging it, is the first step for several diagnostics or treatment processes. As the cell membrane is easy to bend but resistant to stretching, the exposure of the cell to a shear rate during a short period of time can be sufficient to damage the membrane and facilitate the extraction of DNA. However, how to induce high shear stresses on cells in small microliter volumes samples has remained an elusive problem...

Particle image velocimetry and particle tracking velocimetry have played pivotal roles in flow and particle characterization, owing to their non-invasive and accurate data collection methods. However, their broader application in the biomicrofluidics field is constrained by challenges, such as intensive calibration, high post-processing costs, and optical compatibility issues, especially in settings where space is a bottleneck. This article describes recent advancements in non-iterative ray tracing that promise more streamlined post-capture calibration and highlights examples of applications and areas that merit further technological investigation...

The human vasculature is essential in organs and tissues for the transport of nutrients, metabolic waste products, and the maintenance of homeostasis. The integration of vessels in in vitro organs-on-chip may, therefore, improve the similarity to the native organ microenvironment, ensuring proper physiological functions and reducing the gap between experimental research and clinical outcomes. This gap is particularly evident in drug testing and the use of vascularized models may provide more realistic insights into human responses to drugs in the pre-clinical phases of the drug development pipeline...