Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great ...potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.
Biodevices are crucial for monitoring vital physiological signals, managing chronic health conditions, developing artificial organs for assisting people with disabilities, and conducting various ...clinical and surgical procedures. However, existing biodevices are mostly composed of rigid components, which can cause discomfort to the user, whereas the high stiffness of implants is known to be the major cause of inflammation and scarring. Gallium‐based liquid metals are intrinsically soft and possess desirable properties, including low toxicity, high conductivity, and deformability, which make them ideally suited for developing soft, deformable, reconfigurable, and healable biodevices. Herein, recent advancements in the emerging field of liquid‐metal‐based biodevices are discussed. This includes a description of the properties of gallium‐based liquid metals which make them so distinct from conventional materials, a brief outline of various techniques devised for fabrication of liquid‐metal‐based devices/structures, and an overview of the diverse range of wearable or implantable liquid‐metal‐enabled biodevices. The outlook and challenges are also discussed.
Liquid metals show great potentials for use in biodevices due to their many beneficial properties, such as low toxicity, high conductivity, and deformability. Herein, unique properties of liquid metals are discussed, device fabrication methods are briefly outlined, and then many uses of liquid metals in biodevices are elaborated. Finally, a foresight is offered to exemplify future challenges.
Cardiovascular diseases are the leading cause of mortality, morbidity, and hospitalization around the world. Recent technological advances have facilitated analyzing, visualizing, and monitoring ...cardiovascular diseases using emerging computational fluid dynamics, blood flow imaging, and wearable sensing technologies. Yet, computational cost, limited spatiotemporal resolution, and obstacles for thorough data analysis have hindered the utility of such techniques to curb cardiovascular diseases. We herein discuss how leveraging machine learning techniques, and in particular deep learning methods, could overcome these limitations and offer promise for translation. We discuss the remarkable capacity of recently developed machine learning techniques to accelerate flow modeling, enhance the resolution while reduce the noise and scanning time of current blood flow imaging techniques, and accurate detection of cardiovascular diseases using a plethora of data collected by wearable sensors.
The human circulatory system is a marvelous fluidic system, which is very sensitive to biophysical and biochemical cues. The current animal and cell culture models do not recapitulate the functional ...properties of the human circulatory system, limiting our ability to fully understand the complex biological processes underlying the dysfunction of this multifaceted system. In this review, we discuss the unique ability of microfluidic systems to recapitulate the biophysical, biochemical, and functional properties of the human circulatory system. We also describe the remarkable capacity of microfluidic technologies for exploring the complex mechanobiology of the cardiovascular system, mechanistic studying of cardiovascular diseases, and screening cardiovascular drugs with the additional benefit of reducing the need for animal models. We also discuss opportunities for further advancement in this exciting field.
TRPV4 is a non-selective cation channel that tunes the function of different tissues including the vascular endothelium, lung, chondrocytes, and neurons. GSK1016790A is the selective and potent ...agonist of TRPV4 and a pharmacological tool that is used to study the TRPV4 physiological function
and
. It remains unknown how the sensitivity of TRPV4 to this agonist is regulated. The spatial and temporal dynamics of receptors are the major determinants of cellular responses to stimuli. Membrane translocation has been shown to control the response of several members of the transient receptor potential (TRP) family of ion channels to different stimuli. Here, we show that TRPV4 stimulation with GSK1016790A caused an increase in Ca
that is stable for a few minutes. Single molecule analysis of TRPV4 channels showed that the density of TRPV4 at the plasma membrane is controlled through two modes of membrane trafficking, complete, and partial vesicular fusion. Further, we show that the density of TRPV4 at the plasma membrane decreased within 20 min, as they translocate to the recycling endosomes and that the surface density is dependent on the release of calcium from the intracellular stores and is controlled via a PI3K, PKC, and RhoA signaling pathway.
Macrophages are heterogeneous innate immune cells that are functionally shaped by their surrounding microenvironment. Diverse macrophage populations have multifaceted differences related to their ...morphology, metabolism, expressed markers, and functions, where the identification of the different phenotypes is of an utmost importance in modelling immune response. While expressed markers are the most used signature to classify phenotypes, multiple reports indicate that macrophage morphology and autofluorescence are also valuable clues that can be used in the identification process. In this work, we investigated macrophage autofluorescence as a distinct feature for classifying six different macrophage phenotypes, namely: M0, M1, M2a, M2b, M2c, and M2d. The identification was based on extracted signals from multi-channel/multi-wavelength flow cytometer. To achieve the identification, we constructed a dataset containing 152,438 cell events each having a response vector of 45 optical signals fingerprint. Based on this dataset, we applied different supervised machine learning methods to detect phenotype specific fingerprint from the response vector, where the fully connected neural network architecture provided the highest classification accuracy of 75.8% for the six phenotypes compared simultaneously. Furthermore, by restricting the number of phenotypes in the experiment, the proposed framework produces higher classification accuracies, averaging 92.0%, 91.9%, 84.2%, and 80.4% for a pool of two, three, four, five phenotypes, respectively. These results indicate the potential of the intrinsic autofluorescence for classifying macrophage phenotypes, with the proposed method being quick, simple, and cost-effective way to accelerate the discovery of macrophage phenotypical diversity.
Arterial endothelium experience physical stress associated with blood flow and play a central role in maintaining vascular integrity and homeostasis in response to hemodynamic forces. Blood flow ...within vessels is generally laminar and streamlined. However, abrupt changes in the vessel geometry due to branching, sharp turns or stenosis can disturb the laminar blood flow, causing secondary flows in the form of vortices. Such disturbed flow patterns activate pro-inflammatory phenotypes in endothelial cells, damaging the endothelial layer and can lead to atherosclerosis and thrombosis. Here, we report a microfluidic system with integrated ridge-shaped obstacles for generating controllable disturbed flow patterns. This system is used to study the effect of disturbed flow on the cytoskeleton remodeling and nuclear shape and size of cultured human aortic endothelial cells. Our results demonstrate that the generated disturbed flow changes the orientation angle of actin stress fibers and reduces the nuclear size while increases the nuclear circularity.
Customised audio signals, such as musical notes, can be readily generated by audio software on smartphones and played over audio speakers. Audio speakers translate electrical signals into the ...mechanical motion of the speaker cone. Coupling the inlet tube to the speaker cone causes the harmonic oscillation of the tube, which in turn changes the velocity profile and flow rate. We employ this strategy for generating programmable dynamic flow patterns in microfluidics. We show the generation of customised rib and vortex patterns through the application of multi-tone audio signals in water-based and whole blood samples. We demonstrate the precise capability to control the number and extent of the ribs and vortices by simply setting the frequency ratio of two- and three-tone audio signals. We exemplify potential applications of tube oscillation for studying the functional responses of circulating immune cells under pathophysiological shear rates. The system is programmable, compact, low-cost, biocompatible, and durable. These features make it suitable for a variety of applications across chemistry, biology, and physics.
Skin is exposed to a variety of potential stressors and stimulators that may impact homeostasis, healing, tumor development, inflammation, and irritation. As such it is important to understand the ...impact that these stimuli have on skin health and function, and to develop therapeutic interventions. Animal experiments have been the gold standard for testing the safety and efficacy of therapeutics and observing disease pathology for centuries. However, complex ethics, costs, time consumption, and interspecies variation limit the transferability of results to humans and reduce their repeatability and reliability. Furthermore, traditional 2D cell studies are not representative of human tissue. Skin tissue is a dynamic environment, and when cells are isolated in unphysiologically stiff, static petri dishes their behavior, and phenotypic expression is altered. Increasingly complex in vitro models of human skin, including organoids, 3D bioprinting, and skin‐on‐a‐chip platforms, present the opportunity to gain insight into how stressors affect tissue at a cellular level in a controlled and repeatable environment. This insight can be leveraged to further understand pathological skin conditions and better formulate and validate drugs and therapeutics. Here, we will discuss the application of in vitro skin modeling to investigating the effects of mechanical, electromagnetic, and chemical stressors on skin.
Skin acts as an interface between ourselves and our external environment. Consequently, our skin must interact with a variety of potential stressors while retaining homeostatic balance. Increasingly complex models of human skin are being developed, including organoids and skin‐on‐chip platforms, that offer increased physiological relevance. The present review collates the application of different in vitro models of human skin to investigating the impact of mechanical, electromagnetic, and chemical stressors. It also highlights advantages, limitations, and future avenues for advancements of in vitro skin models.
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