Showing papers in "Biomedical Microdevices in 2022"

Nano-functionalized paper-based IoT enabled devices for point-of-care testing: a review

Abstract: Over the last few years, the microfluidics phenomenon coupled with the Internet of Things (IoT) using innovative nano-functional materials has been recognized as a sustainable and economical tool for point-of-care testing (POCT) of various pathogens influencing human health. The sensors based on these phenomena aim to be designed for cost-effectiveness, make it handy, environment-friendly, and get an accurate, easy, and rapid response. Considering the burgeoning importance of analytical devices in the healthcare domain, this review paper is based on the gist of sensing aspects of the microfabricated paper-based analytical devices (μPADs). The article discusses the various used design methodologies and fabrication approaches and elucidates the recently reported surface modification strategies, detection mechanisms viz., colorimetric, electrochemical, fluorescence, electrochemiluminescence, etc. In a nutshell, this article summarizes the state-of-the-art research work carried out over the nano functionalized paper-based analytical devices and associated challenges/solutions in the point of care testing domain.

Dielectrophoretic separation of blood cells

Abstract: Microfluidic dielectrophoretic (DEP) devices enable the label-free separation and isolation of cells based on differences in their electrophysiological properties. The technique can serve as a tool in clinical diagnostics and medical research as it facilitates the analysis of patient-specific blood composition and the detection and isolation of pathogenic cells like circulating tumor cells or malaria-infected erythrocytes. This review compares different microfluidic DEP devices to separate platelets, erythrocytes and leukocytes including their cellular subclasses. An overview and experimental setups of different microfluidic DEP devices for the separation, trapping and isolation or purification of blood cells are detailed with respect to their technical design, electrode configuration, sample preparation, applied voltage and frequency and created DEP field based and related to the separation efficiency. The technique holds the promise that results can quickly be attained in clinical and ambulant settings. In particular, point-of-care-testing scenarios are favored by the extensive miniaturization, which would be enabled by microelectronical integration of DEP devices.

Biosensors and machine learning for enhanced detection, stratification, and classification of cells: a review

Abstract: Biological cells, by definition, are the basic units which contain the fundamental molecules of life of which all living things are composed. Understanding how they function and differentiating cells from one another, therefore, is of paramount importance for disease diagnostics as well as therapeutics. Sensors focusing on the detection and stratification of cells have gained popularity as technological advancements have allowed for the miniaturization of various components inching us closer to Point-of-Care (POC) solutions with each passing day. Furthermore, Machine Learning has allowed for enhancement in the analytical capabilities of these various biosensing modalities, especially the challenging task of classification of cells into various categories using a data-driven approach rather than physics-driven. In this review, we provide an account of how Machine Learning has been applied explicitly to sensors that detect and classify cells. We also provide a comparison of how different sensing modalities and algorithms affect the classifier accuracy and the dataset size required.

Well-free agglomeration and on-demand three-dimensional cell cluster formation using guided surface acoustic waves through a couplant layer

Abstract: Three-dimensional cell agglomerates are broadly useful in tissue engineering and drug testing. We report a well-free method to form large (1.4-mm) multicellular clusters using 100-MHz surface acoustic waves (SAW) without direct contact with the media or cells. A fluid couplant is used to transform the SAW into acoustic streaming in the cell-laden media held in a petri dish. The couplant transmits longitudinal sound waves, forming a Lamb wave in the petri dish that, in turn, produces longitudinal sound in the media. Due to recirculation, human embryonic kidney (HEK293) cells in the dish are carried to the center of the coupling location, forming a cluster in less than 10 min. A few minutes later, these clusters may then be translated and merged to form large agglomerations, and even repeatedly folded to produce a roughly spherical shape of over 1.4 mm in diameter for incubation-without damaging the existing intercellular bonds. Calcium ion signaling through these clusters and confocal images of multiprotein junctional complexes suggest a continuous tissue construct: intercellular communication. They may be formed at will, and the method is feasibly useful for formation of numerous agglomerates in a single petri dish.

A new insight into a thermoplastic microfluidic device aimed at improvement of oxygenation process and avoidance of shear stress during cell culture

Abstract: Keeping the oxygen concentration at the desired physiological limits is a challenging task in cellular microfluidic devices. A good knowledge of affecting parameters would be helpful to control the oxygen delivery to cells. This study aims to provide a fundamental understanding of oxygenation process within a hydrogel-based microfluidic device considering simultaneous mass transfer, medium flow, and cellular consumption. For this purpose, the role of geometrical and hydrodynamic properties was numerically investigated. The results are in good agreement with both numerical and experimental data in the literature. The obtained results reveal that increasing the microchannel height delays the oxygen depletion in the absence of media flow. We also observed that increasing the medium flow rate increases the oxygen concentration in the device; however, it leads to high maximum shear stress. A novel pulsatile medium flow injection pattern is introduced to reduce detrimental effect of the applied shear stress on the cells.

Compartmentalized organ-on-a-chip structure for spatiotemporal control of oxygen microenvironments

Abstract: Abstract Hypoxia is a condition where tissue oxygen levels fall below normal levels. In locally induced hypoxia due to blood vessel blockage, oxygen delivery becomes compromised. The site where blood flow is diminished the most forms a zero-oxygen core, and different oxygenation zones form around this core with varying oxygen concentrations. Naturally, these differing oxygen microenvironments drive cells to respond according to their oxygenation status. To study these cellular processes in laboratory settings, the cellular gas microenvironments should be controlled rapidly and precisely. In this study, we propose an organ-on-a-chip device that provides control over the oxygen environments in three separate compartments as well as the possibility of rapidly changing the corresponding oxygen concentrations. The proposed device includes a microfluidic channel structure with three separate arrays of narrow microchannels that guide gas mixtures with desired oxygen concentrations to diffuse through a thin gas-permeable membrane into cell culture areas. The proposed microfluidic channel structure is characterized using a 2D ratiometric oxygen imaging system, and the measurements confirm that the oxygen concentrations at the cell culture surface can be modulated in a few minutes. The structure is capable of creating hypoxic oxygen tension, and distinct oxygen environments can be generated simultaneously in the three compartments. By combining the microfluidic channel structure with an open-well coculture device, multicellular cultures can be established together with compartmentalized oxygen environment modulation. We demonstrate that the proposed compartmentalized organ-on-a-chip structure is suitable for cell culture.

Multi-objective optimisation of polymerase chain reaction continuous flow systems

Abstract: A surrogate-enabled multi-objective optimisation methodology for a continuous flow Polymerase Chain Reaction (CFPCR) systems is presented, which enables the effect of the applied PCR protocol and the channel width in the extension zone on four practical objectives of interest, to be explored. High fidelity, conjugate heat transfer (CHT) simulations are combined with Machine Learning to create accurate surrogate models of DNA amplification efficiency, total residence time, total substrate volume and pressure drop throughout the design space for a practical CFPCR device with sigmoid-shape microfluidic channels. A series of single objective optimisations are carried out which demonstrate that DNA concentration, pressure drop, total residence time and total substrate volume within a single unitcell can be improved by up to [Formula: see text]5.7%, [Formula: see text]80.5%, [Formula: see text]17.8% and [Formula: see text]43.2% respectively, for the practical cases considered. The methodology is then extended to a multi-objective problem, where a scientifically-rigorous procedure is needed to allow designers to strike appropriate compromises between the competing objectives. A series of multi-objective optimisation results are presented in the form of a Pareto surface, which show for example how manufacturing and operating cost reductions from device miniaturisation and reduced power consumption can be achieved with minimal impact on DNA amplification efficiency. DNA amplification has been found to be strongly related to the residence time in the extension zone, but not related to the residence times in denaturation and annealing zones.

Self-sealing MEMS spray-nozzles to prevent bacterial contamination of portable inhalers for aqueous drug delivery

Abstract: Pulmonary drug delivery by portable inhalers is the gold standard in lung disease therapy. An increasing focus on environmentally friendly inhalation currently spurs the development of propellant-free devices. However, the absence of propellants in the drug creates a need for suitable sealing systems that can ensure the pathogenic safety of devices. Traditionally, liquid drug inhalers incorporate a spray nozzle and a separate check valve. Here we show a fully integrated MEMS-based spray system for aqueous drug solutions and demonstrate its bacterial safety. The device comprises a thin silicon membrane with spray orifices, which self-seal against a compliant parylene valve seat underneath. This sealing system prevents bacterial ingrowth in its default closed state, while actuation lifts the membrane from the valve seat upon pressurization and sprays an inhalable aerosol from the nozzles. To seal against bacterial contamination effectively, we found that a contact force between the valve seat and the membrane (featuring the spray nozzles) is needed. In our testing, both self-sealing and an otherwise identical unvalved version of the spray chip can be bacterially safe in continued use when thoroughly cleaned of excess fluids and subjected to low bacterial loads for brief periods. However, when directly exposed to [Formula: see text] CFU/ml of our test organism Citrobacter rodentium for 24 h, unvalved systems become contaminated in nearly 90% of cases. In contrast, self-sealing spray chips reduced contamination probability by 70%. This development may enable preservative-free drug formulations in portable inhalers that use propellant-free aqueous drug solutions.

Fabrication and characterization of core–shell microparticles containing an aqueous core

Abstract: Abstract Core–shell microparticles containing an aqueous core have demonstrated their value for microencapsulation and drug delivery systems. The most important step in generating these uniquely structured microparticles is the formation of droplets and double emulsion. The droplet generator must meet the performance and reliability requirements, including accurate size control with tunability and monodispersity. Herein, we present a facile technique to generate surfactant-free core–shell droplets with an aqueous core in a microfluidic device. We demonstrate that the geometry of the core–shell droplets can be precisely adjusted by the flow rates of the droplet components. As the shell is polymerized after the formation of the core–shell droplets, the resulting solid microparticles ensure the encapsulation of the aqueous core and prevent undesired release. We then study experimentally and theoretically the behaviour of resultant microparticles under heating and compression. The microparticles demonstrate excellent stability under both thermal and mechanical loads. We show that the rupture force can be quantitatively predicted from the shell thickness relative to the outer shell radius. Experimental results and theoretical predictions confirm that the rupture force scales directly with the shell thickness. Graphical abstract