Nanotechnology in tissue engineering: expanding possibilities with nanoparticles.

Tissue engineering is a multidisciplinary field that merges engineering, material science, and medical biology in order to develop biological alternatives for repairing, replacing, maintaining, or boosting the functionality of tissues and organs. The ultimate goal of tissue engineering is to create biological alternatives for repairing, replacing, maintaining, or enhancing the functionality of tissues and organs. However, the current landscape of tissue engineering techniques presents several challenges, including a lack of suitable biomaterials, inadequate cell proliferation, limited methodologies for replicating desired physiological structures, and the unstable and insufficient production of growth factors, which are essential for facilitating cell communication and the appropriate cellular responses. Despite these challenges, there has been significant progress made in tissue engineering techniques in recent years. Nanoparticles hold a major role within the realm of nanotechnology due to their unique qualities that change with size. These particles, which provide potential solutions to the issues that are met in tissue engineering, have helped propel nanotechnology to its current state of prominence. Despite substantial breakthroughs in the utilization of nanoparticles over the past two decades, the full range of their potential in addressing the difficulties within tissue engineering remains largely untapped. This is due to the fact that these advancements have occurred in relatively isolated pockets. In the realm of tissue engineering, the purpose of this research is to conduct an in-depth investigation of the several ways in which various types of nanoparticles might be put to use. In addition to this, it sheds light on the challenges that need to be conquered in order to unlock the maximum potential of nanotechnology in this area.

Innovative PNA-LB mediated allele-specific LAMP for KRAS mutation profiling on a compact lab-on-a-disc device.

Tailored healthcare, an approach focused on individual patients, requires integrating emerging interdisciplinary technologies to develop accurate and user-friendly diagnostic tools. KRAS mutations, prevalent in various common cancers, are crucial determinants in selecting patients for novel KRAS inhibitor therapies. This study presents a novel state-of-the-art Lab-on-a-Disc system utilizing peptide nucleic acids-loop backward (PNA-LB) mediated allele-specific loop-mediated isothermal amplification (LAMP) for detecting the frequent G12D KRAS mutation, signifying its superiority over alternative mutation detection approaches. The designed Lab-on-a-Disc system demonstrated exceptional preclinical and technical precision, accuracy, and versatility. By applying varying cutoff values to PNA- LB LAMP reactions, the assay's sensitivity and specificity were increased by 80 % and 90 %, respectively. The device's key advantages include a robust microfluidic Lab-on-a-Disc design, precise rotary control, and a cutting-edge induction heating module. These features enable multiplexing of LAMP reactions with high reproducibility and repeatability, with CV% values less than 3.5 % and 5.5 %, respectively. The device offers several methods for accurate endpoint result detection, including naked-eye observation, RGB image analysis using Python code, and time of fluorescence (Tf) values. Preclinical specificity and sensitivity, assessed using different cutoffs for Eva-Green fluorescence Tf values and pH-sensitive dyes, demonstrated comparable performance to the best standard methods. Overall, this study represents a significant step towards tailoring treatment strategies for cancer patients through precise and efficient mutation detection technologies.

Real-time monitoring and actuation of a hybrid siphon valve for hematocrit-independent plasma separation from whole blood.

Centrifugal microfluidics have emerged as a pivotal area of research spanning multiple domains, including medicine and chemistry. Among passive valving strategies, siphon valves have gained prominence due to their inherent simplicity and self-reliance, eliminating the need for external equipment. However, achieving optimal valve performance mandates supplementary elements like surface adjustments or pneumatic pressure. These introduce intricacies such as time-dependent behavior and augmented spatial demands. This research introduces inventive design and manufacturing methodologies to amplify siphon valve functionality. Our proposed innovation situates the siphon microchannel on the external surface of the primary chamber, linked via an inlet. The crux of novelty lies in the adaptable material selection for the microchannel's upper or lower surfaces, allowing the integration of hydrophilic materials such as glass or super hydrophilic coverslips, ensuring a leakage-free operation. Our approach offers a streamlined concept and manufacturing process, ensures consistent time-independent functionality, and accommodates the integration of multiple siphon valves within a solitary chamber, tailored for specific applications. Experimental evaluations validate a robust alignment between acquired data and analytical outcomes based on a modified equation. A customized disc is engineered, featuring four siphon valves meticulously calibrated for hematocrit (HCT) levels spanning from 20% to 50% at 10% intervals. Harnessing these valves yields a substantial surge in plasma separation efficiency, scaling up to 75%. Notably, this performance eclipses traditional single-valve reliant microfluidic methodologies, achieving a purity level exceeding 99% in plasma separation. These findings underscore the auspicious practical applicability of our proposed technique in plasma separation, fostering heightened platelet concentration, and expediting blood sample analysis.

A curved expansion-contraction microfluidic structure for inertial based separation of circulating tumor cells from blood samples.

The rare presence of circulating tumor cells (CTCs) in the bloodstream has made their recording and separation one of the major challenges in the recent decade. Inertia-based microfluidic systems have received more attention in CTCs separation due to their feasibility and low cost. In this research, an inertial microfluidic system is proposed using a curved expansion-contraction array (CEA) microchannel to separate CTCs from white blood cells (WBCs). First, the optimal flow rate of the proposed microfluidic device was determined to maximize the separation efficiency of the target cells (CTCs) from the non-target ones (WBCs). Then, the efficiency and purity of the straight and curved-CEA microchannels were assessed. The experimental results indiated that the proposed system (curved-CEA microchannel) can offer the highest efficiency (-80.31%) and purity (-91.32%) at the flow rate of -7.5 ml/min, exhibiting ∼11.48% increment in the efficiency compared to its straight peer.

Recent advances in isolation and detection of exosomal microRNAs related to Alzheimer's disease.

Alzheimer's disease, a progressive neurological condition, is associated with various internal and external risk factors in the disease's early stages. Early diagnosis of Alzheimer's disease is essential for treatment management. Circulating exosomal microRNAs could be a new class of valuable biomarkers for early Alzheimer's disease diagnosis. Different kinds of biosensors have been introduced in recent years for the detection of these valuable biomarkers. Isolation of the exosomes is a crucial step in the detection process which is traditionally carried out by multi-step ultrafiltration. Microfluidics has improved the efficiency and costs of exosome isolation by implementing various effects and forces on the nano and microparticles in the microchannels. This paper reviews recent advancements in detecting Alzheimer's disease related exosomal microRNAs based on methods such as electrochemical, fluorescent, and SPR. The presented devices' pros and cons and their efficiencies compared with the gold standard methods are reported. Moreover, the application of microfluidic devices to detect Alzheimer's disease related biomarkers is summarized and presented. Finally, some challenges with the performance of novel technologies for isolating and detecting exosomal microRNAs are addressed.

Robotic digital microfluidics: a droplet-based total analysis system.

Developing automated platforms for point-of-need testing is a crucial global demand. Digital microfluidics is a promising solution for expanding integrated testing devices featuring ultimate control over the chemical and biological reactions in micro/nanoliter droplets. In this study, robotic digital microfluidics (RDMF) is introduced for the mechanical manipulation of the droplets precisely and inexpensively. A controllable and multifunctional arm equipped with several actuators is responsible for dispensing and manipulating droplets on a disposable superhydrophobic cartridge. The platform has been demonstrated with diverse functions, including droplet dispensing, transport, mixing, aliquoting, and splitting. Moreover, incorporating magnetic and heating modules into the system can realize particle manipulation and droplet heating. The liquid handling operations are investigated from both experimental and modeling perspectives. Handling a wide range of droplet sizes without needing high-voltage electric sources, integrability with different detection techniques, and ease of manufacturing are the main advantages of the RDMF platform compared to conventional digital microfluidic systems. The availability of a complete fluidic toolbox and multiple detection choices make RDMF promising for droplet-based total analysis technology. The system was applied for a urinalysis test to show its versatility in handling complex biochemical assays. The results entirely matched those obtained based on laboratory gold standard techniques.

Cross flow coupled with inertial focusing for separation of human sperm cells from semen and simulated TESE samples.

A triplet spiral channel coupled with cross-flow filtration has been designed and fabricated in an effort to separate sperm cells from either semen or simulated testicular sperm extraction (TESE) samples. This device separates a fraction of cells from the sample by taking advantage of inertial focusing combined with hydrodynamic filtration in multiple micro-slits. Compared to the conventional swim-up technique, the proposed microfluidic device is capable of efficiently separating sperm cells without any tedious semen sample processing and centrifugation steps with a lower level of reactive oxygen species and DNA fragmentation. The device processing capability on the simulated TESE samples confirmed its proficiency in retrieving sperm cells from the samples with an approximate yield of 76%. Conclusively, the introduced microfluidic device can pave the path to proficiently separate sperm cells in assisted reproductive treatment cycles.

Frequency dependent multiphase flows on centrifugal microfluidics.

The simultaneous flow of gas and liquids in large scale conduits is an established approach to enhance the performance of different working systems under critical conditions. On the microscale, the use of gas-liquid flows is challenging due to the dominance of surface tension forces. Here, we present a technique to generate common gas-liquid flows on a centrifugal microfluidic platform. It consists of a spiral microchannel and specific micro features that allow for temporal and local control of stratified and slug flow regimes. We investigate several critical parameters that induce different gas-liquid flows and cause the transition between stratified and slug flows. We have analytically derived formulations that are compared with our experimental results to deliver a general guideline for designing specific gas-liquid flows. As an application of the gas-liquid flows in enhancing microfluidic systems' performance, we show the acceleration of the cell growth of E. coli bacteria in comparison to traditional culturing methods.

The Effect of Moment of Inertia on the Liquids in Centrifugal Microfluidics.

The flow of liquids in centrifugal microfluidics is unidirectional and dominated by centrifugal and Coriolis forces (i.e., effective only at T-junctions). Developing mechanisms and discovering efficient techniques to propel liquids in any direction other than the direction of the centrifugal force has been the subject of a large number of studies. The capillary force attained by specific surface treatments, pneumatic energy, active and passive flow reciprocation and Euler force have been previously introduced in order to manipulate the liquid flow and push it against the centrifugal force. Here, as a new method, the moment of inertia of the liquid inside a chamber in a centrifugal microfluidic platform is employed to manipulate the flow and propel the liquid passively towards the disc center. Furthermore, the effect of the moment of inertia on the liquid in a rectangular chamber is evaluated, both in theory and experiments, and the optimum geometry is defined. As an application of the introduced method, the moment of inertia of the liquid is used in order to mix two different dyed deionized (DI) waters; the mixing efficiency is evaluated and compared to similar mixing techniques. The results show the potential of the presented method for pumping liquids radially inward with relatively high flow rates (up to 23 mm³/s) and also efficient mixing in centrifugal microfluidic platforms.