Biomicrofluidics最新文献

Bio-microfluidic technologies offer promising applications in diagnostics and therapy, yet they face significant technical challenges, particularly in the need for external power sources, which limits their practicality and user-friendliness. Recent advancements have explored innovative methods utilizing body fluids, motion, and heat to power these devices, addressing the power supply issue effectively. Among these, body-motion and body-heat-powered systems stand out for their potential to create self-sustaining, wearable, and implantable devices. In this Perspective, we focus on the principles and applications of hydrovoltaic cells, biofuel cells, and piezoelectric and triboelectric nanogenerators. Recent strides in energy conversion efficiency, coupled with the development of biocompatible and durable materials, are driving innovation in bio-integrated electronics. Integration with bio-microfluidic platforms further enhances the linkage to the human body and the potential of these devices for personalized healthcare applications. Ongoing research into these areas promises to deliver sustainable and user-friendly solutions for continuous monitoring, diagnostics, and therapy, potentially revolutionizing the landscape of healthcare delivery.

Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia. In recent years, CAR T-cell therapies have been investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, cytokine release syndrome (CRS) is an unexpected side effect that is potentially life-threatening. Our aim is to reduce pro-inflammatory cytokine release associated with CRS by controlling CAR surface density on CAR T cells. We show that CAR expression density can be titrated on the surface of primary T cells using an acoustic-electric microfluidic platform. The platform performs dosage-controlled delivery by uniformly mixing and shearing cells, delivering approximately the same amount of CAR gene coding mRNA into each T cell.

Platelet transfusion is a lifesaving therapy intended to prevent and treat bleeding. However, in addition to platelets, a typical unit also contains a large volume of supernatant that accumulates multiple pro-inflammatory contaminants, including residual leukocytes, microaggregates, microparticles, antibodies, and cytokines. Infusion of this supernatant is responsible for virtually all adverse reactions to platelet transfusions. Conventional methods for removing residual leukocytes (leukoreduction) and reducing the volume of transfused supernatant (volume reduction) struggle to mitigate these risks holistically. Leukoreduction filters can remove leukocytes and microaggregates but fail to reduce supernatant volume, whereas centrifugation can reduce volume, but it is ineffective against larger contaminants and damages platelets. Additionally, platelet purification based on these methods is often too logistically complex, time-consuming, and labor-intensive to implement routinely. Emerging microfluidic technologies offer promising alternatives through passive separation mechanisms that enable cell separation with minimal damage and drastically reduced instrumentation size and facility requirements. This review examines recent innovations in microfluidic cell separation that can be used for leukoreduction and volume reduction of platelets. It begins by defining the performance requirements that any separation method must meet to successfully replace conventional methods currently used to perform these tasks. Standard performance metrics are described, including leukocyte depletion efficiency, degree of volume reduction, processing throughput, and platelet recovery. Finally, the review outlines the primary challenges that must be overcome to enable simple-to-use, disposable microfluidic devices capable of both reducing the platelet unit volume and removing pro-inflammatory contaminants, while preserving most functional platelets for transfusion.

Drug delivery technologies, which are a crucial area of research in the field of cell biology, aim to actively or passively deliver drugs to target cells to enhance therapeutic efficacy and minimize off-target effects. In recent years, with advances in drug development, particularly, the increasing demand for macromolecular drugs (e.g., proteins and nucleic acids), novel drug delivery technologies and intracellular cargo delivery systems have emerged as promising tools for cell and gene therapy. These systems include various viral- and chemical-mediated methods as well as physical delivery strategies. Physical methods, such as electroporation and microinjection, have shown promise in early studies but have not been widely adopted due to concerns regarding efficiency and cellular viability. Recently, microfluidic technologies have provided new opportunities for cargo delivery by allowing for precise control of fluid dynamic parameters to achieve efficient and safe penetration of cell membranes, as well as for foreign material transport. Microfluidics-based mechanical delivery methods utilize biophysical phenomena, such as cell constriction and fluid shear, and are associated with high throughput and high transfection efficiency. In this review, we summarize the latest advancements in microfluidic mechanical delivery technologies, and we discuss constriction- and fluid shear-induced delivery strategies. Furthermore, we explore the potential application of artificial intelligence in optimizing cargo delivery technologies, aiming to provide theoretical support and practical guidance for the future development of novel cellular drug delivery technologies.

Accurate detection of pathogenic nucleic acids is crucial for early diagnosis, effective treatment, and containment of infectious diseases. It facilitates the timely identification of pathogens, aids in monitoring disease outbreaks, and helps prevent the spread of infections within healthcare settings and communities. We developed a multi-layered, paper-based microfluidic and miniaturized electrophoresis system for rapid nucleic acid extraction, separation, amplification, and detection, designed for resource-limited settings. Constructed from acrylic, transparency film, pressure-sensitive adhesion, and Whatman paper using a CO₂ laser, the setup simplifies traditional methods and eliminates the need for complex equipment. DNA extraction and purification are achieved using Zweifach-Fung bifurcation and Fahraeus effect principles, with detection via a hydrogel-assisted colorimetric isothermal reverse transcriptase-loop-mediated isothermal amplification technique. The system accurately identified the SARS-CoV-2 N-gene and β-actin human gene, validated by a compact electrophoresis setup. In clinical validation with 12 patient specimens, the system demonstrated a positive predictive agreement of 83.0% and a negative predictive agreement of 100%. The system achieves a limit of detection of 1 copy/μl and can potentially transform nucleic acid detection assays in healthcare settings. This study addresses key challenges in nucleic acid detection, such as ensuring sample quality and quantity, reducing reliance on sophisticated equipment, preventing contamination, simplifying procedures, and providing rapid and accurate diagnostics for emerging pathogens.

Rheotaxis is one of the major migratory mechanisms used in autonomous swimmers such as sperms and bacteria. Here, we present a microfluidic chip using joint rheotaxis and boundary-following behavior that selects sperms based on the motility and persistence. The proposed device consists of a channel decorated with diamond-shaped pillars that create spots of increased velocity field and shear rate. These spots are supposed as hydrodynamic barriers that impede the passage of less motile sperms through the channels, while highly motile sperms were able to overcome the generated barrier and swim through the structures. The proposed device was able to populate the chamber with sorted sperms that were fully viable and motile. The experimental results validated the separation of highly motile sperms with enhanced motility parameters compared with the initial sample. Our device was able to improve linear straight velocity, curvilinear velocity, and average path velocity of the sorted population surpassing 35%, compared with the raw semen. The processing time was also reduced to 20 min.

Single-cell printing technology has arisen as a potent instrument for investigating cell biology and disease pathophysiology. Nonetheless, current single-cell printing methodologies are hindered by restricted throughput, a limited field of view, and diminished efficiency. We present an innovative single-cell printing chip that utilizes thermal inkjet technology for single-cell printing, therefore addressing these constraints. We have accomplished high-throughput, wide-field, and efficient single-cell printing by merging a high-density thermal foam-based inkjet nozzle array on a chip with high-speed cameras and computer vision technologies for optical image capture and single-cell identification training. We have shown the efficacy and adaptability of the printing chip by printing various concentrations of Chinese hamster ovary cells and human embryonic kidney 293 cells. The printing of a single 96-well plate is accomplished in 2-3 min, facilitating one-time loading and uninterrupted multi-plate paving. Our thermal bubble single-cell printing chip serves as a viable platform for high-throughput single-cell analysis applications.

Microfluidic devices have many unique practical applications across a wide range of fields, making it important to develop accurate models of these devices, and many different models have been developed. Existing modeling methods mainly include mechanism derivation and semi-empirical correlations, but both are not universally applicable. In order to achieve a more accurate and general modeling process, the use of data-driven modeling has been studied recently. This review highlights recent advances in the application of data-driven modeling techniques for simulating and designing microfluidic devices. First, it introduces the application of traditional modeling approaches in microfluidics; subsequently, through different database sources, it reviews studies on data-driven modeling in three categories; and finally, it raises some open issues that require further investigation.

The transformative potential of microfluidics in the development of mRNA vaccines is explored in this review, highlighting its pivotal role in enhancing easy-to-use functionality, efficacy, and production efficiency. Moreover, we examine the innovative applications of microfluidics in biomedical research, including its contribution to the rapid and cost-effective synthesis of lipid nanoparticles for mRNA delivery and delve into the advantages of mRNA vaccines, such as targeted delivery and controlled expression. Furthermore, it outlines the future prospects of microfluidic devices, their cutting-edge examples in both research and industry, and the potential to revolutionize vaccine formulation and production. The integration of microfluidics with mRNA vaccine development represents a significant advancement in public health and disease prevention strategies.

Considerable attention has been given to elasto-inertial microfluidics, which are widely applied for the focusing, sorting, and separation of particles/cells. In this work, we propose a novel yet simple fabrication process for a microchannel with a cruciform section, where elasto-inertial particle focusing is explored in a viscoelastic fluid. SU-8 master molds for polydimethylsiloxane (PDMS) structures were fabricated via standard photolithography, and then plasma bonding, following self-alignment between two PDMS structures, was performed for the formation of a microchannel with a cruciform section. The particle behaviors inside the fabricated microchannel were experimentally investigated for various flow rates and particle sizes and compared with those inside a microchannel with a square cross section. The experimental results revealed that 3D particle focusing was achieved in the center under viscoelastic fluid flow over a wide range of flow rates without any shear thinning. Even for small particles (∼2 μm), single-line particle focusing was observed in the microchannel with a cruciform section but not in a square microchannel with the same hydraulic diameter (D_h  = 75 μm). The effects of four reflex angles (270°) on particle focusing were quantitatively evaluated through numerical simulation. The simulation revealed that the migration pattern of particles is governed by the combined effect of the reflex angles and fluid inertia, leading to characteristic particle focusing behavior within the cross section of the cruciform microchannel. These findings agree well with the experimental results, which highlight the superior capability of the cruciform microchannel for inertial particle focusing across a wide range of particle sizes.