Lab on a Chip最新文献

Microfluidic-based material synthesis is uniquely suited for the fabrication of reproducible and controllable products due to the highly controlled reaction environments in microscale dimensions. With many passive and active micromixers emerging for the on-chip material synthesis needs, the use of electrokinetic driven fluid to form turbulence actuation is yet an unexplored technique with much-unrealized potential. In this study, we used an electrokinetic turbulent micromixer for the controllable synthesis of phospholipid vesicles by nanoprecipitation. By imposing a transverse electric field upon coflowing reagent-containing solvent and antisolvent streams, the two fluids experience rapid mixing with bilayer lipid fragments generated. Phospholipid vesicles are facilitated under the effect of the electric field and turbulent flow. Depending on the voltage of the AC electric field, concentrations and types of phospholipids, and flow parameters, phospholipid vesicles of different sizes and morphologies can be synthesized in a single microfluidic chip, rather than a complex batch process in traditional methods. The time is no more than even a single second. The method is compatible for integration into a platform to produce phospholipid vesicles for chemistry and biomedical applications.

Organ-chip technology, in contrast to cell culture and animal models, offers a promising platform for accelerating drug development. However, current chip designs simulate human organ functions and there is a lack of multi-organ chip designs that can simultaneously study drug efficacy and hepatorenal toxicity. Here, we developed a novel microfluidic multi-organ chip that integrated cholangiocarcinoma organoids (CCOs) with recellularized liver slices (RLS) and recellularized kidney slices (RKS), to simultaneously assess anti-cholangiocarcinoma drug efficacy and hepatorenal toxicity. Co-culture of patient-derived CCOs with RLS and RKS was successfully achieved for 7 days under flow conditions with enhanced liver and renal cell functions. Furthermore, an in vitro biomimetic model showed IC₅₀ values of trastuzumab emtansine (T-DM1) of around 6.42 ± 7.34 μg mL^-1 in four clinical cases, with one outlier of 77.77 μg mL^-1 due to patient variability. Post-treatment, RLS and RKS cell viability remained high at 75.67% and 81.03%, respectively, suggesting low hepatorenal toxicity of T-DM1 for treating cholangiocarcinoma. Our study demonstrates the use of an organoid-slice-on-a-chip (OSOC) platform for personalized drug efficacy and toxicity assessment, particularly aiming at leveraging anticancer drugs for off-label use to save patient lives.

The complexity of the eukaryotic glycosylation machinery hinders the development of cell-free protein glycosylation since in vitro methods struggle to simulate the natural environment of the glycosylation machinery. Microfluidic technologies have the potential to address this limitation due to their ability to control glycosylation parameters, such as enzyme/substrate concentrations and fluxes, in a rapid and precise manner. However, due to the complexity and sensitivity of the numerous components of the glycosylation machinery, very few "glycobiology-on-a-chip" systems have been proposed or reported in the literature. Herein, we describe the design, fabrication and proof-of-concept of a droplet-based microfluidic platform able to mimic N-linked glycan processing along the secretory pathway. Within a single microfluidic device, glycoproteins and glycosylation enzymes are encapsulated and incubated in water-in-oil droplets. Additional glycosylation enzymes are subsequently supplied to these droplets via picoinjection, allowing further glycoprotein processing in a user-defined manner. After system validation, the platform is used to perform two spatiotemporally separated consecutive enzymatic N-glycan modifications, mirroring the transition between the endoplasmic reticulum and early Golgi.

Bioinspired ionic power devices have been investigated due to their high biocompatibility and potential for sustainable energy conversion through ion concentration gradients. However, recent research into portable ionic power devices has primarily focused on hydrogel-based stacking elements, such as ion-selective gels and ionic reservoirs, to enhance productivity. However, this approach results in ionic resource consumption for the operating time. In this study, we propose a portable ionic power generator that provides continuous electricity by integrating multi-ionic reverse electrodialysis (MRED) with a passive capillary micropump for electrolyte absorption. The integrated MRED system was fabricated on a portable fluidic chip with optimizations of absorbing performance, electrolyte concentration, and shortcut current regulation attaining maximum potential of 267.45 mV and current of 4.42 mA. Furthermore, consistent and continuous performance for 25 min was achieved by incorporating cotton flow resistors, which modulate the electrolyte absorbing rate at the electrolyte contact region of the pumps. The electric potential was controlled by adjusting the cotton mass inspiring controllable drug release via iontophoresis where high voltage enhances charged drug penetration. This study paves the way for a new form of ionic power supply for patch-type wearable health devices.

Extracellular vesicles (EVs) are nanoscale membrane vesicles actively released by cells into a variety of biofluids. EVs carry myriad molecular cargoes; these include classical genetic biomarkers inherited from the parent cells as well as EV modifications by other entities (e.g., small molecule drugs). Aided by these diverse cargoes, EVs enable long-distance intercellular communication and have been directly implicated in various disease pathologies. As such, EVs are being increasingly recognized as a source of valuable biomarkers for minimally-invasive disease diagnostics and prognostics. Despite the clinical potential, EV molecular profiling remains challenging, especially in clinical settings. Due to the nanoscale dimension of EVs as well as the abundance of contaminants in biofluids, conventional EV detection methods have limited resolution, require extensive sample processing and can lose rare biomarkers. To address these challenges, new micro- and nanotechnologies have been developed to discover EV biomarkers and empower clinical applications. In this review, we introduce EV biogenesis for different cargo incorporation, and discuss the use of various EV biomarkers for clinical applications. We also assess different chip-based integrated technologies developed to measure genetic and modified biomarkers in EVs. Finally, we highlight future opportunities in technology development to facilitate the clinical translation of various EV biomarkers.

During oil extraction, the recovery rates of traditional methods have been gradually declining. CO₂-enhanced oil recovery (CO₂-EOR) has been utilized since the 1960s; however, in recent years, it has garnered renewed attention due to its environmental benefits and economic advantages. However, there are few reports addressing multiphase mass transfer in micro- and nano-scale pores. This study employs microfluidic technology to simulate the pore structures of real reservoir rocks. A fracture-matrix porous medium chip with a network channel structure and a microscale porous medium chip featuring multiple pore-throat ratios were designed to investigate the effects of cross-scale interactions, network channel geometries, and the Jamin effect on fluid flow patterns and oil recovery rates during both CO₂ miscible and CO₂ immiscible flooding processes. The experiments demonstrated that the cross-scale effect facilitates the rapid achievement of a 100% recovery rate during CO₂ miscible flooding, but exacerbates gas channeling during CO₂ immiscible flooding, resulting in a decreased recovery rate. The Jamin effect becomes more pronounced with increasing pore-throat ratios, and the substantial capillary resistance generated by this effect in regions with high pore-throat ratios significantly reduces the rate of increase in recovery during CO₂ miscible flooding, as well as the overall recovery rate during CO₂ immiscible flooding. This study enhances the understanding of multiphase mass transfer in reservoir conditions and provides critical insights for optimizing CO₂-EOR strategies, ultimately contributing to more efficient oil recovery and supporting sustainable practices in the energy sector.

The viscosity and density of liquids are the most extensively studied material properties, as their accurate measurement is critical in various industries. Although developments in micro-viscometers have overcome the limitations of traditional bulky methods, more accessible technologies are required. Here, we introduce a novel magnetic levitation-based method to measure the viscosity and density of solutions in a microcapillary channel. This principle exploits microparticles as microsensors to correlate levitation time and height with solutions' viscosity and density, using buoyancy and drag forces. The platform has an integrated lensless holographic microscope, providing a hybrid system for in situ and precise measurements. By utilizing this hybrid technology, portable, rapid and cost-effective measurements can be conducted. This platform enables viscosity and density measurements within 7 minutes, achieving high accuracies of at least 97.7% and 99.9%, respectively, across an operation range of 0.84-5.09 cP and 1.00-1.09 g cm^-3. The platform is utilized to clearly distinguish differences in the spent cell culture medium across various cell lines. This method, as presented, can be readily applied to measure a diverse array of liquids in multiple domains, encompassing biotechnology, medicine, and engineering.

This study introduces a modular centrifugal platform developed for stepwise gradient elution in reversed-phase liquid chromatography, featuring adjustable mixing and automated position-switching mechanisms. Traditional methods of gradient elution rely on precision syringes and mixers to control eluent composition, but incorporating external pumping systems into centrifugal platforms presents substantial technical and economic challenges. To overcome these limitations, an adjustable eluent mixer was designed to generate concentration gradients by utilizing Coriolis-induced metering and shake-mode mixing processes. The eluent composition was controlled by varying the platform's rotational speed, with the effects of geometric and operational parameters on liquid distribution thoroughly analyzed. An operating curve was established to correlate methanol-water eluent compositions with rotational speed. Furthermore, a switchable fraction collector capable of automated position switching was developed to collect eluates from each elution step. By synchronizing rotational speed with ratchet-driven movements, the outer ring containing multiple fraction collectors rotates relative to the inner disk, enabling efficient replacement of filled collectors. Experimental results demonstrated the successful separation and collection of water-soluble dyes, highlighting the platform's potential as a cost-effective and precise solution for chromatographic applications.

Powerless micropumps are in increasing demand for applications requiring portability, simplicity, and long-term operation. However, several existing passive pumps have limitations such as sustained high flow rates and extended operational periods. Inspired by the unique structural characteristics of Luffa cylindrica, this study aims to develop a biomimetic micropump capable of long-term and high-flow operation. By examining the water transport mechanisms in a hierarchical porous structure, we designed and fabricated micropumps that replicate these mechanisms. A key aspect of this design is the integration of flow resistors, which enables precise control over the absorption rates and extend the pumping duration. The cone-shaped agarose aerogel (AAG) micropump operates for over 930 min with an average flow rate of 5.6 μl min^-1, demonstrating significant longevity. The agarose superabsorbent polymer aerogel (ASAG) micropump, while having a shorter operational duration of approximately 620 min, exhibited a significantly higher average pumping rate of 13.2 μl min^-1. This study highlights the potential of bio-inspired designs for advancing efficient and powerless pumping systems. The proposed micropump shows promise for applications in microfluidic devices and reverse electrodialysis systems, where continuous and sustainable fluid transport is essential.

Glioblastoma is one of the most malignant tumors in the world, but the development of its therapies remains limited. Herein, a microfluidic chip that mimics the cerebrospinal fluid (CSF) circulation microenvironment is proposed to study the migration characteristics of glioblastoma U87-MG cells and U251 cells in complex environments where glioblastoma coexists with diseases that elevate CSF levels. In the presence of interstitial flow (IF), changing both cell densities and the cellular environment results in increased cell motility, including an increase in the number of migrating cells, the mean displacement of the top 30% fastest-moving cells, and the overall mean displacement. Then, through dynamic migration characterization analysis, it was found that IF enhances cell velocity and speed. Importantly, cells exposed to IF tend to migrate in directions with smaller angles of deviation from the opposite direction of IF. Finally, cytoskeleton inhibitors and decreased expressions of focal adhesion proteins, such as cytochalasin D, FAK inhibitors (VS-6063 and PF-573228), and FAK siRNA, were both proved to decrease the cells' response to IF. This work not only demonstrates the effect of IF on glioblastoma cell migration, but also indicates the reliability of microfluidic chips for modeling complex physiological environments, which is expected to be further developed for drug screening.