Lab on a Chip最新文献

Size-controlled monodisperse droplets are indispensable in food, cosmetics, and healthcare industries. Although emulsion formation from bulk phases is well-explored, a robust in situ method to continuously reform existing emulsions is unavailable. Remarkably, we introduce a continuous flow acousto-microfluidics technique which enables simultaneous trapping–coalescence–splitting of droplets to reform an existing polydisperse emulsion into size-controlled droplets with improved monodispersity. In contrast to conventional approaches, our platform enables controlling droplet characteristics in situ by regulating acoustic power without altering hydrodynamical parameters thereby improving response time and facilitates continuous nozzle-less clogging-free droplet generation from a liquid plug in a chamber instead of from a liquid stream at a narrow junction. The technique can process polydisperse droplets produced not only due to fluid-source fluctuations or unstable jetting regime but also externally by non-microfluidic or inexpensive setups. Our theoretical scaling suggests that the sum of capillary (Ca) and acousto-capillary (Ca_a) numbers ∼ (1), and predicts the generated droplet size, both agreeing well with the experimental findings. We identify acousto-visco-capillary number, Ca_av = (Ca Ca_a)^1/2, which governs the generated droplet size. We also explore and characterize acoustic streaming- and coalescence-based mixing of samples inside the trapped plug. Distinctively, our platform is amenable to continuous mixing of inhomogeneous droplets, offering monodisperse mixed-sample droplets, and holds the potential to match current throughput standards through suitable design modifications.

Cilial pumping is a potent mechanism used to control and manipulate fluids on microscales. Recently, we introduced an electronically driven μ-cilial platform that can create arbitrary flow patterns in liquids near a surface with the potential for various engineering applications. This μ-cilial platform, however, utilized the coupling between elasticity and viscous drag to obtain pumping and had several limitations. For example, each cilium could only pump in one direction. Thus, to create bidirectional flows, it was necessary to fabricate and separately actuate two oppositely facing cilia. As another example, the generation of non-reciprocal cilial motions, a necessary condition for pumping at these scales, could only be achieved by matching the elastic stresses inherent in actuating the cilia with the viscous drag forces generated by the flows. This criterion severely restricted the frequency range over which the cilia could be operated and resulted in a small swept area, both of which restricted the volume of fluid being pumped in each cycle. These limitations contrast with the capabilities of natural cilia, which can achieve omnidirectional transport and operation over a broad range of frequencies. In natural cilia, these capabilities arise from their complex internal structure. Inspired by this strategy we designed hinged cilia and show they can achieve bidirectional pumping of larger fluid volumes over a broad range of frequencies. Finally, we demonstrate that even regular arrays of individually controlled hinged cilia can generate a variety of flow patterns using fewer cilia than in previous cilia metasurface designs.

Microfluidic mixing has significant applications in various fields, including materials synthesis and biochemical analysis. In this study, we propose a universal strategy to enhance mixing efficiency in microfluidic chips. This strategy initially divides the liquid into branches, which then converge in an interdigitated manner at the beginning of the mixing segment. This branch-convergence structure reduces the flow width of each liquid, thereby decreasing the diffusion distances required for mixing. Under the conditions of this study, the mixing efficiency could be improved by approximately 10 times. Importantly, this enhancement strategy only requires changing the structure of the liquid inflow channel without changing the structure of the mixing segment. Thus, this strategy has broad applicability, any mixing section with different principles and structures can be connected downstream of the branch-convergence structure. In addition, we applied this universal mixing enhancement strategy to the continuous synthesis of lactic-co-glycolic acid nanoparticles, resulting in a higher uniformity of synthesized nanoparticles compared to unenhanced devices.

Presumptive drug screening enables timely procurement of search and arrest warrants and represents a crucial first step in crime scene analysis. Screening also reduces the burden on forensic laboratories which often face insurmountable backlogs. In most scenarios, on-site presumptive drug screening relies on chemical field tests for initial identification. However, even when used appropriately, these test kits remain limited to subjective colorimetric analysis, produce false positive or negative results with excessive sample quantities, and are known to cross-react with numerous innocuous substances. Previous efforts to develop microfluidic devices that incorporate these chromogenic indicator reagents address only a few of the many challenges associated with these kits. This is especially true for samples where the drug of interest is present as a lacing agent. This work describes the development of a centrifugal microfluidic device capable of integrating facile sample preparation, by way of a 3D printed snap-on cartridge amenable to microwave assisted extraction, followed by chromatographic separation and chromogenic detection on-disc. As cannabis is among the most widely used controlled substance worldwide, and displays strong interference with these indicator reagents, mock samples of laced marijuana are used for a proof-of-concept demonstration. Post extraction, the microdevice completes high throughput metering just prior to simultaneous reaction with four of the most commonly employed microchemical tests, followed by objective image analysis in CIELAB (a device-independent color model). Separation and recovery of a representative controlled substance with 93% efficiency is achieved. Correct identification, according to hierarchical cluster analysis, of three illicit drugs (e.g., heroin, phencyclidine, and cocaine) in artificially laced samples is also demonstrated on-disc. The cost effective microdevice is capable of complete automation post-extraction, with a total analysis time (including extraction) of <8 min. Finally, sample consumption is minimized, thereby preventing the complete destruction of forensic evidence.

Measurements of cell lineages are central to a variety of fundamental biological questions, ranging from developmental to cancer biology. However, accurate lineage tracing requires nearly perfect cell tracking, which can be challenging due to cell motion during imaging. Here we demonstrate the integration of microfabrication, imaging, and image processing approaches to demonstrate a platform for cell lineage tracing. We use quantitative phase imaging (QPI), a label-free imaging approach that quantifies cell mass. This gives an additional parameter, cell mass, that can be used to improve tracking accuracy. We confine lineages within microwells fabricated to reduce cell adhesion to sidewalls made of a low refractive index polymer. This also allows the microwells themselves to serve as references for QPI, enabling measurement of cell mass even in confluent microwells. We demonstrate application of this approach to immortalized adherent and nonadherent cell lines as well as stimulated primary B cells cultured ex vivo. Overall, our approach enables lineage tracking, or measurement of lineage mass, in a platform that can be customized to varied cell types.

The spread of metastatic cancer cells poses a significant challenge in cancer treatment, making innovative approaches for early detection and diagnosis essential. Dielectrophoretic impedance spectroscopy (DEPIS), a powerful tool for cell analysis, combines dielectrophoresis (DEP) and impedance spectroscopy (IS) to separate, sort, cells and analyze their dielectric properties. In this study, we developed and built out-of-plane inkjet-printed castellated arrays to map the dielectric properties of MDA-MB-231 breast cancer cell subtypes across their metastatic potential. This was realized via modulating the expression of connexin 43 (Cx43), a marker associated with poor breast cancer prognosis and increased metastasis. We employed DEP-based trapping, followed by EIS measurements on bulk cell population, for rapid capture and differentiation of the cancer cells according to their metastatic state. Our results revealed a significant correlation between the various MDA-MB-231 metastatic subtypes and their respective dielectrophoretic and dielectric properties. Notably, cells with the highest metastatic potential exhibited the highest membrane capacitance 16.88 ± 3.24 mF m⁻², followed by the less metastatic cell subtypes with membrane capacitances below 14.3 ± 2.54 mF m⁻². In addition, highly metastatic cells exhibited lower crossover frequency (25 ± 1 kHz) compared to the less metastatic subtypes (≥27 ± 1 kHz), an important characteristic for cell sorting. Finally, EIS measurements showed distinct double layer capacitance (C_DL) values at 1 kHz between the metastatic subgroups, confirming unique dielectric and dielectrophoretic properties correlated with the metastatic state of the cell. Our findings underscore the potential of DEPIS as a non-invasive and rapid analytical tool, offering insights into cancer biology and facilitating the development of personalized therapeutic interventions tailored to distinct metastatic stages.

Small-scale robots with shape anisotropy have garnered significant scientific interest due to their enhanced mobility and precise control in recent years. Traditionally, these miniature robots are manufactured using established techniques such as molding, 3D printing, and microfabrication. However, the advent of microfluidics in recent years has emerged as a promising manufacturing technology, capitalizing on the precise and dynamic manipulation of fluids at the microscale to fabricate various complex-shaped anisotropic particles. This offers a versatile and controlled platform, enabling the efficient fabrication of small-scale robots with tailored morphologies and advanced functionalities from the microfluidic-derived anisotropic microparticles at high throughput. This review highlights the recent advances in the microfluidic fabrication of anisotropic microparticles and their potential applications in small-scale robots. In this review, the term ‘small-scale robots’ broadly encompasses micromotors endowed with capabilities for locomotion and manipulation. Firstly, the fundamental strategies for liquid template formation and the methodologies for generating anisotropic microparticles within the microfluidic system are briefly introduced. Subsequently, the functionality of shape-anisotropic particles in forming components for small-scale robots and actuation mechanisms are emphasized. Attention is then directed towards the diverse applications of these microparticle-derived microrobots in a variety of fields, including pollution remediation, cell microcarriers, drug delivery, and biofilm eradication. Finally, we discuss future directions for the fabrication and development of miniature robots from microfluidics, shedding light on the evolving landscape of this field.

Rapid and sensitive detection of pathogens in various samples is crucial for disease diagnosis, environmental surveillance, as well as food and water safety monitoring. However, the low abundance of pathogens (<10 CFU) in large volume (1 mL−1 L) samples containing vast backgrounds critically limits the sensitivity of even the most advanced techniques, such as digital PCR. Therefore, there is a critical need for sample preparation that can enrich low-abundance pathogens from complex and large-volume samples. This study develops an efficient electrostatic microfiltration (EM)-based sample preparation technique capable of processing ultra-large-volume (≥500 mL) samples at high throughput (≥10 mL min⁻¹). This approach achieves a significant enrichment (>8000×) of extremely-low-abundance pathogens (down to level of 0.02 CFU mL⁻¹, i.e., 10 CFU in 500 mL). Furthermore, EM-enabled sample preparation facilitates digital amplification techniques sensitively detecting broad pathogens, including bacteria, fungi, and viruses from various samples, in a rapid (≤3 h) sample-to-result workflow. Notably, the operational ease, portability, and compatibility/integrability with various downstream detection platforms highlight its great potential for widespread applications across diverse settings.

To report the testing signal of an immunochromatographic assay for on-site quantitative detection, a portable and user-friendly smartphone-based biosensing platform is developed in this study. This innovative system is composed of an ambient light sensor inherent smartphone reader and a 3D-printed handhold device, a quantitative tool capable of directly interpreting carbon nanoparticle (CNP)-conjugated immunochromatographic strips. To showcase the platform capability, the smartphone-based immunochromatography system (SPICS) reader and device were successfully used in CNP strips for rapid detection of the early pregnancy marker human chorionic gonadotropin in female urine (HCG; limit of detection [LOD]: 0.30 mIU mL⁻¹), prostate-specific antigen in patient blood (PSA; LOD: 0.28 ng mL⁻¹) and ampicillin residue in animal milk (AMP; LOD: 0.23 ng mL⁻¹). The results were fully correlated with conventional commercial instruments (R² = 0.99). The SPICS platform exhibits significant advantages, including portability, cost-effectiveness, easy operation, and rapid and quantitative detection, making it a valuable on-site diagnosis tool for use in home and community healthcare facilities.

Akin to the impact that digital microelectronics had on electronic devices for information technology, digital microfluidics (DMF) was anticipated to transform fluidic devices for lab-on-a-chip (LoC) applications. However, despite a wealth of research and publications, electrowetting-on-dielectric (EWOD) DMF has not achieved the anticipated wide adoption, and commercialization has been painfully slow. By identifying the technological and resource hurdles in developing DMF chip and control systems as the culprit, we envision democratizing DMF by building a standardized design and manufacturing platform. To achieve this vision, we introduce a proof-of-concept cloud platform that empowers any user to design, obtain, and operate DMF chips (https://edroplets.org). For chip design, we establish a web-based EWOD chip design platform with layout rules and automated wire routing. For chip manufacturing, we build a web-based EWOD chip manufacturing platform and fabricate four types of EWOD chips (i.e., glass, paper, PCB, and TFT) to demonstrate the foundry service workflow. For chip control, we introduce a compact EWOD control system along with web-based operating software. Although industrial fabrication services are beyond the scope of this work, we hope this perspective will inspire academic and commercial stakeholders to join the initiative toward a DMF ecosystem for the masses.