Lab on a Chip最新文献

The first step in blood testing necessitates blood separation to obtain an adequate volume of plasma. Traditional centrifugation is bulky, expensive and electricity-powered, which is not suitable for micro-scale blood plasma separation in point-of-care testing (POCT) cases. Microfluidic paper-based plasma separation devices present a promising alternative for plasma separation in such occasions. However, they are limited in terms of plasma yield, which hinders analyte detection. Herein, we proposed a humidity-enhanced paper-based microfluidic plasma separation method to address this issue. Specifically, paper was first treated by blood-typing antibodies, then samples of whole blood were introduced into the prepared paper. After waiting for 5 min for RBC agglutination and plasma wicking under high humidity, micro-scale plasma separation from whole blood was achieved. As a result, an extremely high plasma yield of up to 60.1% could be separated from whole blood through using Xuan-paper. Meanwhile, the purity of plasma could reach 99.99%. Finally, this innovative approach was effortlessly integrated into distance-based glucose concentration detection, enabling rapid determination of blood glucose levels through naked-eye observation. Considering the simplicity and inexpensiveness of this method, we believe that this technology could be integrated to more paper-based microfluidic analytical devices for rapid and accurate detection of plasma analytes in POCT.

There is an ongoing need to do more with less and provide highly multiplexed analysis from limited sample volumes. Improved “sample sparing” assays would have a broad impact across pediatric and other rare sample type studies in addition to enabling sequential sampling. This capability would advance both clinical and basic research applications. Here we report the micro blood analysis technology (μBAT), a microfluidic platform that supports multiplexed analysis of neutrophils from a single drop of blood. We demonstrate the multiplexed orthogonal capabilities of μBAT including functional assays (phagocytosis, neutrophil extracellular traps, optical metabolic imaging) and molecular assays (gene expression, cytokine secretion). Importantly we validate our microscale platform using a macroscale benchmark assay. μBAT is compatible with lancet puncture or microdraw devices, and its design facilitates rapid operations without the need for specialized equipment. μBAT offers a new method for investigating neutrophil function in populations with restricted sample amounts.

The differences in the cross-sectional positions of cells in the detection area have a severe negative impact on achieving accurate characterization of the impedance spectra of cells. Herein, we proposed a three-dimensional (3D) inertial focusing based impedance cytometer integrating sheath fluid compression and inertial focusing for the high-accuracy electrical characterization and identification of tumor cells. First, we studied the effects of the particle initial position and the sheath fluid compression on particle focusing. Then, the relationship of the particle height and the signal-to-noise ratio (SNR) of the impedance signal was explored. The results showed that efficient single-line focusing of 7–20 μm particles close to the electrodes was achieved and impedance signals with a high SNR and a low coefficient of variation (CV) were obtained. Finally, the electrical properties of three types of tumor cells (A549, MDA-MB-231, and UM-UC-3 cells) were accurately characterized. Machine learning algorithms were implemented to accurately identify tumor cells based on the amplitude and phase opacities at multiple frequencies. Compared with traditional two-dimensional (2D) inertial focusing, the identification accuracy of A549, MDA-MB-231, and UM-UC-3 cells using our 3D inertial focusing increased by 57.5%, 36.4% and 36.6%, respectively. The impedance cytometer enables the detection of cells with a wide size range without causing clogging and obtains high SNR signals, improving applicability to different complex biological samples and cell identification accuracy.

Effective continuous glucose monitoring solutions require consistent sensor performance over the lifetime of the device, a manageable variance between devices, and the capability of high volume, low cost production. Here we present a novel and microfabrication-compatible method of depositing and stabilizing enzyme layers on top of planar electrodes that can aid in the mass production of sensors while also improving their consistency. This work is focused on the fragile biorecognition layer as that has been a critical difficulty in the development of microfabricated sensors. We test this approach with glucose oxidase (GOx) and evaluate the sensor performance with amperometric measurements of in vitro glucose concentrations. Spincoating was used to deposit a uniform enzyme layer across a wafer, which was subsequently immobilized via glutaraldehyde vapor crosslinking and patterned via liftoff. This yielded an approximately 300 nm thick sensing layer which was applied to arrays of microfabricated platinum electrodes built on blank wafers. Taking advantage of their planar array format, measurements were then performed in high-throughput parallel instrumentation. Due to their thin structure, the coated electrodes exhibited subsecond stabilization times after the bias potential was applied. The deposited enzyme layers were measured to provide a sensitivity of 2.3 ± 0.2 μA mM⁻¹ mm⁻² with suitable saturation behavior and minimal performance shift observed over extended use. The same methodology was then demonstrated directly on top of wireless CMOS potentiostats to build a monolithic sensor with similar measured performance. This work demonstrates the effectiveness of the combination of spincoating and vapor stabilization processes for wafer scale enzymatic sensor functionalization and the potential for scalable fabrication of monolithic sensor-on-CMOS devices.

Climate change presents a mounting challenge with profound impacts on ocean and marine ecosystems, leading to significant environmental, health, and economic consequences. Microfluidic technologies, with their unique capabilities, play a crucial role in understanding and addressing the marine aspects of the climate crisis. These technologies leverage quantitative, precise, and miniaturized formats that enhance the capabilities of sensing, imaging, and molecular tools. Such advancements are critical for monitoring marine systems under the stress of climate change and elucidating their response mechanisms. This review explores microfluidic technologies employed both in laboratory settings for testing and in the field for monitoring purposes. We delve into the application of miniaturized tools in evaluating ocean-based solutions to climate change, thus offering fresh perspectives from the solution-oriented end of the spectrum. We further aim to synthesize recent developments in technology around critical questions concerning the ocean environment and marine ecosystems, while discussing the potential for future innovations in microfluidic technology. The purpose of this review is to enhance understanding of current capabilities and assist researchers interested in mitigating the effects of climate change to identify new avenues for tackling the pressing issues posed by climate change in marine ecosystems.

Microfluidic flow reactors functionalized with immobilized human liver microsomes (HLM chips) represent a powerful tool for drug discovery and development by enabling mechanism-based enzyme inhibition studies under flow-through conditions. Additionally, HLM chips may be exploited in streamlined production of human drug metabolites for subsequent microfluidic in vitro organ models or as metabolite standards for drug safety assessment. However, the limited shelf life of the biofunctionalized microreactors generally poses a major barrier to their commercial adaptation in terms of both storage and shipping. The shelf life of the HLM chips in the wetted state is ca. 2–3 weeks only and requires cold storage at 4 °C. In this study, we developed a freeze-drying method for lyophilization of HLMs that are readily immobilized inside microfluidic pillar arrays made from off-stoichiometric thiol–ene polymer. The success of lyophilization was evaluated by monitoring the cytochrome P450 and UDP-glucuronosyltransferase enzyme activities of rehydrated HLMs for several months post-freeze-drying. By adapting the freeze-drying protocol, the HLM chips could be stored at room temperature (protected from light and moisture) for at least 9 months (n = 2 independent batches) and up to 16 months at best, with recovered enzyme activities within 60–120% of the non-freeze-dried control chips. This is a major improvement over the cold-storage requirement and the limited shelf life of the non-freeze-dried HLM chips, which can significantly ease the design of experiments, decrease energy consumption during storage, and reduce the shipping costs with a view to commercial adaptation.

This review summarizes programmable microfluidics, an advanced method for precise fluid control in microfluidic technology through microchannel design or liquid properties, referring to microvalves, micropumps, digital microfluidics, multiplexers, micromixers, slip-, and block-based configurations. Different microvalve types, including electrokinetic, hydraulic/pneumatic, pinch, phase-change and check valves, cater to diverse experimental needs. Programmable micropumps, such as passive and active micropumps, play a crucial role in achieving precise fluid control and automation. Due to their small size and high integration, microvalves and micropumps are widely used in medical devices and biological analysis. In addition, this review provides an in-depth exploration of the applications of digital microfluidics, multiplexed microfluidics, and mixer-based microfluidics in the manipulation of liquid movement, mixing, and splitting. These methodologies leverage the physical properties of liquids, such as capillary forces and dielectric forces, to achieve precise control over fluid dynamics. SlipChip technology, which branches into rotational SlipChip and translational SlipChip, controls fluid through sliding motion of the microchannel. On the other hand, innovative designs in microfluidic systems pursue better modularity, reconfigurability and ease of assembly. Different assembly strategies, from one-dimensional assembly blocks and two-dimensional Lego®-style blocks to three-dimensional reconfigurable modules, aim to enhance flexibility and accessibility. These technologies enhance user-friendliness and accessibility by offering integrated control systems, making them potentially usable outside of specialized technical labs. Microfluidic programmable strategies for channels and flow hold promising applications in biomedical research, chemical analysis and drug screening, providing theoretical and practical guidance for broader utilization in scientific research and practical applications.

Microfluidic devices with open lattice structures, equivalent to a type of porous media, allow for the manipulation of fluid transport processes while having distinct structural, mechanical, and thermal properties. However, a fundamental understanding of the design principles for the solid structure in order to achieve consistent and desired flow patterns remains a challenge, preventing its further development and wider applications. Here, through quantitative and mechanistic analyses of the behavior of multi-phase phenomena that involve gas–liquid–solid interfaces, we present a design framework for microfluidic devices containing porous architectures (referred to as poroFluidics) for deterministic control of multi-phase fluid transport processes. We show that the essential properties of the fluids and solid, including viscosity, interfacial tension, wettability, as well as solid manufacture resolution, can be incorporated into the design to achieve consistent flow in porous media, where the desired spatial and temporal fluid invasion sequence can be realized. Experiments and numerical simulations reveal that different preferential flow pathways can be controlled by solid geometry, flow conditions, or fluid/solid properties. Our design framework enables precise, multifunctional, and dynamic control of multi-phase transport within engineered porous media.

Point-of-care testing of pathogens is becoming more and more important for the prevention and control of food poisoning. Herein, a power-free colorimetric biosensor was presented for rapid detection of Salmonella using a microfluidic SlipChip for fluidic control and Au@PtPd nanocatalysts for signal amplification. All the procedures, including solution mixing, immune reaction, magnetic separation, residual washing, mimicking catalysis and colorimetric detection, were integrated on this SlipChip. First, the mixture of the bacterial sample, immune magnetic nanobeads (IMBs) and immune Au@PtPd nanocatalysts (INCs), washing buffer and H₂O₂–TMB chromogenic substrate were preloaded into the sample, washing and catalysis chambers, respectively. After the top layer of this SlipChip was slid to connect the sample chamber with the separation chamber, the mixture was moved back and forth through the asymmetrical split-and-recombine micromixer by using a disposable syringe to form the IMB–Salmonella–INC sandwich conjugates. Then, the conjugates were captured in the separation chamber using a magnetic field, and the top layer was slid to connect the washing chamber with the separation chamber for washing away excessive INCs. Finally, the top layer was slid to connect the catalysis chamber with the separation chamber, and the colorless substrate was catalyzed by the INCs with peroxidase-mimic activity to generate color change, followed by using a smartphone app to collect and analyze the image to determine the bacterial concentration. This all-in-one microfluidic biosensor enabled simple detection of Salmonella as low as 101.2 CFU mL⁻¹ within 30 min and was featured with low cost, straightforward operation, and compact design.

A novel microfluidic paper-based analytical device with dual colorimetric and electrochemical detection (dual μPAD) was developed for the assessment of transferrin saturation (TSAT) in samples from ischemic stroke patients. TSAT was calculated from the ratio between transferrin-bound iron, which was colorimetrically measured, and the total iron-binding capacity, which was electrochemically measured. To this end, a μPAD was smartly designed, which integrated both colorimetric and electrochemical detection reservoirs, communicating via a microchannel acting as a chemical reactor, and with preloading/storing capabilities (reagent-free device). This approach allowed the dual and simultaneous determination of both parameters, providing an improvement in the reliability of the results due to an independent signal principle and processing. The μPADs were validated by analyzing a certified reference material, showing excellent accuracy (E_r ≤ 5%) and precision (RSD ≤ 2%). Then they were applied to the analysis of diagnosed serum samples from ischemic stroke patients. The results were compared to those provided by a free-interference method (urea-PAGE). Impressively, both methods exhibited a good correlation (r = 0.96, p < 0.05) and no significant differences were found between them (slope 1.0 ± 0.1 and the intercept 1 ± 4, p < 0.05), demonstrating the excellent accuracy of our approach during the analysis of complex samples from ischemic stroke patients, using just 90 μL of clinical samples and taking less than 90 min in comparison with the 18 hours required by the urea-PAGE approach. The developed fully integrated colorimetric-electrochemical μPAD is a promising ready to use reagent-free device for the point-of-care testing of TSAT, which can be used to assist physicians in the fast diagnosis and prognosis of ischemic strokes, where the decision-time is crucial for the patient's survival.