Session T34: Micro/Nano scale Flows: Devices and Applications

Systematic framework for a real-time algorithm and machine interfaces for microfluidic cross-slot particle trapping at high strain rates

The stagnation point flow formed within a microfluidic cross-slot device is a potential tool for single-cell experiments to understand a cell's mechanoresponse. The orthogonal orientation of the channel inlets and outlets generates a pure straining flow, in such a way that the centre of the cross-slot junction is the stagnation point where a cell can be trapped and then exposed to different flow strain rates. While numerous studies have been conducted to trap different biological specimens, based on a real-time image-based feedback control technique, a detailed understanding of how the real-time algorithm and machine interfaces affect the trapping at high strain rates is still not clear. Here, we present a systematic framework for the hydrodynamic trapping of a particle in cross-slot channels with different algorithm models in different machines and operating systems. Our results demonstrate that the stability of a trapped particle at high strain rates is significantly impacted by the chosen machine interfaces which contribute to different time delays of the real-time algorithm. The different time delays correlate with the stability of the trapped particle at varying strain rates. Additionally, it was found that achieving a higher strain rate for a trapped particle does not only depend on the reduced time delay concerning the algorithm model and machine interface but also the particle resolution (px/μm). Finally, for the proof-of-concept studies, we extended our experiments in trapping a red blood cell at higher strain rates to reveal the deformation dynamics of an individual cell. Therefore, we anticipate our measurements would provide a reference framework for trapping different blood cells at high strain rates for detailed characterization between healthy and diseased cells.   

Collagen Tube-Based Model to Study Small Airway Collapse-Reopening Dynamics

The human respiratory system consists of a hierarchical network of extracellular matrix based tubular structures, lined by an epithelium that is exposed to complex biomechanical stimuli. Airway collapse-reopening dynamics has previously been studied numerically and in experiments performed in synthetic polymer tubes. Microfluidic airway-on-a-chip models have replicated the spatial arrangement of different cells and circumferential stretch. Their reliance on rigid synthetic membranes or walls however fails to mimic the composition, softness and resulting compliance of human airways. Here, we present a soft 3D collagen-based, tubular airway model with a lumen lined by an epithelial layer. The collapsible, stretchable, and perfusable nature of this structure recapitulates physiological airway dynamics, including wall shear stress, cyclic stretch, overdistension, as well as compliant repetitive collapse and reopening phenomena.

Relationships between the transmural pressure and the tube cross section favorably compare with previous studies performed in synthetic tubes. We further explore conditions relevant to ventilation induced lung injury and captured both the overdistension as well as the collapse and reopening scenarios. Our findings suggest the former to not significantly affect cell viability while the latter lead to acute cell death. We observed that increasing expiratory airflow resistance resulted in a slower collapse velocity and reduced severity of cell injury. The integrity of the epithelial barrier was compromised during repetitive collapse and reopening cycles but remained intact during overdistension. Our extracellular matrix based small airway model provides a valuable and adaptable platform for studying lung physiology, particularly related to conditions relevant in ventilation-induced lung injury. The ability to replicate the complex biomechanical microenvironment of the respiratory system enhances our understanding of small airway epithelial function and disease progression.

 

The presented approach enhances our understanding of lung physiology, especially for ventilation-induced lung injury, while holding promise for broad application in organ-on-a-chip models for different tubular tissues.   

Experimental study of flow physics of platelets and its application on microfluidics platform

Platelets are the key element in the formation of blood clots to stop bleeding at the site of cut or injury. They are non-deformable, discoid shape cell fragments of 1 µm thickness and 2-4 µm in diameter. The morphological properties and flow physics of platelets in the presence of other blood cells play a crucial role for their quick response in the micro vessels. Here, we propose development of microfluidics platform for the experimental study of flow physics of platelets and investigation of effect of various parameters such as concentration of other blood cells and flow rates on it. Later, we utilized our experimental observations for the isolation of platelet derived products e.g., platelet-rich plasma (PRP) and platelet-poor plasma (PPP) from blood samples. These platelets derived products have great clinical relevance and are widely used in disease diagnostics, dermatology, and transfusion purposes. Therefore, isolation of platelet derived products has great value in medical settings. The proposed microfluidics platform separated PRP with ~15-fold enrichment of platelets above normal physiological level and PPP with <1000 platelets/µl and ~95% purity by altering the flow physics of platelets in the microchannel. Afterwards, an extensive biological evaluation of the platelet derived products shows no adverse effect on the quality post isolation from microfluidics platform.    

Droplet Sorting Computer

We develop a simple combined design framework to design a microfluidic droplet sorting computer. The framework uses suitable design parameters and Multi-Agent Reinforcement Learning (MARL) to optimize the microfluidic device. The sorting computer, which constitutes an optimized network topology and minimized inter-droplet spacing, routes all the drops toward one of the outlets through simple hydrodynamic interactions. The design has sufficient robustness and stability for various operating parameters, such as inlet spacing and droplet properties. Its optimized hydrodynamic interactions between the drops facilitate the device's scalability to a large number of drops. We envision that the framework and the device design would yield faster and more efficient design of lab-on-chip devices and facilitate microfluidic adoption in commercial processes.   

Separation of live and dead yeast cells using AC insulator-based dielectrophoresis

Insulator-based dielectrophoresis (iDEP) is an emerging technique for particle and cell handling in microfluidic devices. It utilizes the electric field gradients induced by insulating structures to generate negative or positive DEP. We report in this work a separation of live and dead yeast cells in a ratchet microchannel using AC iDEP. By tuning the AC field frequency, we achieve the positive dielectrophoretic motion of live cells towards the tips of the ratchets, where the electric field is locally the highest. In contrast, dead cells undergo a negative dielectrophoretic motion towards the bases of the ratchets, where the electrical field is locally the lowest. We also examine how the variation of AC field amplitude affects the frequency range for this viability-based cell separation. Moreover, we investigate if a DC bias can be added to the electric field for achieving a continuous-flow separation.   

A constant flow rate pulse-driven microfluidic patch-pump for transdermal drug delivery

Syringes and tethered infusion pumps with needles and cannulae have been the standard method for delivering liquid pharmaceuticals across the skin barrier for decades. But these delivery methods have limitations including painful cannula insertion and interference with daily activity, which can lead to non-adherence to prescribed liquid infusion regimens. To address these limitations, we are developing pulse-driven microfluidic patch-pumps inspired by principles of insect respiration that are extremely low-profile compared to standard wearable infusion pumps because they do not require a motor or batteries. The devices can be integrated with microneedle arrays to mitigate needle insertion pain. Previously, we developed patch-pump devices whose flow rate increased or decreased with the actuating heart rate, the latter of which is ideal for insulin delivery. We have recently developed devices whose flow rate does vary with heart rate. By testing the devices with a pressurized air-driven pulse simulator, we identified devices that generate constant flow rates ranging from 0.2 mL/hr, suitable for the delivery of insulin, to 10 mL/hr, suitable for the delivery of chemotherapies and analgesics.   

Electrokinetic micro- and nanoparticle trapping using electrospun conductive nanofiber mats

Dielectrophoresis (DEP) is a microfluidic technique that can collect and trap micro- and nanoparticles by subjecting them to nonuniform electric fields.  The DEP force is proportional to the gradient of the electric field squared (▽E²), so DEP is dependent upon field nonuniformity.  DEP particle trapping suffers from low throughput because field nonuniformities are typically focused at sharp features such as electrode edges.  Conductive nanofiber mats can distribute high DEP forces across a mesh of sharp features.  Our nanofiber mats are created using electrospinning.  Carbon nanotubes are added to a solution of polyacrylonitrile dissolved in N, N-dimethyl formamide; this solution is electrospun and then pyrolyzed.  The conductive nanofibers have diameters of 267 ± 94 nm and conductivity between 2 – 5 S/cm.  Proof-of-concept experiments with the mats demonstrated voltage and frequency dependence of DEP particle trapping, and we successfully trapped particles as small as 20 nm in diameter.  Our recent experiments have incorporated the mats into microfluidic wells to investigate DEP particle trapping across larger mat surface areas.  Analysis of the mats with trapped particles provides insight for comparison of trapping at different particle sizes, applied voltages, and field frequencies.  We suspect electrohydrodynamic flows significantly affect particle trapping in these experiments.   

Design of Compact Micro-Labyrinths for Low-Cost Drip Irrigation

There is an urgent need for sustainable agricultural intensification. Drip irrigation can save up to 50% more water than traditional irrigation technologies by supplying water using a network of pressurized tubing with flow metering devices called emitters bonded to them. Emitters operate using a turbulent labyrinth passage with staggered teeth-like structures (L ~ 0.01-0.1 mm) that promote energy dissipation. Despite its sophistication and water-saving ability, the adoption and retention of drip irrigation are limited by the high material cost of drip emitters. Designing compact, affordable emitter labyrinths (<1 inch long compared to typical 2 inches) is challenging due to the operating physics of emitters and their vast design space. We use manufacturing constraints and geometric relationships to identify two key parameters in the labyrinth – tooth tip gap and depth - that could be tuned to create high-resistance, compact labyrinths. Subsequent sensitivity analysis sheds light on 3 distinct fluid dynamical operating regimes in the labyrinth which yield design guidelines for the creation of low-cost emitters that can be up to 40% more compact than comparable commercial products. The sensitivity analysis could also be used to guide the hydraulic design of similar microfluidic devices for applications such as microreactors, particle separators, mixing-enhancing devices, etc.