Commercial Microfluidic System Research Articles

Machine learning for predicting microfluidic droplet generation properties

Computational Fluid Dynamics (CFD) simulators are an integral tool for designing commercial microfluidic systems — allowing engineers to estimate key performance metrics prior to physical prototyping. However, CFD simulations can take from hours to weeks, depending on the simulation fidelity. This introduces a significant delay in the design iteration loop. In this work, we employ machine learning methodologies to provide estimates of performance metrics directly from microfluidic geometries in inkjet printheads — providing approximate performance metrics in seconds. Specifically, we develop a Convolutional Neural Network (CNN) based approach that operates directly on voxelized slices of printhead geometry to predict characteristics of droplet generation. This approach does not encode significant biases for the task or physics knowledge and relies on a training set of 20,000 prior simulation results to learn. Despite this, our experiments on this large dataset demonstrate that the learned model can closely approximate the CFD results at a fraction of the time cost for some performance metrics — opening the doors to real-time metric estimation as part of the microfluidic system design process. Further, we examine the learned latent representation and find it encodes a reasonable notion of geometric similarity between printhead architectures. This can allow engineers to search for existing designs with similar characteristics and help reduce duplicated effort.

The roadmap to micro: Generation of micron-sized polymeric particles using a commercial microfluidic system.

Microfluidic-assisted particle fabrication provides a route to circumvent the disadvantages associated with traditional methods of polymeric particle generation, such as low drug loading efficiency, challenges in controlling encapsulated drug release rates, batch-to-batch variability in particle physical properties and formulation instability. However, this approach primarily produces particles with nanometer size dimensions, which limits drug delivery modalities. Herein, we systematically studied parameters for the generation of micron-sized poly(lactic-co-glycolic) acid (PLGA) particles using a microfluidic system, the NanoAssemblr benchtop. Initially, we used two organic solvents that have been reported suitable for the fabrication of PLGA nanoparticles - acetone and acetonitrile. Subsequently, we methodically manipulated polymer concentration, organic: aqueous flow rate ratios, total flow rate, organic phase composition, and surfactant concentration to develop a route for the fabrication of micron-sized PLGA particles. Further, we incorporated hydroxychloroquine (HCQ), a clinically approved drug for malaria and lymphoma, and measured how its incorporation impacted particle physicochemical properties. Briefly, altering the organic phase composition by including ethyl acetate (less polar solvent), resulted in micron-scale particles, as well as increased polydispersity indexes (PDIs). Adjusting the surfactant concentration of poly vinyl alcohol (PVA) after the addition of these solvent mixtures rendered large particles with lower PDI variability. Moreover, encapsulation of HCQ influenced particle hydrodynamic diameter and PDI in a PVA concentration dependent manner. Finally, we demonstrated that unloaded and HCQ-loaded microparticles did not affect the viability of RAW 264.7 macrophages. This study provides an itinerary for fabricating biocompatible, drug-loaded, micron-sized polymeric particles, particularly when the drug of interest is not readily soluble in conventional organic solvents.

Optical Projection Tomography Using a Commercial Microfluidic System.

Optical projection tomography (OPT) is the direct optical equivalent of X-ray computed tomography (CT). To obtain a larger depth of field, traditional OPT usually decreases the numerical aperture (NA) of the objective lens to decrease the resolution of the image. So, there is a trade-off between sample size and resolution. Commercial microfluidic systems can observe a sample in flow mode. In this paper, an OPT instrument is constructed to observe samples. The OPT instrument is combined with commercial microfluidic systems to obtain a three-dimensional and time (3D + T)/four-dimensional (4D) video of the sample. “Focal plane scanning” is also used to increase the images’ depth of field. A series of two-dimensional (2D) images in different focal planes was observed and compared with images simulated using our program. Our work dynamically monitors 3D OPT images. Commercial microfluidic systems simulate blood flow, which has potential application in blood monitoring and intelligent drug delivery platforms. We design an OPT adaptor to perform OPT on a commercial wide-field inverted microscope (Olympusix81). Images in different focal planes are observed and analyzed. Using a commercial microfluidic system, a video is also acquired to record motion pictures of samples at different flow rates. To our knowledge, this is the first time an OPT setup has been combined with a microfluidic system.

Preparation of Nanostructured Lipid Drug Delivery Particles Using Microfluidic Mixing.

Cubosomes are highly ordered self-assembled lipid particles analogous to liposomes, but with internal liquid crystalline structure. They are receiving interest as stimuli responsive delivery particles, but their preparation typically requires high energy approaches such as sonication which is not favourable in many applications. Here we investigated the impact of microfluidic preparation on particle size distribution and internal structure of cubosomes prepared from two different lipid systems, phytantriol and glyceryl monooleate (GMO). The impact of relative flow rates of the aqueous and organic streams, the total flow rate and temperature were investigated in a commercial microfluidic system. The particle size distribution and structure were measured using dynamic light scattering and small angle X-ray scattering respectively. Phytantriol based particles were robust to different processing conditions, while cubosomes formed using GMO were more sensitive to composition both locally and globally, which reflects their preparation using other techniques. Thus, in summary microfluidics represents a reproducible and versatile method to prepare complex lipid particle dispersions such as cubosomes.

Hardware and software modifications on the Advion NanoTek microfluidic platform to extend flexibility for radiochemical synthesis

Microfluidic systems are currently receiving a lot of attention in the PET radiochemistry field, due to their demonstrated ability to obtain higher incorporation yields with reduced total processing time and using a decreased amount of precursors. The Advion NanoTek LF was the first commercial microfluidic system available for radiochemistry that allows basic parameter optimization to be performed. In this paper we report hardware and software modifications that would allow better performing procedures, higher product throughput and flexibility to utilize the system. In particular, HPLC purification and SPE formulation have been fully integrated.

Advances in microfluidic materials, functions, integration, and applications.

Advances in microfluidic materials, functions, integration, and applications.

18F]Radiochemistry using the NanoTek Microfluidic Synthesis System

The use of continuous-flowmicrofluidics in radiochemistry has only emerged in recent years. Microfluidic devices feature channels with internal diameters of 10–300 mm, which process fluids with high speed and precision, resulting in improved mixing efficiency. Other advantages ofmicrofluidic technology include shorter reaction times, greater radiochemical yield (RCY), and reduced consumption of reagents. Recently, the first account of a positron emission tomography (PET) radiotracer for human use produced on a batch-mode microfluidics system was reported. Currently, the most employed commercial microfluidic system in radiochemistry is the NanoTek Microfluidic Synthesis System manufactured by Advion (Fig. 1) and its components and method of operation have been described in detail previously. Although the system has been applied to radiochemical syntheses using radioisotopes such as carbon-11, nitrogen-13, and technetium-99m, the overwhelming majority of research using the NanoTek system has been directed towards fluorine-18 (F, t1/21⁄4 109.7min) radiochemistry. Some recent, noteworthy examples are highlighted below and their results compared with conventional radiochemical methods.

Phonons in a one-dimensional microfluidic crystal

The development of a general theoretical framework for describing the behaviour of a crystal driven far from equilibrium has proved difficult1. Microfluidic crystals, formed by the introduction of droplets of immiscible fluid into a liquid-filled channel, provide a convenient means to explore and develop models to describe non-equilibrium dynamics2, 3, 4, 5, 6, 7, 8, 9, 10, 11. Owing to the fact that these systems operate at low Reynolds number (Re), in which viscous dissipation of energy dominates inertial effects, vibrations are expected to be over-damped and contribute little to their dynamics12, 13, 14. Against such expectations, we report the emergence of collective normal vibrational modes (equivalent to acoustic 'phonons') in a one-dimensional microfluidic crystal of water-in-oil droplets at Reapprox10-4. These phonons propagate at an ultra-low sound velocity of approx100 mum s-1 and frequencies of a few hertz, exhibit unusual dispersion relations markedly different to those of harmonic crystals, and give rise to a variety of crystal instabilities that could have implications for the design of commercial microfluidic systems. First-principles theory shows that these phonons are an outcome of the symmetry-breaking flow field that induces long-range inter-droplet interactions, similar in nature to those observed in many other systems including dusty plasma crystals15, 16, vortices in superconductors17, 18, active membranes19 and nucleoprotein filaments20.