Droplet-based Microfluidic Devices Research Articles

Understanding droplet formation in T-shaped channels with magnetic field influence: A computational investigation

This study investigates the production of ferrofluid droplets in a T-junction geometry using the level set method and magnetic force manipulation in the three-dimensional. The analysis reveals key insights into droplet formation processes in four stages: entering, blocking, necking, and detachment. The results show that increasing the Capillary number leads to a significant decrease in volume for non-ferrofluid droplets. Application of a magnetic force enhances the balance of forces during droplet formation, directly impacting droplet volume. Moreover, increasing the magnetic Bond number substantially increases droplet volume, with a more pronounced effect at lower Capillary numbers. Modifying magnetic properties influences droplet volume, with doubling the magnetization results in a significant volume increase. Overall, magnetic forces emerge as a crucial control parameter for droplet volume in ferrofluid systems, offering potential applications in droplet-based technologies and microfluidic devices.

Dynamics of a viscoelastic droplet migrating in a ratchet microchannel under AC electric field

Droplet-based microfluidic devices can be powered or manipulated by applying an external electric field, and the ability to precisely control the flow in such devices is essential for various engineering and biomedical applications. In this numerical study, we investigate the deformation dynamics of a viscoelastic droplet in a ratchet microchannel under the influence of an AC electric field. We employ the leaky-dielectric electrohydrodynamic model for both the immiscible fluid phases coupled with the Oldroyd-B model for the droplet fluid. The effect of geometrical parameters such as the type of ratchet and the wavenumber of the ratchets along with the flow parameters such as the electrocapillary number, Weissenberg number and the capillary number significantly affect the droplet shape dynamics and the polymer chain extension. For the parameters considered in this work, the electric force tends to stretch the droplet in the streamwise direction and enhances the droplet deformation and polymer extension. Several interesting effects arise as a result of the coupling of the periodic hydrodynamic forcing of the ratchet walls and the electric field. Specifically, an exponential rise in the polymer chain extension for higher ratchet wavenumbers is observed, along with the cross-stream migration of the droplet for higher electrocapillary numbers when it reaches the outlet of the ratchet constriction.

Evaluation of Acoustophoretic and Dielectrophoretic Forces for Droplet Injection in Droplet-Based Microfluidic Devices.

Acoustophoretic forces have been successfully implemented into droplet-based microfluidic devices to manipulate droplets. These acoustophoretic forces in droplet microfluidic devices are typically generated as in acoustofluidic devices through transducer actuation of a piezoelectric substrate such as lithium niobate (LiNbO3), which is inherently accompanied by the emergence of electrical fields. Understanding acoustophoretic versus dielectrophoretic forces produced by electrodes and transducers within active microfluidic devices is important for the optimization of device performance during design iterations. In this case study, we design microfluidic devices with a droplet injection module and report an experimental strategy to deduce the respective contribution of the acoustophoretic versus dielectrophoretic forces for the observed droplet injection. Our PDMS-based devices comprise a standard oil-in-water droplet-generating module connected to a T-junction injection module featuring actuating electrodes. We use two different electrode geometries produced within the same PDMS slab as the droplet production/injection channels by filling low-melting-point metal alloy into channels that template the electrode geometries. When these electrodes are constructed on LiNbO3 as the substrate, they have a dual function as a piezoelectric transducer, which we call embedded liquid metal interdigitated transducers (elmIDTs). To decipher the contribution of acoustophoretic versus dielectrophoretic forces, we build the same devices on either piezoelectric LiNbO3 or nonpiezo active glass substrates with different combinations of physical device characteristics (i.e., elmIDT geometry and alignment) and operate in a range of phase spaces (i.e., frequency, voltage, and transducer polarity). We characterize devices using techniques such as laser Doppler vibrometry (LDV) and infrared imaging, along with evaluating droplet injection for our series of device designs, constructions, and operating parameters. Although we find that LiNbO3 device designs generate acoustic fields, we demonstrate that droplet injection occurs only due to dielectrophoretic forces. We deduce that droplet injection is caused by the coupled dielectrophoretic forces arising from the operation of elmIDTs rather than by acoustophoretic forces for this specific device design. We arrive at this conclusion because equivalent droplet injection occurs without the presence of an acoustic field using the same electrode designs on nonpiezo active glass substrate devices. This work establishes a methodology to pinpoint the major contributing force of droplet manipulation in droplet-based acoustomicrofluidics.

Pinning-depinning transition of droplets on inclined substrates with a three-dimensional topographical defect.

Droplets on inclined substrates can depin and slide freely above a critical substrate inclination angle. Pinning can be caused by topographical defects on the substrate, and understanding the influence of defect geometry on the pinning-depinning transition is important for diverse applications such as fog harvesting, droplet-based microfluidic devices, self-cleaning surfaces, and inkjet printing. Here, we develop a lubrication-theory-based model to investigate the motion of droplets on inclined substrates with a single three-dimensional Gaussian-shaped defect that can be in the form of a bump or a dent. A precursor-film/disjoining-pressure approach is used to capture contact-line motion, and a nonlinear evolution equation is derived which describes droplet thickness as a function of the position along the substrate and time. The evolution equation is solved numerically using an alternating direction implicit finite-difference scheme to study how the defect geometry influences the critical inclination angle and the shape of a pinned droplet. It is found that the critical substrate inclination angle increases as the defect becomes taller/deeper or wider along the direction lateral to the droplet-sliding direction. However, the critical inclination angle decreases as the defect becomes wider along the sliding direction. Below the critical inclination angle, the advancing contact line of the droplet at the droplet centerline is pinned to the defect at the point having maximum negative slope. Simple scaling relations that reflect the influence of defect geometry on the droplet retention force arising from surface tension are able to account for many of the trends observed in the numerical simulations.

Numerical simulation of deformable droplets in three-dimensional, complex-shaped microchannels

The physics of drop motion in microchannels is fundamental to provide insights when designing applications of drop-based microfluidics. In this paper, we develop a boundary-integral method to simulate the motion of drops in microchannels of finite depth with flat walls and fixed depth but otherwise arbitrary geometries. To reduce computational time, we use a moving frame that follows the droplet throughout its motion. We provide a full description of the method, including our channel-meshing algorithm, which is a combination of Monte Carlo techniques and Delaunay triangulation, and compare our results to infinite-depth simulations. For regular geometries of uniform cross section, the infinite-depth limit is approached slowly with increasing depth, though we show much faster convergence by scaling with maximum vs average velocities. For non-regular channel geometries, features such as different branch heights can affect drop partitioning, breaking the symmetric behavior usually observed in regular geometries. Moreover, non-regular geometries also present challenges when comparing the results for deep and infinite-depth channels. To probe inertial effects on drop motion, the full Navier–Stokes equations are first solved for the entire channel, and the tabulated solution is then used as a boundary condition at the moving-frame surface for the Stokes flow inside the moving frame. For moderate Reynolds numbers up to Re = 5, inertial effects on the undisturbed flow are small even for more complex geometries, suggesting that inertial contributions in this range are likely small. This work provides an important tool for the design and analysis of three-dimensional droplet-based microfluidic devices.

A three-dimensional level set method for droplet sorting using a non-uniform electric field

In this research, we have developed a computational method for droplet sorting using a non-uniform electric field. The method is based on a three-dimensional level-set method and the leaky-dielectric electrohydrodynamics (EHD) model. Level-set method is used for modeling the interface of the two-phase flow system. The electrostatic phenomenon is dealt with the leaky dielectric-leaky dielectric fluid system. At first, we validated our developed model for a classical flow case: a droplet subjected to a uniform electric field. The results obtained from the present computational method show good agreement with the existing results from the literature. After validation, we implemented the developed code in a practical application of droplet sorting using a non-uniform electric field (known as dielectrophoresis) in a rectangular microchannel with an orthogonal side channel. We mainly focus on the sorting of the droplet without and with the electric field effect as a function of different parameters of the problem. Depending on the intensity of the physical parameters, the droplet can flow into either the downstream main channel or it can sort into the orthogonal side branch. The sorting of a droplet is characterized by the critical branch ratio, qc above which the droplet enters the side branch. The results and conclusions from the present thesis facilitate the understanding of the fundamental principles and mechanisms of electrohydrodynamics (EHD)-based droplet sorting using dielectrophoresis in microfluidic channels. Therefore, present results can have potential usefulness toward the design and development of droplet-based microfluidic devices.

Development of a programmable magnetic agitation device to maintain colloidal suspension of cells during microfluidic syringe pump perfusion.

Droplet-based microfluidic devices have been used to achieve homogeneous cell encapsulation, but cells sediment in a solution, leading to heterogeneous products. In this technical note, we describe automated and programmable agitation device to maintain colloidal suspensions of cells. We demonstrate that the agitation device can be interfaced with a syringe pump for microfluidic applications. Agitation profiles of the device were predictable and corresponded to device settings. The device maintains the concentration of cells in an alginate solution over time without implicating cell viability. This device replaces manual agitation, and hence is suitable for applications that require slow perfusion for a longer period of time in a scalable manner.

Understanding the Link between Inflammasome and Apoptosis through the Response of THP-1 Cells against Drugs Using Droplet-Based Microfluidics.

Droplet-based microfluidic devices are used to investigate monocytic THP-1 cells in response to drug administration. Consistent and reproducible droplets are created, each of which acts as a bioreactor to carry out single cell experiments with minimized contamination and live cell tracking under an inverted fluorescence microscope for more than 2 days. Here, the effects of three different drugs (temsirolimus, rifabutin, and BAY 11-7082) on THP-1 are examined and the results are analyzed in the context of the inflammasome and apoptosis relationship. The ASC adaptor gene tagged with GFP is monitored as the inflammasome reporter. Thus, a systematic way is presented for deciphering cell-to-cell heterogeneity, which is an important issue in cancer treatment. The drug temsirolimus, which has effects of disrupting the mTOR pathway and triggering apoptosis in tumor cells, causes THP-1 cells to express ASC and to be involved in apoptosis. Treatment with rifabutin, which inhibits proliferation and initiates apoptosis in cells, affects ASC expression by first increasing and then decreasing it. CASP-3, which has a role in apoptosis and is directly related to ASC, has an increasing level in inflammasome conditioning. Thus, the cell under the effect of rifabutin might be faced with programmed cell death faster. The drug BAY 11-7082, which is responsible for NFκB inhibition, shows similar results to temsirolimus with more than 60% of cells having high fluorescence intensity (ASC expression). The microfluidic platform presented here offers strong potential for studying newly developed small-molecule inhibitors for personalized/precision medicine.

Autonomous droplet transport on a chemically homogenous superhydrophilic surface

The autonomous and directional transport of microdroplets is critical to the development of self-powered droplet-based microfluidic devices. So far the studies on the self-transport of droplets have employed chemically inhomogeneous surfaces. Remarkably, we observed the self-propulsion of aqueous droplets on a chemically homogeneous superhydrophilic surface. The self-transport phenomenon is attributed to the existence of a precursor layer between droplet and surface that minimizes contact line pinning and droplet is driven by a net force owing to the asymmetry in the precursor layer width across droplet. We provide a theoretical model considering the electrostatic, capillary, and evaporation induced forces to quantitatively predict transport velocity which is in good agreement with experimental observations. The effect of droplet volume, surface roughness, relative humidity, and composition on the droplet velocity is studied. We demonstrated the directional self-transport and coalescence of droplets on a superhydrophilic track in a superhydrophobic background and the self-transport of droplets containing biological cells depicting biological cargos.

Flow regime mapping for a two-phase system of aqueous alginate and water droplets in T-junction geometry

Microfluidic systems are an interesting topic for investigation due to their wide-spreading applications. Nowadays, polymeric solutions are used mainly for the generation of microparticles in biomedical engineering, food, and pharmaceutical industries. Droplet-based microfluidic devices have proposed an extensive interest in many applications such as chemical/biological/nanomaterial preparation to understand deeply the droplet size and formation in microchannels. However, numerous experimental and numerical studies have been done for oil–water combination, polymeric solutions behavior in the presence of oil has not been investigated widely. Therefore, it is important to understand the droplet formation mechanisms in a microfluidic device for both water and polymeric solutions to determine the flow regime mapping in order to control the characteristic of the produced droplets. Also, in many studies, the length of the droplets as a parameter to investigate the droplet size was studied. In this study, droplet generation in the T-shaped microfluidic junction with an enlarged horizontal outlet channel was studied to have opportunity to determine the diameter of spherical droplets. The water and the alginate 1% (w/v) solutions were used separately as a dispersed phase, and the mineral oil was used as the continuous phase in which the solution's flow rates were varied over a wide range. To perform numerical simulations of the droplet formation, a two-phase level set method was used which is a suitable method for the investigation and simulation of immiscible fluids. The flow regime mapping for the two different aqueous solutions was obtained. Furthermore, the influences of flow rates on droplet size, droplet generation frequency was quantified. In this study, flow regime, droplet size, and droplet frequency were studied. In general, flow rates of the oil and aqueous fluids readily control five main flow regimes including backflow, laminar flow, dripping flow, squeezing flow, jetting flow, and fluctuated flow. It was observed that generated droplets with alginate solution as dispersed phase were more in the region of the jetting flow regime while water droplets were more in the region of the dripping flow regime, this can be due to the difference in characteristics of polymeric solution and water. For both aqueous phases, larger droplets were obtained when flow rates of oil were decreased and aqueous phases were increased. Also, the frequency of droplet generation increases and decreases by increasing oil phase flow rate and increasing aqueous phase flow rate, respectively. In the same flow rates of aqueous phase and oil, the sizes of water droplets are larger than the alginate droplets and also water has a higher frequency of droplet generation compared to alginate. Finally, we characterized all the obtained data for flow regimes due to the capillary number (Ca) of the continuous phase. The findings of this study can help for better understanding of the detailed process of droplet generation of water and alginate solution as dispersed phase separately with mineral oil as the continuous phase in a T-junction geometry microfluidic and know the effect of characteristics of solutions as a dispersed flow in flow regimes.

Numerical and experimental investigation of a flow focusing droplet-based microfluidic device

Droplet-based microfluidic devices are widely used for drug delivery and cell transport. In most of these applications, flow characteristics and geometry strongly affect the droplet generation process. In this study, a flow focusing droplet generator was designed using numerical simulation. Among all the simulation methods, the 2D phase field method was used to predict the process in a newly designed microfluidic device before fabrication. To this end, the numerical method was verified according to previous research, including ten different cases, which demonstrated its applicability in this regard. The deviation of simulations from experiments was less than 5%. The device was then simulated over a wide range of flow rate ratios (φ) and fabricated based on these results. Following fabrication, experiments were conducted for different ratios. The experimental results were compared with the simulations qualitatively and quantitatively. The investigation revealed pre-estimation effectiveness, indicating that the deviation of simulations from experiments was at most 11%. A wide range of φ from 0.25 to 1.05 was applied to study the droplet generation characteristics during the tests. Furthermore, two fundamental modes were introduced, and the flow regime shift from squeezing to dripping was studied over a wide range of φ. Given the droplets’ shape, the transition procedure is divided into three stages: pre-transition, transition, and post-transition. This study’s results can be used to investigate the capabilities of a newly designed microdevice before fabrication and choose the best flow regime that simultaneously reduces shear stress on cells and increases droplet generation frequency and monodispersity. Finally, this passive design can transport cells inside droplets up to 280 samples per second.

Numerical study of thermocapillary migration behaviors of droplets on a grooved surface with a three-dimensional color-gradient lattice Boltzmann model

Thermocapillary actuation is used extensively in droplet-based microfluidic devices to manipulate the dynamic behaviors of droplets. In this study, a three-dimensional color-gradient lattice Boltzmann model is used to investigate the migration behaviors of droplets in the Wenzel state on a grooved surface that is subject to a uniform temperature gradient. On the solid surface, the wetting boundary condition is used to improve the accuracy of the simulations and to suppress spurious velocities at the contact line. The model is used to simulate the thermocapillary migration of a three-dimensional deformable droplet and the thermocapillary migration of a two-dimensional droplet on a solid substrate, and its accuracy is verified against theoretical predictions. The migration behavior of droplets on a smooth surface is investigated, and the flow field and corresponding temperature field around the droplets are analyzed. The experimental findings numerically confirm that a surface with micro-grooves parallel to the temperature gradient can accelerate thermocapillary migration to a greater extent than a smooth surface, indicating the influence of the grooves. The influence of the viscosity ratio is investigated, and it is found that the use of high-viscosity fluids is an effective means of obstructing migration. To determine the influence of surface roughness, a systematic and parametric study of groove depth and width is conducted. Finally, the influence of the orientation of the surface topography is investigated, and it is demonstrated that a surface with micro-grooves perpendicular to the temperature gradient can obstruct migration.

Interfacial viscosity-induced suppression of lateral migration of a surfactant laden droplet in a nonisothermal Poiseuille flow

Understanding and modulating the cross-stream motion of a surfactant-coated droplet in pressure driven flow has great implications in many practical applications. A combination of interfacial viscosity and Marangoni stress acting over a surfactant-coated droplet in pressure driven flow offers greater flexibility to modulate the cross-stream motion of it. Despite the intense theoretical and numerical research towards manipulating the surfactant-laden Newtonian droplets in Poiseuille flow, the experimental investigations are seldom explored. Herein, we report our study on understanding the influence of interfacial viscosity on the cross-stream motion of a surfactant-coated Newtonian droplet in both isothermal and non-isothermal Poiseuille flow from a theoretical as well as an experimental perspective. A theoretical model has been developed to understand the effect of interfacial viscosity on the lateral migration of a droplet under the assumptions of no shape deformation and negligible fluid inertia or thermal convection. Theoretical analysis is performed under two limiting conditions: (i) when the transport of surfactants is dominated by surface-diffusion and (ii) when the transportation of surfactants is dominated by surface-convection. Our theoretical analysis shows that both the dilatational as well as the shear surface viscosities suppress the lateral migration velocity of the droplet. Experiments have been performed to validate the theoretically predicted droplet trajectories and to understand the influence of channel confinement on the lateral migration of the droplet. It has been observed from the experiments that the droplet travels faster towards the centerline of the flow in a highly confined domain. The results presented in this study could provide new vistas in designing and analyzing various droplet-based microfluidic, biomedical and bio-microfluidic devices.

Machine learning enables design automation of microfluidic flow-focusing droplet generation

Droplet-based microfluidic devices hold immense potential in becoming inexpensive alternatives to existing screening platforms across life science applications, such as enzyme discovery and early cancer detection. However, the lack of a predictive understanding of droplet generation makes engineering a droplet-based platform an iterative and resource-intensive process. We present a web-based tool, DAFD, that predicts the performance and enables design automation of flow-focusing droplet generators. We capitalize on machine learning algorithms to predict the droplet diameter and rate with a mean absolute error of less than 10 μm and 20 Hz. This tool delivers a user-specified performance within 4.2% and 11.5% of the desired diameter and rate. We demonstrate that DAFD can be extended by the community to support additional fluid combinations, without requiring extensive machine learning knowledge or large-scale data-sets. This tool will reduce the need for microfluidic expertise and design iterations and facilitate adoption of microfluidics in life sciences.

Droplet Based Microfluidic Electrochemical Detection of Uric Acid, Ascorbic Acid and Dopamine

Droplet based microfluidic devices offer numerous advantages, such as lesser sample volume, rapid analysis rate, and lower contamination issues. Moreover, out of several detection methods in microfluidic devices, electrochemical based sensing is superior owing to the well-established attributes such as specificity, lower limit of detection, rapid detection and the process possibility in a microfluidic environment. Although electrochemical sensing has been widely harnessed with continuous flow-based microfluidic devices, opportunities are still lying with droplet based microfluidic devices. Hence, the aforementioned unique features of Droplet based microfluidic devices are still untapped. The fusion of electrochemical detection with droplet based microfluidic devices is one way to realize smart Lab on chip devices. Performing electrochemical detections in specially designed and fabricated droplet-based microfluidic devices, with microchannels including electrodes, enable to conduct biochemical assays in a high throughput manner. In this work, a three-electrode system is printed on a glass substrate with conductive carbon paste using inkjet printing technology. One of the electrodes is modified with silver paste to use as a reference electrode. A microfluidic channel is fabricated using low-cost and clean-room free direct laser writing technology; and soft lithography technique is used for preparing PDMS mould. The mould is then bonded to a glass substrate with microelectrodes with a width of 300 µm and uniform spacing of 300 µm using plasma activation. Monodisperse and equidistant droplets are generated in the microfluidic device using oil as the continuous phase and analyte as the dispersed phase. The efficacy of the microfluidic device for electrochemical detection was measured using Cyclic Voltammetry technique for analytes such as Uric acid, Ascorbic acid and Dopamine. Flow rates of the dispersed phase are varied from 25 µl/min to 100 µl/min while maintaining the constant continuous phase to attain droplets of different sizes. The effect of droplet size carrying the analyte on electrochemical detection was investigated. The influence of varied scan rates (20 mV/sec to 100 mV/sec) on the detection of analytes was also studied. The selection of an appropriate scan rate for different flow rates was investigated and was set accordingly to the droplet generation frequency. In addition, the change in cyclic voltammetry with the response to the variation of concentration of the analyte was also explored. The steps of the proposed process are illustrated in Figure 1. Figure 1

Extractive crystallization of cabotegravir in droplet-based microfluidic devices

Monodisperse emulsions of solvent saturated with the active pharmaceutical ingredient (API) cabotegravir were generated by microfluidic devices. In contrast to model oil-water emulsions that provide idealized conditions for obtaining highly monodisperse emulsions, APIs impart strict limitations on solvent choice. To provide a suitable environment in which extractive crystallization could occur, and to enhance reproducibility, co-solvents were introduced. Subsequently, the effect of each solvent component on morphology and size was observed. Through the manipulation of solvent composition, particles of both plate-like and spherical multi-crystal agglomerates were obtained, providing the ability to tune the operating conditions to provide particles with desirable characteristics such as size, shape and flowability. Scale-up of the manufacturing process was addressed through the application of existing microfluidic parallelization techniques, resulting in a 100-fold increase in throughput over a single-channel device. Subsequently, the obtained pure, and excipient-bound, API spherical agglomerates, were subjected to batch isolation and washing.

An Interface-Particle Interaction Approach for Evaluation of the Co-Encapsulation Efficiency of Cells in a Flow-Focusing Droplet Generator.

Droplet-based microfluidics offers significant advantages, such as high throughput and scalability, making platforms based on this technology ideal candidates for point-of-care (POC) testing and clinical diagnosis. However, the efficiency of co-encapsulation in droplets is suboptimal, limiting the applicability of such platforms for the biosensing applications. The homogeneity of the bioanalytes in the droplets is an unsolved problem. While there is extensive literature on the experimental setups and active methods used to increase the efficiency of such platforms, passive techniques have received less attention, and their fundamentals have not been fully explored. Here, we develop a novel passive technique for investigating cell encapsulation using the finite element method (FEM). The level set method was used to track the interfaces of forming droplets. The effects of walls and the droplet interfaces on relatively large cells were calculated to track them more accurately during encapsulation. The static surface tension force was used to account for the effects of the interfaces on cells. The results revealed that the pairing efficiency is highly sensitive to the standard deviation (SD) of the distance between the cells in the entrance channel. The pairing efficiency prediction error of our model differed by less than 5% from previous experiments. The proposed model can be used to evaluate the performance of droplet-based microfluidic devices to ensure higher precision for co-encapsulation of cells.

Decontamination of ambient RNA in single-cell RNA-seq with DecontX

Droplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq). However, ambient RNA present in the cell suspension can be aberrantly counted along with a cell’s native mRNA and result in cross-contamination of transcripts between different cell populations. DecontX is a novel Bayesian method to estimate and remove contamination in individual cells. DecontX accurately predicts contamination levels in a mouse-human mixture dataset and removes aberrant expression of marker genes in PBMC datasets. We also compare the contamination levels between four different scRNA-seq protocols. Overall, DecontX can be incorporated into scRNA-seq workflows to improve downstream analyses.

A centrifugal microfluidic emulsifier integrated with oil storage structures for robust digital LAMP.

Centrifugal droplet-based microfluidic devices have been applied to biomedical analysis and diagnostics recently. However, in centrifugal droplet-based microfluidic devices, droplets are tightly packed (i.e., the oil film between neighbouring droplets is thin). Therefore, droplet coalescence usually occurs especially during thermal incubation process. To preserve individual droplets in the devices, we report a new design for monodisperse droplet generation and storage that exploits a centrifugal configuration for droplet emulsification and oil-storage structures (OSSs) for regulation of the thickness of oil film between neighbouring droplets. The centrifugal emulsifier was well designed to ensure uniform droplet generation. Meanwhile, the OSSs could store oil during centrifugal emulsification while release oil before thermal incubation, which "loosen" tightly packed droplets to prevent droplets from coalescing. In this paper, the working process of OSS was analysed, and its shape and size were optimized. Then, the optimized OSSs were integrated into a centrifugal emulsifier for droplet digital loop mediated isothermal amplification (ddLAMP) by which detection of JAK2 V617F mutation within myeloproliferative neoplasms with a dynamic range of 101 to 104 copies per μL was achieved. We anticipate that the simplicity and robustness of our system make it attractive as an inexpensive and easy-to-operate device for DNA amplification, particularly applicable in point-of-care settings.

Automatic Droplet Sequence Generation for Microfluidic Networks With Passive Droplet Routing

Droplet-based microfluidic devices are a well-established and highly potential Labs-on-Chip technology as droplets are especially suited to encapsulate biological samples like cells, proteins, or DNA. These droplets are injected in a continuous phase and flow through closed microchannels to modules executing operations on the droplets-eventually realizing a (bio-)chemical experiment. Moreover, this technology even allows for the realization of multiple experiments on a single device by letting droplets take different paths through the microfluidic network. This requires, however, a mechanism to route the droplets along these paths. To this end, the concept of passive droplet routing has been suggested which entirely avoids complex valves or switches and, instead, realizes the routing by exploiting the hydrodynamic effect that a droplet will always flow along the path with the highest volumetric flow rate. Since droplets themselves affect the volumetric flow rate, a dedicated sequence of droplets can define what path is taken and, hence, what experiment is executed. However, determining such a droplet sequence is a nontrivial task, as it is nonobvious how much droplets are needed, when to inject them, and how they are interacting. In this paper, we are addressing this issue by providing, for the first time, an automatic method for the generation of droplet sequences realizing the desired experiments on a given network. Evaluations confirm the practicability of the proposed solution. Moreover, the suitability of the obtained droplet sequences is additionally validated through simulations on the 1D analysis model.