Microfluidic droplet control by photothermal interfacial flow

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Droplet-based microfluidics is an emerging field that can perform a variety of discrete operation of tiny amount of reagent or individual cell. Noncontact manipulation of droplets in a microfluidic platform can be achieved by using the Marangoni convection due to a local temperature gradient given by the irradiation of heating light. This method provides noncontact, selective and flexible manipulation for droplets flowing in microfluidic network. Although the potential of this selective operation method of droplets was confirmed, the driving force exerted on droplets has not been quantitatively obtained. In this study, we have developed a measurement system of the temperature field around droplets during the manipulation by light irradiation and evaluated the manipulation force. In O/W emulsion system with oleic acid and buffer solution, oleic acid for droplet and buffer solution for continuous phase, the temperature distribution around the droplets was measured by laser-induced fluorescence. From the balance of drag force and photo-induced Marangoni force, the driving force was determined. From the results, we confirmed the applicability of the noncontact droplet manipulation using the photothermal Marangoni effect

Opposed flow focusing: evidence of a second order jetting transition

We propose a novel microfluidic "opposed-flow" geometry in which the continuous fluid phase is fed into a junction in a direction opposite the dispersed phase. This pulls out the dispersed phase into a micron-sized jet, which decays into micron-sized droplets. As the driving pressure is tuned to a critical value, the jet radius vanishes as a power law down to sizes below 1 $\mu$m. By contrast, the conventional "coflowing" junction leads to a first order jetting transition, in which the jet disappears at a finite radius of several $\mu$m, to give way to a "dripping" state, resulting in much larger droplets. We demonstrate the effectiveness of our method by producing the first microfluidic silicone oil emulsions with a sub micron particle radius, and utilize these droplets to produce colloidal clusters

Emulsion characterization via microfluidic devices : A review on interfacial tension and stability to coalescence

Emulsions have gained significant importance in many industries including foods, pharmaceuticals, cosmetics, health care formulations, paintings, polymer blends and oils. During emulsion generation, collisions can occur between newly-generated droplets, which may lead to coalescence between the droplets. The extent of coalescence is driven by properties of dispersed and continuous phases, e.g. density, viscosity, ion strength and pH, and system conditions, e.g. temperature, pressure or any external applied forces. In addition, the diffusion and adsorption behaviors of emulsifiers which govern the dynamic interfacial tension of the forming droplets, the surface potential, and the duration and frequency of the droplet collisions, contribute to the overall rate of coalescence. An understanding of these complex behaviors, particularly those of interfacial tension and droplet coalescence during emulsion generation, is critical for the design of an emulsion with desirable properties and the optimization of the processing conditions. However, in many cases, the time scales over which these phenomena occur are extremely short, typically a fraction of a second, which makes their accurate determination by conventional analytical methods extremely challenging. In the past few years, with advances in microfluidic technology, many attempts have demonstrated that microfluidic systems, characterized by micrometer-size channels, can be successfully employed to precisely characterize these properties of emulsions. In this review, current applications of microfluidic devices to determine the equilibrium and dynamic interfacial tension during the droplet formation, and to investigate the coalescence stability of dispersed droplets applicable to the processing and storage of emulsions, are discussed.Peer reviewe

Materials science and the sensor revolution

For the past decade, we have been investigating strategies to develop ways to provide chemical sensing platforms capable of long-term deployment in remote locations1-3. This key objective has been driven by the emergence of ubiquitous digital communications and the associated potential for widely deployed wireless sensor networks (WSNs). Understandably, in these early days of WSNs, deployments have been based on very reliable sensors, such as thermistors, accelerometers, flow meters, photodetectors, and digital cameras. Biosensors and chemical sensors (bio/chemo-sensors) are largely missing from this rapidly developing field, despite the obvious value offered by an ability to measure molecular targets at multiple locations in real-time. Interestingly, while this paper is focused on the issues with respect to wide area sensing of the environment, the core challenge is essentially the same for long-term implantable bio/chemo-sensors4, i.e.; how to maintain the integrity of the analytical method at a remote, inaccessible location

Measuring Electric Charge and Molecular Coverage on Electrode Surface from Transient Induced Molecular Electronic Signal (TIMES).

Charge density and molecular coverage on the surface of electrode play major roles in the science and technology of surface chemistry and biochemical sensing. However, there has been no easy and direct method to characterize these quantities. By extending the method of Transient Induced Molecular Electronic Signal (TIMES) which we have used to measure molecular interactions, we are able to quantify the amount of charge in the double layers at the solution/electrode interface for different buffer strengths, buffer types, and pH values. Most uniquely, such capabilities can be applied to study surface coverage of immobilized molecules. As an example, we have measured the surface coverage for thiol-modified single-strand deoxyribonucleic acid (ssDNA) as anchored probe and 6-Mercapto-1-hexanol (MCH) as blocking agent on the platinum surface. Through these experiments, we demonstrate that TIMES offers a simple and accurate method to quantify surface charge and coverage of molecules on a metal surface, as an enabling tool for studies of surface properties and surface functionalization for biochemical sensing and reactions

Droplet Microfluidics

Droplet microfluidics has dramatically developed in the past decade and has been established as a microfluidic technology that can translate into commercial products. Its rapid development and adoption have relied not only on an efficient stabilizing system (oil and surfactant), but also on a library of modules that can manipulate droplets at a high-throughput. Droplet microfluidics is a vibrant field that keeps evolving, with advances that span technology development and applications. Recent examples include innovative methods to generate droplets, to perform single-cell encapsulation, magnetic extraction, or sorting at an even higher throughput. The trend consists of improving parameters such as robustness, throughput, or ease of use. These developments rely on a firm understanding of the physics and chemistry involved in hydrodynamic flow at a small scale. Finally, droplet microfluidics has played a pivotal role in biological applications, such as single-cell genomics or high-throughput microbial screening, and chemical applications. This Special Issue will showcase all aspects of the exciting field of droplet microfluidics, including, but not limited to, technology development, applications, and open-source systems

On-chip titration of an anticoagulant argatroban and determination of the clotting time within whole blood or plasma using a plug-based microfluidic system

This paper describes extending plug-based microfluidics to handling complex biological fluids such as blood, solving the problem of injecting additional reagents into plugs, and applying this system to measuring of clotting time in small volumes of whole blood and plasma. Plugs are droplets transported through microchannels by fluorocarbon fluids. A plug-based microfluidic system was developed to titrate an anticoagulant (argatroban) into blood samples and to measure the clotting time using the activated partial thromboplastin time (APTT) test. To carry out these experiments, the following techniques were developed for a plug-based system: (i) using Teflon AF coating on the microchannel wall to enable formation of plugs containing blood and transport of the solid fibrin clots within plugs, (ii) using a hydrophilic glass capillary to enable reliable merging of a reagent from an aqueous stream into plugs, (iii) using bright-field microscopy to detect the formation of a fibrin clot within plugs and using fluorescent microscopy to detect the production of thrombin using a fluorogenic substrate, and (iv) titration of argatroban (0-1.5 mu g/mL) into plugs and measurement of the resulting APTTs at room temperature (23 degrees C) and physiological temperature (37 degrees C). APTT measurements were conducted with normal pooled plasma (platelet-poor plasma) and with donor's blood samples ( both whole blood and platelet-rich plasma). APTT values and APTT ratios measured by the plug-based microfluidic device were compared to the results from a clinical laboratory at 37 degrees C. APTT obtained from the on-chip assay were about double those from the clinical laboratory but the APTT ratios from these two methods agreed well with each other

Microbubble generation and application in healthcare

The aim of this work is to investigate the application of microbubbles for targeted drug delivery and anticancer drug sensitivity investigations. Microbubbles were prepared using a microfluidic device to act as a carrier for drug delivery or building scaffolds for three-dimensional (3D) cell culture. The lifetime and bursting process of alginate microbubbles and the role of microbubbles for delivering drugs through oral administration were investigated. It was shown that the collection of microbubbles in calcium chloride solution or glycerol, along with the incorporation of gold nanoparticles into the shell of the microbubbles increased the lifetime of the microbubbles. To mimic the physiological condition, the stability of the generated microbubbles was examined under acidic pH and body temperature. Simulation of the oesophageal condition using porcine tissue showed the enhanced absorption of the drug using alginate microbubbles. This result supports the application of microbubbles for oral drug delivery to oesophageal mucosa. The other application of microbubbles in regard to anticancer drugs in this work was to measure the sensitivity of myeloid leukaemia cells to various types of antileukaemia agents in a 3D culture. A porous calcium alginate foam-based scaffold was developed using microfluidic technology. The foam-based 3D culture supported the growth and proliferation of both normal haematopoietic and leukaemia cells. The myeloid differentiation in both leukaemia and normal haematopoietic cells was enhanced in the foam-based 3D culture, compared to the 2D culture. The sensitivity of the leukaemia cell line models; K562 and HL60 and primary acute myeloid leukaemia (AML) cells to antileukemia agents; Imatinib and doxorubicin were reduced in the 3D compared to the 2D culture, which is similar to as was reported in vitro investigations. The result of this study proposes the application of calcium alginate foams as scaffold in 3D culture for antileukaemia sensitivity screens in drug discovery investigations.The other application of microbubbles in regard to anticancer drugs in this work was to measure the sensitivity of myeloid leukaemia cells to various types of antileukaemia agents in a 3D culture. A porous calcium alginate foam-based scaffold was developed using microfluidic technology. The foam-based 3D culture supported the growth and proliferation of both normal haematopoietic and leukaemia cells. The myeloid differentiation in both leukaemia and normal haematopoietic cells was enhanced in the foam-based 3D culture, compared to the 2D culture. The sensitivity of the leukaemia cell line models; K562 and HL60 and primary acute myeloid leukaemia (AML) cells to antileukemia agents; Imatinib and doxorubicin were reduced in the 3D compared to the 2D culture, which is similar to as was reported in vitro investigations. The result of this study proposes the application of calcium alginate foams as scaffold in 3D culture for antileukaemia sensitivity screens in drug discovery investigations

A microfluidic system for localised growth of biofilms and studies of realated biochemical kinetics

Nous avons développé une biopuce de microfluidique qui est capable de surveiller continuellement la population de cellules dans les biofilms en conditions d'écoulement laminaire bien contrôlées. Ce dispositif microfluidique est capable de modeler la formation des biofilms linéaires en utilisant une approche de flux basé sur un modèle. Les considérations de conception et méthodologie de fabrication d'un micro-bioréacteur à deux niveaux, inclus le flux basé sur un modèle (FT-μBR) qui génère un flux de croissance du biofilm entouré par les 3 côtés par un flux de confinement et inhibiteur de croissance. Grâce à une combinaison d'expériences et de simulations, nous avons évalué et exploité exhaustivement les paramètres de contrôle pour manipuler les dimensions du modèle de flux de croissance du biofilm. Ce dispositif est ensuite utilisé pour développer des modèles linéaires du biofilm avec des dimensions contrôlables. Une étude de validation de principe utilisant le dispositif démontre son utilité dans la réalisation des mesures de taux de croissance du biofilms dans différents environnements de force de cisaillement. Cela ouvre la voie à des études quantitatives sur les effets de l'environnement des cisaillements locaux sur les propriétés des biofilms et pour la synthèse d'une nouvelle génération de biomatériaux fonctionnels ayant des propriétés contrôlables.We have developed a microfluidic biochip that is capable of continuously monitoring cell population in biofilms under well-controlled laminar flow conditions. This microfluidic device capable of patterning linear biofilm formations using a flow-templating approach. The design considerations and fabrication methodology of a two level flow-templating micro-bioreactor (FT-μBR) generates a biofilm growth stream surrounded on 3 sides by a growth inhibiting confinement stream. Through a combination of experiments and simulations we comprehensively evaluate and exploit control parameters to manipulate the biofilm growth template stream dimensions. The FT-μBR is then used to grow biofilm patterns with controllable dimensions. A proof-of-principle study using the device demonstrates its utility in conducting biofilm growth rate measurements under different shear stress environments. This opens the way for quantitative studies into the effects of the local shear environment on biofilm properties and for the synthesis of a new generation of functional biomaterials with controllable properties