Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

https://iopscience.iop.org/article/10.1088/0034-4885/75/1/016601/pdf

Droplet based microfluidics

Advanced materials and processing for drug delivery: The past and the future

Precise and effective control of droplet generation is critical for applications of droplet microfluidics ranging from materials synthesis to lab-on-a-chip systems. Methods for droplet generation can be either passive or active, where the former generates droplets without external actuation, and the latter makes use of additional energy input in promoting interfacial instabilities for droplet generation. A unified physical understanding of both passive and active droplet generation is beneficial for effectively developing new techniques meeting various demands arising from applications. Our review of passive approaches focuses on the characteristics and mechanisms of breakup modes of droplet generation occurring in microfluidic cross-flow, co-flow, flow-focusing, and step emulsification configurations. The review of active approaches covers the state-of-the-art techniques employing either external forces from electrical, magnetic and centrifugal fields or methods of modifying intrinsic properties of flows or fluids such as velocity, viscosity, interfacial tension, channel wettability, and fluid density, with a focus on their implementations and actuation mechanisms. Also included in this review is the contrast among different approaches of either passive or active nature.

Passive and active droplet generation with microfluidics: a review

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)62639-2.pdf

Tuberculosis prevalence in China, 1990–2010; a longitudinal analysis of national survey data

Precise, tunable emulsions and foams produced in microfluidic geometries have found wide application in biochemical analysis and materials synthesis and characterization. Superb control of the volume, uniformity, and generation rate of droplets and bubbles arises from unique features of the microscale behavior of fluid interfaces. Fluid interfaces confined within microfluidic channels behave quite differently than their counterparts in unbounded flows. Confinement inhibits capillary instabilities so that breakup occurs by largely quasi-static mechanisms. The three-dimensional flow near confined interfaces in rectangular geometries and feedback effects from resistance changes in the entire microfluidic network play important roles in regulating the interfacial deformation. Timescales for transport of surfactants and particles to interfaces compete with flow timescales at the microscale, providing further opportunity for tuning the interfacial coverage and properties of individual droplets and bubbles.

Droplets and Bubbles in Microfluidic Devices

Droplet emulsification in microfluidic devices involves the constant formation of fresh interfaces between two immiscible fluids. When the multiphase system contains surfactant, dynamic mass transfer of the surfactant onto the interface results in a dynamic interfacial tension different from the static interfacial tension measured in an equilibrium state. In this work, we have systematically investigated the effects of surfactant concentration and type on the dynamic interfacial tension of two different liquid-liquid two phase systems [N-hexane/water-sodium dodecyl sulfate (SDS) and N-hexane/water-cetyltrimethylammonium bromide (CTAB)] rapidly producing relatively small droplets in coaxial microfluidic devices. Dynamic interfacial tension experiments using the pendent drop method and a tensiometer were conducted, and a semiempirical equation was developed to put into context the effects of surfactants and the experimental conditions on droplet formation and dynamic interfacial tension in dynamic microchannel flows. The results presented in this work provide a more in-depth understanding of the dynamic effects of surfactants on droplet formation and the precise controllable preparation of monodispersed droplets in microfluidic devices.

The dynamic effects of surfactants on droplet formation in coaxial microfluidic devices.

This work describes a novel microfluidic method to prepare monodispersed chitosan microspheres by using the solvent extraction method. Our strategy is that a chitosan/acetic acid aqueous solution is emulsified in an organic phase containing the extractant by using the co-flowing shear method in a co-axial microfluidic device. The formed droplets are in situ solidified within a synthesizing channel by the extraction of acetic acid from the chitosan aqueous droplets to the organic solution. Based on this approach, the size of chitosan microspheres can be successfully controlled from 100 μm to 700 μm in diameter with a variation of less than 4%. Furthermore, high loading efficiency (>95%) of Bovine serum albumin (BSA) can be in situ encapsulated. The present method has the advantages of actively controlling the droplet diameter, narrow size distribution, good sphericity, and having a simple and low cost process, with a high throughput. This approach for the preparation of chitosan microspheres will provide many potential applications for pharmaceutical area.

Preparation of monodispersed chitosan microspheres and in situ encapsulation of BSA in a co-axial microfluidic device.

In this study, we developed a new method for the direct measurement of differential pressures in a co-flow junction microfluidic device using a Capillary Laplace Gauge (CLG). The CLG – used inside the microchannel device – was designed using a tapered glass-capillary set up in co-flow junction architecture with a three-phase liquid–liquid–gas system with two flowing liquid phases and an entrained gas phase. By taking advantage of the Laplace equation, basic geometric relations and an integrated image analysis program, the movement of the entrained gas phase with the flow of the liquid-phases is tracked and monitored, allowing the gauge to function as an ultra-sensitive, integrated, differential pressure sensor measuring fluctuations in the liquid-dispersed phase channel pressure as small as tens of Pascals caused by droplet formation. The gauge was used to monitor the drop formation and breakup process in a co-flow junction microfluidic device under different flow conditions across a large range (1 × 10−3 to 2.0 × 10−1) of capillary numbers. In addition to being able to monitor short and long term dispersed phase pressure fluctuation trends for both single drop and large droplet populations, the gauge was also used to clearly identify a transition between the dripping and jetting flow regimes. Overall, the combination of a unique, integrated image analysis program with this new type of sensor serves as a powerful tool with great potential for a variety of different research and industrial applications requiring sensitive microchannel pressure measurements.

Direct measurement of the differential pressure during drop formation in a co-flow microfluidic device

We conducted a case-control study to investigate risk factors for multidrug-resistant tuberculosis (MDR TB) in the People's Republic of China. Genotyping analysis was used to estimate the percentage of cases from recent transmission among 100 MDR TB case-patients hospitalized during April 2007-July 2009. Molecular subtyping of isolates showed that 41% of MDR TB strains clustered. Beijing genotype was found in 94% of the MDR TB isolates and 79% of the pan-susceptible isolates. In multivariate analysis, MDR TB was independently associated with Beijing genotype, retreatment for TB, symptoms lasting >3 months before first evaluation at the hospital, lack of health insurance, and being a farmer (vs. being a student). MDR TB was associated with Beijing genotype and lower socioeconomic status. A large percentage of MDR TB cases seemed to result from recent transmission. Early detection, effective treatment, and infection control measures for MDR TB are needed to reduce transmission.

/pdf/multidrug-resistant-tuberculosis-people-s-republic-of-china-3ez42tutym.pdf

Chris P. Tostado

Papers

The dynamic effects of surfactants on droplet formation in coaxial microfluidic devices.

Preparation of monodispersed chitosan microspheres and in situ encapsulation of BSA in a co-axial microfluidic device.

Direct measurement of the differential pressure during drop formation in a co-flow microfluidic device

Multidrug-Resistant Tuberculosis, People’s Republic of China, 2007–2009

The effects of hydrophilic surfactant concentration and flow ratio on dynamic wetting in a T-junction microfluidic device