1. Overview of droplet microfluidics
Microfluidics enables fine control of a wide range of fluids at the micro-scale by manipulating immiscible continuous and dispersed phases to generate microdroplets. This allows one to precisely regulate the composition and geometric characteristics of the particles.
Utilizing these advantages, microfluidics can generate engineered particles with controlled size, monodispersity, diverse morphology, and specific functionality.
In microfluidic systems, the size and stability of droplet generation is influenced by a number of factors.
These include external factors such as the viscosity and surface tension of the fluid, temperature, flow rate, and channel geometry, as well as the flow rates of the dispersed and continuous phases, the nature of the fluid, and the geometry of the microchannels.
The methods of droplet generation can be categorized into passive and active methods depending on the force.
2. Passive method of droplet generation
Droplets generated with the passive method are characterized by uniform size, good monodispersity, and uniform spatial distribution, and this method is effective in avoiding external interference and eliminating cross-infection.
Depending on the channel geometry, the passive method is mainly categorized into T-shaped structure, flow-focused structure, co-axial flow-focused structure and step structure. Among them, T-shaped structure and flow-focused structure are the most commonly used.
1) T-structure
The main reason for droplet formation is the hydrostatic pressure equilibrium in a two-phase fluid, not shear stress.
The T-structured channel generates droplets by either a squeezing or a jetting mechanism, where jets are generated at high flow rates and low interfacial tensions, and squeezing is generated at low flow rates.
Based on the T-channel, Y-, V-, and K-constructions have been developed, in which bubbles or waste droplets from droplet generation in the V-construction channel are discharged through an additional channel.
2) Flow Focusing Structure
In contrast to the T-shaped structure, the flow-focused structure allows for the generation of controlled droplets that are smaller than the pore size and uniform in size.
The fluid in the continuous phase in the two vertical channels of the flow focusing structure squeezes the dispersed phase and forms droplets in or downstream of the holes.
The location of droplet breakage from the dispersed-phase body depends on the flow channel geometry and the two-phase flow rate.
3) Coaxial flow focusing structure
The droplets of the co-axial flow focusing structure form a channel similar to a coaxial sleeve, where the dispersed phase in the small-diameter channel flows in parallel with the continuous phase in the large-diameter channel, and the dispersed phase is broken into droplets by the extrusion of the continuous phase.
4) Ladder structure
The droplet formation of the step structure is guided by the Laplace pressure difference for the spontaneous generation of droplets.
The dispersed phase will flow in narrow channels before passing through the continuous phase reservoir containing the step structure and splitting spontaneously into microdroplets before entering the step structure.
This method is characterized by low shear, flow insensitivity, simple structure and easy integration.
3. Active method of droplet generation
In contrast, the droplet generation device of the active method is more complex, more delicately fabricated, has better droplet control, and is capable of generating a wide range of droplets for a variety of experiments.
Active methods include electrically driven, inkjet printing, micro-valve-driven, light-driven, magnetic-driven and acoustic-driven methods.
1) Electric drive method
Electrically driven methods mainly include dielectrophoresis and electrowetting. The dielectrophoresis method forms droplets by pulling fluid from a reservoir, while the electrowetting method utilizes an applied electric field to change the interfacial free energy between the fluid and the contact surface, causing the fluid to wet the surface.
When the electric field is turned off, the surface becomes hydrophobic, and the liquid previously impregnated on the surface breaks off from the reservoir and forms droplets.
2) Inkjet printing method
Inkjet printing is a non-impact dot-matrix printing technique that ejects droplets in microliter or even nanoliter volumes directly under pressure from the printer nozzle.
Inkjet printing methods are categorized into continuous inkjet and on-demand inkjet. On-demand inkjet is further categorized into thermal inkjet, piezoelectric inkjet, electrostatic inkjet, and acoustic inkjet based on the method of droplet formation.
3) Micro valve actuation method
The micro-valve actuation method is a droplet generation method based on the T-channel method, which enables precise generation and manipulation of individual droplets.
A micro-valve layer connected to a pneumatic drive is integrated into the T-channel to regulate droplet generation and size by controlling the opening and closing of the pneumatic valve.
4) Other Driving Methods
The light-driven method utilizes a strongly converging beam of light to generate two-phase microdroplets. In the light-driven method, the laser pulse forms gas pockets at the interface between the dispersed and continuous phases, truncating the continuous phase into the dispersed phase, thereby forming droplets.
The magnetic actuation method generates droplets by controlling a magnetic fluid through an external magnetic field. The size and density of the droplets depend on the position of the magnet and the magnitude of the magnetic force.
The acoustic actuation method vibrates the tip of a capillary tube by sound waves, causing droplets to flow at the tip of the capillary tube. By adjusting the amplitude and waveform of the acoustic wave, the droplet size and generation frequency can be controlled. This method has the advantages of integration and low power consumption and does not require the design of microfluidic channels or surface modification.
4. Applications of droplet microfluidics in various fields
1) Biosensing
Microfluidics is widely used in bioanalysis, including single-cell analysis, protein analysis, enzyme analysis, and nucleic acid analysis, because of its ability to produce droplets of tiny size, large specific surface area, high flux, stable reaction conditions, and high reaction efficiency.
Biosensing devices can detect target biomolecules with the advantages of low sample dose, high throughput and efficient detection. Particles containing sensing elements prepared using microfluidics have been developed for biosensing.
The researchers built a miniaturized colorimetric DNA biosensor based on non-hybridized DNA-functionalized gold nanoparticles and used capillary coaxial microfluidics to fabricate microcapsules.
By encapsulating nanosensors such as glucose-responsive quantum dots and heparin-responsive gold nanorods in a liquid core, the required sample volume was effectively reduced.
2) Space medicine
Microfluidic devices are characterized by small size, high integration, low consumption, etc. They are able to overcome the disturbances caused by microgravity and have been widely used in aerospace medicine in recent years.
Using photolithography and oblique exposure technology, the research institute has fabricated a microfluidic device with three-dimensional focusing function through an indirect microchannel fabrication process, which is capable of accurately detecting the number of blood red blood cells and has been successfully applied to aerospace medical testing.
In addition, a plug-and-play microfluidic device prepared by the unsheathed flow channel focusing method, which is capable of effectively classifying and counting lymphocyte subpopulations, has been successfully applied to the immune monitoring test and training of China's manned spaceflight.
3) Environmental testing
With the progress of modern society, the destruction of the natural environment by human beings has led to a series of environmental pollution problems, which not only jeopardize human health, but also pollute the natural environment. Microfluidic technology can detect microenvironmental parameters of environmental pollution such as temperature, osmotic pressure concentration and pH value in air pollution, water pollution and soil pollution.
The researchers involved have designed a microfluidic gas collection platform that can perform multiplexed mass spectrometry (MS) analysis, which is widely used for indoor and outdoor air pollutant analysis by obtaining information on inhaled gases through an array of droplets on the surface of alveolar arrays.
Environmental testing researchers have developed a real-time on-line detection device based on honeycomb-type (PDMS wafer/silicon wafer/PDMS wafer) microchannel extraction to detect elemental sulfur in soil and groundwater.
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