Droplet Microfluidic Chip Customization and Processing

Droplet microfluidic chip is a new technology for manipulating small volume liquid, which is rapidly developed in the field of microfluidic chip. Under the action of microchannels, incompatible liquids can form a series of microdroplets, and each isolated and non-interfering droplet can be used as a microreactor to complete the relevant biochemical reaction and detection. Therefore, droplet microfluidic technology has the characteristics of small droplet volume, low sample consumption, flexible control, rapid mass transfer in droplets, and high detection / separation frequency. Especially when applied to high-throughput screening, it can greatly improve the scale, speed and cost of screening, and significantly enhance the practicability of high-throughput screening technology.

Droplet Chip Fabrication Techniques

According to the participation of external energy, Alfa Chemistry can provide two types of microdroplet chip fabrication technology, which are passive and active respectively.

1. Passive Droplet Generation

Passive droplet formation means that only the hydrodynamic pressure of the fluid exists during the droplet formation process, without external energy input. Through the structural design of the micro-channel of the microfluidic chip, the immiscible two-phase or multi-phase fluid is injected from the outside to realize the formation of droplets. The main generation methods include T-shaped structure method, flow focusing method, and capillary flow confocal method.

Fig.1 Schematic representation of a droplet-based microfluidics system. A Basic design and passive methods of droplet formation, B cross-flowing, C flow focusing, D co-flowing

• T-shaped Structure Method

The two phases of oil and water are respectively introduced from the corresponding ports of the chip and flow through the intersection of the T-shaped structure, forming an oil/water interface at the T-shaped structure. When the oil/water interfacial tension is insufficient to maintain the shear force of the oil phase, the water phase breaks to form a liquid drop.

• Flow Focusing Method

Compared with the single-side extrusion of the discrete phase fluid in the T-shaped structure method, the continuous phase in the flow focusing method squeezes the discrete phase from both sides, and the oil/water interface becomes unstable at the downstream constriction channel to form droplets.

• Capillary Flow Confocal Method

In the process of chip fabrication, the capillary flow confocal method does not need lithography technology or ultra-clean laboratory for microchannel processing, which is simpler than the former two methods; structurally, this method uses the nesting relationship of capillaries to make the continuous phase "squeeze" around the discrete phase radially to form a "shrinking neck", so that the front end of the discrete phase fluid is "unstable", thus generating droplets.

2. Active Droplet Generation

The active control method is to control the surface energy of microfluidics by adding external energy during the droplet generation process. There are many methods for active droplet generation, mainly including magnetic control, mechanical control, thermal control, and electric control.

• Magnetic Control Method

The application of magnetic force in the generation and control of microdroplets mainly depends on the volume dynamic response of special fluid (magnetic fluid) to magnetic field. Magnetic fluid is a liquid containing suspended magnetic particles, such as ferromagnetic fluid. The ferromagnetic fluid has superparamagnetism and can be magnetized without magnetic memory. Once the external magnetic field is removed, the nanoparticles in the ferromagnetic fluid will become non-magnetic. The ferromagnetic fluid can be either water-based or oil-based and can be used as both discrete phase and continuous phase. The generation of microdroplets by magnetic control in microchannel is mainly based on T-type structure and flow focus structure chip in passive control.

• Mechanical Control Method

The process of mechanically controlling the generation of micro-droplets involves the physical deformation of the fluid interface, and the power sources that cause the deformation of the fluid interface include hydraulic, pneumatic, piezoelectric, and other methods. For example, the mechanical components in the droplet generation process are controlled hydraulically and pneumatically, and the on-off control of the flow path is usually performed by valves integrated into the microfluidic device.

• Thermal Control Method

The energy sources of droplet generation and control by thermal control method include resistance heating at the node and local heating by focusing laser beam. Its essence is to make use of the temperature-dependent characteristics of the fluid, most of the fluid viscosity and interfacial tension will decrease with the increase of temperature, and the most direct reflection of these two changes is the change of capillary number (Capillarynumber, Ca).

• Electric Control Method

The so-called electric control method is to realize the generation and control of microdroplets by applying voltage to the fluid in the microchannel. The available voltage source can be either AC or DC. For DC control, the voltage remains constant during the whole process of droplet generation. In AC control, the fluctuation frequency of voltage is different from that of droplet generation. For high frequency AC control, the frequency of control signal is much higher than that of droplet generation. In a chip generated by applying a voltage to control droplets, the electrode applying the voltage is in contact with the liquid.

Applications

With the increasing enrichment and maturity of droplet splitting, fusion, mixing, sorting and other manipulation techniques, droplet microfluidic technology is gradually becoming a tool with good application prospects in chemical analysis and biochemical analysis.

• Multidimensional Separation

The main advantage of multidimensional separation over traditional one-dimensional separation is the significantly improved resolution, making it more suitable for separation analysis of complex systems. Two-dimensional separations of peptide mixtures were performed using droplets as a novel interface technology to transport samples between dimensions.

• Polymerase Chain Reaction of Droplets

Polymerase chain reaction (PCR) is widely used in biological and medical fields, and it is the most important and effective method in DNA analysis. The droplet PCR technology combining PCR technology with droplet microfluidic technology can significantly reduce the consumption of samples and reagents, and greatly shorten the amplification reaction time.

• Protein Crystallization

Protein crystallization is of great significance for determining its tertiary structure, studying its physiological function and drug development. In the process of protein crystallization, the optimization of reagent concentration is often time-consuming and laborious. In addition, when studying some rare samples with a small amount of samples, it is necessary to control the consumption of samples. The crystallization process of proteins can be completed rapidly, cost-effectively and controllably by using the droplet microfluidic system.

• Single Cell Detection

Because the droplet can provide a controllable microenvironment, a single cell or even a single microbe can be encapsulated into the droplet for analysis and detection. The cells in the droplet exist independently and are not interfered by external conditions, and rapid single cell detection can be realized without complex processing.

If you need droplet microfluidic chip processing and customized services, please feel free to contact our experts for a free consultation.

References

• Pattanayak, P.; et al. Microfluidic chips: recent advances, critical strategies in design, applications and future perspectives. Microfluidics and nanofluidics. 2021 Dec;25:1-28.
• Zhu P, Wang L. Passive and active droplet generation with microfluidics: a review. Lab on a Chip. 2017;17(1):34-75.
• Khater, A.; et al. Dynamics of temperature-actuated droplets within microfluidics. Scientific Reports. 2019 Mar 7;9(1):3832.
• Zhu, P.; et al. Droplet generation in co-flow microfluidic channels with vibration. Microfluidics and Nanofluidics. 2016 Mar;20:1-0.

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