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Home » Resources » Expertise » Microfluidics case studies » Microfluidic Control of Complex Emulsions for Chemical Sensing

Microfluidic Control of Complex Emulsions for Chemical Sensing

This case study explores a microfluidic approach to real-time chemical sensing using self-assembled complex emulsions. Formed with a tailored CNFCPEG molecule, a novel α-cyanostilbene core bearing a PEG chain for water solubility and a semi-perfluoroalkyl tail, the emulsions exhibit structure-dependent fluorescence for detecting iodine through visible color changes. The RayDrop microfluidic device, combined with the Flow-EZ™ for precise droplet formation and flow control, ensures consistent emulsion production and sensitive detection.

The RayDrop is developed and manufactured by Secoya Technologies

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A Paper from the National Dong Hwa University 

Rakesh, N., Tu, H.-L., Chang, P.-C., Gebreyesus, S. T., Lin, C.-J., Innovative Real-Time Flow Sensor Using Detergent-Free Complex Emulsions with Dual-Emissive Semi-Perfluoroalkyl Substituted Α-Cyanostilbene. Adv. Sci. 2023, 2304108. 

This study is a collaboration between National Dong Hwa University and the Institute of Chemistry at Academia Sinica Nangang (Taiwan), led by Prof. Che-Jen Lin. His group focuses on three key areas: designing stimuli-responsive luminescent materials for sensing and bioimaging, developing organic porous frameworks for catalysis and energy storage, and creating soft materials integrated with microfluidic sensing for real-time detection and intelligent applications.  

Learn more about the CJLin Group 

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Testimonial

“Our experience using the LineUp Flow EZTM pressure pump with the RayDrop chip has been positive. The pump’s high precision and accuracy have allowed us to achieve consistent and reproducible results in our microfluidic experiments. Additionally, the pump’s compact size and user-friendly interface have made integrating into our existing setup easy. The combination of Fluigent’s LineUp Flow EZTM pressure pump and RayDrop chip has great potential for advancing microfluidic research, and we are excited to continue exploring their capabilities in our ongoing studies.“

Che-Jen Lin, Ph.D., Assistant Professor at National Dong Hwa University. Organic Chemistry
Fluigent and National Dong Hwa University

Why generate complex emulsions?

Emulsions are microscale spheroid structures formed by blending two immiscible liquids (often an oil phase and an aqueous phase). What differentiates complex emulsions (figure 1b) from simple emulsions (figure 1a) is their multi-layered structure.

Within a complex emulsion, micro droplets of one liquid are intricately dispersed within another, forming a heterogeneous droplet with exceptional properties. When properly generated and stabilized, complex droplets can be used to encapsulate active or reactive compounds, such as Active Pharmaceutical Ingredients,[2] or to design innovative functional particles. [3]

Some complex droplets can adopt temporary Janus configurations. Janus droplets have two distinct faces (figure 1c), each featuring unique properties achieved through selective surface modifications.[4] Their surface properties dynamically adjust over time or in response to external stimuli.

Examples of Complex emulsions
Figure 1: Examples of simple emulsions and complex emulsions. a) Single emulsions. Scale bar of 200 μm. Images b) and c) show complex emulsion droplets, where b) shows double emulsion complex droplets with a scale of 100 μm, and c) shows a Janus shape complex emulsion droplet with scale bar of 50 μm.

Generating complex droplets

Emulsion Setup

In this study, complex emulsions were generated with a mixture of hydrocarbon oil (heptane) and fluorocarbon oil (FC-770). To ensure a homogeneous solution, the mixture of heptane and FC-770 was heated above the upper critical temperature (50°C). 4×10-7 mmol of CNFCPEG was dissolved in 500µL of heptane and 500µL of FC-770.

Complex emulsion setup
Figure 2: Complex emulsion setup using FlowEZ and Raydrop SE

To generate complex emulsifications, the researchers employed Secoya’s single emulsion Raydrop coupled with Fluigent’s Flow EZTM flow controller to facilitate the creation of highly monodispersed droplets. Through this setup, they achieved precise control over pressures and flow rates, leading to the generation of controlled monodisperse droplets in the 50 to 80 µm range.  

Raydrop single emulsion principle
Figure 3: Raydrop SE principle

Raydrop Double Emulsion

Alternatively, an easier way to produce double emulsions is by using the new double emulsion Raydrop developed by Secoya. Thanks to its double nozzles, this new Raydrop can generate double emulsions in one step, creating a core-shell structure. The size of the core and shell can be precisely controlled, offering versatility in applications such as drug delivery systems.

Double emulsion generation
Figure 4A: Double emulsion generation with the Raydrop DE
double emulsion droplet
Figure 4B: The double emulsion Raydrop offers precise control of shell thickness.

Using complex emulsions to measure iodine concentration

The key role of CNFCPEG

In this study, CNFCPEG, an innovative compound, plays a major role in stabilizing complex emulsions without the need for external surfactants. CNFCPEG also exhibits two fluorescence colors (blue and green) depending on its aggregation state. When CNFCPEG aggregates in an organic phase, a blue color is observed, while the green excimer is observed when CNFCPEG self-assembles at the fluorinated oil/water interface (F/W). By evaluating fluorescence emissions, the distinction between H/F/W and F/H/W emulsions becomes clear and easily distinguishable.

Heptane-FC 770-CNFCPEG complex emulsion in DI water presents the H/F/W morphology. Addition of iodine to the DI water reduces the hydrophilicity of CNFCPEG’s PEG group, leading to an instantaneous morphology shift from H/F/W to Janus to F/H/W complex emulsion. This morphological shift, combined with the fluorescent color change, makes it possible to to detect the presence of iodine in water. 

CNFCPEG partition alongside the emission colors
Figure 5: Microscopic bright-field side view, bright-field bottom view, and fluorescence bottom view of H/F/W emulsions in 0.5 wt.% FS-30 and F/H/W emulsions in 0.5 wt.% Tween-20 (scale bar: 50 µm). The schematic illustration depicts CNFCPEG partition alongside the emission colors exhibited by the double emulsions. [1]

Complex droplets as iodine real-time sensing platform

To enhance the precision and accuracy of data acquisition in real-time flow sensing, the researchers designed a Multiple-well Flow PDMS Chip (MWFC) that allows for parallel tracking of multiple droplets (figure 6). This innovative chip facilitates the monitoring of droplet behavior, morphological changes, and interactions within complex droplets.

Droplets settling into micro-wells
Figure 6: Droplets settling into micro-wells [1]
Morphological changes of complex emulsions
Figure 7: a) Schematic drawing of the method used to monitor morphology in MWFC. b) Morphological changes of complex emulsions in the chip under the flow of iodine(aq) (0.1 mg mL−1) at a flow rate of 0.5 mL min−1. (scale bar: 50 µm) c) The relation between time to morphological change and iodine concentration at a flow rate of 0.5 mL min−1. [1]

Iodine was injected into the MWFC, inducing a decrease in the hydrophobic nature of the CNFCPEG and initiating an instantaneous morphological change in the stabilized complex droplets (figure 7b, figure 8). The droplets transitioned from H/F/W to Janus more quickly with increasing iodine concentration. Slower flow rates corresponded to longer transition times, providing quantitative insights into analytes (figure 7c).

Droplet Changes to H/F/W
Figure 8: Droplet Changes to H/F/W – Janus – F/H/W with addition of iodine [1]

Conclusion

In this case study, amphiphilic α-cyanostilbene CNFCPEG stabilized complex emulsions without the need for external surfactants, exhibiting morphology-dependent fluorescence that allowed for real-time iodine sensing through visible emission color shifts.

By integrating the RayDrop for precise droplet formation and FlowEZ for accurate flow control, this system enabled consistent and reproducible sensing without the need for bulky equipment.

The results highlight the potential of this approach for developing portable, real-time chemical and biological sensing technologies, offering an approach for on-site monitoring in fluid environments 

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References

[1]Rakesh, N., Tu, H.-L., Chang, P.-C., Gebreyesus, S. T., Lin, C.-J., Innovative Real-Time Flow Sensor Using Detergent-Free Complex Emulsions with Dual-Emissive Semi-Perfluoroalkyl Substituted Α-Cyanostilbene. Adv. Sci. 2023, 2304108. https://doi.org/10.1002/advs.202304108

 [2]Linghao Qin, Yawei Niu, Yuemin Wang, and Xiaomei Chen, Molecular Pharmaceutics 2018 15 (3), 1238-1247, DOI: 10.1021/acs.molpharmaceut.7b01061 

[3]Justin R. Finn, Janine E. Galvin, Modeling and simulation of CO2 capture using semipermeable elastic microcapsules, International Journal of Greenhouse Gas Control, Volume 74, 2018, Pages 191-205, ISSN 1750-5836, https://doi.org/10.1016/j.ijggc.2018.04.022. 

[4]Bradley D. Frank, Markus Antonietti, and Lukas Zeininger, Macromolecules 2021 54 (2), 981-987, DOI: 10.1021/acs.macromol.0c02152

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