Dendronized fluorosurfactant for highly stable water-in-fluorinated oil emulsions with minimal inter-droplet transfer of small molecules

Mohammad Suman Chowdhury,Pradip Dey,David A Weitz,John Heyman,Xingcai Zhang,Shalini Kumari,Wenshan Zheng,Rainer Haag

doi:10.1038/s41467-019-12462-5

Mohammad Suman Chowdhury, Pradip Dey + Show 6 more

Open Access

https://doi.org/10.1038/s41467-019-12462-5

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Abstract

Fluorosurfactant-stabilized microfluidic droplets are widely used as pico- to nanoliter volume reactors in chemistry and biology. However, current surfactants cannot completely prevent inter-droplet transfer of small organic molecules encapsulated or produced inside the droplets. In addition, the microdroplets typically coalesce at temperatures higher than 80 °C. Therefore, the use of droplet-based platforms for ultrahigh-throughput combination drug screening and polymerase chain reaction (PCR)-based rare mutation detection has been limited. Here, we provide insights into designing surfactants that form robust microdroplets with improved stability and resistance to inter-droplet transfer. We used a panel of dendritic oligo-glycerol-based surfactants to demonstrate that a high degree of inter- and intramolecular hydrogen bonding, as well as the dendritic architecture, contribute to high droplet stability in PCR thermal cycling and minimize inter-droplet transfer of the water-soluble fluorescent dye sodium fluorescein salt and the drug doxycycline.

Highlights

Fluorosurfactant-stabilized microfluidic droplets are widely used as pico- to nanoliter volume reactors in chemistry and biology
Droplets are often unstable during thermal cycling, reducing reliability of the polymerase chain reaction, (PCR)[4,15], which is an extremely efficient method for nucleic acid amplification and is a critical step in most genetic analyses
We synthesized three surfactants that are consisted of tri-glycerol-based dendritic polar heads, which have four hydroxy (–OH) groups, and PFPE polymer chains with three different fluorine chain lengths of high (H), medium (M), and low (L) molecular weights (MW), providing H-dendritic tri-glycerol (dTG), M-dTG, and L-dTG, respectively, are shown in Fig. 1

Summary

Results and discussion

We synthesized three surfactants that are consisted of tri-glycerol-based dendritic polar heads (dTG), which have four hydroxy (–OH) groups, and PFPE polymer chains with three different fluorine chain lengths of high (H), medium (M), and low (L) molecular weights (MW), providing H-dTG, M-dTG, and L-dTG, respectively, are shown in Fig. 1 (bottom panel). The combination of mono-glycerol (G) with medium and low MW PFPE chains created M–G and L–G surfactants, respectively, as illustrated in Fig. 1 (top panel). These five di-block dendronized surfactants allow us to systematically investigate the effect of polar head group geometries and the number of –OH groups on droplet stability and performance under demanding conditions. We chose relatively large droplets because droplet stability decreases with droplet size and we

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Methods

Dox Inducible cell

Code availability