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Artificial cell synthesis production principle picture by AI et al. (2019), artificial and natural cell comparison by Trantidou et al. (2017), liposome production with octanol by Deshpande et al. (2016)

MICROFLUIDIC PACK FOR ARTIFICIAL CELL CREATION

Artificial cell droplet microfluidic pack

Plug-and-play pack for artificial cell formation using microfluidic droplets
Monodisperse and unilamellar vesicles

Bottom-up approach to build biomimetic structures

Automatized artificial cell production

Study the structure and function of living cells for developing novel therapeutics and insights on the origin of life

Great monodispersity and reproducibility

Microfluidics offers better control than electroformation or other artificial cell synthetizing methods

A pack for artificial cells, protocells, and GUVs production

Creating artificial cells is a trending topic for researchers studying the origin of life or manufacturing synthetic building blocks for prospective applications like diagnostics or drug delivery. Microfluidics allows better reproducibility, monodispersity, vesicle size control, encapsulation efficiency, and membrane homogeneity, which makes it the most efficient method to create artificial cells.

We assembled a beginner-friendly pack with high-precision microfluidic instruments, including an OB1 flow controller with flow sensors for continuous flow rate control that you can combine with your homemade microfluidic chip or with a double emulsion microfluidic chip from ChipShop. This pack can be customized depending on your specific needs. Microfluidic chips are transparent and can be easily combined with microscopy.

 

Furthermore, Elveflow ESI software can be easily integrated with other instruments thanks to open SDK libraries. This pack can be personalized to produce artificial cells, including giant unilamellar vesicles (GUVs) or simple/double emulsions. Our experts will help you determine your needs depending on your application and provide continuous and full customer support to fulfill your experiment goals.

Our researchers assembled a microfluidic platform to obtain vesicles that mimic cell functions for researchers and industries that want to transition to microfluidic technology. Artificial cells are more accessible to analyze and control and can be designed with specific variables and parameters that are more easily maintained than natural ones.

 

This beginner-friendly microfluidic pack for artificial cell production is perfect for obtaining monodisperse and stable biomimetic cell-like bilayer structures. The flexible ESI software for sequence setting and automation allows improved reproducibility and sample use optimization.

OB1 MK4 flow controller (Elveflow) provides pulseless and fast response flow control coupled with flow rate sensors (MFS or BFS series, Elveflow) for feedback loops with the OB1. This is the most stable and precise microfluidic solution on the market, especially compared to syringes and peristaltic pumps.

Graph Flow control reactivity

The production of the double emulsion at the base of this particular artificial cell synthesis method is a well-studied application in microfluidics because of its advantages compared to bulk techniques. 

The artificial cell is formed thanks to two junctions inside the microfluidic chip that allow water-in-oil-in-water (WOW) monolayered droplets to be produced. Water-in-oil (WO) droplets could already be considered as artificial cells but oil as a continuous phase lacks biocompatibility. It is possible to use a homemade microfluidic chip, usually in Polydimethylsiloxane (PDMS), for double emulsion droplet production or a droplet generator chip from microfluidic ChipShop (fluidic 1032).

A critical step in obtaining artificial cells is to properly functionalize the microfluidic chip to have a first hydrophobic junction and a second hydrophilic junction by changing the material’s surface properties.

Artificial cells functionnalisation montage

Artificial cell droplet pack setup

The pack contains several instruments that can form the following platform. Each instrument is compatible with the others, piloted by the same software and comes with a dedicated user guide for beginner friendly step-by-step setup.

Artificial cells montage for droplet GUVs production

The artificial cell droplet pack contains:

  • OB1 flow controller (Elveflow) 
  • 3 flow sensors (Elveflow) 
  • Fittings, tubings & luers
  • Reservoirs
  • Elveflow software (Elveflow) 
  • User guides for instruments
  • Can contain the fluidic 1032 microfluidic chip from microfluidic ChipShop

Microfluidic artificial cells applications

Using lipid vesicles to produce protocells to study the origin of life or to produce artificial cells that will mimic some functions of natural cells to investigate their properties and dynamic behaviors is a recent, trending and very dynamic research subject in the past few years. The full complexity of a natural cell has still yet to be fully mimicked with a bottom-up method [1].

The challenge is to reproduce the cell membrane that contains receptors that communicate, move, and sense their local environment. The inner part of the cell contains genetic material and enzymes responsible for cellular processes such as replication, protein synthesis and metabolism or growth-related processes [2].

 

There are several ways to produce artificial cells using microfluidics. Giant unilamellar vesicles (GUVs) are capsules formed by lipid bilayer membranes (or liposomes) bigger than 10 µm in diameter that present high similarity with cellular membrane and can be used as compartments to create artificial cells [3]. It has been shown that GUVs can be used to encapsulate proteins, DNA and RNA [4].

Microfluidics is the best method to produce artificial cells with improved vesicle size consistency, membrane homogeneity, encapsulation efficiency and throughput in comparison to batch methods. Several methods have been used to produce GUVs inside a microfluidic chip with double emulsions [5-8].

Artificial cell GUV production
On-chip production of liposomes from Deshpande et al. [16]

Proteins can be incorporated to giant unicellular vesicles bilayered membranes to mimic cellular functions including the development of diseases, metabolism, and homeostasis [9]. The composition of the membrane can be tuned by changing the composition of the lipids or the lipid mixtures used to produce the artificial cells [10].

Artificial cells can be stable for more than a month [11-12].

Using microfluidics is also very useful for the creation of artificial organelles in artificial cells [13-14]. 

References

1. Walde, P. (2010), Building artificial cells and protocell models: Experimental approaches with lipid vesicles. Bioessays, 32: 296-303.
2. Martino Chiara and deMello Andrew J. 2016 Droplet-based microfluidics for artificial cell generation: a brief review Interface Focus.

3. Sato, Y.; Takinoue, M. Creation of Artificial Cell-Like Structures Promoted by Microfluidics Technologies. Micromachines 2019, 10, 216.
4. Yu B, Lee RJ, Lee LJ. 2009 Microfluidic methods for production of liposomes. Methods Enzymol. 465, 129–141.
5. Petit, Julien, et al. “Vesicles-on-a-chip: A universal microfluidic platform for the assembly of liposomes and polymersomes.” The European Physical Journal E 39.6 (2016): 1-6.
6. Deshpande, S.; Caspi, Y.; Meijering, A.E.; Dekker, C. Octanol-assisted liposome assembly on chip. Nat. Commun. 2016, 7, 10447.
7. Arriaga, Laura R., et al. “Ultrathin shell double emulsion templated giant unilamellar lipid vesicles with controlled microdomain formation.” small 10.5 (2014): 950-956.
8. Van Swaay D, deMello A. 2013Microfluidic methods for forming liposomes. Lab Chip 13, 752–767.
9. Kamiya, K. Development of Artificial Cell Models Using Microfluidic Technology and Synthetic Biology. Micromachines 2020, 11, 559
10. M. Komiya, M. Kato, D. Tadaki, T. Ma, H. Yamamoto, R. Tero, Y. Tozawa, M. Niwano, A. Hirano-Iwata, Chem. Rec. 2020, 20, 730.
11. Osaki, Toshihisa, and Shoji Takeuchi. “Artificial cell membrane systems for biosensing applications.” Analytical chemistry 89.1 (2017): 216-231.
12. Martino, Chiara, et al. “Protein expression, aggregation, and triggered release from polymersomes as artificial cell‐like structures.” Angewandte Chemie 124.26 (2012): 6522-6526.
13. Masamune Morita, Dr, Kaoru Katoh, and Naohiro Noda. “Direct observation of bacterial growth in giant unilamellar vesicles: a novel tool for bacterial cultures.” ChemistryOpen 7.11 (2018): 845.
14. Yamashita, Hitoyoshi, et al. “Generation of monodisperse cell-sized microdroplets using a centrifuge-based axisymmetric co-flowing microfluidic device.” Journal of bioscience and bioengineering 119.4 (2015): 492-495.
15. Deshpande, S., Caspi, Y., Meijering, A. et al. Octanol-assisted liposome assembly on chip. Nat Commun 7, 10447 (2016).

Customize your microfluidic instrument pack

The fluidic 1032 droplet generator chip from microfluidic ChipShop contains three parts, each containing two junctions close together that can be used to produce double emulsions including GUVs. The chip is available in polycarbonate (PC) and in Cyclic Olefin Copolymer (Topas COC).

Fluidic 1032 from microfluidic ChipShop

Our Packs are fully customizable to fit your needs perfectly. Our microfluidic specialists and researchers will help you choose the best instruments and accessories. They will accompany the setup of your microfluidic platform until you obtain your first experimental results.

We assembled other packs for cell biology like the cell size sorting and the cell aligner packs.

Contact our experts to answer any questions about this artificial cell droplet microfluidic pack and how it can match your specifications!

 

– Check our other Packs for various applications –

How can we help your experiment

The packs applications are still under development, so we are not able to give you the tips or troubleshooting advice that we usually give in our user guides and application notes for the possible challenges you could face for a specific application experiment. That being said, we can always guarantee reliable and high-precision microfluidic flow control. Our microfluidic instruments are high-performance, versatile and user-friendly. Our experts will bring support and expertise during the setup and implementation of this sensor calibration pack.

Yes! Our experts will establish which instruments are best suited for your application, such as the type of flow sensor or the number of flow controller channels you need to perform your experiment. Send us a message: innovation@microfluidic.fr.

You can order our instruments on the product section of our website.

Funding and Support

The Protomet and ACDC projects results helped develop this instrument pack, with funding from the European Union’s Horizon 2020 MSCA-ITN under grant agreement No 813873 (ProtoMet) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 824060 (ACDC project).

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