Synthesis of methylene blue and some new thioether derivatives with an enhanced electrochemical microflow cell

Project Information

BlueFlowCell

Grant agreement ID: 896473

DOI

10.3030/896473

Project closed

EC signature date 17 March 2020

Start date 1 September 2020

End date 31 August 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 184 707,84

EU contribution

€ 184 707,84

Coordinated by

BLACK HOLE LAB
France

Periodic Reporting for period 1 - BlueFlowCell (Synthesis of methylene blue and some new thioether derivatives with an enhanced electrochemical microflow cell)

Reporting period: 2020-09-01 to 2022-08-31

Summary of the context and overall objectives of the project

Methylene blue is the first fully synthetic drug used in medicine, the most effective and safe medicines needed in a health system. These compounds are synthesized commercially by chemical methods that suffer from
ignificant limitations, such as expensive and toxic reagents, solvents, tedious work-up, safety problems. Organic electrosynthesis is recognized as a typical environmentally friendly process with features that many of which cannot be achieved by other methods. Within this field, the use of microreactors in continuous flow is also concurrent with electrochemistry because of its convenient advantages over batch, such as no supporting electrolyte; high electrode surface-to-reactor volume ratio, and, short residence time. in this project, we will first design and manufacture an electrochemical microflow cell prototype with the help of photolithography technique to fabricate microchannels. Its efficiency will be tested with the known reaction and the effect of height and geometry of microchannels on electrosynthesis efficiency and mass transfer will then be investigated. After the optimal parameters are determined, Methylene blue will finally be synthesized with the improved flow reactor to demonstrate the efficiency. As well as, during the whole of the project the ER will gain maximum knowledge in microfluidic integrated devices and benefit from entrepreneurship skills.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Development of a new microfabrication process to allow the fabrication of microfluidic chip on conductive material to be able to do electrochemistry.

In order to have a conductive electrode and contre-electrode the fluidic system need to be create using metallic substrate, moreover since the height of the channels may have to be under 100µm, only a lithography process could acheive the resolution and the versatility require. A first work have been done to test the know processes and materials used by the company but none could do the work and so a new photo resist and a new process has to be developed. From this work the KN30 and the process present in the image "Conductive substrate process" has been created enable a reproductible and new microfabrication process. From an inexpected point of view, the process developed allow a robust lithography process without the use of solvent so don't have to be execute under a fume hood. It's a really nice aspect that the company BlackHole Lab used also to create a non solvent microfabrication kit for their customer.

Design and optimisation of chips to perform methylene blue synthesis.

Two main aspects in the geometry of the chip has to be taking in a account, the height of the channel that is know control by the KN30 process developed in the project and the time residency inside the deivce, highly linked to the total lengh of the channel. From this work and statement the design shown in the picture "DeviceDesign" have been imagined.


Development of a kit for fast reproduction of PMMA chip.
On a parrallele direction and because BlackHole Lab have seen the potential of the KN30 microfabrication process, a new way to do plastic (PMMA) device have been developed. Microfluidic have been spread more and more these last years and more people are using it. The access to the microfluidic needs to be simpler and faster, with simple process and cheap device. For this reason having a way to propose a PMMA microfbarication process it's a big asset.

- Mold replication using hot embossing process
The KN30 microfbarication process has been modify to create not the fluidic device itself has previsously but to create a mold that is highly robust and can support high temperature and pressure.
Thanks to this robustness the mold can be used in hot embossing process has shown in the picture "PMMAFastProduction process".

- PMMA bonding using a mix chemical/heat/pressure solution
Once the PMMA is mold, we hav obtained some open structure and it needs to be close to have the fluidic device. The bonding is maybe the most difficult and sensitive part of the process. But thanks to a combinaison of a chemical (using chloroforme) an heat and a pressure treatment describe in the picture "PMMAFastProduction process_Bonding" a repetable way have been found.

Communication and Dissemination
Conference presentations, reviews, published abstracts and lectures
• Published Reviews, Elvesys website ( Figure 21)
1. Chemical resistance of microfluidic materials
https://www.elveflow.com/microfluidic-reviews/general-microfluidics/chemical-resistance-ofmicrofluidic-materials/
2. Chemical synthesis with microfluidics
https://www.elveflow.com/microfluidic-reviews/general-microfluidics/chemical-synthesis-with-microf
luidics-review/
• Poster, NanoBioTech conference- Montreux, Switzerland 5-17 November 2022
• Published Abstract, Shima MOMENIAZANDARIANI, Sebastian Cargou, and
Benjamin Sevenie. NanoBioTech, Annual european conference on micro & nanoscale
technologies for the biosciences ( Figure 21)

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project allow the development of several unique results and namely the use of the KN30 photoresist material for the creation of chip on metal substrate but also to create enough robust mold for hot embossing processes. These results have lead to different commercial offers and many other possiblities have to been exploited yet.

Schematic of the whole process of hot embossing of PMMA; a) steel mold after development and post-ba

Schematic of the whole process of bonding PMMA-PMMA sheets using solvent vapor, a) hot embossed PMMA

Transparent plastic mask showing spiral and serpentine patterns

schematic of the whole process of mold fabrication using hot embossing: a) clean and dehydrated stee