WO2024165885A1

WO2024165885A1 - Microfluidic device for the synthesis of micro and nanoproducts and method of manufacturing said microfluidic device

Info

Publication number: WO2024165885A1
Application number: PCT/IB2023/051053
Authority: WO
Inventors: Lucía Laura Policastro; Juan Martín Cabaleiro; María Cristina Soraires Santacruz; Elena María Sanmarco; Lisbeth Alexandra Benavides Castillo
Original assignee: Fernandez Perez Bani Raquel; Consejo Nacional de Investigaciones Cientificas y Tecnicas CONICET; Comision Nacional de Energia Atomica CNEA
Current assignee: Fernandez Perez Bani Raquel; Consejo Nacional de Investigaciones Cientificas y Tecnicas CONICET; Comision Nacional de Energia Atomica CNEA
Priority date: 2023-02-06
Filing date: 2023-02-06
Publication date: 2024-08-15
Anticipated expiration: 2025-08-06

Abstract

Microfluidic device for the synthesis of micro and nanoproducts and manufacturing method of said microfluidic device. The microfluidic device comprises a top piece made of photopoly- merizable resin, which in turn comprises at least two inlet holes and at least one outlet hole; one or more bottom pieces made of photopolymerizable resin, which in turn comprise microchannels; and fastening means between the top piece and the bottom piece or bottom pieces. The manu- facturing method comprises a step of modeling the pieces of the microfluidic device; a 3D printing stage of the pieces of the microfluidic device; a post-processing stage of the pieces of the microfluidic device; and a stage of assembling of the microfluidic device.

Description

Microfluidic device for the synthesis of micro and nanoproducts and method of manufacturing said microfluidic device

The present invention relates to a microfluidic device for the synthesis of micro and nanoproducts and to a manufacturing method thereof.

The technical field to which the present invention belongs is that of physical devices for mixing fluids for the manufacture of micro and nanoproducts of interest in the chemical, cosmetic, food and pharmaceutical industries.

Microfluidics is a scientific and technological area in constant development. In recent years, microfluidic devices, also known as chips, have shown unique advantages over the synthesis of micro and nanoproducts, the latter being efficient vehicles for drug encapsulation and transport [Liu, D., Zhang, H., Fontana, F., Hirvonen, J. T. & Santos, H. A. Current developments and applications of microfluidic technology toward clinical translation of nanomedicines. Adv. Drug Deliver. Rev. 128, 54–83 (2018)]. Compared to traditional methods, microfluidic technology can be relevant in the pharmaceutical field to produce micro- and nano-products in a scalable and reproducible way.

The key aspects of microfluidic devices are the small dimensions of the channels that allow a laminar flow regime [Jakub Novotný, F. F. Fluid manipulation on the micro-scale: Basics of fluid behavior in microfluidics. J. Sep. Sci. 40, 1–44 (2016)] and the use of software to control fluid dynamics, allowing precise mixing of reagents [Sackmann, E. K., Fulton, A. L. & Beebe, D. J. The present and future role of microfluidics in biomedical research. Nature 507, 181–189 (2014)]. Several considerations must be taken into account in order to prototype high-efficiency microfluidic devices [Zhang, H., Zhu, Y. & Shen, Y. Microfluidics for Cancer Nanomedicine: From Fabrication to Evaluation. 1800360, 1–25 (2018)]: the dimensions and geometries of the microchannels, the number of inlets, and the materials used to fabricate the devices. The above parameters determine the quality of the products.

The most commonly used materials for the fabrication of microfluidic devices include elastomeric and thermoplastic materials. Although these materials, as raw material, are easily accessible to laboratories due to their low cost, the manufacturing methods associated with obtaining microfluidic devices, such as lithography and/or micro-machining (CNC), have the great disadvantage of being expensive and/or long-lasting processes. [Damiati, S., Kompella, U. B., Damiati, S. A. & Kodzius, R. Microfluidic devices for drug delivery systems and drug screening. Genes (Basel). 9, (2018)]. Furthermore, these materials are not suitable for the use of organic solvents, reagents that are essential in the synthesis of micro and nanoproducts. For example, polydimethylsiloxane (PDMS), is one of the most widely used materials for manufacturing devices, which is highly susceptible to swelling or deforming when exposed to organic solvents such as acetone [Baroud, C. N. Microchannel deformations due to solvent induced PDMS swelling. 2972–2978 (2010) doi:10.1039/c003504a]; [Genzer, J., Park, I., Efimenko, K. & Sjo, J. Rapid Removal of Organics and Oil Spills from Waters Using Silicone Rubber “Sponges”. 318–327 (2009) doi:10.1080/01932690802540384]; [Lee, J. N., Park, C. & Whitesides, G. M. Solvent Compatibility of Poly (dimethylsiloxane)-Based Microfluidic Devices. 75, 6544–6554 (2003)].

Swelling of microfluidic channels affects fluid flow and uncontrolled product generation [Damiati, S., Kompella, U. B., Damiati, S. A. & Kodzius, R. Microfluidic devices for drug delivery systems and drug screening. Genes (Basel). 9, (2018); Communication, S. Predictive model on micro droplet generation through mechanical cutting. 431–438 (2009) doi:10.1007/s10404-009-0412-y]. In addition, PDMS can contaminate solutions flowing through the channels with unreacted oligomers or absorb organic molecules from solution [Regehr, K. J. et al. Biological implications of polydimethylsiloxane-based microfluidic cell culture. 2132–2139 (2009) doi: 10.1039/b903043c; Toepke, M. W. & Beebe, D. J. PDMS absorption of small molecules and consequences in microfluidic applications. 1484–1486 (2006) doi:10.1039/b612140c].

Although these problems have been partially solved with the use of other materials such as glass or polytetrafluoroethylene (PTFE) and cyclic olefin copolymer (COC), the complexity of the microfluidic device fabrication method using these materials remains [Damiati, S., Kompella, U. B., Damiati, S. A. & Kodzius, R. Microfluidic devices for drug delivery systems and drug screening. Genes (Basel). 9, (2018); Nguyen, N. T., Shaegh, S. A. M., Kashaninejad, N. & Phan, D. T. Design, fabrication and characterization of drug delivery systems based on lab-on-a-chip technology. Adv. Drug Deliver. Rev. 65, 1403–1419 (2013)].

3D printing technology represents a set of powerful techniques under precise digital control that enables cost-effective, time-saving, easy-to-manufacture and high-efficiency objects [Bhattacharjee, N., Urrios, A., Kang, S. & Folch, A. The upcoming 3D-printing revolution in microfluidics. Lab Chip 16, 1720–1742 (2016)]. Therefore, based on 3D printing technology, different types of prototypes can be developed as an opportunity to address a variety of health problems [Hiroyuki Tetsuka and Su Ryon Shin. Materials and Technical Innovations in 3D Printing in Biomedical Applications. (2020) doi:10.1039/D0TB00034E; Manuscript, A. Point-of-Care Testing: Applications of 3D Printing. (2017) doi:10.1039/C7LC00397H].

Among the 3D printing technologies, stereolithography (or “SLA”, “Stereo Litography Apparatus”), fused deposition modeling (or “FDM”, for its acronym in English “Fused Deposition Modelling”) and the injection printing of a photopolymer (PolyJet^TM), are the most relevant techniques for the development of different types of devices.

SLA 3D printing technology enables the production of 3D parts from a photoresin precursor using a light-curing light source [Bhattacharjee, N., Urrios, A., Kang, S. & Folch, A. The next 3D printing revolution in microfluidics. Lab Chip 16, 1720-1742 (2016); Cabot, J. M., Fuguet, E., Roses, M., Smejkal, P. & Breadmore, M. C. Novel instrument for automated pKa determination by Internal Standard Capillary Electrophoresis Novel instrument for automated pK a determination by Internal Standard Capillary Electrophoresis. (2015) doi:10.1021/acs.analchem.5b00845; Kotz, F. et al. Three-dimensional printing of transparent fused silica glass. nat. publ. Gram. 544, 337–339 (2017); Shallan, A. I., Smejkal, P., Corban, M., Guijt, R. M. & Breadmore, M. C. Cost-effective three-dimensional printing of visibly transparent microchips in minutes. (2014); Li, F., Macdonald, N. P., Guijt, R. M. & Breadmore, M. C. Increasing functionalities of 3D-printed microchemical devices using single-material, multi-material, and print-pause-print 3D printing. Lab Chip 19, 35–49 (2019); Anciaux, S. K., Geiger, M. & Bowser, M. T. 3D Printed Micro Free-Flow Electrophoresis Device. (2016) doi:10.1021/acs.analchem.6b01573].

Currently, there are commercially available resins that open the possibility of designing biomedical devices and creating 3D objects with precise architectures, small in size. Since there is direct or indirect contact between the materials used in 3D printed microfluidic devices and biological samples, the biocompatibility of the materials is of paramount importance. Among the components of photoresins, the polymerized materials are generally not cytotoxic. However, toxicities can arise from unreacted monomer as well as photoinitiator or absorbent leaching out of the part and interacting with the sample.

The amount of leachables is greatly affected by factors including geometry and resin formulation, among others. Various strategies have been employed to reduce the cytotoxicity of printed parts. Most of the potentially cytotoxic components are removed by subsequent washing of the 3D printed parts with a suitable solvent. It is also common to use a UV light post-treatment to increase the conversion of monomer to polymer, since in printing the polymerization never reaches full conversion.

In the state of the art there are various microfluidic devices for the production of nanoparticles, such as the invention proposed in patent US10843194B2 entitled "Microfluidic mixing devices and systems" where the microfluidic device is made of PDMS material using positive molds that, in turn, were manufactured by lithography. Likewise, patent US9381477B2 entitled "Microfluidic synthesis of organic nanoparticles" describes chips made by different techniques such as lithography, engraving, stamping or molding of a polymeric surface.

Elastomeric materials such as PDMS are polymers widely used in microfluidic chips using techniques such as lithography. However, despite the fact that these materials have the advantage of optical transparency, they are not suitable for use with organic solvents, since they deform in their presence. The use of organic solvents is essential for most syntheses of micro and nanoproducts. The deformation of the microchannels affects the flow of liquids. Thus, these materials have limitations in the application of chemical synthesis.

On the other hand, microfluidic devices made of materials resistant to organic solvents such as glass, certain metals or silicones manage to overcome this limitation of use. In this sense, the patent US9381477B2 mentioned above refers to glass, metals or silicones as possible materials for the chips. Another patent that mentions chips made of glass and/or silicone is WO2020115178A2 entitled "Microfluidic devices". However, it is highlighted that microfluidic devices made of these materials are difficult to prototype since the manufacturing methods are complex because, among other things, they require clean areas.

In comparison with patent CN105727857A entitled "Microfluidic apparatus produced by 3D printing", this one has as its object a microfluidic device manufactured by 3D printing and uses photopolymerizable resins, but the technology used is different from that of the present invention because uses digital light processing (DLP) technology. In addition, its use is proposed for the production of double emulsions of water/oil/water (W/O/W), without mentioning the use of organic solvents, an advantage that is exposed in the present invention through the use of resins resistant to organic solvents for the synthesis of micro and nanoproducts.

Finally, it is worth mentioning that none of the above background describes a microfluidic device resistant to organic solvents that allows the synthesis of micro and nanoproducts, and that comprises two or more pieces joined together by clamping means. This has the advantage of being easy to manufacture in less complex laboratories, through, for example, 3D printing by stereolithography.

Object of the Invention

The object of the present invention is a microfluidic device, made of photopolymerizable resin, resistant to organic solvents, to be used in the synthesis of micro and nanoproducts, and the manufacturing method of said microfluidic device.

The microfluidic device comprises a top piece, which in turn comprises at least two inlet holes and at least one outlet hole; one or more bottom pieces, which in turn comprise microchannels; and fastening means between said top piece and said bottom pieces. Its manufacturing method comprises a modeling stage of the pieces of the microfluidic device; a 3D printing stage of the pieces of the microfluidic device; a post-processing stage of the pieces; and a stage of assembly of the microfluidic device.

The use of the photopolymerizable resin material has the advantage that it resists organic solvents frequently used in organic chemistry, such as ethanol, methanol, acetone and chloroform, among others. Likewise, said resin can be used to obtain a quick and simple manufacturing of the microfluidic device with 3D printing.

For greater clarity and understanding of the object of the present invention, the following drawings of a variant of the microfluidic device and its manufacturing method are presented:

Fig.1A

Top view of the top piece (10) of the preferred embodiment.

Fig.1B

Top view of the bottom piece (20) of the preferred embodiment.

Fig.1C

Top view of the microfluidic device of the preferred embodiment.

Fig.2

Diagram of the microchannels (21) in a zigzag shape (213) of the microfluidic device of the preferred embodiment.

Fig.3

Diagram of a preferred embodiment of the manufacturing method with 3D printing by stereolithography of the microfluidic device of the preferred embodiment.

Fig.4

Scanning Electron Microscopy (SEM) images of the microfluidic device of the preferred embodiment, before and after acetone treatments: a) 0 min, b) 2 min, c) 30 min and d) 60 min.

Fig.5

Analysis by gas chromatography coupled to mass spectrometry (GC-MS) of the organic solvent used for the synthesis of the polymeric micelles, before and after coming into contact with the microchannels, of the preferred embodiment.

Fig.6

Image taken by SEM of the microfluidic device manufactured by 3D printing of the preferred embodiment, after treatment with acetone until evident damage. The treatment consisted of putting the microfluidic device in contact with acetone under mechanical agitation.

References in the Drawing

Microfluidic device: (10) Top piece: (11) Inlet hole, (12) Outlet hole; (20) Bottom piece: (21) Microchannels: (211) Inlet Channel, (212) Entry Angle (213) Zigzag; (30) Fastening means; (40) Computer; (50) 3D printer; (60) Light source.

Description of the Invention

The device of the present invention is described below:

A microfluidic device for the synthesis of micro and nanoproducts, comprising:

• a top piece, comprising at least two inlet holes, which allow the aqueous and organic phases to enter, and at least one outlet hole, through which the micro and nanoproducts of the synthesis are obtained;

• one or more bottom pieces, comprising microchannels, which allow mixing and diffusion between the phases; and

• fastening means, which allow assembly between the top piece and the bottom pieces;

wherein said top piece and said bottom piece or bottom pieces are made of photopolymerizable resin, where said photopolymerizable resin is resistant to organic solvents;

wherein said photopolymerizable resin is selected from the group comprising acrylic and epoxy-acrylic resins;

wherein said top and bottom pieces are joined together by said fastening means; and

wherein said inlet holes and said outlet hole or outlet holes are located coincident at the height of the ends of said microchannels.

The method of the present invention is described below:

A method of manufacturing a microfluidic device for the synthesis of micro and nanoproducts, comprising the following steps:

a) Modeling in 3D said microfluidic device in computer-aided design (CAD);

b) Exporting said 3D models from step a) to STL format files;

c) Importing said files from step b) into a 3D printing software, and establish in said 3D printing software a printing layer height parameter, and a curing time parameter (The printing software divides the structure to be printed according to with the print layer thickness set, get a series of slices of equal thickness, determine the precise position, illumination intensity, and projection illumination time of each slice);

d) Generating new STL format files with the printing parameters of step c);

e) Entering the STL format files from step d) in a 3D printer;

f) Printing with said 3D printer from step e) said pieces from step a) in photopolymerizable resin;

g) Removing the printed pieces from the printing support of said 3D printer;

h) Washing said printed pieces of said step g) with a solvent compatible with said photopolymerizable resin used in said step f);

i) Carrying out a post-processing of said printed pieces; and

j) Assembling the microfluidic device;

• wherein said step a) comprises 3D modeling a top piece and one or more bottom pieces in computer-aided design (CAD);

• wherein said step c) comprises importing said files from step b) to the 3D printing software, and establishing in said 3D printing software the printing layer height parameter, between 0.025 mm and 0.1 mm, and the time parameter curing, between 3 and 15 seconds;

• wherein said step e) comprises entering the STL format files from step d) in a 3D printer with a photopolymerizing light source, comprising a wavelength between 300 and 410 nm;

• wherein said step f) comprises printing with said 3D printer of step e) said pieces of step a) in photopolymerizable resin resistant to organic solvents, which is selected from the group comprising acrylic and epoxy-acrylic resins;

• wherein said step i) comprises curing said printed and washed pieces with a light source with a wavelength between 300 and 410 nm for 1 to 5 minutes; and

• wherein said step j) comprises assembling said microfluidic device by assembling said upper part obtained in said step i) to said lower part(s) obtained in said step i), by means of fastening means.

Example of Preferred Embodiment

For the microfluidic device for the synthesis of micro and nanoproducts and the manufacturing method of said microfluidic device described in the present invention, the following preferred embodiment was carried out:

, , show a variant of the microfluidic device for the synthesis of micro and nanoproducts of the present invention, printed in 3D, where said microfluidic device comprises:

• a top piece (10), comprising two inlet holes (11), one through which the aqueous phase enters and the other through which the organic phase enters, and an outlet hole (12), through which the micro and synthesis nanoproducts;

• a bottom piece (20), comprising a microchannel (21) comprising two inlet channels (211) connected in a "Y" or "V" shape, forming an angle of 90° (212) with each other, and they converge in a zigzag (213); and

• fastening means (30), comprising 3Dresyn WC ClearTM photopolymerizable acrylic resin, which allows assembly and fastening between said top piece (10) and said bottom piece (20);

wherein said top piece (10) and said bottom piece (20) are made of 3Dresyn WC Clear^TM photopolymerizable acrylic resin, which is resistant to organic solvents;

wherein said top piece (10) and said bottom piece (20) are joined together by said fastening means (30);

wherein said inlet holes (11) are located coincident with the ends of said inlet channels (211) of said microchannel (21);

wherein said outlet hole (12) is located coincident with the height of the end of said zigzag (213) of said microchannel (21); and

wherein said microchannel (21) is 300 µm wide and 300 µm deep.

shows a diagram of the microchannel (21) of the microfluidic device of the preferred embodiment, which allows the generation of micro and nanoproducts. It comprises two inlets, one through which the aqueous phase enters and another for the organic phase. The two inlet channels (211) of the microchannel (21) come together in a zigzag (213) where the mixing of the reagents takes place. The geometry of the zigzag channel with its curves and twists forces the fluids to generate transverse flows, inducing chaotic advection within a laminar regime. This process favors the mixing of aqueous and organic solutions, forming the micro and nanoproducts of interest [Manz, Andreas and Neuzil, Pavel and O'Connor, Jonathan S and Simone, Giuseppina. Microfluidics and Lab-on-a-chip. The Royal Society of Chemistry. 2021].

On the other hand, shows a diagram of a preferred embodiment of the manufacturing method by 3D printing by stereolithography of the microfluidic device.

For the manufacture of the microfluidic device, it was printed in 3D by stereolithography (SLA) according to the following steps:

a) Modeling in 3D said top piece (10) of said microfluidic device and said bottom piece (20) of said microfluidic device in computer-aided design (CAD) (40);

b) Exporting said 3D models from step a) to STL format files, a standard file type for 3D printers;

c) Importing said files from step b) into the 3D printing software, and setting in said 3D printing software the print layer height parameter equal to 0.025 mm, and the curing time parameter equal to 8 seconds;

d) Generating new STL format files with the printing parameters of step c);

e) Entering the STL format files from step d) into an LCD-based SLA 3D printer (50) operating with a nominal curing light source of 405 nm wavelength and a pixel size of 47 µm in the image plane (Anycubic Photon®);

f) Printing on said 3D printer (50) from step e) said pieces (10) (20) from step a) in 3Dresyn WC ClearTM light-curing acrylic resin, which is resistant to organic solvents, biocompatible, translucent and washable with water;

g) Removing the printed pieces from the printing support of said 3D printer (50);

h) Washing said printed pieces of step g) with distilled water;

i) Curing said printed pieces under a 45 W LED source (60) with a wavelength of 405 nm for 1 minute;

j) Assembling the microfluidic device by gluing said top piece (10) and said bottom piece (20), using said 3Dresyn WC ClearTM photopolymerizable resin as fastening mean (30), distributing it on the surface of said top piece (10) and of said bottom piece (20), in such a way that said resin (30) does not enter the microchannel (21); and

k) Curing said microfluidic device under a 45 W LED source (60) with a wavelength of 405 nm for 5 minutes (This further ensures the absence of uncured resin before use).

In order to characterize the resistance to organic solvents that are commonly used in the synthesis of micro and nanoproducts, the microfluidic device with the exposed microchannel of the preferred embodiment was shaken under mechanical mixing in acetone at three different times: 2, 30 and 60 minutes. Subsequently, the resistance of the microchannels of the microfluidic device to the organic solvent was analyzed by means of scanning electron microscopy (SEM) studies, as shown in . It was observed that the microstructure of the channels is not altered, even after one hour of contact with the pure organic solvent. It is noteworthy that both the walls and edges of the zigzag, as well as the bottom of the microchannel, do not show cracks or other signs of degradation.

On the other hand, in addition to the possible migration of the resin components due to problems related to printing, the printed materials could be dissolved by the solvent used as organic phase in the synthesis of micro and nanoproducts. To ensure that the resin components of the present microfluidic device are not removed during synthesis, the organic phase (without any dissolved component) was flowed through the microchannels used for the synthesis of micro and nanoproducts and further by a microfluidic device without prior use. The organic solvent before and after flowing through the zig-zag microchannels was analyzed by gas chromatography coupled to mass spectrometry (CG-MS).

While the chemical composition of most resins used in SLA printers remains a trade secret, data sheets from safety guidelines indicate that the resins generally contain acrylate and/or methacrylate monomers. A qualitative analysis was performed using CG-MS in scanning mode to study the probable presence of resin derivatives and methacrylate-type residues. In scanning mode, only the first quadrupole is used, the ions that can be observed in the mass spectrum correspond to the molecular ion and/or to fragments generated by the high energy of the electrons with which the molecule is bombarded. shows the results of the CG-MS analyses, where it can be seen that there are no signs referring to the release of resin components in the organic solvent that circulates through the new or used microfluidic device.

For comparison, a new zigzag microchannel was shaken in acetone until obvious damage occurred. The acetone collected after stirring was analyzed by GC-MS under the same conditions as above, the results were plotted in . Six peaks are present in the chromatogram, which are detailed in Table 1, some of the ions (147, 91) coincide with those reported by Oskui et al [Oskui, S. M. et al. Assessing and Reducing the Toxicity of 3D-Printed Parts. Environment. Sci.Technol. Lett. 3, 1–6 (2016)], where the results showed that at least three different chemical species were present in their leachate; these species have different retention times in gas chromatography (GC) but very similar fragments in mass spectrometry (MS), as in the embodiment of the present invention. This supports the hypothesis that short-chain monomers or polymers are present in the leachate from the damaged microfluidic device, but not in the new and used microchannels. The visibly affected microstructure of the microfluidic device is shown in . This image of the 3D printed microfluidic device of the preferred embodiment was obtained after immersing it in acetone under mechanical agitation. This experiment allowed us to evaluate, under extreme conditions, the damage produced in the microfluidic device by the action of organic solvents such as acetone.

[Table 1] Major ions in acetone peaks after shaking a microchannel until obvious damage:

Retention Time [min]	m/z Ratio fragments	Compound dropped by library (% chance)
4.60	40, 81, 65, 109	3,5 heptadien-2-one, 6-methyl (75)
5.20	41, 91, 77, 147, 119	3,5 dodeadiyne, 2-methyl (73)
5.75	91, 146, 164, 117, 39	Benzoic acid, 2,4,6-trimethyl(75)
5.80	40, 78, 142, 105	Phenylphophonous acid (72)
6.20	77, 40, 158, 213, 105	Phosphonic acid, phenyl, diethylester(79)
14.45	147, 77, 91, 40, 119	Ethy mesityglyoxylate (82)

Claims

A microfluidic device for the synthesis of micro and nanoproducts, characterized in that it comprises:
• a top piece, comprising at least two inlet holes, and at least one outlet hole;
• one or more bottom pieces, comprising microchannels; and
• fastening means;
wherein said top piece and said bottom piece or bottom pieces are made of photopolymerizable resin, wherein said photopolymerizable resin is resistant to organic solvents;
wherein said photopolymerizable resin is selected from the group comprising acrylic and epoxy-acrylic resins;
wherein said top piece and said bottom piece or bottom pieces are joined together by said fastening means; and
wherein said inlet holes and said outlet hole or outlet holes are located coincident at the height of the ends of said microchannels.
The microfluidic device according to claim 1, characterized in that it preferably comprises:
• a top piece, comprising two inlet holes and one outlet hole;
• a bottom piece, comprising a microchannel comprising two inlet channels connected in a "Y" or "V" shape, forming an angle of 90° with each other, and converging in a zigzag; and
• fastening means.
The microfluidic device according to any of claims 1 and 2, characterized in that said fastening means preferably comprise a layer of photopolymerizable resin on said top piece and a layer of photopolymerizable resin on said bottom piece or bottom pieces.
The microfluidic device according to any of claims 1 to 3, characterized in that it is preferably for the continuous synthesis of micro and nanoproducts.
A method of manufacturing a microfluidic device for the synthesis of micro and nanoproducts, comprising the following steps:
a) Modeling in 3D said microfluidic device in computer-aided design (CAD);
b) Exporting said 3D models from step a) to STL format files;
c) Importing said files from step b) into a 3D printing software, and establishing in said 3D printing software a print layer height parameter, and a curing time parameter;
d) Generating new STL format files with the printing parameters of step c);
e) Entering the STL format files from step d) in a 3D printer;
f) Printing with said 3D printer from step e) said pieces from step a) in photopolymerizable resin;
g) Removing the printed pieces from the printing support of said 3D printer;
h) Washing said printed pieces of step g) with a solvent compatible with said photopolymerizable resin used in said step f);
i) Carrying out a post-processing of said printed pieces; and
j) Assembling the microfluidic device;
wherein said method is characterized in that:
• said step a) comprises 3D modeling a top piece and one or more bottom pieces in computer-aided design (CAD);
• said step c) comprises importing said files from said step b) into the 3D printing software, and setting in said 3D printing software the print layer height parameter, comprised between 0.025 and 0.1 mm, and the curing time parameter, between 3 and 15 seconds;
• said step e) comprises entering the STL format files of said step d) in a 3D printer with a photopolymerizing light source, comprising a wavelength between 300 and 410 nm;
• said step f) comprises printing with said 3D printer of said step e) said pieces of step a) in photopolymerizable resin resistant to organic solvents, which is selected from the group comprising acrylic and epoxy-acrylic resins;
• said step i) comprises curing said printed and washed pieces with a light source with a wavelength between 300 and 410 nm for 1 to 5 minutes; and
• said step j) comprises assembling said microfluidic device by assembling said top piece obtained in said step i) to bottom piece or bottom pieces obtained in said step i), by fastening means.
The method of manufacturing a microfluidic device for the synthesis of micro and nanoproducts according to claim 5, characterized in that said step c) is preferably importing said files from step b) to the 3D printing software, and establishing in said printing software 3D a print layer height parameter equal to 0.025 mm, and a curing time parameter equal to 8 seconds.
The method of manufacturing a microfluidic device for the synthesis of micro and nanoproducts according to claims 5 and 6, characterized in that it preferably comprises an additional step k), after said step j), wherein said step k) is curing said microfluidic device with a light source with wavelength between 300 and 410 nm for 1 to 5 minutes.
The method of manufacturing a microfluidic device for the synthesis of micro and nanoproducts according to claim 7, characterized in that said step k) is preferably curing said microfluidic device with an LED source with a wavelength of 405 nm for 5 minutes.