Chemical resistance of microfluidic materials

Written by Shima Momeniazandariani
Published October 2021
Contact: partnership@elvesys.com, Elvesys SAS, 172 Rue de Charonne 75011 Paris

Introduction to chemical resistance of microfluidic materials

For most applications, several materials are valid and the choice may depend on other criteria than chemical resistance such as price, production time, recycling options.

An exception: Glass as a universal chemical resistant

Figure 2. Glass-based microfluidic systems are used as (a) microreactors and (b) micromixers [3]

However, it also has some disadvantages. Microfabrication of glass is expensive and it involves the use of dangerous etching steps which are time-consuming and heavy cost issues, hence most fabrication laboratories avoid the use of glass microchips. It should be mentioned that a cleanroom is necessary for glass manufacturing [4]. Therefore, many research groups are working on alternative materials. Because of these drawbacks and the alternatives introduced, Glass-based chips lost their popularity and are not the main material used in microfluidics anymore. Plastic or polymer microfluidic platforms represent an inexpensive and easy-to-produce alternative [5]. However, these alternative materials to glass are not always adapted for experiments using harsh chemicals. Follow this review and find out more about these materials and their chemical resistance to help you decide which one is the best choice for your own microfluidic device.

Aqueous solution-resistant microfluidic devices

If you are simply searching for a biocompatible microfluidic device and your main laboratory experiments are involving aqueous solutions, polydimethylsiloxane (PDMS) based chips are very well suited for the rapid prototyping of transparent, biocompatible devices. PDMS chips are valuable for bio-related research, such as cell culture, cell screening, diagnostic and biochemical assays [6]. An example of an electrochemical Point-of-Care (PoC) device fabricated with PDMS is shown in Figure 3. This microfluidic device consists of: (i) a PDMS layer with sensor electrodes; (ii) a PDMS microfluidic device with four channels and one outlet opening; and (iii) an adhesive layer on the skin [7].

Figure 3. (A) Photograph of a wearable microfluidic. (B) Pictorial representation of a microfluidic device composed of: (i) top PDMS layer with probing electrodes; (ii) PDMS microfluidic device; and (iii) adhesive layer on the skin. (C) Schematic representation of sweat collection and electrode operation on skin [7]

Alcohol-resistant microfluidic devices

Microfluidic devices are usually made from thermoplastics such as Poly(methyl methacrylate) (PMMA), Polycarbonate (PC), and polystyrene (PS) which are generally well-compatible with alcohols. However, using other organic solvents such as ketones and hydrocarbons will be problematic. Figure 4 shows several examples of PMMA microfluidic devices for effective mixing [8].

Figure 4. (a) PMMA Microfluidic mixer cascade for effective mixing (b) Enhanced mixer structure of 600 µm periodic structures. (c)Three-dimensional PMMA microchannel around a straight channel [8]

Chemical resistance of microfluidic materials against Acid/base and organic polar solvents

If you only use polar solvents, Cyclic Olefin Copolymer/polymer (COC/COP) can be a good choice. COC is a thermoplastic which has a good chemical resistance to acids (e.g., hydrogen chloride, sulfuric acid, and nitric acid); bases (e.g., sodium hydroxide and ammonia); and most organic polar solvents such as acetone, methanol, and isopropyl alcohol, although it is soluble in nonpolar organic solvents including toluene and naphthalene [9]. Moreover, this material has the advantages of being UV transparent and biocompatible. Figure 5 demonstrates an example of COP microfluidic chips for analytical purposes. Liu et al. have fabricated chip-based HPLC (High Performance Liquid Chromatography) containing in situ photopolymerizations of polymethacrylate monolithic stationary phases [10]. Faure et al. [11] also reported the synthesis of an acrylate monolith into a COC plastic microdevice for electrochromatography purposes that exhibits the potential of this polymer in the fabrication of novel microfluidic analytical instruments.

Figure 5. Schematic diagrams of the HPLC chips (a) Microchip design and (b) experimental system for online sample cleanup and enrichment, then HPLC separation with an integrated 5 mm long SPE trap column and 15 cm long separation column [10]

Chloroform resistant microfluidic devices

When it comes to pharmaceutical applications or nanoparticles synthesis, some specific organic solvents will be more preferable. Chlorinated solvents such as chloroform and dichloromethane are two important solvents used in these applications. Among the different varieties of polymers utilized for fabricating microfluidic devices, thiol-ene polymers (TEs) is a promising alternative to glass thanks to its unique properties such as biocompatibility,  high optical transparency,  dual-wetting properties, oxygen uptaking, and inherently high solvent resistance. Additionally, all of these important aspects can be easily modulated and fitted to the application of the demand through changing the monomer ratios, heat treatment, and curing steps of polymerization. This option is also better compared to other polymers as thiol-ene polymers have a significantly higher chemical resistance than PDMS, PMMA, and COCs. A review on thiol-ene based polymer is written by Kutter research group [12]. Table 1 shows a swelling comparison of TEs, PDMS, and COCs in the moszt commonly used solvents. Sa, Sb, and Sc represent respectively: percent swelling in 2 mm polymer squares after 24 h immersion, percent swelling in 500 µm wide channels after 24 h solvent immersion, and percent weight increase over the course of 8 weeks. It is also worth mentioning that the swelling percentage is calculated using the following equation [13].

The results demonstrated a significant improvement of solvent resistance of TEs than other polymer materials which guarantee its applicability in a variety of applications.

Table 1. TE swelling, in comparison to PDMS and COCs [12]

Jörg Kutter [13] research group has also developed a new modified thiol-ene polymer that is compatible with very harsh chemicals (solvents) that are required for the production of drug carriers and  nanoparticles,  extraction,  purifications, and separation approaches.  Figure 6 shows one of the thiol-ene microfluidic chip applications in the context of pharmaceuticals to produce magnetic microspheres of 1-3 µm diameter size which are ideal for effective drug delivery.

Figure 6 :  Example of a thiol-ene flow-focusing chip used for magnetic microspheres production; chip dimensions: 50 µm depth, 100 µm wide, and a 200 µm deep [13]

Generally, thiol-ene, with its unique properties, can be considered as an attractive alternative material for microfluidic devices requiring versatile chemistries and organic solvents; such as synthesis and analysis applications. As an example, Figure 7 represents toluene droplets generation in thiol-ene microchannels which demonstrated the chemical resistance of this polymer against harsh solvents [14].

Figure 7. a) Schematic of the fabrication process of thiol-ene device with three-dimensional geometry prepared by the rapid molding technique. b) Toluene droplet generation with homogeneous size distribution [14]

Solvent resistant teflon microfluidic chip

Among various kinds of materials, fluoropolymers popularly known as Teflon are extraordinary alternatives to glass or silicon and are fully suited to organic chemistry thanks to their excellent solvent resistance. Fluoropolymers with such a high degree of solvent compatibility opened a new door to perform organic synthesis in microfluidic reactors and gained popularity among chemists. Polytetrafluoroethylene (PTFE), perfluoroalkoxy alkane (Teflon PFA) and fluorinated ethylenepropylene (Teflon FEP) can be used for microfluidic devices because of their chemical inertness and compatibility with organic solvents [15].  Wang et al, reported a kind of solvent-resistant and degradable fluoroelastomer shown on Figure 8 [15]. Their work has led to the development of a new way to fabricate sustainable and recyclable microfluidic devices.

Figure 8. (a) Schematic illustration of the PFU-2 microfluidic chip (b-d) SEM images of microstructures on PFU-2 from different templates [15]

As another example and in regards with the microreactor applications for controlled synthesis of nanoparticles, deMello research group have developed a capillary based droplet reactor fabricated from PTFE for the synthesis of metal (Ag), metal oxide (TiO2) and semiconductor (CdSe) nanoparticles Figure 9 [16].

Figure 9. (a) Schematic of a PTFE capillary-based droplet microreactor for controlled synthesis of nanoparticles (b) Photograph showing the titania synthesis in the teflon droplet reactor [16]

On the whole, if you are aiming to perform chemical reactions in microfluidics and need a highly compatible device with chemicals and solvents, fluorinated polymers are the best choice for you and you won’t need to spend excess costs from using glass-based chips. However, you should have considered the fact that these type of polymers requires high-temperature hot embossing  and their bonding  to glass tends to be weak

Hybrid microfluidic chip: A novel approach making for high chemical resistance

Finding a single material that has all of the desired properties and specifications is an important issue. This is why hybrid microfluidic systems have been introduced. Hybrid devices are composed of multiple different types of materials. Therefore, the resulting devices can have additional features with advantages of all mixed materials while avoiding their limitations. A broad range of biological and biomedical applications using these hybrid microfluidic devices focused on paper/polymer hybrid systems are discussed in detail in the newly published review by XiuJun Li research group [17]. Recently Palleau et al. have developed a new approach of combination of two specific epoxy materials. The final fabricated chips have demonstrated transparency and biocompatibility. The solvents which are tested in this device were very well suited with ethanol, acetone, toluene, hexane, sodium hydroxide, and nitric acid, although it was not suitable for using highly concentrated (15 M) nitric acid, DMF, and THF. The presented chips can also be bonded on various types of surfaces (Figure 10) [18].

Figure 10. (a) The picture of proposed epoxy-based microfluidic chip (b) adhesion of microstructured epoxy-based microfluidic top chip onto various surface materials [18]

For a quick prototyping of a solvent-resistant microfluidic device, it is also possible to modify the surface of PDMS and increase the resistance against various solvents, while retaining the inherent bulk properties of PDMS. Kim et al, reported an easy method for a stable surface modification of PDMS using an organic/inorganic hybrid material (HR4) (Figure 11 [19]).

Figure 11. Schematic diagram of the surface modification of PDMS channels and microfluidic device fabrication process [19]

On another note, Kreutzer research group have modified the PDMS micromolding procedure with a thin perfluoropolyether (PFPE) layer and developed solvent-resistant PFPE-PDMS devices (Figure 12) [20].

Figure 12. (A) Device production of a PFPE microfluidic device, encased in PDMS. A typical demolding result is shown in (B) An example of the final device is shown in (C) [20]

PFPE has long-term chemical stability and is compatible with aggressive acids and bases, however it is less resistant to very strong bases. In this paper, as a sample reaction, deprotection of phenylalanine methyl ester using trifluoroacetic acid (TFA) in chloroform, has been performed to demonstrate the strength of PFPE-PDMS platform in organic synthesis. It has proved the high chemical resistance of PFPE-PDMS to the relevant organic solvents and aggressive reagents commonly used in organic synthesis (Table 2).

Table 2. Swelling and weight change of PFPE exposed to common solvents for organic synthesis [20]

Conclusion about chemical resistance of materials for microfluidic devices

To sum up, we have reviewed microfluidic devices in terms of materials and their chemical resistance and solvent compatibility to show its unique advantages in handling various chemical reactions and across multiple fields and disciplines such as biological, medical, chemical and engineering sciences. While glass-based microfluidic devices have fared far better with regard to solvent variety, the high costs of fabrication are prohibitive. Polymeric materials are more versatile and easier to machine than glass and so have gained more popularity especially in the area of low-cost and high-volume production that are attractive for commercial applications. The only challenge remaining is to solve the solvent compatibility to suit a particular application. Recent research has overcome these shortcomings and nowadays, different varieties of polymers with high chemical resistance are introduced. If you are using aqueous solutions, we propose elastomers such as PDMS or any widely used thermoplastics like PMMA, PS or COC.. Although PDMS is incompatible with many solvents, at the same time, the surface modification is possible to increase its solvent resistance. Are you using different types of alcohol in your project?  PMMA, PS, and PC-based devices are good to use as they are alcohol-resistant materials. COC/COP is compatible with all the polar solvents, acids, and bases. If you are looking for a completely solvent-resistant device that is even compatible with chlorinated solvents, the microfluidic devices fabricated with thiol-ene polymers and Teflon are the best choice. In the end, if you couldn’t find a single material of your demand,  there is still a way; you can even use hybrid devices combining different materials that are well suited according to your application.

Acknowledgement

References