nanocoatings for Microfluidics



SCRATCHING THE SURFACE OF MICROFLUIDICS

Although there is no strict definition of the term ‘microfluidics’, it is clear that it refers to handling small volumes of fluids. In this context, a ‘small volume’ is roughly defined as anything from 1 microliter (1 μl = 1 mm3) down to the femtoliter (1 fl = 1 μm3) range. For technologies and devices dealing with even smaller volumes and dimensions, the term ‘nanofluidics’ may also be used.

To prepare and manipulate such small volumes, channels, reservoirs and other structures with dimensions in the micrometer range are required. The design and manufacture of such devices and the development of enabling (microfabrication) technologies is an integral part of microfluidics. Because of the small dimensions involved, surface interactions and surface properties such as wettability and bioadhesion play a major role in microfluidic devices. Therefore, surface modification is a key enabling technology in microfluidics. Surfix has extensive experience with the development of nanocoatings for microfluidic devices.




A major part of the work on microfluidics is aimed at applications in Lab-on-a-Chip systems, for example for the development of
 devices for Point-of-Care diagnostics. However, microfluidic devices are encountered in many more application areas, 
such as:

  • Drug discovery
  • Cell analysis
  • Genetic testing
  • Organ-on-Chip


The examples above are from the biomedical domain, but microfluidics are also employed in numerous other fields, e.g.:

  • Environmental analysis
  • Food analysis
  • Agriculture
  • Cosmetics 



SURFACE MODIFICATION FOR MICROFLUIDICS


Glass / silicon 

Since the early days of microfluidics, silicon and glass have been important materials for device fabrication. From a surface chemical point of view, silicon and glass are similar, since the surface of both materials basically consists of silicon oxide, which is hydrophilic due to the presence of polar silanol (Si-OH) groups.


Most microfluidic applications involve water or aqueous solutions. In this case having a hydrophilic surface is generally preferred, since it facilitates passive transport of the liquid through the chip by capillary flow. The natural hydrophilicity of silicon (oxide) and glass surfaces is one of the reasons for the popularity of these materials. However, for applications involving non-polar liquids (oils) a hydrophobic surface is more suitable, and this can be achieved by surface modification with a hydrophobic nanocoating. Moreover, due to their high surface energy hydrophilic surfaces are prone to protein adsorption, which is undesirable. This problem can be overcome by applying a protein-repellent antifouling nanocoating in the channel.


The possibility to create patterned nanocoatings by local surface modification yields local control of the wettability and/or antifouling properties, which enables advanced functionalities such as control of liquid flow (see example 1) or the generation of double emulsions in a single microfluidic chip (see example 2).


POlymers

In the past years, polymers have become increasingly popular, and are now the most used materials for making microfluidic devices. Compared to inorganic materials, polymers enable low-cost manufacturing, provided a sufficient number of devices is produced. High quality polymers with a wide range of properties are available, and advances have been made in microfabrication technologies for polymers. Therefore, it is predicted that the use of polymers will keep increasing. Due to its ease of fabrication, the elastomer poly(dimethylsiloxane) (PDMS) has been the most popular polymer in academic research. However, for industrial manufacturing thermoplastics such as cyclic olefin (co)polymer (COP, COC), polycarbonate (PC) and poly(methyl methacrylate) (PMMA) are much more suitable.


In contrast to glass, most polymers used for fabricating microfluidic devices are hydrophobic, which impedes filling of channels by capillary flow. Moreover, proteins and other biomolecules tend to adsorb to the hydrophobic polymers, leading to issues in biological applications. Both problems can be overcome by applying a nanocoating that has both hydrophilic and antifouling properties.


The possibility to create patterned nanocoatings by local surface modification yields local control of the wettability and/or antifouling properties, which enables advanced functionalities such as control of liquid flow (see example 1) or the generation of double emulsions in a single microfluidic chip (see example 2). In the R&D project Coat PoCKET, a microfluidic chip with advanced functionalities enabled by patterned nanocoatings is being developed.

paper

An interesting alternative for some applications is the use of (nitro)cellulose paper. The porous hydrophilic structure enables transport of aqueous liquids by wicking, which has been used for many years in lateral flow assays such as the well-known home pregnancy test. Making a paper microfluidic device involves defining channels by local hydrophobization of the (nitro)cellulose matrix. Surfix’s hydrophobic nanocoating can be used for this purpose, and this application is being investigated and developed in the R&D project Multidetect.




EXAMPLE 1: HYDROPHOBIC PATCHES

Water in a hydrophilic channel forms a concave meniscus, while in a hydrophobic channel, the meniscus is convex. This is illustrated in the microscopy images beside. Hydrophilic channels facilitate capillary flow of aqueous solutions, but the flow is effectively stopped when the liquid encounters a hydrophobic patch. This is due to the sudden change in wettability and capillary pressure at the hydrophilic/hydrophobic border, as schematically illustrated below. Thus, a locally applied hydrophobic nanocoating can be used as a passive capillary valve, stopping the liquid at a predetermined position in the channel. The valve can be ‘opened’ by applying a pressure pulse, pushing the liquid over the hydrophobic barrier. Once the liquid interface has passed the hydrophobic patch, filling of the channel will continue by capillary action.


EXAMPLE 2: DOUBLE EMULSIONS


An emulsion consists of liquid droplets dispersed in another, immiscible liquid, e.g. water droplets in oil or oil droplets in water. Emulsions are studied and applied in widely varying fields and industries such as food, pharma, cosmetics, chemistry and agriculture. Microfluidics can be used to generate highly monodisperse emulsions by bringing together both liquids on the micron scale in a controlled way, and numerous designs for microfluidic droplet or emulsion generators have been described.

Hydrophilic chips are preferred for making oil-in-water (O/W) emulsions, while water-in-oil (W/O) emulsions are best prepared in a hydrophobic chip. So depending on the chip material, a hydrophobic or hydrophilic nanocoating may be required to obtain the desired surface wettability. Beside ‘simple’ O/W or W/O emulsions, more complex combinations are also possible, e.g. double emulsions consisting of three alternating oil and water layers (i.e. O/W/O or W/O/W). For some applications, double emulsions have considerable benefits. For example, it has been shown that water-soluble drugs are released at a controlled rate from double emulsions over a longer period of time compared to single emulsions.

Microfluidic double emulsions are generally prepared in two steps, first making a single emulsion (say O/W), and then adding the second oil layer to yield an O/W/O double emulsion. This is schematically illustrated in the image beside. However, as mentioned above generation of the first O/W emulsion requires a hydrophilic chip, while a hydrophobic chip is needed for the second emulsification step. This problem can be solved by using two separate chips (a hydrophobic and a hydrophilic one). However, a more practical and elegant solution is to use local surface modification to apply a hydrophobic and/or hydrophilic nanocoating and make the right combination of hydrophobic and hydrophilic channels in a single chip.




EXAMPLE 3: COATING AND BONDING


After fabrication of microfluidic features, substrates generally need to be sealed using a cover or ‘lid’ to create functional devices. Obviously, this should not lead to changes in the dimensions or physical and chemical properties of the device. Therefore, sealing or bonding is a critical step in the fabrication of microfluidic devices, and several technologies are available to achieve strong, leak-tight bonds between parts. Some techniques employ an intermediate adhesive layer, while others allow direct bonding of substrates by e.g. thermal fusion bonding, solvent bonding, or (ultrasonic or laser) microwelding.

If a nanocoating needs to be applied, it is crucial to decide if this should be done before or after bonding and closing the chip. From a manufacturing point of view, coating of open (non-bonded) channels is easier and more scalable than coating inside a closed microchannel. However, applying a nanocoating before bonding brings two important requirements: 

  • the nanocoating should not interfere with the bonding process
  • the bonding conditions (e.g. surface activation, temperature, solvents) should not affect the nanocoating

In other words, the nanocoating and bonding processes should be mutually compatible. For this purpose, it is beneficial to use local surface modification and apply the nanocoating only where it is needed, i.e. inside the channel. The rest of the substrate remains uncoated and can be used for bonding. If, on the other hand, a uniform nanocoating is applied, the coating will also be present on the bonding surface and interfere with the bonding process. Thus, using patterned nanocoatings improves the compatibility of bonding and nanocoating processes and facilitates the fabrication of microfluidic devices with optimized surface properties.