GB2471522A

GB2471522A - Microfluidic devices

Info

Publication number: GB2471522A
Application number: GB0911572A
Authority: GB
Inventors: Wolfgang Andreas Bauer; Wilhelm T S Huck; Martin Fischlechner
Original assignee: Cambridge Enterprise Ltd
Current assignee: Cambridge Enterprise Ltd
Priority date: 2009-07-03
Filing date: 2009-07-03
Publication date: 2011-01-05
Anticipated expiration: 2029-07-03
Also published as: US20150073061A1; US8834966B2; US9707557B2; EP2448678A1; EP2448678B1; WO2011001185A1; US20120168010A1; GB0911572D0; GB2471522B

Abstract

A layer-by-layer deposition method for forming multiple layers of material onto the walls of a channel of a microfluidic device is disclosed. The method comprises: loading a tube with a series of segments of solution, a segment of solution bearing a material to be deposited; coupling the tube to the microfluidic device channel; and injecting the segments of solution into the microfluidic device using a syringe such that the segments of solution pass, in turn, through the channel depositing successive layers of material to perform layer-by-layer deposition onto the walls of the channel. The segments may be separated by water for rinsing the channel after deposition or air. Embodiments of the methods are particularly useful for automated surface modification of plastic, for example PDMS (Poly(dimethylsiloxane)), microchannels. Applications including inkjet printing, chemical or biochemical sensors, and lab-on-chip devices are disclosed.

Description

I

Microfluidic Devices

FIELD OF THE INVENTION

This invention relates to methods for modification of the surfaces of a channel of a microfluidic device, to apparatus for performing such methods, and to microfluidic devices fabricated using or treated by such methods. Embodiments of the methods are particularly useful for automated surface modification of plastic, for example PDMS (PoIy(dimethylsiloxane)), microchannels.

BACKGROUND TO THE INVENTION

For several reasons poly(dimethylsiloxane) (PDMS) is one of the most commonly used materials in microfluidic chip fabrication. Compared to silicon and glass devices, PDMS based chips can be manufactured much faster, easier and cheaper by means of soft lithography. Due to its elasticity pumps and valves can be introduced into PDMS devices. Furthermore, PDMS can be cured at low temperature, it is transparent down to 280 nm, biologically inert and non-toxic as well as permeable to gases. It also readily seals with other materials, such as glass and poly(methyl methacrylate), which allows for the fabrication of hybrid chips. However, significant limitations concerning the application of PDMS in microfluidic devices arise from the high hydrophobicity of the material. For instance, the creation of oil-in-water emulsions inside microfluidic chips requires an effective wetting of the microchannel walls with the continuous aqueous phase. Therefore, a surface modification is often necessary, although rather challenging because of the inertness of PDMS.

In literature numerous ways of PDMS surface modification can be found. One possible approach comprises the exposure of PDMS to various energy sources, such as oxygen plasma. In this context, the generation of hydrophilic surfaces by oxidation is only temporary though since PDMS is known to regain its original hydrophobic surface properties over time, a phenomenon referred to as hydrophobic recovery.

Alternatively, chemical vapor deposition (CVD) can be used to introduce permanent coatings and hence adjust the surface properties of PDMS. However, since this method requires unhindered access of the vapor to the substrate it is limited to the modification of non-assembled microfluidic chips. This is a significant drawback as the coating must then be stable enough to endure the bonding procedure typically involving plasma treatment.

Furthermore, PDMS surfaces can be modified covalently, most commonly via graft photo-polymerization. A simple one-step strategy is available which allows for the tailoring of PDMS surface properties by grafting various monomers. Again problems arise for assembled channels though, since polymerization predominantly occurs in the channel lumen rather than at the walls. The pre-adsorption of a suitable photo-initiator solves this problem, but requires additional preparation steps making the procedure more elaborate. Similarly, other covalent modification strategies, such as the generation of a glass coating via sol-gel methods offer the possibility to modify PDMS permanently, but again in a rather complex, labor-intensive and time-consuming manner.

Another surface modification method is based on the layer-by-layer (LbL) self-assembly of polyelectrolyte multilayers (PEMs) by alternate adsorption of polycations and polyanions. This versatile approach was introduced by the group of Decher [G.

Decher, J. D. Hong, J. Schmitt, Thin Solid Films, 1992, 210/211, 831-835; G. Decher, Y. Lvov, J. Schmitt, Thin Solid Films, 1994, 244, 772-777; G. Decher, Science, 1997, 277, 1232-1237].

Based on these results Katayama et a! [H. Katayama, Y. Ishihama, N. Asakawa, Anal.

Chem., 1998, 70, 2254-2260; H. Katayama, Y. Ishihama, N. Asakawa, Anal. Chem., 1998, 70, 5272-5277] developed an LbL procedure allowing for the treatment of capillary inner walls. Various other groups like Barker et a!, [S. L. R. Barker, M. J. Tarlov, H. Canavan, J. J. Hickman, L. E. Locascio, Anal. Chem., 2000, 72, 4899-4903; S. L. R. Barker, D. Ross, M. J. Tarlov, M. Gaitan, L. E. Locascio, Anal. Chem., 2000, 72, 5925-5929.] Henry et a! [Y. Liu, J. C. Fanguy, J. M. Bledsoe, C. S. Henry, Anal.

Chem., 2000, 72, 5939-5944] and Hahn et a!. [K.W.Ro, W-J. Chang, H. Kim, Y.-M.

Koo, J. H. Hahn, Electrophoresis, 2003, 24, 3253-3259] are using similar protocols in order to modify surface properties of microfluidic channel walls. However, all of these coating procedures rely on the manual flushing of a microfluidic chip with different polyelectrolyte solutions. As additional washing steps need to be carried out in between and all polyelectrolyte and washing solutions have to be individually injected into the device, kept inside the channels for some time and removed afterwards this method can easily become a tedious and labor-intensive task, too.

Further background prior art can be found in US6,860,980 and W02005/052035.

There is therefore a need for improved techniques for surface modification of channels of a microfluidic device.

SUMMARY OF THE INVENTION

According to the present invention there is therefore provided a method of layer-by-layer deposition of a plurality of layers of material onto the walls of a channel of a microfluidic device, the method comprising: loading a tube with a series of segments of solution, a said segment of solution bearing a material to be deposited; coupling said tube to said microfluidic device; and injecting said segments of solution into said microfluidic device such that said segments of solution pass, in turn, through said channel depositing successive layers of material to perform said layer-by-layer deposition onto said walls of said channel.

In preferred embodiments of the method the tube is loaded so that there are gas, typically air, gaps between successive segments of solution, to act as spacers to thereby inhibit mixing of the solution in adjacent segments. In embodiments segments of solution bearing material to be deposited have segments of washing fluid between them, for example, water and/or an aqueous washing solution.

In embodiments the tube is loaded by coupling an end of the tube to each of a set of solutions in turn in reverse order to that in which the solutions are to be pumped through the microfluidic device (so that the tube need not be turned around once loaded). In embodiments of the method the solution is injected at a controlled, for example, constant flow rate. In this way the duration of the deposition of a layer can be controlled by controlling the flow rate and physical length of a segment of solution bearing the material to be deposited.

In embodiments the channel of the microfluidic device is defined in a plastic, and the method further comprises pre-treating this plastic channel by exposure to an energy source, for example a plasma, to generate a hydrophilic surface for the channel. As previously mentioned this hydrophilic surface can undergo hydrophobic recovery and therefore, in embodiments of the method, the layer-by-layer deposition is commenced before this hydrophobic recovery has proceeded more than 10%, 20%, 30%, 40% or 50%.

In embodiments the plastic may comprise PDMS, but embodiments of the method are also suitable for many other plastic/polymer materials, including but not limited to: polystyrene, PETG (Poly(ethylene terephthalate glycol)), PMMA (poly(methacrylate)) and polycarbonate.

In preferred embodiments of the method the material to be deposited comprises polyelectrolyte. The skilled person will be aware of many suitable materials in some preferred implementations of the method the polyelectrolyte solutions comprise solutions of positively and negatively charged polyelectrolytes, for example PAH and PSS respectfully. In this way alternating positively and negatively charged polyelectrolyte layers may be deposited on the walls of the microchannel to provide a multilayer coating. In embodiments the segments of polyelectrolyte are separated by aqueous washing solution and a gas (air) gap at either or both ends. The skilled person will be aware, however, that embodiments of the above described technique may be employed to deposit a layer or layers of many other different materials.

The invention also provides a method of fabricating a microfluidic device including treating one or more channels of the device as described above. The invention further provides a microfluidic device fabricated using or treated by a method as described above.

Embodiments of the above described method are particularly advantageous for treating the device for processing droplets of an emulsion in an aqueous stream of fluid, such as an oil-in water emulsion.

The invention also provides apparatus for layer-by-layer deposition of a plurality of layers of material onto the walls of a channel of a microfluidic device, the apparatus comprising: a system for loading a tube with a series of segments of solution, a said segment of solution bearing a material to be deposited; and a system for injecting said segments of solution into said microfluidic device such that said segments of solution pass, in turn, through said channel depositing successive layers of material to perform said layer-by-layer deposition onto said walls of said channel.

In embodiments the system for injecting the solution segments into the rnicrofluidic device may comprise a controlled-rate pump, for example, a syringe pump; the same or a similar arrangement may be employed for loading the tube with the segments of solution prior to injection. In embodiments the tubing comprises a length of replaceable flexible tubing, for example of plastic, which may conveniently be cut to remove unwanted contamination. Additionally or alternatively a fluid switch or multiplexer may be employed to selectively couple the tubing to a plurality of reservoirs bearing solutions to be loaded into the tube and/or to selectively couple the tube to a microfluidic device to be treated.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects of the invention will now be further described, by way of example only, with reference to the accompanying figures in which: Figures Ia and lb show, respectively, a schematic diagram illustrating a method and apparatus according to an embodiment of the invention, and a cross section through a treated wall of a microfluidic channel; Figures 2a and 2c shows fluorescence analysis of automated LbL (layer-by-layer) PDMS surface modification showing, respectively, (a) schematics of flushing sequences with varying number n of fluorescently labelled PAH segments, (b) fluorescence microscopic image of four straight rnicrofluidic channels (fluorescence intensity increases with increasing n), (c) fluorescence microscopic analysis of a wiggle channel reveals a homogeneous coating even for this geometry; and Figures 3a to 3d show the influence of PDMS surface modification on the formation and stability of oil-in-water droplets, scale bar = 100pm, respectively (a), (b) without further treatment of the channels instabilities and phase reversion occur; (c), (d), after LbL deposition of a PEM-the PDMS surface maintains its hydrophilicity even after 2.5 weeks of storage under air allowing for the formation of monodisperse and stable droplets.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

We will describe a LbL approach which provides time-saving, automated surface modification process (Figure 1) and which allows for the creation of stable oil-in-water droplets. Figure 1 shows a schematic illustration of the automated LbL surface modification of a microfluidic channel. In Figure Ia defined segments of aqueous solutions of NaCI, a positively and a negatively charged polyelectrolyte (PAH and PSS, respectively), separated by air and stored within the tubing, are sequentially flushed through the microfluidic channel at a constant flow rate. In Figure lb at the PDMS surface a coating of alternating positive and negative polyelectrolyte layers is successively built up.

A key feature is the loading of a piece of tubing with defined solution segments, separated by air. In this regard, one end of the tubing is attached to a syringe and the other end is dipped into the solution which shall enter the channel last later on. Having withdrawn a solution segment of a certain length into the tubing the latter is pulled out of the solution. An air segment is drawn in and the contaminated part of the tubing which was in contact with the solution is simply cut off. The next solution segment can be sucked in likewise and so on. In order to build up a polyelectrolyte multilayer we load the tubing alternately with segments of poly(allylamine hydrochloride) (PAH) and poly(sodium styrene sulfonate) (PSS) solutions (1 mg polyelectrolyte in I ml 0.5 M aqueous NaCI solution in both cases) with 0.1 M aqueous NaCI washing solution segments in between. But the concept can of course be applied for all imaginable combinations of solutions. The loading of the tubing with the desired number of segments is the only task within the procedure which is, in embodiments, carried out manually but usually takes no longer than 10 minutes (in other implementations this may be automated). Subsequently, the tubing is connected to the microfluidic chip directly after plasma treatment and assembly, when the channel walls are still hydrophilic. Using a syringe pump the segments successively enter the chip, flush it and are blown out again by the respective following air segment in a completely automatic fashion. Applying a constant flow rate the length of the individual segment precisely determines the time the corresponding solution stays inside the microchannel. The final washing step is performed with distilled water in order to remove traces of salt from the channel walls.

We were already able to show the successful operation of this concept (Figure 2) Within a fluorescence study we systematically varied the number n of fluorescently labeled PAH segments within the tubing (2a). The analysis of the microchannels under the fluorescence microscope revealed an increase in fluorescence intensity with increasing numbers of labeled segments (2b). This proves that we are able to build up PEMs onto the channel walls in a controlled manner. Our automated LbL approach is not limited to straight channels but also allows for a homogeneous coating of more complex geometries (2c).

Furthermore, we studied extensively the effects of channel surface properties on the formation and stability of oil-in-water droplets. Referring to Figure 3, when the PDMS is not further modified after plasma treatment the hydrophobic recovery leads to instabilities and even phase reversion within no more than one hour, even if the experiment is started immediately after oxidation and chip assembly (3a), (3b). In contrast, when depositing a PEM by our automated procedure the hydrophilicity is preserved and stable, monodisperse oil-in-water droplets can be formed even after storing the device under air for at least 2.5 weeks after modification (3c), (3d).

Since our automated surface modification method deals with a fundamental issue in microfluidics, i.e. the fast creation of hydrophilic PDMS channels with long-term stability, the possible benefits are substantial. Whenever well-defined oil-in-water droplet are to be generated in microfluidic devices, e.g. for organic synthesis or for the creation of nano-and microparticles, our approach is a potentially useful option. Being not restricted to surface modification based on polyelectrolyte solutions and allowing for the selective modification of certain channels within one chip our technique also opens up new avenues for applications beyond the examples described above. Broadly speaking we have described a new automated technique for the modification of PDMS microchannels. Embodiments of the method may be employed with channels of a range of sizes, but are preferably employed with channels having a maximum transverse dimension of less than 1mm, and maybe employed with much smaller channels, for example less than 1 pm maximum transverse dimension. Embodiments of the methods combine a convenient and time-saving process on the assembled chip with versatility and long-term channel hydrophilicity.

Applications of embodiments of the invention are not limited to chips and may be employed with other microfluidic systems including, but not limited to: inkjet print heads, niicroarrays and other chemical/biochemical sensors and, more generally, to a range of microfluidic systems for handling fluids. Embodiments are, however, particularly advantageous for on-chip microfluidic structures such as so-called lab-on-a-chip (LOC) devices.

No doubt many other effective alternatives will occur to the skilled person. It will be understood that the invention is not limited to the described embodiments and encompasses modifications apparent to those skilled in the art lying within the spirit and scope of the claims appended hereto.

Claims

CLAIMS: 1. A method of layer-by-layer deposition of a plurality of layers of material onto the walls of a channel of a microfluidic device, the method comprising: loading a tube with a series of segments of solution, a said segment of solution bearing a material to be deposited; coupling said tube to said microfluidic device; and injecting said segments of solution into said microfluidic device such that said segments of solution pass, in turn, through said channel depositing successive layers of material to perform said layer-by-layer deposition onto said walls of said channel.
2. A method as claimed in claim I wherein said loading further comprises loading said tube with gas between said segments of solution to separate said segments of solution.
3. A method as claimed in claim I or 2 wherein said loading further comprises loading said tube with a segment of washing fluid between two of said segments of solution bearing material to be deposited.
4. A method as claimed in claim 1, 2 or 3 wherein said loading comprises coupling an end of said tube to each of a set of said solutions in turn in a reverse order to an order in which materials in said solutions are to be deposited and withdrawing said segments of said solution into said tube.
5. A method as claimed in any preceding claim wherein said injecting comprises injecting at a controlled rate, and further comprising controlling a duration of deposition of a said layer using a combination of said controlled rate and a physical length of a said segment in said tube.
6. A method as claimed in any preceding claim wherein said channel of said microfluidic device is defined in a plastic, the method further comprising pre-treating said plastic channel by exposure to an energy source to generate a hydrophilic surface on said walls of said channel, wherein said hydrophilic surface undergoes hydrophobic recovery, and wherein of said layer-by-layer deposition of said plurality of layers of material is started prior to 50% hydrophobic recovery of said hydrophobic surface.
7. A method as claimed in any preceding claim wherein said loading of said tube comprises loading said tube with successive said segments of solution comprising, alternately, positively and negatively charged polyelectrolyte each separated by washing solution and at least one gap segment from which fluid is substantially absent.
8. A method of using a microfluidic device to process droplets of an emulsion in an aqueous stream of fluid, the method comprising depositing a plurality of layers of material onto the walls of a channel of the microfluidic device using the method of any one of claims 1-7 to render said walls hydrophilic, and processing said droplets of said emulsion by passing said aqueous stream through said channel of said microfluidic device.
9. A method of fabricating a microfluidic device comprising treating the microfluidic device using the method of any one of claims I to 7.
10. A microfluidic device fabricated using or treated by the method of any one of claims I to 7.
11. Apparatus for layer-by-layer deposition of a plurality of layers of material onto the walls of a channel of a microfluidic device, the apparatus comprising: a system for loading a tube with a series of segments of solution, a said segment of solution bearing a material to be deposited; and a system for injecting said segments of solution into said microfluidic device such that said segments of solution pass, in turn, through said channel depositing successive layers of material to perform said layer-by-layer deposition onto said walls of said channel.