What role will materials play in making microfluidics a success?

Up until a few days ago I was pretty much unaware of microfluidics despite unwittingly being reliant on them. From blood vessels to the way moisture flows through plants, examples of microfluidics are everywhere in nature and much, if not all, of the life on the planet is driven by their function. The process that nature has been so elegantly able to exploit is increasingly being industrialised for a host of applications.

Initial developments began in the early 1980s driven primarily by the development of inkjet print heads. Since then advances in microfluidic technology has continued to revolutionise many molecular biology processes such as DNA analysis.

However, engineers working within medical and healthcare sectors are increasingly utilising these techniques to isolate the contents of various fluids for analysis. The aim is to develop microfluidic based devices capable of continuous sampling and real-time testing of air and water for biochemical toxins and other potentially dangerous pathogens. It is hoped the technology will enable a 'bio-based smoke alarm' for early warning of potential contaminants.

Microfluidics relies on the flow of liquid through tiny channels of the order of 100µm across. For polymers channels are etched, machined or moulded in to polymer films typically with a square cross-section, as circular cross-sections are more difficult. These channels can be treated to enable specific surface properties from being hydrophobic to hydrophilic or with specific biochemistry. This enables a continuous flow of liquid, or for droplets to remain fully formed whilst passing through the various channels and, if desired, to be analysed independently.

The layout and geometry of the channels on the polymer substrate can resemble that of a printed circuit board, however the purpose is to force liquids to combine or separate to enable some specific part of the liquid to be isolated and tested. To demonstrate the devices, coloured dyes are often injected in to them to visualise the pattern that the fluids have to travel through.

Microlitres of fluid tend to have factors such as surface tension, energy dissipation, and fluidic resistance dominate a system allowing these specific fluid behaviours to be studied and exploited. In doing so, information about the contents of the overall fluid is revealed.

A fluid passing through such small channels produces phenomena that can be quite unintuitive when first observed. For example, the Reynolds number is typically very low. This is the ratio between the effect of a fluids momentum against the effect of its viscosity. The result is that fluid interactions can be highly controlled in a flowing system.

"You don't see the chaotic mixing that you normally expect from moving liquids," says Tim Ryan, managing director of Epigem, a polymer micro engineering company specialising in the development and manufacture of microfluidic devices and micro optical components. "When you turn on a tap you get lots of bubbles and the whole thing is turbulent. In microfluidics the flow tends to be smooth and laminar so liquids don't really mix, other than very gradually through the process of diffusion. So you find some unusual things that allow for some elegant synthesis and analysis."

Epigem recently secured £2million of healthcare funding to begin working with doctors and medical specialists to develop microfluidic systems that will enable real-time and low cost analysis of blood, water and milk. At the moment, these fluid samples have to be sent to specialist labs for analysis to see exactly what a given fluid sample is comprised of. Part of the project is to identify opportunities to engineer inline monitors, to give instant feedback on any contaminants or potential health risks in a fluid sample.

The technology has the potential to dramatically speed up analysis by making it a continuous process rather than a sample led one. This will also reduce the cost of associated control measures. The deliverables focus around water, blood and milk and want to miniaturise the various separation and analytical processes to allow work to be carried out in real-time with high specificity and information content on smaller, but more frequent, samples.

"Epigem is using its experience of manufacturing microfluidic devices to design the systems to be used," says Ryan. "So we want to be able to take samples of a fluid, that might be via an inline device fitted to a water pipe, and be able to instantly isolate and identify the different sizes of bacteria and viruses contained within it. We are helping develop these instruments with other partners and we need to make sure that the data we are able to provide is exactly what they need."

The project needs the integration of multiple materials and functions including microelectronics, controlling electrodes, used in the manipulation and analysis of liquids, as well as micro-optics to allow samples to be analysed automatically or viewed under a microscope if required. As natural nano and micro particles often need to be studied in isolation, these projects are designing the process – and appropriate channel geometry – that will select and trap the various 'species' that might be present in the liquids being assessed.

Micro manufacturing
For the production of microfluidic device boards the use of transparent, recyclable acrylic sheets is convenient with channels, wells and through hole vias produced using automated machining combined with an aromatic epoxy for fine channels and microstructures typically 10 to 100µm in size. Opaque chemically and thermally resistant thermoplastics including PEEK are available as are a range of functional inserts including PDMS elastomer seals for interfacing, reuseably, to delicate MEMs sensors or glass / quartz windows or cultured cells. Plus Epigem's electrodes are embedded in the lid or base of a device to prevent leaking.

Epigem produce customised devices with a wide range of plug and play connectivity options for fluidic (gas and liquid) and electrical, optical, acoustics, magnetic I/O from its base in Redcar just outside Middlesbrough in a custom made clean room and hopes it is ready to serve very higher volume applications where its capabilities in reel to reel printed electronics such as film coating, printing, embossing, etching and electroplating will come into play using, for example, PET and PEN film as the substrate for flexible process boards and multilayer laminates.

"There could be significant benefit for early detection in this decentralised testing model and there are many high volume applications that could benefit from it in addition to well established examples such as pregnancy and diabetes testing," says Ryan. "Another exciting prospect going forward is not just to analyse the fluids but also to mimic specific environments. So there is interest in taking parts of the body and recreating the conditions in terms of their micro environment. For example, we might grow living cells and put them in the same environment as the blood stream to allow us to study their effect as if it were in a real living body. This could replace animal models in clinical trials, so it is trying to create something that is closer to real life."

Application: Lab-on-a-chip
Lab-on-a-chip (LOC) is a device that integrates one or several laboratory functions on a single piece of polymer material. These are only millimetres to a few square centimetres in size. The chip is usually a small plastic based film or block that has been machined to have many different sized channels at different geometries. The layout of these channels separate a liquid so a droplet isolated and analysed as necessary. Chemical analysis, environmental monitoring, medical diagnostics as well as areas of synthetic chemistry such as rapid screening and microreactors for pharmaceutics are all potential areas of interest.

Author
Justin Cunningham

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