Engineering Insight

Applying Microfabrication Techniques to the Manufacture of Multifunctional Lab-on-Chip Devices


Posted by Camilla Andersson on February 1, 2013

Multifunctional microfluidic systems are gaining popularity in the life sciences. Their manufacture requires a fully integrated process chain and command of several advanced microfabrication technologies.


Miniaturisation enables the development of sensitive devices that, because of their compact dimensions, lend themselves to applications requiring high levels of parallelisation. At the same time, the use of appropriate microfabrication and wafer-level processes enables the manufacture of large volumes of components (singulated or in arrays) at relatively low cost. Consequently, the development of miniaturised analytical instrumentation is now a major aspect of research across many of the applied sciences.

Figure 1: Microelectromechanical system chips, sometimes called lab-on-chip systems, integrate several laboratory functions.
 

In particular, there is growing interest in the use of microfabrication methods—a combination of physical chemistry, electrical and/or optical properties at a small scale—for the production of a multi-µ-functional system. In clinical, environmental and life-science applications, so-called lab-on-chip (LOC) systems integrate several laboratory functions on a single chip (Figure 1). Passive or active LOC devices endowed with multi-µ-functionality can provide a cost-effective solution for clinical point-of-care and other diagnostic tasks, environmental monitoring and biochemical and forensic screening applications.

Compared with conventional screening methods, LOC technology achieves faster results with fewer inputs: less volume, less power, less waste and less time. The net result is faster and more-efficient processing at a lower price point, so the possibilities as well as the opportunities are significant.

Microfluidics in lab-on-chip devices
Microfluidic channels in LOCs reliably and accurately transport minute amounts of fluid or gas. Fluids in the microchannels can be transferred by means of external actuation (pumping or the application of electric fields, for example). However, capillary force is sufficient to induce liquid flow (albeit at very low rates), and this can be an attractive alternative to complex active actuation. The end user can freely choose the route that is best suited to an application, as the technological issues have long been resolved.

 Figure 2: Printed electronics can extend the functionality of lab-on-chip devices.

The behaviour of fluids at the microscale can differ significantly from macrofluidic behaviour, and this can be exploited in microfluidic systems to enable, for example, high-resolution printing systems that eject picolitre volumes of ink, or high-throughput screening at the nanolitre volume level using arrayed systems. More often than not, these types of structures require supplementary surface modification at well-defined locations (for example, at points around individual elements of an array) to achieve the desired functionality and, thus, the intended analysis.

Material choices
Silicon is an established medium for microfluidic and LOC systems, largely because of the extensive microfabrication tool kit and associated facilities readily available to process the material. Glass is the material of choice when on-chip processes need to be observed, and where the system may also need to provide some degree of optical performance. Both materials can be accurately etched and machined to yield the required structure, are chemically inert, physically robust and massively abundant. Certain types of glass also can be moulded.

Figure 3: CDA and University of Helsinki researchers developed a µPESI platform.

Nevertheless, the vast majority of applications are equally well served by various types of plastics, such as polycarbonate, PMMA and cyclo-olefin-copolymers. In addition to matching the performance of glass in many applications, these materials are lighter and more cost-efficient, and they lend themselves to high-volume injection moulding processes. CDA GmbH (Suhl, Germany) is a specialist manufacturer of microfabricated multi-µ-functional products in plastic, including components and devices for microfluidic and micro-optical applications.

CDA’s microfabrication techniques permit the manufacture of accurate microchannels with high aspect ratios to facilitate the precise transfer of liquid or droplets along the channels. Typical channel depths range from 50 nm to 250 µm in high aspect ratios. An array of micropillars embedded in a wider channel is an alternative technique for moving fluids across the chip.

Component and system manufacture

Figure 4: Micropillars in a microfludic channel are used to bring samples to an ESI tip.

To build complex structures, CDA uses a modified mastering and injection moulding approach with subsequent multistep postprocessing techniques.

Development begins with mastering, meaning that optical lithographic, diamond turning or etching processes are used to achieve the types of fundamental structure specified by a customer. Prototyping is followed by transfer to volume production, including process qualification for quality assurance. If masters already exist, they can be flexibly incorporated into the workflow. The special replication technology allows structure resolution well below the wavelength of visible light, with positioning accuracy of around 1 µm. For more sophisticated structures, subsequent bonding, machining, metallisation, assembly and surface treatment steps allow the realisation of complex, multifunctional devices. As many as 40 different process steps can be part of the assembly process of a single device.

Application diversity through added functionality
Various functionalities can be combined in the LOC to optimise its performance. Transparent materials allow the flexible integration of optical elements (Figure 2) to couple excitation light into and fluorescent light out of a structure, for example. Surface patterning at the submicrometre level and coatings can enhance specific optical performance. Coatings can also induce specific physical properties: hydrophilic surfaces improve capillary flow of polar liquids, while hydrophobic coatings such as PTFE can reduce cross-contamination among arrayed devices.

Plastic welding can be used to effectively bond the device and to impart gas-tight sealing to specific areas of a device. The use of systems without optical absorbers minimises contamination issues in certain critical biological and chemical systems.

A recent development at CDA involves the use of printed electronics (Figure 3) in a device as a track circuit, switch or capacitive and inductive electronic component. Through a combination of multilayering and structuring steps, these elements can be creatively and cost-effectively integrated in an LOC system. The process is capable of high-volume production speeds and achieves feature sizes down to 100 µm.

A case in point
 

 Figure 5: Micropillars in a microfludic channel are used to bring samples to an ESI tip.

CDA has manufactured a micropillar array electrospray ionisation, or μPESI, platform1 (Figure 4). Sixty identical μPESI chips are equally distributed around the periphery of a disc, each of which has a sample introduction spot connected to a straight flow channel that ends in a sharp ESI tip. The channel is embedded with a regular array of micropillars (Figure 5) that provide sufficient capillary force to drive a liquid sample from the introduction spot to the ESI tip without external actuation. In the platform, each individual microchip is surrounded by a hydrophobic coating to prevent cross contamination and is fabricated with all the necessary conducting paths for ESI implementation.

Integrated approach
Clinical, environmental and life-science applications benefit from the introduction of integrated biochemical analysis devices and cost-efficient LOC systems. The vast majority of these devices can be fabricated from plastic and incorporate multi-µ-functionality through the combination of multiple technologies in a single system. The manufacture of such devices requires an interdisciplinary and fully integrated approach, and requires expertise in the fields of lithography-based microsystem technology, micro-optics, nanotechnology and precision engineering.

References
1. http://www.ncbi.nlm.nih.gov/pubmed/21769340



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