Production of Plastic Components for Microfluidic Applications

a report by

D r N o r b e r t G o t t s c h l i c h

Greiner Bio-One

M i c r o f l u i d i c s

Microstructured components are being used in anincreasing number of different applications. The fieldof microfluidics is concerned with the handling ofsmall amounts of liquids and the handling of liquidswithin small geometric dimensions. In many cases,this involves the transfer of liquids in channels withcross-sections of just a few micrometres. The mainareas in which microfluidics are applied are:

• analytics/diagnostics (electrophoresis and lab-on-a-chip);

• chemistry (micromixers, reactors and heatexchangers);

• drug discovery; and

• liquid handling.

Manu f a c t u r i n g P r o c e s s e s f o rM i c r o s t r u c t u r e d C ompon e n t s

Up to now, microchannel structures have mostlybeen manufactured with small footprints and mainlyin glass or silicon, using standard etching techniques.The high precision and reproducibility of thistechnology – adapted from the semiconductorindustry – and the high chemical resistance of thesematerials speak in favour of this approach. Thisprocess has disadvantages if the component is to bemanufactured in large numbers. It is often desirable tosupply microfluidic components as disposableproducts (e.g. in order to prevent cross-contamination). This makes it necessary to include asmany parts as possible on a single wafer, to reduce thecosts associated with the production process.However, microfluidic components, although oftencalled microchips, are not as small as computer chips.For reasons of easy handling and in order to combineseveral functions on the component, the chips aregenerally not smaller than a few square centimetres.

Microstructured parts can also be made of plastic byhot embossing, injection moulding or injection-compression moulding. Plastics have the advantages

that they are much cheaper than glass or even silicon,that there is a large choice of different materials andthat large areas can be structured cheaply. Thousandsof microstructured plastic products can bemanufactured from one single master.

In the case of hot embossing, the microstructuredmould insert is pressed into a plastic substrate at atemperature above the glass transition temperature ofthe plastic. The mould insert is then cooled until theplastic starts to solidify again and the two are pulledapart. Structures of less than 1µm can be moulded withstructural precision using the hot embossing process.

In contrast, in micro-injection moulding, thepolymer is melted and then injected into a heatedcavity containing the microstructured mould insert.After opening the cavity, the injection-mouldedplastic components are ejected. Compared with hotembossing, shorter cycle times can be achieved ininjection moulding (by a factor of 10 to 100).

In many cases, the microstructured surface must besealed with a lid in order to produce a closed-channelsystem. In the simplest case, a lid or foil is glued ontothe plastic component. In this process, contaminantsor adhesives must not find their way into thechannels and deformation of the channel geometrymust not take place. Different joining methods suchas laser welding, ultrasonic welding, adhesivetechniques and diffusion bonding are used for thispurpose. Figure 1 shows the cross-section through aclosed microchannel of 100µm x 50µm.

Of decisive importance for the quality of the plasticcomponent is the precise manufacturing of themould insert. Depending on the structural size,precision and aspect ratio of the structure to bemoulded, different production methods are used (seeTable 1). Micro-milling techniques are used toproduce structures down to around 50µm in size.Micro-erosion techniques can be used to produceeven smaller structures.

Using the LIGA process (a German acronym thatstands for lithography, electroplating and moulding),mould inserts with the smallest of structures can be

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produced. If this method is used with ultravioletlithography, structures of down to 5µm in size withdeep-etch X-ray lithography of as small as 0.2µm canbe produced. A further advantage of these mouldinserts is their low surface roughness of less than10nm. These mould inserts can be used for both hotembossing and injection moulding. However, theoperating lives of such tool inserts are much shorterthan those of steel inserts. Figure 2 shows a tool insertmade of brass, produced by micro-milling, as well asa detailed view of a tool insert made of nickel,produced by ultraviolet LIGA.

Ma t e r i a l s a n d F o rma t s o f M i c r o f l u i d i c S t r u c t u r e s

The choice of material depends on the later field ofapplication of the components. Common selectioncriteria are:

• transparency;

• sterilisability;

• chemical resistance;

• biocompatibility; and

• surface properties (e.g. wetability).

In addition, the choice of material is also affected byaspects of manufacturing technology. In order tooptimally fill the cavities, the material should havevery good flow properties. A large number ofdifferent plastics can be used. Amorphousthermoplastics based on polystyrene, poly-methylmethacrylate, acrylonitrile butadiene orpolycarbonate are often used. Very good opticaltransparency and thermal properties are also providedby cycloolefin copolymer. Of the partially crystallinethermoplastics, materials on the basis ofpolypropylene or polyethylene are often used. Iftransparency of the component is not required but


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Figure 1: Light microscopic image of the cross-section

through a microchannel (100µm x 50µm) produced by

injection moulding in polystyrene. Before polishing,

the structure was embedded in plastic (identifiable in

the picture as a dark area). The good filling of the

moulding tool is shown by the clean edges formed

Bottom of picture: scanning electron microscope image of the cross-section through

a closed microchannel (100µm x 50µm), moulded in polymethylmethacrylate.

The cross-sectional image does not reveal any gaps or joint zones – proof of a

successful joining method.

Table 1: Comparison of the most commonly used

methods for manufacturing mould inserts for

microfluidic components made of plastic

Method Typical (lateral) Typical aspect

structural size [µm] ratio

Micro-milling 50–1000 1–10

Erosion methods 20–1000 1–50

Laser processing 5–50 1–50

Ultraviolet LIGA 5–500 1–3

X-ray LIGA 0.2–500 1–500

Figure 2: Mould insert made of brass, manufactured by micro-milling (a) and detail of a mould insert made

of nickel, manufactured by ultraviolet LIGA (b)

a) b)

Product ion o f P las t i c Components for Mic ro f lu id i c App l i ca t ions

good temperature and chemical resistance are,polyetheretherketone is ideal. The properties of thematerial can also be improved by additional surfacetreatments after moulding (e.g. plasma treatment).

Although the channels of a microfluidiccomponent are very small, this does not necessarilymean that the periphery required to operate thesystem is also small. The positions of the accessholes or possible electrical contacts as well as theformats of the component are determined by thenecessary interaction with peripheral devices.Starting with the standardised grid dimensions ofmicroplates with 96, 384 and 1,536 wells, GreinerBio-One has developed microplates with closed,microstructured channels made of plastic, in co-operation with the Karlsruhe Research Centre.The plate contains 96 identical channel structuresfor capillary electrophoresis (CE). Each individualstructure consists of two intersecting channels, atthe end of which there are access openings forpipetting the samples. The positions of thereservoirs are consistent with the standardised griddimensions of microplates, so that standardpipetting robots can be used for filling thereservoirs. Electrical contacts for the 384 openings(reservoirs) are provided via conductors that areintegrated into the microstructured plastic plate(see Figure 3). Another format often used in thefield of life sciences is the microscope slide formatof 25mm x 75mm. Figure 4 shows microscopeslides manufactured by injection moulding withmicrochannels for CE.

App l i c a t i o n s

Often, only aspects of the manufacturing technologyare considered and the quality of a microstructuredcomponent is only assessed on the basis of geometricfactors. However, it is the combination of thematerial chosen, the moulding and if necessary thesealing method that leads to a functioningmicrofluidic component.

The transport of liquids in microchannels is ofteninduced electrically. Many chemical analyses that areconducted in microchannels (especially CE) arebased on electrokinetic effects, called electro-osmosis and electrophoresis. It is important to knowthat the electrically induced movement of the liquidis an effect caused by the channel wall and that theflow velocity is dependent on the surface charge ofthe channels.

Many thermoplastics are mixtures of differentpolymers or contain additives for stabilising orimproving the flow properties in injectionmoulding. The electrically induced movement ofthe liquid can therefore, as a general rule, only be


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Figure 3: Microplate made of polymethylmethacrylate

with 96 microfluidic channel structures and integrated

conductors for capillary electrophoresis (CE). For

electrical contacting of the 384 reservoirs of the 96

CE units, conductors 400nm high and 400µm broad

were applied by means of physical vapour deposition

Figure 4: Microstructured Part with the Footprint of

a Microscope Slide

Figure 5: Electrokinetic injection of a fluorescent

dye into the microchannel. In the left-hand picture,

the liquid moves from top to bottom when a

potential is applied between reservoirs 2 and 4.

After application of a potential between reservoirs

1 and 3, the volume present in the intersection of

the channels is injected into the separation channel

determined experimentally. Ideally, thesemeasurements and function tests can be conductedon the finished component by the manufacturers ofthe plastic components.

Figure 5 shows a channel structure for CE. Thestructure consists of two intersecting channels, atthe end of which there are access openings forpipetting the samples. In order to move andseparate the sample mixture to be analysed in adefined way, electrical potentials are appliedexternally to the reservoirs. After the samplemixture has been separated, the constituents areoptically detected at the end of the separation

channel. A typical application is the separation ofDNA-restriction fragments.

A further interesting application of microfluidicstructures is in the field of protein crystallisation. Alarge number of different variables influence crystalgrowth, so the optimal conditions for crystallisation,especially of biological macromolecules, are notgenerally predictable. Hundreds of tests are oftennecessary to optimise crystallisation conditions. Withthe use of pipetting robots and standardisedmicroplates, it is possible to test a large number ofcrystallisation conditions in a short period of time andwith relatively small sample amounts. Microstructuresoffer interesting perspectives here. As a result of thesmall dimensions of the microchannels, only anextremely small volume of protein solution is required(see Figure 6). ■


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Figure 6: Protein Crystal in a Microchannel

Contact Information

Greiner Bio-One

Maybachstrasse 2

D-72636 Frickenhausen

Germany

Tel.: +49 7022 948 0

Fax: +49 7022 948 514

e-Mail: [email protected]

http://www.gbo.com/bioscience

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Production of Plastic Components for Microfluidic Applications