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Making Microfluidics: Compression molding as an alternative to PDMS and injection molding for microfluidic devices

Injection molding, a mainstay for the manufacture and fabrication of thermoplastic parts, has proven itself useful in the production of plastic microarray and microfluidic devices. The advent of microinjection molding, which offers exquisite temperature control and precision microfabricated mold inserts, has brought numerous disposable plastic microdevices to market, such as the Simoa™ Disc (Quanterix), DropPlate (Unchained Labs), and MALDI-MS (Biomérieux / Shimadzu Biotech).

In injection molding, thermoplastic is injected in molten form into a closed cavity, allowing for higher throughput and superior durability compared to the traditional material of microfluidics, polymethylsiloxane (PDMS.) The downsides of this process include high mold costs, long tool fabrication time, and significant geometric limitations on possible microfeatures.

An alternative form of manufacturing, embossing, offers numerous advantages. In embossing, plastic starts in solid form inside an open cavity and is thermoformed by a combination of heat and pressure as the cavity closes. Microfluidic devices fabricated by embossing have improved replication accuracy, less shrinkage and warpage, and lower overall cost compared to devices made using injection molding^[1,2].

Comparison of injection molding and embossing. Demonstrates, among other differences, the uniformity of temperature between part and mold in embossing.

Figure 1: Comparison of injection molding and embossing processes.

Embossing with soft tools

Embossing itself can take several different forms. The most widely-used version, known as “hot embossing” or “hard embossing”, involves pushing a heated mold into a plastic block or sheet, imprinting features onto the plastic surface.

Edge Embossing uses a form of embossing called “soft embossing”, where mold surfaces are made from a high-durometer elastomeric material that faithfully reproduces features ranging in size from macroscale through-holes and reservoirs to microscale channels, wells, and even sub-micron features. Unlike hard embossing, the entire shot of plastic reaches a uniform melting temperature, allowing thermoforming of both large features and exquisite microscale features. The elastomeric nature of the tool’s surface allows for the molding of delicate microfeatures with high aspect ratios and little to no draft angle, as well as a gentle ejection process that prevents damage to the part or the tool.

Fabricating microfluidic devices by soft embossing

To illustrate how the embossing process is implemented, consider the steps involved in fabricating a microfluidic device designed to generate picoliter-sized droplets. A simplified schematic of a droplet generating device is shown in Figure 2. The device functions by introducing two immiscible fluids at a T-junction. By varying the flow rates, fluid properties, and channel dimensions, monodispersed droplets of tunable sizes can be produced at kHz rates^[3].

Illustration demonstrating a means of generating microscale droplets using two inlets feeding microfluidic channels joined at a T-junction, and a single outlet.

Figure 2 – Droplet generating device featuring two inlets that meet at an interface producing regular microscale droplets. As the dispersed phase fluid (supplied by inlet 1) enters the primary channel containing the continuous phase (supplied by inlet 2) the dispersed phase is exposed to shear forces that elongate the portion of the fluid extending into the primary channel, eventually forming a neck and breaking off into monodispersed droplets.

1) Template microfabrication

The first step in fabrication is to translate the 2D layout from Figure 2 into a “template” that matches the 3D topography of the microfluidic device. There are several approaches to fabricating a template, but the most common method for generating micron-scale features is to use photolithographic tools to generate a silicon wafer with photoresist structures (positive features) or an etched geometry (negative features) as shown in Figure 3.

Silicon wafer bearing positive and negative features for microfluidic channels joined at a T-junction.

Figure 3 – Illustration of a silicon wafer featuring positive features (bottom left) and negative features (bottom right).

2) Tool fabrication

In standard hot embossing, this silicon wafer can be used directly as a template to imprint the microfluidic pattern into a plastic blank, but the tool will wear over time, until the wafer must be replaced.

Edge Embossing uses the silicon wafer (or any other type of template) to build a secondary elastomeric tool. The elastomeric tool is an accurate negative replica of the template structure, translated into a durable but flexible elastomer. This tool can be used to emboss thousands of parts with challenging microfeatures, all while preserving the integrity of the original template.

3) Blank selection

The soft embossing tool is used to imprint or mold a blank plastic substrate. The blank is typically sized to dimensions very close to those of the final part. As a result, the polymer requires minimal flow to form the surface structures, in contrast to injection molding, where significant flow is required to fill the mold cavity.

Edge Embossing can produce parts using most thermoplastic polymers. We stock frequently ordered materials such Cyclic Olefin Copolymer (COC), Cyclic Olefin Polymers (COP), Polypropylene (PP), Polycarbonate (PC), Polystyrene (PS), and Polymethyl Methacrylate (PMMA). We can also source custom resins or work with client-supplied materials.

4) Embossing

The embossing process is comprised of 4 steps and requires a specialized press that allows precise control of temperature and force:

The soft embossing tool and plastic blank are heated to a material-optimized temperature.
The soft embossing tool is pressed with controlled force into a plastic blank, creating the desired microfluidic geometry.
Both the soft embossing tool and device are actively cooled. By continually applying force during cooling, shrinkage and warpage due to cooling are minimized.
After the soft embossing tool and device have sufficiently cooled, they are separated, or de-molded. The plastic microfluidic device is now ready for post-processing.

Edge embossing offers post-processing services, including packaging and lidding of the final microfluidic device.

Illustration showing an embossing tool under under heat applying force to a blank, which is allowed to cool and then de-molded.

Figure 4 – Illustration of the embossing process.

Greater design flexibility and extended master lifetime

The process described above offers several advantages compared to techniques using rigid microfabricated mold inserts.

The elastomeric nature of the secondary tool allows for the production of device geometries that would otherwise be problematic, including zero-draft angle, high aspect ratios, and undercut features.
The original master mold is preserved in its original condition, used only once to create the secondary tool.
The secondary tool can be used to create tens of thousands of final parts. The cost of generating a new secondary tool is significantly lower than making a new microfabricated master.

Plastic parts with less built-in stress

Another major advantage the soft embossing process is the low thermal stresses in the final manufactured parts.

In injection molding, there is a significant thermal gradient between the tool itself and the molten resin introduced into the cavity. This gradient, combined with the high-speed flow of the plastic, causes substantial internal stresses in the finished part. Such stresses can lead to warp, premature fatigue, and substantial nonuniformity of optical properties.

For hard embossed parts, although resin motion is reduced by eliminating the molten injection step, there is still a sharp temperature gradient between the tool and the plastic, and between the thermoformed and non-thermoformed portion of the finished part. This can result in significant stresses.

In soft embossed parts, the entire mold is heated and cooled at the same time as the plastic, and the resin is stationary inside the cavity. Since all the plastic (not just the surface) is heated and cooled to a uniform temperature during the cycle, all major sources of stress are eliminated.

Summary

There are many approaches to transitioning microfluidic design to a manufacturable plastic device. Compared to other techniques, soft embossing imposes fewer design constraints on the geometries of microfeatures, produces parts with less built-in stress, and requires a significantly lower investment for tool production and replacement.

References:

[1] Wu, C.H. & Kuo, H.C. J Mech Sci Technol (2007) 21: 1477

[2] Worgull, M., Heckele, M. & Schomburg, W.K. Microsyst Technol (2005) 12: 110

[3] Teh, S., Lin R., Hung L. & Lee A. Lab on a chip (2008) 8: 198

Sealing Methods for Embossed Microfluidic Devices

Blog / By Edge Precision Manufacturing

Open geometries are an inherent characteristic of the embossing process. In the fabrication of microfluidic devices, embossing is often used to pattern open-faced, recessed microfluidic pathways on the surface of a polymer substrate. While a subset of microfluidic devices, such as open capillary systems, are designed to operate in an open configuration, most microfluidic applications require the channels to be enclosed on all sides. For example, the simple microfluidic device shown in Figure 1 has channels that are that only partially defined by the embossed substrate and require an additional lidding step to seal the device.

Figure 1 – An example embossed microfluidic device. The device on the left illustrates an open channel geometry, while the device on the right shows the addition of material that closes channels while still allowing access to inlets and outlets.

Generally, a lid serves three purposes^[1]:

It fully defines the boundaries of the channels.
It seals the enclosed volume to allow for fluid flow.
It facilitates selective access to parts of the device, such as inlets and outlets.

There are a few common techniques for sealing microfluidic devices made from thermoplastic. The suitability of each approach for a given application will depend on factors including substrate material, critical dimensions, intended operating conditions (temperature and fluid pressure) and the chemical sensitivity of the assay.

Direct Bonding and Indirect Bonding

Sealing techniques fall into two categories: direct bonding, in which two components are bonded through alteration of the polymer’s surface characteristics, and indirect bonding, in which an intermediate layer adheres the two surfaces^[2]. The advantages and drawbacks of each bonding method depend on the specific application and the polymer material of the embossed device. The compatibility of different polymers with each bonding method is summarized in Table 1.

Table 1 – Suitability of bonding method for common polymer substrates: Highly suitable (+++) to non-applicable (-).

Adhesive Bonding

There are two types of indirect adhesive bonding: pressure sensitive and structural. Pressure sensitive adhesives (PSA) are engineered tapes that feature a carrier film and an adhesive coating that is activated by application of uniform pressure. Structural adhesives are liquid based epoxies or adhesives that are activated by chemical processes; for instance, UV- activated adhesives.

Perhaps most suited for rapid-prototyping and disposable devices^[3], PSA films have a thin adhesive coating on one side of a plastic carrier film. Lamination of such a material to seal a microfluidic device is often straightforward, typically done at room temperature, by hand or with the aid of a laminator machine.

Microfluidic devices lidded with PSA film are desirable for their ease of fabrication. However, interior channels are often exposed to the adhesives present on the tape. There are several commercially available PSA tapes coated with adhesives that feature low leachables, minimal outgassing, and low autofluorescence — for example, 3M 9795R or ARseal™ 90697. Recent studies on PSA used for lidding have shown functional biocompatibility of specific types of PSAs that make it feasible for organ-on-a-chip devices^[4].

In practice, PSA film lamination has limitations specific to the geometry of the microfluidic device. The unsupported region of the lamination film, over channels or other features, can deform inward. The degree of deformation is dependent on several variables, including the amount of force supplied during the lamination process. However, a more structurally robust PSA that limits deformation during lamination can be used^[5].

Solvent Bonding

Solvent bonding is a direct bonding method, where the surface of the two polymeric layers are softened with solvents and pressed together. By applying specific solvents to the material surfaces, the polymer-chains gain a degree of mobility and the ability to form new bonds as the solvent evaporates. This method requires specific knowledge of polymer-solvent solubility and may require increased temperatures in order to reach required solubility for creation of bonds^[6]. This technique can lead to very strong bonds, as compared to thermal bonding^[7], but process parameters, such as excessive solvent exposure time, can lead to deformation or obstruction of the channels^[6]. Finally, solvent bonding may be problematic for some applications as residual solvent may be present in the device that can have adverse effects on sensitive chemical assays.

Thermal Bonding

Like solvent bonding, thermal diffusion bonding relies on the interdiffusion of polymer chains at the interface between polymer layers. Instead of introducing a solvent, polymer chains are mobilized by heating the layers to, or near, the glass transition temperature, the point at which the polymer-chains gain sufficient thermal energy to diffuse and form new chain-to-chain bonds upon cooling. In addition to temperature, bonding pressure and hold-time affect the strength of the diffusion bond. Above the glass transition temperature, the material properties of the polymer change, resulting in a marked decrease in stiffness^[8]. Bonding the device at the glass transition temperature may have undesirable effects, such as deformation of channel geometries^[7]. Therefore, the temperature used to thermally bond the lid to the device is typically lower than the glass transition temperature^[9] and should be optimized experimentally for each polymer and application.

Bonding duration and channel width both affect the degree of channel distortion during thermal bonding, as illustrated in Figure 2. Using a laser confocal microscope to image through a lidded device, height profiles of the top and bottom surfaces of a bonded microfluidic channel were mapped and compared to the initial unbonded geometry. A cross section of the height profile shows that both the top and bottom surfaces of the bonded device have crept into the channel under pressure, reducing the height of an initially 50µm tall channel. The reduction in channel height for designs with three different channel widths and two different bonding times are shown in the bar graph in figure 2c). Excessive bonding temperature, time, and pressure may lead to lid sagging and should be dialed back to a point where feature deformation is minimized while still achieving the target bond strength.

Figure 2 – a) 3D height profile of a thermally bonded microfluidic T-junction. b) Cross sectional height profile showing top and bottom surface of the channel. c) Reduction in channel height due to lid sagging for 3 different channel widths and two different bonding durations. These acrylic parts were bonded at 100°C under a pressure of 2MPa.

Surface Activation

In addition to the methods of sealing microfluidic devices listed above, device lidding can also be facilitated by surface activation, in which the surfaces to be bonded are exposed to chemically altering process such as oxygen plasma, UV-ozone, or silane modification. Generally, these processes do not penetrate the material, but only activate the exposed surface of the polymer, introducing functional groups. For instance, PMMA exposure to oxygen plasma leads to the temporary creation of reactive oxygen-containing groups^[10]. These reactive groups allow for the creation of a strong chemical bond when two activated surfaces are brought together. Surface activation can be combined with thermal or solvent bonding to significantly increase the overall bond strength^[3].

Sealing an embossed component is a critical step in realizing a fully functional microfluidic device. As discussed above, there are several factors to consider when selecting the right bonding technique for your application. As such, this step should be taken into consideration early in the process of designing a microfluidic device and selecting its materials. Edge embossing, a custom embossing company, offers post-processing services including packaging and lidding of the final microfluidic device.

References:

Considerations When Switching from PDMS to Thermoplastic Microfluidics

Blog / By Edge Precision Manufacturing

PDMS is an elastomer which holds many appealing properties for use in microfabricated systems. It has been widely used in research since its first published use by George Whiteside’s group in 1997^[1]. Since then, ease of fabrication and relatively low costs have made PDMS a staple of microfluidic research.

The PDMS fabrication process involves mixing elastomer and curing agent, which is then cast on a mold. This mold is typically either cured PDMS, polymer, or (most commonly) a wafer prepared using photolithography. While this process offers much for research and prototyping purposes, low throughput and difficulty of scale-up mean that development of mass produced PDMS parts is unfeasible.

Therefore, the majority of commercial microfluidics parts are manufactured from rigid thermoplastic. Many parts, however, must be transitioned from their original PDMS prototypes to thermoplastic during commercial development. Here, we present some necessary considerations for this process.

Thermoplastics

A range of thermoplastics are used in microfluidics and each has different properties which are desirable for different applications. The most regularly used are polycarbonate (PC), polystyrene (PS), poly(methyl methacrylate) (PMMA), polyvinyl chloride (PVC), polyimide (PI), and the group of cyclic olefin polymers (CO polymers) which includes cyclic olefin copolymer (COC), cyclic olefin polymer (COP), and cyclic block copolymer (CBC)^[2].

Mechanical Properties

PDMS is a flexible silicone which, when placed under pressure, will deform. Researchers have used this property to integrate pressure actuated valves into parts in order to control fluid flow. When transitioning from PDMS to thermoplastic, alternative flow control systems must be implemented and flow control elements must be in place to replicate the valves integrated into PDMS parts.

Contrariwise, the flexibility of PDMS parts makes integration with hardware, such as fluidic connectors and device holders, more difficult. This problem is alleviated when moving to thermoplastic, which is easier to integrate with robust surrounding fluidics, sensors, and hardware.

Biocompatibility

PDMS parts are widely used in biological and biochemical research applications such as cell culture and biocatalysis. While non-toxic to cells, PDMS is prone to adsorption of biomolecules due to the hydrophobicity of its surface. Many thermoplastics used in microfabrication also exhibit high biocompatibility and offer improved adsorption properties compared to PDMS. Treated PC and PS are used in conventional cell culture systems. Following treatment, PC, PS, and CO polymers also allow for high cell viability and growth, while PMMA has been shown to be less suitable for cell culture applications. The adsorption properties of the thermoplastic has been shown to be similar, with PC, PS and CO polymers demonstrating lower adsorption rates than PMMA and PDMS. These properties can be further improved with surface treatment through chemical, UV-ozone, or plasma treatment^[3].

Gas Permeability

PDMS has a much greater level of gas permeability than thermoplastic. In applications requiring gaseous exchange, careful consideration must be taken when transitioning from PDMS to thermoplastic. Of the most widely used thermoplastics, CO polymers are the most gas permeable, followed by PC and PS, with PMMA being the least gas permeable^[4]. The low gaseous exchange rates of thermoplastics, however, are usually insufficient to maintain controlled oxygen, carbon dioxide, and pH conditions in systems which require close microenvironment control. In these cases, either a window of gas-permeable membrane or a method of flowing fresh solution through the system may be required.

Fluid Interfacing

Methods of controlling the hydrophilicity of both PDMS and thermoplastics have been widely documented in research. Increased hydrophilicity can be achieved through a range of techniques, the most common of which is plasma treatment. Surface activation is widely used in PDMS part fabrication as a bonding technique, a means for greatly increasing hydrophilicity^[5], and for improved fluid flow through microchannels. The same techniques can be used to increase the hydrophilicity of each of the thermoplastics discussed above. Plasma and UV-ozone treatments and salinization processes have been widely shown to be effective techniques for the activation of PDMS, COC, PMMA, PC, and PS. Thermoplastics are more responsive to surface activation techniques than PDMS, meaning a greater range of fluid interfacing conditions are possible in systems made of thermoplastic. Like PDMS, thermoplastic surfaces are also prone to hydrophobic recovery over time, meaning that treatments are not permanent and will reverse. This must be factored into the fabrication process of the part^[3].

Chemical Resistance

Many thermoplastics have wider chemical compatibility than PDMS. Therefore, when transitioning from PDMS, there are a wealth of options depending on the required application. PDMS has poor resistance to solvents and both acids and bases compared to PC, PMMA, PS and CO polymers. CO polymers have excellent solvent resistance properties and offer the widest range of acid and base tolerance, of commonly used thermoplastics^[6].

Lidding/Bonding

Lidding is the process of enclosing the features of a microfluidic part to ensure that it is leak free and the contents are fully enclosed. Most PDMS parts are lidded by bonding the underside of the part to a glass slide following activation of the surfaces, typically through plasma treatment. A range of techniques are available for the sealing of thermoplastic systems, which can be reviewed in our article on microfluidic lidding. Briefly, a range of solvent, adhesive, and thermal bonding techniques are available for the bonding of thermoplastic parts. The bonding technique must be carefully chosen and optimized in order to maintain the surface properties, features, and optical properties of the part. Each of the techniques is more suitable to large-scale part production than the PDMS glass bonding techniques usually used in small-scale research laboratory settings.

Optical Properties

Many microfabricated parts require optics to monitor the processes in the system. PDMS and glass have high transmittance and optical transparency across most useful wavelengths. The most commonly used thermoplastic materials are transparent and show near-100% transmittance over a wide range of wavelengths. Of these, CO polymers have the best transmittance, with high transmission between 300 and 1200 nm. PMMA also has a very wide range of transmission wavelengths, followed by PS and PC.

Glass and PDMS have lower autofluorescence levels than commonly used thermoplastics, but they are comparable for most applications, with CO polymers exhibiting the lowest autofluorescence^[7].

Fabrication Techniques

Typical PDMS parts fabrication involves casting PDMS on a pre-prepared mold. While suitable for early prototyping and development of parts, this is unfeasible for mass production. When moving to thermoplastics, there are a range of fabrication techniques available for both rapid prototyping and mass production of replicated parts. This means there are suitable processes for each stage of the development of a microfabricated part.

Prototyping Methods

Laser ablation
- A range of laser ablation techniques have been used for fabrication of thermoplastic parts. Broadly, laser ablation methods are low cost, rapid, and useful for prototyping. They involve the removal of material with a focused laser beam, which causes melting. While quick, this limits feature size, surface roughness, and resolution^[8].

Micromilling
- A relatively low throughput technique, micromilling allows for smaller features, improved surface roughness, and better feature resolution compared to other prototyping techniques. It is suitable for fabrication with all commonly used thermoplastics^[9].

Replication Methods
- Once the design of a thermoplastic part is finalized, the most efficient and commonly used techniques involve the replication of the design from a mold. There are a range of techniques to achieve this.

Injection Molding
- Injection molding is one of the most well-characterized methods for mass production of microfabricated parts. High up-front costs during mold development and production are balanced by reproducible, high throughput, and low cost part production. Thermoplastics are melted at high temperatures and injected into a mold before cooling. This allows for the production of parts whose feature size, resolution, and surface roughness is limited to that of the mold^[10].

Embossing
- This process involves heating a preformed thermoplastic blank above its glass transition temperature but below its melting temperature, inside of an embossing tool. The part is then embossed under pressure, cooled, and de-molded to transfer the desired design from the embossing tool onto the part. Feature size, resolution, and roughness are dictated by the embossing tool used. This process offers advantages such as reduced shrinkage and warping of the microfabricated part, as well as high throughput. It is well suited for most thermoplastics.

A full consideration of the relative advantages of this technique can be found in our article comparing soft embossing to injection molding and PDMS.

Final thoughts

PDMS continues to be a critical material for testing microfluidic concepts in the lab, but there are many reasons to transition to different materials when developing a microfluidic product. In most cases, the material properties of PDMS are not suited to the final application, and it is not feasible to manufacture PDMS devices at scale, due to the cost constraints and volume requirements of commercializing a consumable device. Thermoplastics offer an attractive alternative that is well suited to large-scale manufacturing and has been vetted in many biomedical products. When making the switch to thermoplastics, there are substantial benefits to doing so early-on in the product development cycle. Some modifications to your process are likely, but addressing these changes early can prevent larger and more costly headaches down the road.

References