continuous flow microchannel reactor

Microfluidic Chip holders

Various materials can be applied in the production of microfluidic devices. Each material has different characteristics and hence, requires a distinct micro-structuring technique. For metal, the relevant technologies are precision mechanical machining, laser machining, and electro discharge machining. For silicon, we use wet chemical etching and dry etching (DRIE). Wet chemical etching is also a suitable technology for structuring glass, but in addition to that, direct laser structuring, powder or sandblasting as well as photostructuring can be chosen according to the requirements. Elastomers can only be processed via casting.

The most flexible material is the thermoplastic polymer. Thermoplastic polymers can be processed via injection molding, thermoforming, hot embossing, laser machining, and precision mechanical machining. Here injection molding as a replicative technology allows for the most cost-efficient fabrication of micro-structured devices.

The fabrication of a lab-on-a-chip system requires more than just the micro-structured part. Usually, you need at least a cover lid placed on the micro-structures, requiring special assembly technologies. For glass and silicon, established processes are at hand, easily exceeding 100°C temperature, even for “cold” processes. The elastomer silicone can be easily mounted onto itself or glass and silicon, but the joint can be released.

Microfluidic chips can be produced using various methods (photolithography, molding, etching, embossing, 3D printing), allowing to design micrometric structures such as channels, chambers and wells. The main materials for chip production are inorganic materials (glass, silicon, ceramic…), polymers (COC, PMMA, PDMS …), or organic materials (generally paper). The material dictates chip properties. It is thus essential to consider the end-application while selecting or producing a chip.

I. INORGANIC MATERIALS: SILICON AND GLASS

Glass Microfluidic Chips & Glass Microchannel Processing

Glass is the material of choice if you work with elevated temperatures or organic solvents. We offer standardized glass microfluidic chips in microscopy slide format with through-holes as fluidic interface. They are made by wet etching (isotropic etching) to achieve quite smooth surfaces. In order to facilitate the handling of these glass chips, respective accessories are available.Custom designs can be realized on demand.

Inorganic materials were the first to be used in microfluidics as they were previously also used in applications with microchannels, such as glass or quartz capillaries for gas chromatography and capillary electrophoresis (CE). With the introduction of the MEMS technology, the first-generation microfluidic chips were prepared in silicon or glass, usually processed with standard photolithography. Glass is optically transparent and is an insulator, while silicon is opaque. Glass and silicon are highly rigid materials, have high stability at high temperature and are highly resistant to organic solvents. Moreover, as glass/silicon chips are usually produced via photolithography, it allows to reach sub micrometer channel dimensions with high reproducibility. Compared with standard CE, on-chip CE is lower in cost, easier to parallel, and offers valve-free injection (utilizing the electroosmotic flow), which can separate analytes within seconds. Because of the high thermostability and solvent compatibility, on-chip reactions and droplet formation are also well-suited applications with silicon/glass.

The main issue with these materials is their production cost: expensive and dangerous chemicals are involved, usually requiring well-trained lab technicians and expensive facilities. These chips are not suited for low/medium scale production. Also, a microfluidic chip in glass is not permeable to gas. Though it is compatible with biological samples, it not suitable for cell culture. Finally, high rigidity makes these materials fragile, and additional care is required when manipulating them.

These limitations led to the development of other chip materials that can be easily fabricated and are compatible for broader biological applications.

PRODUCTION METHODS FOR SILICON MICROFLUIDIC CHIP: PHOTOLITHOGRAPHY

Several methods have been developed for the fabrication of silicon-based microfluidic chips, including bulk micro-machining, surface micromachining and buried channel methods.

II. POLYMERS

Polymer-based microfluidic chips were introduced several years after silicon/glass chips. The wide variety of polymers grants great flexibility in choosing a suitable material with specific properties. Polymers offer an attractive alternative to glass and silicon as they are easy to access, usually less expensive, and with good overall physical properties. Many polymers can be used to build chips, such as polystyrene (PS) polycarbonate (PC), polyvinyl chloride (PVC), cyclic olefin copolymer (COC), polymethylmethacrylate (PMMA) or polydimethylsiloxane (PDMS). Polymers can be classified into three different groups: elastomers, thermoplastics and thermosets.

Elastomers

Elastomers are amorphous polymers maintained above their glass transition temperature, so that considerable molecular reconformation, without breaking of covalent bonds, is feasible. At ambient temperature, such materials are relatively compliant and deformable: they can stretch or compress when external force is exerted, and return to the original shape when the external force is withdrawn. The most popular elastomer in microfluidics is polydimethylsiloxane (PDMS) because it is relatively easy to produce and low-cost. PDMS has additional advantages such as biocompatibility, oxygen and gas permeability, optical transparency, and non-toxicity.

Though PDMS is useful for easy and fast prototyping, soft lithography is not well suited for mass production. Reproducibility is a challenge, and it is time consuming to make a large number of devices. PDMS is also hydrophobic. As a consequence hydrophobic analytes can adsorb onto the PDMS surface, potentially interfering with analysis. Surface treatments can be performed to mitigate issues, but can also be time-consuming and the treatment can lose its efficiency over time. They are not suitable for high pressure operation as higher pressures alter channel geometry and they may be prone to leaking at elevated pressure.

PDMS is the material of choice for fast prototyping of microfluidic devices, and PDMS chips are thus commonly used in laboratories, especially in the academic field. The most popular fabrication method for producing PDMS chip is soft lithography. In this method, liquid PDMS is mixed with a curing agent to crosslink the polymer. The amount of the curing agent used defines the hardness of the final product. The whole solution is subsequently cast over a master (typically silicon-based) mold . The master is placed in an oven at around 60°C for 1 h to 4 h to allow crosslinking. Once cured, the PDMS is easily peeled off from the master mold. At this point, open channels are obtained, and the PDMS needs to be bonded to another surface to form enclosed channels. It can be bonded to several materials, such as glass or back to PDMS. This is done by performing a plasma treatment on the surfaces to be bonded (most common method), mechanical, or chemical bonding.

Thermoplastics

Thermoplastics are highly crosslinked polymers that can retain their shape after cooling. Thermoplastics are usually fabricated by thermomolding that allows the production of thousands of replicas at high rate and low cost, which is excellent for commercial production. It is possible to reach sub micrometer channel dimensions, and they are transparent materials, allowing for microscopic analysis. Depending on their application, the surface of thermoplastics can be modified by coating or surface grafting. Covalently modified surfaces are generally more stable for thermoplastics than PDMS. They can be easily integrated with electrodes for flexible circuits.

PMMA MICROFLUIDIC CHIPS

PMMA, as a low-cost polymer with superior mechanical strength, electrical insulation and transparency compared to PDMS, is a good example of what can be achieved with thermoplastics. PMMA shows high biocompatibility and is a suitable candidate for biomedical and disposable point of care devices. PMMA microfluidic chips are typically fabricated using a hot embossing technique, but mass production of PMMA devices can be achieved with an injection molding method that facilitates shorter fabrication cycle times1. Most production methods for thermoplastics are excellent for commercial production, but not economical for prototype development. As thermoplastics are barely permeable to gas, their sealed microchannels and microchambers are unsuitable for long-term cell study or cell culture.

Thermosets

A thermoset is a polymer that irreversibly becomes rigid when heated. Initially, the polymer is a liquid or soft solid. When heated or radiated, the thermosetting molecules cross-link to form a rigid network that cannot soften before decomposition. These materials are normally stable (even at high temperature), resistant to most solvents, and optically transparent. Microfluidic chips can be entirely fabricated in thermosets, for instance using injection molding methods. Thermosets usually have a higher rigidity compared to elastomers and thermoplastics. With their high cost, their applications in microfluidics are however limited.