Microfluidics and microfluidic devices: A review
A microfluidic chip made of PDMS/glass.
A definition of microfluidics
Microfluidics is the science that deals with the flow of liquid inside micrometer-size channels. At least one dimension of the channel is in the order of a micrometer or tens of micrometers in order to consider it microfluidics (see difference between nanofluidics, microfluidics, millifluidics and the behaviour of fluids at these scales). Microfluidics can be considered both as a science (study of the behaviour of fluids in micro-channels) and a technology (manufacturing of microfluidics devices for applications such as lab-on-a-chip).
What is a microfluidic chip?
A microfluidic chip is a set of micro-channels etched or molded into a material (glass, silicon or polymer such as PDMS, for PolyDimethylSiloxane). The micro-channels forming the microfluidic chip are connected together in order to achieve desired functions (mix, pump, sort, control bio-chemical environment).
This network of micro-channels trapped in the microfluidic chip is connected to the outside by inputs and outputs pierced through the chip, as an interface between the macro- and micro-world.
It is through these holes that the liquids (or gas) are injected and removed from the microfluidic chip (through tubing, syringe adapters or even simple holes in the chip) with external active systems (pressure controller, push-syringe or peristatic pump) or passive ways (e.g. hydrostatic pressure).
If researchers can now choose between a full set of materials to build his microfluidic chips, one must consider that, initially, the fabrication process of a microfluidic chip was based on photolithographic methods, derived from the well-developped semiconductor industry.
The use of diverse materials for microfluidics chips such as polymers (e.g. PDMS), ceramics (e.g. glass), semi-conductors (e.g. silicon) and metal is currently possible because of the development of specific processes: deposition and electrodeposition, etching, bonding, injection molding, embossing and soft lithography (especially with PDMS).
Access to these materials makes it possible to design microfluidic chips with new features like specific optical characteristics, biological or chemical compatibility, faster prototyping or lower production costs, possibility of electrosensing, etc… The final choice depends on the aimed application.
Nowadays, a lot of researchers use PDMS and soft-lithography due to their easiness and fast process. They allow researchers to rapidly build prototypes and test their applications/setups, instead of wasting time in laborious fabrication protocols. Contrary to common beliefs, soft-lithography does not require hundreds of square meters of clean room space. Indeed, a little bench space under a lab fume hood is sufficient to place essential rapid PDMS prototyping instruments to quickly assess microfluidic concepts and obtain publishable results.
Birth of microfluidics: A bit of History
As reminded before, the technologies developed to miniaturize transistors and manufacture microprocessors have enabled to fabricate microscopic channels and integrate them on chips. Thus, the history of microfluidics will take us to the first lunar expedition, from our printer heads to our hospitals.
The first transistor (replica)
The 50’s saw the invention and development of the first transistors. Made in blocks of semiconductors, they have gradually replaced the lamps previously used in the manufacture of electronic devices (radio, computer …)
In the 60’s, space research, via the Apollo program with a budget of $25 billion, gave an opportunity to fund research programs on the miniaturization of computers to take them to space and particularly the moon.
The development of technologies such as photolithography have enabled the miniaturization and integration of thousands of transistors on semiconductor wafers, mainly of silicon.
This research led to the production of the first integrated circuits and then the first microprocessors.
An example of MEMS
Over the 80’s, the use of silicon etching procedures, developed for microelectronics industry, allowed the manufacture of the first device containing mechanical micro-elements integrated on a silicon wafer.
These new types of devices called MEMS (Micro Electro Mechanical Systems) gave rise to industrial applications, particularly in the field of pressure sensors and printer heads.
Glass microfluidic chip
In the 90’s, many researchers investigated the applications of MEMS in biology, chemistry and biomedical fields. These applications needed to control the movement of liquids in micro-channels and have significantly contributed to the development of microfluidics.
A major research effort was made to develop laboratories on a chip to enable the integration of almost all the processes required for complete biological, chemical and biomedical protocols on a single microfluidic chip.
At that time, the majority of microfluidic devices were still made of silicon or glass, and thus, required the heavy infrastructure of microelectronics industry.
Starting the 2000’s, technologies based on molding micro-channels in polymers such as PDMS experienced strong growth. Cost reduction and production time decrease of these devices enabled a large number of laboratories to conduct researches in microfluidics.
Today, thousands of researchers are working in microfluidics to extend its application fields especially towards biology, chemistry and biomedical field.
Microfluidic technology: How to fabricate a microfluidic chip
The simplest current microfluidic devices consist in micro-channels molded in a polymer that is bonded to a flat surface (a glass slide for example).The polymer most commonly used for molding microfluidic chips is PDMS. The PDMS is a transparent, biocompatible (very similar to silicone gel used in breast implants), deformable and inexpensive elastomer. It is easy to mold and bond on glass. For all these reasons, it is appreciated by researchers.
The fabrication of a simple microfluidic chip requires several steps.
We describe here the fabrication of a microfluidic chip by soft-lithography methods .
Photolithographic mask made on a glass substrate with etched chrome
The design of microfluidic channels:
The fabrication of a microfluidic device starts with the design of microfluidic channels with a dedicated software (AUTOCAD, Illustrator, LEDIT…). Once this design is made, it is transfered on a photomask: chrome coated glass plates or plastic films for the most common templates. This can be done with dedicated manufacturers or in a clean room for glass masks. The micro-channels are so printed with UV opaque ink (if the substrate is a plastic film) or etched in chromium (if the substrat is a glass plate).
The fabrication of microfluidic mold by photolithography:
This step corresponds to the transfer of microchannels pattern from the photomask into real micro-channels on a mold. Micro-channels are “sculpted” on the mold; resulting in replicas that will enable the carving of channels into the future material of microfluidic chips.
(1) Resin is spread on a flat surface (often a silicon wafer) with the desired thickness (which determines the height of microfluidic channels)
(2) The resin, protected by the photomask with the microchannel pattern, is thus partially exposed to UV light. Therefore, in the case of a negative resin like SU8 type, only the parts representing the channels are exposed to UV light and cured, the other parts of the mold being protected by the opaque areas of the mask.
(3) The mold is developed in a solvent that etches the areas of resin that were not exposed to UV light.
(4) We obtain then a microfluidic mold with a resin replica of the patterns from the photomask (future micro-channels make “reliefs” on the mold). The height of the channels is determined by the thickness of the original resin spread on the wafer. Most of the time, the mold is then treated with Silane to facilitate the release of microfluidic devices during molding steps (see next paragraph).
The molding of microfluidic chips:
(1) The molding step allows mass-producing of microfluidic chips from a mold.
(2) A mixture of PDMS (liquid) and crosslinking agent (to cure the PDMS) is poured into the mold and put at high temperature.
(3) Once the PDMS is hardened, it can be taken off the mold. We obtain a replica of the micro-channels on the PDMS block.
+ Microfluidic device completion:
(4) To allow the injection of fluids for future experiments, the inputs and outputs of the microfluidic device are punched with a needle or a puncher of the size of future connection tubes.
(5) Finally, the face of the block of PDMS with micro-channels and the glass slide are treated with plasma.
(6)The plasma treatment allows PDMS and glass bonding to close the microfluidic chip.
The chip is now ready to be connected to microfluidic reservoirs and pumps using microfluidic tubing. Tygon tubing and Teflon tubing are the most commonly used tubings on microfluidic setups.
Integration of complex functions:
In addition, many microfluidic devices incorporate other features that require the integration of electrodes, nanostructures or surface functionalizations. This type of additional steps use generally standard techniques of micro and nanotechnology (thin film deposition, plasma etching, self assembled monolayers).
Applications of microfluidics
The Microfluidics technology has found many applications, mainly:
- In biomedical field, with the laboratories on a chip because they allow the integration of many medical tests on a single chip.
- In cell biology research because micro-channels have the same characteristic size as biological cells. Thus, microfluidic chips allow easy manipulations of single cells and rapid drugs change.
- In protein crystallization because microfluidic devices allow the generation on a single chip of a large number of crystallization conditions (temperature, pH, humidity…)
- And also many other areas: drug screening, glucose tests, chemical microreactor, electrochemistry, microprocessor cooling (fair return..) or micro fuel cells.
For more tutorial about microfluidics, please visit our other tutorials here: «Microfluidics tutorials». The photos in this article come from the Elveflow® data bank, Wikipedia or elsewhere if precised. Article written by Guilhem Velvé Casquillas and Timothée Houssin.
 Xia, Y. & Whitesides, G. M. Soft Lithography. Angew. Chem. Int. Ed. 37, 550–575 (1998).
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