Microfluidics and microfluidic devices: A review
A definition of microfluidics
Microfluidics deal with the flow of liquids inside micrometer-sized channels. In order to consider it microfluidics, at least one dimension of the channel must be in the range of a micrometer or tens of micrometers (see the difference between nanofluidics, microfluidics, millifluidics and the behavior of fluids at these scales). Microfluidics can be considered both as a science (study of the behavior of fluids in micro-channels) and as a technology (manufacturing of microfluidics devices for applications such as lab-on-a-chip).
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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 the desired features (mix, pump, sort, or control the biochemical environment).
This network of micro-channels trapped into 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 gases) 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 their microfluidic chips, one must consider that, originally, the fabrication process of a microfluidic chip was based on photolithographic methods, derived from the well-developed semiconductor industry.
The use of diverse materials for microfluidics chips such as polymers (e.g. PDMS), ceramics (e.g. glass), semiconductors (e.g. silicon) and metal is currently possible because of the development of specific processes: deposition and electro-deposition, etching, bonding, injection molding, embossing and soft lithography (especially with PDMS). To the best of our knowledge, only a few manufacturers of microfluidic chips offer a wide range of chips or materials.
Accessing 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 electro sensing, etc. The final choice depends on the application.
Nowadays, a lot of researchers use PDMS and soft lithography due to their easiness of use 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 seen before, the technologies developed to miniaturize transistors and manufacture microprocessors have allowed to manufacture 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 50s saw the invention and development of the first transistors. Made in blocks of semiconductors, they gradually replaced the lamps previously used in the manufacture of electronic devices (radios, computers…)
In the 60s, 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 to the moon.
The development of technologies such as photolithography has enabled the miniaturization and integration of thousands of transistors on semiconductor wafers, mainly silicon wafers.
This research led to the production of the first integrated circuits and then the first microprocessors.
An example of MEMS
Over the 80s, 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.
In the early 2000s, technologies based on molding micro-channels in polymers such as PDMS experienced a strong growth. The cost reduction and production time decrease of these devices allowed a large number of laboratories to conduct research in microfluidics.
Today, thousands of researchers are working in microfluidics to extend its application fields, especially towards biology, chemistry and the biomedical field.
Microfluidic technology: How to build a microfluidic chip
The simplest current microfluidic device consists in micro-channels molded in a polymer that is bonded to a flat surface (such as a glass slide). The polymer most commonly used for molding microfluidic chips is PDMS. 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 transferred 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 thus printed with UV opaque ink (if the substrate is a plastic film) or etched in chromium (if the substrate is a glass plate).
The fabrication of microfluidic mold by photolithography:
This step corresponds to the transfer of microchannels patterns 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 then partially exposed to UV light. Therefore, in the case of a negative resin like SU-8 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 then obtain 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 production of microfluidic chips from a mold.
(2) A mixture of PDMS (liquid) and cross-linking agent (to cure the PDMS) is poured into the mold and heated at a 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 PDMS 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.
Integration of complex functions:
In addition, many microfluidic devices incorporate other features that require the integration of electrodes, nanostructures or surface functionalization. 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 the biomedical field, with 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 drug changes.
- 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.
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For more tutorials 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 and revised by Lauren Durieux.
 Xia, Y. & Whitesides, G. M. Soft Lithography. Angew. Chem. Int. Ed. 37, 550–575 (1998).