Microfluidics and microfluidic devices: a review

A definition of microfluidics
Microfluidics is the science that deals with the flow of liquids in channels of micrometer size. At least one dimension of the channel is of the order of a micrometer or tens of micrometers in order to consider it’s 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 microfluidic devices for applications such as lab-on-a-chip).Generally, when researchers speak of microfluidics, they refer to man-made channels. Fluid flows in natural microchannels as blood vessels or plants capillaries are mostly excluded from microfluidics.

What is a microfluidic chip?

Microfluidic chip made of glass PDMS A microfluidic chip made PDMS on glass.

A microfluidic chip is a set of micro-channels etched or molded into a material (glass, silicon or polymer such as PDMS). The micro-channels forming the microfluidic chip are connected together so as to achieve a desired function (mix, pump, redirect and/or allow chemical reactions in a cell).

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 adaptaters or even free holes in the chip).
If a researcher 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 photolithography on silicon methods, derived from the well-developped semiconductor industry. Photolithography is still widely spread, but the use of other materials such as glass, ceramics, metal and polymers is currently possible because of the development of specific processes:Deposition and electrodeposition, etching, bonding, injecting molding, embossing and soft lithography (especialy with PDMS). Access to these materials make it possible to design microfluidic chips with specific optical characteristics, biological or chemical compatibility, faster prototyping or lower production costs, possibility of electrosensing, etc… and the final choice depends on the aimed application.
Nowadays, lots of researchers use PDMS since it is easiness to use and fast to process. It allows researchers to rapidly build a prototype and test their application/setup, instead of wasting time on a laborious fabrication process.

Birth of microfluidics: a bit of History
As reminded before, the technologies developed to miniaturize transistors and manufacture microprocessors have enabled to produce 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.

microfluidic history the first transistor 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 …)
Microfluidic history the first industrial microprocessor industrial microprocessor

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 allow taking them to space and in particular on 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 with them the first microprocessors.

Microfluidic history an example of MEMS An example of MEMS

Over the 80′s, the use of silicon etching procedures, developed for microelectronics industry, allowed the manufacture of the first devices containing movable 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 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 diagnostic operations performed in a hospital 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 the microelectronics industry.

Microfluidic chip Microfluidic chip made of PDMS on glass.

Starting 2000, technologies based on molding micro-channels in polymers such as PDMS (PolyDiMethylSiloxane) experienced strong growth. Reducing costs and production times of 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 via on-chip laboratories for hospitals.

Microfluidic technology: how to manufacture a chip

The simplest microfluidic devices consist in micro-channels molded in a polymer that is bonded to a flat surface (a glass slide as an 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, inexpensive elastomer, easy to mold and bond with glass. For these reasons it has been acclaimed by researchers.
We describe here the manufacture by molding method of a simple microfluidic chip.

The manufacture of a simple microfluidic chip requires several steps:

Microfluidic technology Photolithography mask

The design of microfluidic channels:
 The manufacture of a microfluidic device starts with the design of the channels on a dedicated software (LEDIT, Illustrator …).Once this design is made, it is sent to a manufacturer of photomask to be transferred on a glass medium or a plastic film. The micro-channels are printed with UV opaque ink (if the medium is a plastic film) or chromium (if the medium is a glass plate).

photolithographic process of microfluidic mold

 The manufacture of microfluidic mold by photolithography:
This is the step when the drawings of the microchannels on the photomask are transformed into real micro-channels (the mold).Micro-channels negativ are “sculpted” on the mold; resulting in replicas that will enable carveing the channels into the future material of the microfluidic chip. (1) Resin is spread on a flat surface (often a silicon wafer) with the desired thickness (which determines the height of the channel) (2) The resin, protected by the mask on which channels are drawn, is partially exposed to UV light. Thus (in the case of a negative resin, 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 areas of resin that were not exposed to UV light.

(4) We obtain a microfluidic mold with a resin replica of the patterns that were present on the photomask (future micro-channels are “walls” on the mold).

The height of the channels is determined by the thickness of the original resin. Most of the time the mold is then treated with a stick (Silane) to facilitate the release of microfluidic devices during steps of molding.
Molding process of single layer PDMS microfluidic device The molding of the microfluidic chip:
The molding step allows mass-producing microfluidic chips from a mold (1). (2) A mixture of PDMS (liquid) and crosslinking agent (to harden the PDMS) is poured into the mold and placed in a furnace.

(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.

The completion of the microfluidic device:

(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 punch of the size of future outer tubes.

(5) Finally, the face of the block of PDMS with micro-channels and the glass slide are treated with plasma, in order to (6) bond and close the Microfluidics chip.

Microfluidic chip made of PDMS/glass with electrodes

Integration of complex functions:
 In addition, many microfluidic devices incorporate other features that require the integration of such electrodes, nanostructures or surface functionalization.This type of additional steps generally used standard techniques of microelectronics (thin film deposition, plasma etching).

Applications of microfluidics
Microfluidic technology has found many applications mainly:- In medicine with the laboratories on a chip because they allow the integration of many medical tests on a single chip.- In cell biology researches because the micro-channels have the same characteristic size as the cells and allow such manipulation of single cells and rapid change of drugs.- 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, sugar testers, chemical microreactor, microprocessor cooling (just reward) or micro fuel cells.

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For more tutorial about  microfluidics,

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The photos in this article come from the data bank Elveflow® and Wikipedia.

Article written by Guilhem Velvé Casquillas