Microfluidics is a multidisciplinary field
intersecting engineering, physics, chemistry, biochemistry, nanotechnology, and
biotechnology, with practical applications to the design of systems in which
small volumes of fluids will be handled. Microfluidics emerged in the beginning
of the 1980s and is used in the development of inkjet printheads, DNA chips, lab-on-a-chip
technology, micro-propulsion, and micro-thermal technologies. It deals with the
behavior, precise control and manipulation of fluids that are
geometrically constrained to a small, typically sub-millimeter, scale.
Typically, micro means one of the following features:
- small volumes (µL, nL, pL, fL)
- small size
- low energy consumption
- effects of the micro domain
Typically fluids are moved, mixed, separated or otherwise
processed. Numerous applications employ passive fluid control techniques like
capillary forces. In some applications external actuation means are
additionally used for a directed transport of the media. Examples are rotary
drives applying centrifugal forces for the fluid transport on the passive
chips. Active microfluidics refers to the defined manipulation of the
working fluid by active (micro) components as micropumps or
micro valves. Micro pumps supply fluids in a continuous manner or are used for
dosing. Micro valves determine the flow direction or the mode of movement of
pumped liquids. Often processes which are normally carried out in a lab are
miniaturized on a single chip in order to enhance efficiency and mobility as
well as reducing sample and reagent volumes.
Microscale behavior of fluids
Silicone rubber and glass microfluidic devices. Top: a
photograph of the devices. Bottom: Phase
contrast micrographs of a serpentine channel ~15 μm wide.
The behavior of fluids at the microscale can differ from
'macrofluidic' behavior in that factors such as surface
tension, energy dissipation, and fluidic resistance start to dominate the
system. Microfluidics studies how these behaviors change, and how they can be
worked around, or exploited for new uses.[1][2][3][4]
At small scales (channel diameters of around 100 nanometers
to several hundred micrometers) some interesting and sometimes unintuitive
properties appear. In particular, the Reynolds
number (which compares the effect of momentum of a fluid to the effect of viscosity)
can become very low. A key consequence of this is that fluids, when
side-by-side, do not necessarily mix in the traditional sense, as flow becomes laminar
rather than turbulent; molecular transport between them must
often be through diffusion.[5]
High specificity of chemical and physical properties
(concentration, pH, temperature, shear force, etc.) can also be ensured
resulting in more uniform reaction conditions and higher grade products in
single and multi-step reactions.[6][7]
Key application areas
Microfluidic structures include micropneumatic systems, i.e.
microsystems for the handling of off-chip fluids (liquid pumps, gas valves,
etc.), and microfluidic structures for the on-chip handling of nano- and
picolitre volumes.[8]
To date, the most successful commercial application of microfluidics is the inkjet
printhead. Significant research has also been applied to microfluidic
synthesis and production of various biofunctionalized nanoparticles including quantum
dots (QDs) and metallic nanoparticles,[9][10]
and other industrially relevant materials (e.g., polymer particles).[11]
Additionally, advances in microfluidic manufacturing allow the devices to
produced in low-cost plastics[12]
and part quality may be verified automatically.[13]
Advances in microfluidics technology are revolutionizing molecular
biology procedures for enzymatic analysis (e.g., glucose and lactate
assays), DNA analysis (e.g., polymerase chain reaction and
high-throughput sequencing), and proteomics.
The basic idea of microfluidic biochips is to integrate assay operations such
as detection, as well as sample pre-treatment and sample preparation on one
chip.[14][15]
An emerging application area for biochips is clinical pathology, especially the immediate
point-of-care diagnosis of diseases. In addition, microfluidics-based devices, capable
of continuous sampling and real-time testing of air/water samples for
biochemical toxins
and other dangerous pathogens, can serve as an always-on "bio-smoke
alarm" for early warning.
Continuous-flow microfluidics
These technologies are based on the manipulation of
continuous liquid flow through microfabricated channels. Actuation
of liquid
flow is implemented either by external pressure
sources, external mechanical pumps, integrated mechanical micropumps,
or by combinations of capillary forces and electrokinetic
mechanisms.[16][17]
Continuous-flow microfluidic operation is the mainstream approach because it is
easy to implement and less sensitive to protein fouling problems.
Continuous-flow devices are adequate for many well-defined and simple
biochemical applications, and for certain tasks such as chemical separation,
but they are less suitable for tasks requiring a high degree of flexibility or
ineffect fluid manipulations. These closed-channel systems are inherently
difficult to integrate and scale because the parameters that govern flow field
vary along the flow path making the fluid flow at any one location dependent on
the properties of the entire system. Permanently etched microstructures also
lead to limited reconfigurability and poor fault tolerance capability.
Process monitoring capabilities in continuous-flow systems
can be achieved with highly sensitive microfluidic flow sensors based on MEMS technology which offer
resolutions down to the nanoliter range.
Droplet-based microfluidics
Droplet-based microfluidics as a subcategory of
microfluidics in contrast with continuous microfluidics has the distinction of
manipulating discrete volumes of fluids in immiscible phases with low Reynolds
number and laminar flow regimes. Interest in droplet-based microfluidics
systems has been growing substantially in past decades. Microdroplets offer the
feasibility of handling miniature volumes of fluids conveniently, provide
better mixing and are suitable for high throughput experiments.[18]
Exploiting the benefits of droplet based microfluidics efficiently requires a
deep understanding of droplet generation,[19]
droplet motion, droplet merging, and droplet breakup[20]
Digital microfluidics
Alternatives to the above closed-channel continuous-flow
systems include novel open structures, where discrete, independently
controllable droplets are manipulated on a substrate using electrowetting.
Following the analogy of digital microelectronics, this approach is referred to
as digital microfluidics. Le Pesant et al.
pioneered the use of electrocapillary forces to move droplets on a digital
track.[21]
The "fluid transistor" pioneered by Cytonix[22]
also played a role. The technology was subsequently commercialized by Duke
University. By using discrete unit-volume droplets,[19]
a microfluidic function can be reduced to a set of repeated basic operations,
i.e., moving one unit of fluid over one unit of distance. This
"digitization" method facilitates the use of a hierarchical and
cell-based approach for microfluidic biochip design. Therefore, digital
microfluidics offers a flexible and scalable system architecture as well as
high fault-tolerance capability. Moreover, because each
droplet can be controlled independently, these systems also have dynamic
reconfigurability, whereby groups of unit cells in a microfluidic array can be
reconfigured to change their functionality during the concurrent execution of a
set of bioassays. Although droplets are manipulated in confined microfluidic
channels, since the control on droplets is not independent, it should not be
confused as "digital microfluidics". One common actuation method for
digital microfluidics is electrowetting-on-dielectric (EWOD). Many
lab-on-a-chip applications have been demonstrated within the digital
microfluidics paradigm using electrowetting. However, recently other techniques
for droplet manipulation have also been demonstrated using surface acoustic waves, optoelectrowetting,
mechanical actuation,[23]
etc.
DNA chips (microarrays)
Early biochips were based on the idea of a DNA
microarray, e.g., the GeneChip DNAarray from Affymetrix,
which is a piece of glass, plastic or silicon substrate on which pieces of DNA
(probes) are affixed in a microscopic array. Similar to a DNA
microarray, a protein array is a miniature array where a multitude
of different capture agents, most frequently monoclonal antibodies,
are deposited on a chip surface; they are used to determine the presence and/or
amount of proteins
in biological samples, e.g., blood. A drawback of DNA and protein arrays is that they are neither
reconfigurable nor scalable after manufacture. Digital microfluidics has been described as a
means for carrying out Digital PCR.
Molecular biology
In addition to microarrays, biochips have been designed for
two-dimensional electrophoresis,[24]
transcriptome
analysis,[25]
and PCR amplification.[26]
Other applications include various electrophoresis and liquid chromatography applications for
proteins and DNA, cell
separation, in particular blood cell separation, protein analysis, cell manipulation
and analysis including cell viability analysis [18]
and microorganism
capturing.[15]
Evolutionary biology
Three Micro Habitat Patches MHPs connected by dispersal corridors (indicated here
as
) into a 1D lattice. The ecosystem
service (of habitat renewal) to each MHP represented here as
(red arrows). Each MHP can also hold different carrying
capacity
for its supporting local population of bacterial cells
(depicted in green).
By combining microfluidics with landscape
ecology and nanofluidics, a nano/micro fabricated fluidic landscape
can be constructed by building local patches of bacterial habitat and
connecting them by dispersal corridors. The resulting landscapes can be used as
physical implementations of an adaptive landscape,[27]
by generating a spatial mosaic of patches of opportunity distributed in space
and time. The patchy nature of these fluidic landscapes allows for the study of
adapting bacterial cells in a metapopulation
system. The evolutionary ecology of these bacterial
systems in these synthetic ecosystems allows for using biophysics
to address questions in evolutionary biology.
Microbial behavior
The ability to create precise and carefully controlled chemoattractant
gradients makes microfluidics the ideal tool to study motility, chemotaxis
and the ability to evolve / develop resistance to antibiotics in small
populations of microorganisms and in a short period of time. These
microorganisms including bacteria [28]
and the broad range of organisms that form the marine microbial
loop,[29]
responsible for regulating much of the oceans' biogeochemistry.
Cellular biophysics
By rectifying the motion of individual swimming bacteria,[30]
microfluidic structures can be used to extract mechanical motion from a
population of motile bacterial cells.[31]
This way, bacteria-powered rotors can be built.[32][33]
Optics
The merger of microfluidics and optics is typical known as optofluidics.
Examples of optofluidic devices :
Tuneable Microlens Array[34][35]
Optofluidic Microscopes [36][37][38]
Tuneable Microlens Array[34][35]
Optofluidic Microscopes [36][37][38]
Acoustic droplet ejection (ADE)
Acoustic droplet ejection uses a pulse of
ultrasound
to move low volumes of fluids (typically nanoliters or picoliters) without any
physical contact. This technology focuses acoustic energy into a fluid sample in
order to eject droplets as small as a millionth of a millionth of a liter
(picoliter = 10−12 liter). ADE technology is a very gentle process,
and it can be used to transfer proteins, high molecular weight DNA and live
cells without damage or loss of viability. This feature makes the technology
suitable for a wide variety of applications including proteomics
and cell-based assays.
Fuel cells
For more details on this topic, see Electroosmotic pump.
Microfluidic fuel cells
can use laminar flow to separate the fuel and its oxidant to control the
interaction of the two fluids without a physical barrier as would be required
in conventional fuel cells.[39][40][41]
A tool for cell biological research
Microfluidic technology is creating powerful tools for cell
biologists to control the complete cellular environment, leading to new
questions and new discoveries.[42]
Many diverse advantages of this technology for microbiology are listed below:
- Single cell studies [18]
- Microenvironmental control: ranging from mechanical environment [43] to chemical environment [44]
- Precise spatiotemporal concentration gradients [45]
- Mechanical deformation
- Force measurements of adherent cells
- Confining cells [46]
- Exerting a controlled force [46][47]
- Fast and precise temperature control [48][49]
- Electric field integration [46]
- Cell culture [18]
- Plant on a chip and plant tissue culture [50]
- Antibiotic resistance: microfluidic devices can be used as heterogeneous environments for microorganisms. In a heterogeneous environment is easier for a microorganism to evolve. This can be useful for testing the acceleration of evolution of a microorganism / for testing the development of antibiotic resistance.
Future Directions
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