Microfluidics
is the science of designing, manufacturing, and formulating devices and
processes that deal with volumes of fluid on the order of nanoliters
(symbolized ...
Microfluidics
From Wikipedia, the free encyclopedia
Microfluidics deals with the behaviour, precise control and manipulation of
fluids
that are geometrically constrained to a small, typically
sub-millimeter, scale. It is a multidisciplinary field at the
intersection of
engineering,
physics,
chemistry,
biochemistry,
nanotechnology, and
biotechnology, with practical applications in the design of systems in which low volumes of fluids are processed to achieve
multiplexing, automation, and
high-throughput screening. 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.
Typically,
micro means one of the following features:
- small volumes (μL, nL, pL, fL)
- small size
- low energy consumption
- effects of the microdomain
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 such as
micropumps
or microvalves. Micropumps supply fluids in a continuous manner or are
used for dosing. Microvalves determine the flow direction or the mode of
movement of pumped liquids. Often processes which are normally carried
out in a lab are miniaturised on a single chip in order to enhance
efficiency and mobility as well as reducing sample and reagent volumes.
Microscale behaviour 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 behaviour of fluids at the microscale can differ from "macrofluidic" behaviour in that factors such as
surface tension,
energy dissipation, and fluidic resistance start to dominate the
system. Microfluidics studies how these behaviours change, and how they
can be worked around, or exploited for new uses.
[1][2][3][4]
At small scales (channel size of around 100
nanometers to 500
micrometers) some interesting and sometimes unintuitive properties appear. In particular, the
Reynolds number (which compares the effect of the momentum of a fluid to the effect of
viscosity) can become very low. A key consequence is co-flowing fluids 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 nanoliter (nl) and
picoliter (pl) volumes.
[8] To date, the most successful commercial application of microfluidics is the
inkjet printhead.
[9] Additionally, advances in microfluidic manufacturing allow the devices to be produced in low-cost plastics
[10] and part quality may be verified automatically.
[11]
Microfluidic synthesis of functionalized quantum dots for bioimaging.
[12]
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.
[13][14]
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.
Microfluidic technology has led to the creation of powerful tools for
biologists to control the complete cellular environment, leading to new
questions and discoveries. Many diverse advantages of this technology
for microbiology are listed below:
- General single cell studies including growth [15][16]
- Cellular aging: microfluidic devices such as the "mother machine"
allow tracking of thousands of individual cells for many generations
until they die.[15]
- Microenvironmental control: ranging from mechanical environment [17] to chemical environment [18]
- Precise spatiotemporal concentration gradients by incorporating multiple chemical inputs to a single device [19]
- Force measurements of adherent cells or confined chromosomes:
objects trapped in a microfluidic device can be directly manipulated
using optical tweezers or other force-generating methods [20]
- Confining cells and exerting controlled forces by coupling with external force-generation methods such as Stokes flow, optical tweezer, or controlled deformation of the PDMS device [20][21][22][23]
- Fast and precise temperature control [24][25]
- Electric field integration [22]
- Plant on a chip and plant tissue culture [26]
- Antibiotic resistance: microfluidic devices can be used as
heterogeneous environments for microorganisms. In a heterogeneous
environment, it 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.
Some of these areas are further elaborated in the sections below.
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.
[27][28]
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 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 offers 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 (μl to fl) of fluids
conveniently, provide better mixing, encapsulation, sorting, sensing and
are suitable for high throughput experiments.
[16] Exploiting the benefits of droplet-based microfluidics efficiently requires a deep understanding droplet generation
[29] to perform various logical operations
[30][31] such as droplet motion, droplet sorting, droplet merging, and droplet breakup.
[32]
Two immiscible phases used for the droplet generation are termed as
the continuous phase (medium in which droplets are generated) and
dispersed phase (the droplet phase). The size of the generated droplets
is mainly controlled by the flow rates of the continuous phase and
dispersed phase, interfacial tension between two phases and the geometry
used for the droplet generation.
[33][30]
Generally, three types of microfluidic geometries are utilised for the
droplet generation : (i) T-Junction, (ii) Flow Focusing, and (iii)
Co-Flowing. T-junction geometry follows a linear scaling law
[34] for the droplet generation and hence, simple to use.
Micromagnetofluidic method,
[35] which is the control of magnetic fluids by an applied magnetic field on a microfluidic platform,
[36] offers wireless and programmable control of the magnetic droplets.
[37][38] Hence, the magnetic force can also be used to perform various logical operations,
[39][40] in addition to the hydrodynamic force and the surface tension force.
[37][38]
The magnetic field strength, type of the magnetic field (gradient,
uniform or rotating), magnetic susceptibility, interfacial tension, flow
rates, and flow rate ratios determine the control of the microdroplets
on a micromagnetofluidic platform.
[37]
One of the key advantages of droplet-based microfluidics is the ability to use droplets as incubators for single cells.
[16][41]
Devices capable of generating thousands of droplets per second opens
new ways characterise cell population, not only based on a specific
marker measured at a specific time point but also based on cells kinetic
behaviour such as protein secretion, enzyme activity or proliferation.
[42]
Recently, a method was found to generate a stationary array of
microscopic droplets for single-cell incubation that does not require
the use of a surfactant .
[43]
Droplet based devices have also been used to investigate the conditions necessary for protein crystallization.
[44][45][46]
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.
[47] The "fluid transistor" pioneered by
Cytonix[48] also played a role. The technology was subsequently commercialised by Duke University. By using discrete unit-volume droplets,
[29]
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 "digitisation" 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,
[49] 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,
[50] transcriptome analysis,
[51] and
PCR amplification.
[52] 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
[16] and
microorganism capturing.
[14]
Evolutionary biology
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,
[53]
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.
Cell 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 [54] and the broad range of organisms that form the marine
microbial loop,
[55] responsible for regulating much of the oceans' biogeochemistry.
Microfluidics has also greatly aided the study of
durotaxis by facilitating the creation of durotactic (stiffness) gradients.
Cellular biophysics
By rectifying the motion of individual swimming bacteria,
[56] microfluidic structures can be used to extract mechanical motion from a population of motile bacterial cells.
[57] This way, bacteria-powered rotors can be built.
[58][59]
Optics
The merger of microfluidics and optics is typical known as
optofluidics. Examples of optofluidic devices are tunable microlens arrays
[60][61] and optofluidic microscopes.
Microfluidic flow enables fast sample throughput, automated imaging of large sample populations, as well as 3D capabilities.
[62][63] or superresolution.
[64]
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 litre
(picoliter = 10
−12 litre). 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
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.
[65][66][67]
Future Directions
- On-chip characterization:[68]
- Microfluidics in the classroom: On-chip acid-base titrations [69]
See also
References
The behaviour of fluids at the microscale can differ from "macrofluidic" behaviour in that factors such as surface tension, energy dissipation, and fluidic resistance start to dominate the system. Microfluidics studies how these behaviours change, and how they can be worked around, or exploited for new uses.[1][2][3][4]Silicone rubber and glass microfluidic devices. Top: a photograph of the devices. Bottom: Phase contrast micrographs of a serpentine channel ~15 μm wide.
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.[13][14]Microfluidic synthesis of functionalized quantum dots for bioimaging.[12]
. PMID 20537537.
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