2. Contents
1. What is Microfluidics?
2. Typical Microfluidic systems
3. Where Microfluidics lies
4. Origins, history & milestones
5. Typical components of Microfluidic systems
6. Physics of Microfluidics
7. Differences between micro and macro scale fluidics
8. Flow mechanisms
9. Branches of Microfluidics
10. Applications of Microfluidics
11. Lab on a chip
12. Low cost microfluidics â Paper, Plastic and Textile based microfluidics
13. Other emerging applications
14. Growth
15. References
3. What is Microfluidics?
⢠It is the science and technology of systems that
process or manipulate small (10â9 to 10â18 litres)
amounts of fluids, using channels with dimensions
of tens to hundreds of micrometres
ď Microfluidics in nature: Lung alveoli
4. A typical microfluidic system
DNA separation system
⢠From Agilent-
Caliper
⢠Allow to
characterize DNA
Fragments with
excellent
resolution, and in
a small time
7. How it all started
âThereâs Plenty of Room at the Bottomâ
I would like to describe a field, in which little has
been done, but in which an enormous amount
can be done in principle. This field is not quite
the same as the others in that it will not tell us
much of fundamental physics (in the sense of,
``What are the strange particles?'') but it is more
like solid-state physics in the sense that it might
tell us much of great interest about the strange
phenomena that occur in complex situations.
Furthermore, a point that is most important is
that it would have an enormous number of
technical applications.
8. How microfluidics came to be
⢠Molecular analysis
⢠Biodefence
⢠Molecular biology
⢠Microelectronics
Much of the exploratory research in microfluidic systems has been carried out in a
polymer â poly(dimethylsiloxane), or PDMS, an optically transparent, soft
elastomer.
9. Motivation for miniaturization
⢠Micro scale = laminar flow
⢠Laminar flow allows controlled mixing
⢠Low thermal mass
⢠Efficient mass transport (speedy diffusion)
⢠Good (large) ratio of channel surface area: channel
volume
⢠Single cell and molecule manipulations
⢠Protection against contamination and evaporation
⢠Kinetics easy to study
10. Benefits of size reduction
1. Decreased reagent consumption
2. Small economic footprint
3. Rapid heat transfer and catalysis
4. Fast diffusive mixing
5. Automation and integration
11. History of Microfluidics
⢠1958 Jack Kilby & Robert Norton Noyce (IC)
⢠1959 Richard Feynman: âThereâs Plenty of Room at the Bottomâ
⢠1960s Microelectronic IC
⢠1970s MEMS
⢠1980s Microflow sensor, Microvalves, Micropumps
⢠1990s Microfluidics
12. Milestones
⢠1970 - 1990 : Essentially nothing (apart from the
Stanford gas chromatographer)
⢠1990 : First liquid chromatograph (Manz et al) ΟTAS
concept (Manz, Graber, Widmer, Sens.Actuator,
1991)
⢠1990 -1998 : First elementary microfluidic systems
(micromixers, microreactors, separation systems,..)
⢠1998-2004 : Appearance of soft lithography
technology, which fostered the domain. All sorts of
microfluidic systems with various levels of
complexity are made, using different technologies
13.
14. Generic components of a
microfluidic system
⢠a method of introducing reagents and samples (as
fluids)
⢠methods for moving these fluids around on the
chip, and for combining and mixing them
⢠methods for moving these fluids around on the
chip, and for combining and mixing them
16. ⢠Common fluids used in microfluidic devices
include whole blood samples, bacterial cell
suspensions, protein or antibody solutions and
various buffers
⢠Microfluidic devices can be used to obtain a variety
of interesting measurements including molecular
diffusion coefficients, fluid viscosity, pH, chemical
binding coefficients and enzyme reaction kinetics
17. Physics of microfluidics
⢠Knudsen Number = d/L
Ratio of the molecular mean free path length to a representative physical
length scale
18. ⢠Length-scale ratios dictate approach for understanding flow
⢠Continuum flow region is traditional Chem Engg fluid
mechanics
⢠For microfluidics, Knudsen number is of the order 10-7
How does a small L influence things in the continuum flow
region?
Viscous Forces tend to dominate Inertial Forces ď Re << 1
19. ď Major differences between micro- and
macro- fluidics
⢠Turbulence (or its absence: laminar flow)
-inertia vs viscosity; convective mixing
⢠Electro-osmotic flow (EOF)
-When an ion-containing fluid placed in a microchannel that has fixed
charges on its surface and an electrical potential is applied along the
channel, the fluid moves as a plug rather than with the parabolic-flow
-allows very high resolution separations of ionic species. It is a key
contributor to electrophoretic separations of DNA in microchannels
20. Flow mechanisms
1. Pressure Driven Flow (image on next slide)
-Via positive displacement pumps, such as syringe pumps
-No-slip boundary condition states that the fluid velocity at
the walls must be zero. This produces a parabolic velocity
profile within the channel
-The parabolic velocity profile has significant implications for
the distribution of molecules transported within a channel
-Relative inexpensive and quite reproducible
21.
22. Flow mechanisms
2. Electrokinetic Flow (image on next slide)
-If the walls of a microchannel have an electric
charge, as most surfaces do, an electric double layer
of counter ions will form at the walls. When an
electric field is applied across the channel, the ions in
the double layer move towards the electrode of
opposite polarity. This creates motion of the fluid
near the walls and transfers via viscous forces into
convective motion of the bulk fluid. If the channel is
open at the electrodes, as is most often the case, the
velocity profile is uniform across the entire width of
the channel
24. Branches of microfluidics
1. CONTINUOUS FLOW MICROFLUIDICS
Continuous flow microfluidics enables to manipulate
continuous flow of liquid through micro-channels
thanks to devices such as external pressure pumps or
integrated mechanical micro-pumps. Continuous
flow processes are used in a wide range of
applications like in bioanalytical, chemical, energy
and environmental fields.
25. 2. DIGITAL MICROFLUIDICS
Also called droplet microfluidics or emulsion science,
digital microfluidics is one of the main application field of
microfluidics. It enables to manipulate autonomous
droplets on a substrate using electro-wetting. This allow
to generate and control uniform, reproducible droplets
over the experimentsâ parameters.
Droplets generation can be used in a large scale of
applications like in synthesis of nanoparticles, single cell
analysis, and encapsulation of biological entities. This
technology will probably become an important tool for
drug delivery and biosensing, by providing new solutions
for state-of-the-art diagnostics and therapeutics.
26. 3. OPTOFLUIDICS AND MICROFLUIDICS
Optfluidics is an emerging fast-growing science resulting
from the combination of three fields of science:
microphotonics, optics and microfluidics. Optofluidics
merges light and liquids into miniaturized optical devices
that take advantage of the properties of fluids to
generate high precision and flexibility.
Optofluidic applications include lab-on-chip devices, fluid
waveguides, deformable lenses, microdroplets lasers,
displays, biosensors, optical switches or molecular
imaging tools and energy.
27. 4. ACOUSTOFLUIDICS
Acoustofluidics deals with the use of acoustic fields,
mainly ultrasonics onto fluids within microfluidic
channels allowing to manipulate cells and particles. It
refers to the study and manipulation of acoustic
waves on microscale to nanoscale fluidic
environments.
28. 5. ELECTROPHORESIS AND MICROFLUIDICS
Electrophoresis is a technique used in clinical and
research laboratories in order to separate molecules
based on their size, electrical charge and shape.
An electric current flows through a medium holding
the mixture of molecules. Positively-charged ions
(cations) proceed towards a negative electrode
whereas negatively-charged ions (anions) proceed
towards a positive electrode.
This method is used for both DNA and RNA analysis.
30. Key Application Areas
⢠Polymerase Chain Reactions
⢠Immunoassays
⢠Drug Screening
⢠Electrophoretic separations
⢠Analysis of unpurified blood samples
⢠DNA sequencing
⢠Single Cell manipulation
⢠Screens for protein crystallization conditions
⢠Cell culture studies
31. Lab-on-a-chip:
Start-to-finish systems based on microfluidics
⢠A lab-on-a-chip is a miniaturized device that integrates
onto a single chip one or several analyses which are
usually done in a laboratory
⢠Mainly focuses on human diagnostics and DNA analysis.
Less often, on the synthesis of chemicals
⢠Microfluidic technologies used in lab-on-a-chip devices
enable the fabrication of millions of microchannels,
each measuring mere micrometers, on a single chip
that fits in the palm of your hand.
⢠Eg. Commerically available chips for glucose
monitoring, HIV detection or heart attack diagnostics, A
chip which enables security forces to detect as soon as
possible biological threats towards troops and civilians.
32. Lab-on-a-chip
Advantages Disadvantages
⢠Low cost
⢠High parallelization
⢠Ease of use and
compactness
⢠Reduction of human error
⢠Faster response time and
diagnosis
⢠Low volume samples
⢠Real time process control
and monitoring increase
sensitivity
⢠Expendable: Due to their
low price, automation
and low energy
consumption
⢠Not yet ready for
industrialization
⢠Miniaturization
increases the
signal/noise ratio
⢠Untrained diagnoses
⢠May enable anyone
to sequence the DNA
of others using a drop
of saliva
33. LAB-ON-A-CHIP: CURRENT
RESEARCH FOCUS
⢠The industrialization of lab-on-a-chip technologies
to make them ready for commercialization
⢠The increase in the maximum number of biological
operations on the same chip and the increase in
parallelization to achieve the detection of hundreds
of pathogens in the same microfluidic cartridge
⢠Fundamental research on certain technologies with
a high potential impact, such as DNA reading
through nanopore, which requires more
investigation in order to be applicable.
35. Potential impact on healthcare
services
In a near future, lab-on-a-chip devices, with their ability
to perform complete diagnosis can change our way of
practicing medicine.
⢠Diagnosis will be done by people with lower
qualifications, thus enabling doctors to focus only on
treatment.
⢠Real time diagnosis will increase the chances of survival
for patients
⢠A complete diagnosis will greatly reduce antibio-
resistance, which is currently one of the biggest
challenges
⢠In developing countries, lab-on-a-chip will enable
healthcare providers to open diagnostics to a wider
population
37. Low-cost and high impact microfluidics
1. Paper-based Microfluidics
⢠Available everywhere and cheap
⢠Low fabrication cost
⢠Passive fluid transport through capillary action
⢠Thin, lightweight
⢠Easy to stack, store, and transport
⢠Disposable and Biodegradable
40. Bacterial detection in water using paper-based microfluidics
Methods for Result-analysis
41.
42. ⢠Use of materials such as Polydymethilsiloxane
(PDMS), acrylic(PMMA), Polystyrene, Cycloolefin
⢠For variety of applications that cannot be achieved
with paper
-Able to pattern microstructure, microvalves, etc
-Able to transfer bulk liquid in a micro channel
-Can be used for cell works (separation, cell culture)
-Can be used repetitively
Low-cost and high impact microfluidics
2. Plastic-based Microfluidics
43. Application of plastic-based microfluidics
Acrylic-based Electrochemical Detection of
Nitrate in Water
Current methods
45. Other applications of plastic-
based microfluidics
⢠Rapid Genotyping of Malaria-Transmitting
Mosquitoes
⢠Circulating Tumor Cells Separation
46. ⢠Sports performance measurement such as real-time sweat pH
monitoring
-Connection via Bluetooth for real-time analysis on smartphones
⢠Smart shirts, esp for security forces
Low-cost and high impact microfluidics
3. Textile-based Microfluidics
51. References
⢠George M. Whitesides, The origins and the future
of microfluidics, NATURE|Vol 442|27 July 2006
⢠Lab-on-chip technologies: making a microfluidic
network and coupling it into a complete
microsystemâa review, P Abgrall and A-M Gue, J.
Micromech. Microeng. 17 (2007) R15âR49
⢠Yole Development Report 2015, Yole
DĂŠveloppement, Villeurbanne, France
The control of tiny amounts of gases or liquids in a miniaturized system of channels, pumps, valves, and sensors.
Multo-disciplinary
A talk given by Richard Feynman at Caltech, 1959
gas-phase chromatography (GPC), high-pressure liquid chromatography (HPLC) and capillary electrophoresis (CE) - new, more compact and more versatile formats
major military and terrorist threats-US DoD-detectors for chemical and biological threats
The explosion of genomics in the 1980s, followed by the advent of other areas of microanalysis related to molecular biology, such as high-throughput DNA sequencing, required analytical methods with much greater throughput, and higher sensitivity and resolution than had previously been contemplated in biology.
Speed: diffusion: 1mm -> 15 min, 10Îźm -> 100ms)
3. High S-to-V ratio, Precise temperature control
4. Speed and accuracy of reaction, repeatability
A single chip can do processing from beginning to end, integrating multiple operations
Automation increases throughput,efficiency; Reduction in human error
On large scales, fluids mix convectively: for example, the mixing of milk when it is swirled into coffee, or smoke, leaving a chimney, with air. This type of mixing reflects the fact that in macroscopic fluids, inertia is often more important than viscosity. In microsystems, with water as a fluid, the opposite is true: fluids do not mix convectively â when two fluid streams come together in a microchannel, they flow in parallel, without eddies or turbulence, and the only mixing that occurs is the result of diffusion of molecules across the interface between the fluids.
Examples: Urinalysis, bacterial detection
Detection of nitrate in water is essential because excess nitrate can cause various health problems, most famously Blue-baby syndrome (methanoglobinemia)
Mosquito leg is inserted in a plastic-based microfluidic device and blue-LED light is used for visual amplification. Detection using a call-phone camera.