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Microfluídica Introducción: Fundamentos, Historia, Mo8vación, Aplicaciones, Tendencias… 1 A que llamamos Microfluídica? “Es la ciencia y tecnología que u2liza sistemas que procesan o manipulan can2dades pequeñas de fluidos (entre 10-­‐18 y 10-­‐9 litros), mediante canales cuyo tamaño esta entre decenas y cientos de micrones” G. M. Whitesides Nanofluidics Microfluidics 2 Condición de no 85, NUMBER 5
deslizamiento entre un fluido y un solido and L. Léger, R. Pit, H. Hervet, Phys. Rev. Lef., vol. 85, no. 5, pp. 980–983, Jul. 2000. OLUME
Microfluídica Para que sirve? Inves8gación Básica Inves8gación Aplicada Nuevas o Mejores Tecnologías Cul8vo de Células y respuesta a P Hesbmulos Y S I C A Lexternos R E V I E W L E Mejor: T T E R SCromatograLa 31
Nueva: Separación entrópica of the effective shear rate, g" , and thus of the s
" g.
" Clearly, Dz and
b ! Dz!2 3 "g" 2 g#!
value of the diffusion coefficient
pend on the
anyhow a weak
dependence "D #, and the poo
in the estimate
of D results only in a systematic u
of 20% in the b values.
The diffusion length during t gives an uppe
Dz: Dz ! 2"DF!2g" # . For hexadecane
of the order
of a micrometer, a value that we hav
Disposi8vos y Sistemas P. Frimat, et al,” Lab on a Chip, vol. 11, no. 2, p. 231, 2011. Published on 27 October 2010. Downloaded by RUTGERS STATE UNIVER
Inves8gación Básica scope,
for coupling where
at least
one of molecules
the
differences,
efficient
separation
without
thebeing
use ofsuitable
a gel matrix
ergy,
so DNA
are temporarily
in Fig. 4(A),
flow ratios thus
$1.4 enabling
enabled efficient
arraying
that was
cellular partners can act as microfluidic valve (i.e. adheres and
largely insensitive
to variations
in the size
of the SW480
epithelial
or pulsed
electric fields.
Samples
of long
DNA molecules (5000 to !160,000
trapped at the entrance of the thin regions.
becomes flattened). The coupling principle can also be applied to
cells (Ø SD
$ 3.0pairs)
mm). Recorded
in Fig. 4(B),
only !25%
of traps
base
were efficiently
separated
into
bands incell
15-millimeter-long
chanThe entropic trapping limits the overall motypes with different sizes, with the simple requirement that
were occupied
when
using
flow
ratios
#1.0,
whereas
>98%
of
nels. Multiple-channel devices operating in parallelthe
were
demonstrated.
The
bility
ofMoreover,
DNA molecules
in the channel, and
aperture
is smaller than
the smallest cell
type.
the
traps wereefficiency,
occupied with
flow ratios $1.4.
compactness,
andSingle
easecell
of occupancy
fabrication ofusethe
device
suggest
the arrayingthe
mobility
of DNA
of the
differential
resistance
method
eliminates
the becomes length-depenwas 80.6% (SD $ 4.3) when using a flow ratio of 1.4 and 85.0%
possibility of more practical integrated DNA analysis
Interestingly,
risksystems.
of channel blocking which can occurdent.
with systems
designedlonger DNA molecules
(SD $ 2.8) with a flow ratio of 1.8. The influence of the trap size
12
actually
have higher
mobility in this channel
to contact cells across the width of a single
microchannel.
was also examined and had only a minor impact on cell arraying
Further
developments
were field
required (13).
to provide
aescape
reliable
Gel
electrophoresis
is
the
standard
method
for
In
the
of a DNA molecule from
(13).
A
spatially
varying
but
static
electric
characteristics. In this experiment, >99% of traps were occupied
cell co-culture
Dead, non-adherent
cells
(!10%)
of DNA
by length.
efficiency
of to and
an entropic
trap,
only the part of the molecule
an arraysingle
of constrictions
actplatform.
as size-depenforseparation
trap diameters
ranging
from The
15 mm
(cell-sized)
37 mm.
removed.
However,
flow reversal
cellswith
are the boundary of the thin
gel cell
electrophoresis
deteriorates
seriously,
howthatwhile
is inviable
contact
dent
traps forshould
DNAbe
motion.
Separation
matrices
Single
occupancy was
typically 80%,
with the
exception
of the
flattened
state would
direct region
dead cells
into
neigh- role. Whenever a sufever,traps
for DNA
molecules
plays
a crucial
such as gelsinorthe
polymer
solutions
are notonly
used,
largest
where only
68.6% longer
(SD $ than
6.7) ofabout
traps contained
bouring traps immediately across the microfluidic channel. This
40,000
pairs but
(40significant
kbp). Slab
gel pulsedficient number of DNA monomers are introandmay
the methods
used to fabricate this array are
single
cells.base
This small
reduction
(*p # 0.005)
is solved by exploiting the longer time scales required for cell
be field
caused
the greater freedom
of using
cell placement
the
gelbyelectrophoresis
(PFGE),
time- with
compatible
with silicon-based processing. duced into the high-field thin region (by
flattening than initial adhesion. Within 2 hours of loading, viable
possibility
failing
to divert
thebestreamlines
once the first
cell is
varying of
drive
voltages,
can
used to separate
Therefore,
this
couldadherent
easily be integrated
cellsdevice
become
but retain aBrownian
relativelymotion),
sphericalthe escape of the whole
loaded,
or
that
cell
doublets
were
sheltered
from
flow-induced
longer double-stranded DNA (dsDNA) frag- into a largermorphology.
total analysis
The
At system.
this stage
thebasic
cellular molecule
valve is inisainitiated
partially(14). Longer DNA moldisaggregation
and separation.
ments, but generally
the process is slow, and theory of operation
ecules,
with larger
Ro, have a larger surface
of and
thebydevice
has been
closed state,
flow reversal
dead cells
are diverted
into the
in contact
with the boundary and thererecovery of separated DNA from gel is com- described (14).
Here, we
demonstrate
one apserpentine
channel
and removed
from area
the system.
Following
further
4 hours
incubation,
cellsa flatten
fore have
higher in
probability to escape per
plex. Efficient separation has been reported plication of athe
entropic
trap array
devicethe
by remaining
for arraying
the secondslab
cell type.
Thistime
method
unit
(dueensures
to a higher escape attempt
with pulsed-field capillary gel electrophoresis using it in areadiness
way similar
to conventional
that at least one of the cell partners is viable.
With the
second
frequency),
which
leads to a shorter trapping
(PFCGE) (1–3). However, only one sample
gel PFGE methods.
arraying
of thetrap
cellsarray
are estimated
to bea viable
time and
highersuch
overall mobility (Fig. 1B).
could be run at a time in PFCGE, and so
The basic
designphase,
of the 90%
entropic
that !90% of the pairs are also likely to contain viable cell
multiple capillary systems would be required
b
partners.
for large-scale genome sequencing or DNA
Co-culture
of nm
Fig. 1. Nanofluidic
sep- experiments require time scales of thets order
= 75~100
fingerprinting (4). Moreover, with respect to aration device
td b
= 1.5~3
µm
hours with
to days.AHowever, with
the immediate
introduction of
future integrated bioanalysis systems (5, 6)— many entropic
traps.media following plasma-based device assembly, the
aqueous
the so-called micro total analysis systems ("- (A)
Cross-sectional
PDMS maintainsCathode(-)
a hydrophilic character21 which supports cell
Anode(+)
22
1!2
of
TAS)—it could be cumbersome to introduce a schematic diagram
adhesion and migration. Within 24DNA
hours some cells migrated
Electroforeign sieving matrix into the channel of a the device.outside
the trap region (see Fig. S2(A)†), and to the extremities of
phoresed DNA
the moleserpentine channel by the fourth day of culture (see
highly integrated device.
DNA motion
cules are Fig.trapped
S2(B)†). Migration prevents controlled single cell co-culture.
A variety of microfabricated systems (7–12) whenever they
meet
a this limitation we implemented a plasma stencilling
To
remedy
region
Thin region
have been studied for separation of dsDNA. thin region, because
an within
and Thick
H. trap
G. regions.
Craighead, “Separa8on of Long 22
to pattern
cells
the
This approach
B J. H
However, early artificial gel systems (8, 10) their radiusmethod
of gyrarequires a hydrophobic
PDMS
state which
can
be restored,
DNA M
olecules i
n a
M
icrofabricated Entropic tion (Ro) is much largwith arrays of pillars showed poor dc electrofollowing
plasma bonding, by the diffusive return of oligomers to
er
than
the
thin
region
phoretic separation for long DNA molecules,
Trap Array,” Science, wva1!3
ol. 242Native
88, no. 5468, pp. max
30 µmovernight incubation in a dry state.
depth (here,the
td surface
and ts during
a
b
and the use of pulsed electric fields was rewb
PDMS
surfaces
provide
biologically
inert
backgrounds
1026 –1029, May 2000. which
are the thick and thin
quired (9). More recently, a single-molecule region depths,
26–28
b
resist
cell adhesion.
Hydrophilic patterns for cell adhesion
respecFig.DNA
5 The
cellular
valving(11)
approach
single cellsorting
co-culture. Single
cell(B) Top
sizing
device
and afordiffusion
were
provided
within the microfluidic system by plasma stenciltively).
view
of
arraying
(A) were
and cellular
adhesion,
to a flattened
array (12)
reported.
Despitetransforming
the advantag2Rowith the aqueous flows, the
using a Tesla generator.22 As
the device ling
in operamorphology to act as a valve in the open state (B). Introduction of the
DNA
es of these new systems, it is still unclear how tion. Trapped
plasma
was routed along the linear path of least resistance,
second cell (C) and following further culture the cell flattened and coneventuallythe surface to - produce a hydrophilic state which
+
these systems might be incorporated into estab- molecules oxidizing
G. 1. (a) Schematic of half the flow cell; (b) equivalence
independently by solving numerically the c
tween slip and shear rate. Nuevas oportunidades aprovechando diffusion equations for a two-dimensional mode
las diferencias en el comportamiento a escala microscópica experiment. This agreement between experim
IR) at the solid/liquid interface. Immediately after the
simulated
La $sica no cambia, Dz values means that if numerical pre
eaching pulse, the fluorescence intensity is low (photoist in the relation defining Dz, they remain of t
pero os mthe
ecanismos ominantes ueden er drastically
diferentes. eached probes
are linside
illuminated d
area),
and it
1pand
should snot
affect the estimated
ogressively recovers due to the transport of nonbleached
important to notice that the experiment
i
Ejemplo: Movimiento ItBisrowniano 3 obes into the evanescent wave. The kinetics of fluorestacted the first cell (D).
lished bioanalysis protocols.
This journal
is ª The
Society of
Recently
we Royal
introduced
anChemistry
entropic 2011
trap
array system with lithographically defined constrictions comparable to molecular dimensions;
this system can be used with static (dc) electric
fields to rapidly separate large DNA fragments
School of Applied and Engineering Physics, Cornell
University, Ithaca, NY 14853, USA.
*To whom correspondence should be addressed. Email: hgc1@cornell.edu
C
escape, with a probability of escape proLab Chip, 2011, 11, 231–237 | 235
portional to the length
of the slit that the
DNA molecule covers
(wa and wb). Larger
molecules have a
higher escape probability because they
Fluorescence
cover wider regions of
DNA
microscopy
the slit (wb # wa). (C)
observation
Experimental setup.
Reservoirs are made at both ends of the channel and filled with DNA solution.
buffer
solution
to the BC at a distance L ! 80 nm though the
MEMS, Microfluidica, Lab-­‐on-­‐a-­‐chip, Nanotecnologia, … Inspiración (1959?) 4 Orígenes 70’ Microelectrónica Miniaturización & Integración G. Moore, doble numero de transistores cada año, por lo menos hasta 1975!! 5 Orígenes 70’ Microelectrónica 80’ MEMS Poly 1 (P1) and Poly 2 (P2) layers are shown in magenta and blue, respectively. The active elements
are the P1 triangular plate and beams (visible below the P2 layer due to the conformal deposition
print trough) and the P2 grid on top, forming a capacitor whose electrodes are connected to bond
pads via serpentine springs. The mechanical Q ( 2) is governed by the size and distribution of holes
in the grid and the resonance frequency (19 kHz) by the mass of the P1 plate and stiffness of the
three beams.
D. Lopez, F. Pardo y otros @ Lucent (2005) 6 Orígenes 70’ Microelectrónica Integración y Miniaturización 80’ MEMS Acelerómetros Poly 1 (P1) and Poly 2 (P2) layers are shown in magenta and blue, respectively. The active elements
are the P1 triangular plate and beams (visible below the P2 layer due to the conformal deposition
print trough) and the P2 grid on top, forming a capacitor whose electrodes are connected to bond
pads via serpentine springs. The mechanical Q ( 2) is governed by the size and distribution of holes
in the grid and the resonance frequency (19 kHz) by the mass of the P1 plate and stiffness of the
three beams.
Figure 7.
Scanning electron micrograph of the all-surface-micromachined “tent” microphone made at the MCNC foundry.
determined by the size and tension of the membrane
but by the tunable length of the beams. The assembly
is accomplished in one step by pulling upwards with a
micropipette from the vertex as shown in Figure 8.
Several self-assembly techniques have also been tried
but measurements have not yet been made on these
devices. A sound pressure difference between the
interior and exterior of the chamber forces the membrane to move and the change in capacitance is
detected by a charge sensitive amplifier.
The main construction steps for the “tent” microphone are shown in Figure 8. Here one can see that
the assembly requires the pulling of the apex up out
of the plane and the pushing in from the two sides
to form the tetrahedron. Sealing of the hinge was
194
Hinges
Figure 8.
Main MEMS “tent” microphone construction steps.
Bell Labs Technical Journal
7 Orígenes ADXL50
70’ The ADXL50 is a complete acceleration measurement system
Microelectrónica on a single monolithic IC. It contains a polysilicon
80’ surface-micro machined sensor and signal conditioning circuitry. The
ADXL50 is capable of measuring both positive
and negative acMEMS celeration to a maximum level of ± 50 g.
THEORY OF O P ERATION
Figure 16 is a simplified view of the ADXL50’s acceleration
sensor at rest. The actual structure of the sensor consists of 42
unit cells and a common beam. The differential capacitor sensor
consists of independent fixed plates and a movable “floating”
central plate which deflects in response to changes in relative
motion. The two capacitors are series connected, forming a capacitive divider with a common movable central plate. A force
balance technique counters any impeding deflection due to acceleration and servos the sensor back to its 0 g position.
demodulator will rectify any voltage which is in sync with its
clock signal. If the applied voltage is in sync and in phase with
the clock, a positive output will result. If the applied voltage is in
sync but 180° out of phase with the clock, then the demodulator’s output will be negative. All other signals will be rejected.
An external capacitor, C1, sets the bandwidth of the demodulator.
Acelerómetros The output of the synchronous demodulator drives the preamp
—an instrumentation amplifier buffer which is referenced to
+1.8 volts. The output of the preamp is fed back to the sensor
through a 3 MΩ isolation resistor. The correction voltage required to hold the sensor’s center plate in the 0 g position is a
direct measure of the applied acceleration and appears at the
VPR pin.
OBS
O
TOP VIEW
Poly 1 (P1) and Poly 2 (P2) layers are shown in magenta and blue, respectively. The active elements
are the P1 triangular plate and beams (visible below the P2 layer due to the conformal deposition
TOP VIEW
APPLIED
ACCELERATION
print trough) and the P2 grid on top, forming a capacitor whose electrodes are connected to bond
pads via serpentine springs. The mechanical Q ( 2) is governed by the size and distribution of holes
in the grid and the resonance frequency (19 kHz) by the mass of the P1 plate and stiffness of the
three beams.
CS1
CENTER
PLATE
TETHER
Figure 7.
Scanning electron micrograph of the all-surface-micromachined “tent” microphone made at the MCNC foundry.
CS2
determined by the size and tension of the membrane
but by the tunable length of the beams. The assembly
is accomplished in one step by pulling upwards with a
micropipette from the vertex as shown in Figure 8.
Several self-assembly techniques have also been tried
but measurements have not yet been made on these
devices. A sound pressure difference between the
interior and exterior of the chamber forces the membrane to move and the change in capacitance is
detected by a charge sensitive amplifier.
The main construction steps for the “tent” microphone are shown in Figure 8. Here one can see that
the assembly requires the pulling of the apex up out
of the plane and the pushing in from the two sides
to form the tetrahedron. Sealing of the hinge was
Hinges
BEAM
CENTER
PLATE
FIXED
OUTER
PLATES
194
Figure 8.
Main MEMS “tent” microphone construction steps.
Bell Labs Technical Journal
LETE
BEAM
UNIT CELL
CS1 < CS2
CS1
CS2
CS1
CS2
UNIT CELL
CS1 = CS2
DENOTES ANCHOR
DENOTES ANCHOR
Fig ure 17. T h e A D X L50 S e nsor M o m e ntarily Resp o n din g
8 to a n E xtern ally A p plie d A cceleratio n
When the ADXL50 is subjected to an acceleration, its capacitive
Orígenes 70’ Microelectrónica 80’ MEMS 90’ Microfluidica Lab-­‐on-­‐a-­‐chip (1977) Gas Chromatograph S. C. Terry, J. H. Jerman & J. B. Angell
Poly 1 (P1) and Poly 2 (P2) layers are shown in magenta and blue, respectively. The active elements
are the P1 triangular plate and beams (visible below the P2 layer due to the conformal deposition
print trough) and the P2 grid on top, forming a capacitor whose electrodes are connected to bond
pads via serpentine springs. The mechanical Q ( 2) is governed by the size and distribution of holes
in the grid and the resonance frequency (19 kHz) by the mass of the P1 plate and stiffness of the
three beams.
Acelerómetros Figure 7.
Scanning electron micrograph of the all-surface-micromachined “tent” microphone made at the MCNC foundry.
determined by the size and tension of the membrane
but by the tunable length of the beams. The assembly
is accomplished in one step by pulling upwards with a
micropipette from the vertex as shown in Figure 8.
Several self-assembly techniques have also been tried
but measurements have not yet been made on these
devices. A sound pressure difference between the
interior and exterior of the chamber forces the membrane to move and the change in capacitance is
detected by a charge sensitive amplifier.
The main construction steps for the “tent” microphone are shown in Figure 8. Here one can see that
the assembly requires the pulling of the apex up out
of the plane and the pushing in from the two sides
to form the tetrahedron. Sealing of the hinge was
194
Hinges
Figure 8.
Main MEMS “tent” microphone construction steps.
Bell Labs Technical Journal
Columna de 30um x 200um y 1.5 metros ! Grabado en Silicon 9 Orígenes 70’ Microelectrónica 80’ MEMS 90’ Microfluidica Lab-­‐on-­‐a-­‐chip Poly 1 (P1) and Poly 2 (P2) layers are shown in magenta and blue, respectively. The active elements
are the P1 triangular plate and beams (visible below the P2 layer due to the conformal deposition
print trough) and the P2 grid on top, forming a capacitor whose electrodes are connected to bond
pads via serpentine springs. The mechanical Q ( 2) is governed by the size and distribution of holes
in the grid and the resonance frequency (19 kHz) by the mass of the P1 plate and stiffness of the
three beams.
Acelerómetros Figure 7.
Scanning electron micrograph of the all-surface-micromachined “tent” microphone made at the MCNC foundry.
determined by the size and tension of the membrane
but by the tunable length of the beams. The assembly
is accomplished in one step by pulling upwards with a
micropipette from the vertex as shown in Figure 8.
Several self-assembly techniques have also been tried
but measurements have not yet been made on these
devices. A sound pressure difference between the
interior and exterior of the chamber forces the membrane to move and the change in capacitance is
detected by a charge sensitive amplifier.
The main construction steps for the “tent” microphone are shown in Figure 8. Here one can see that
the assembly requires the pulling of the apex up out
of the plane and the pushing in from the two sides
to form the tetrahedron. Sealing of the hinge was
194
Hinges
Figure 8.
Main MEMS “tent” microphone construction steps.
Bell Labs Technical Journal
(2003) Large Scale IntergaGon T. Thorsen, S. J. Maerkl & S. R. Quake
Miles de válvulas y conexiones
10 Orígenes 70’ Microelectrónica 80’ MEMS 90’ Microfluidica Lab-­‐on-­‐a-­‐chip 00’ Nanotecnología Nanofluidica Poly 1 (P1) and Poly 2 (P2) layers are shown in magenta and blue, respectively. The active elements
are the P1 triangular plate and beams (visible below the P2 layer due to the conformal deposition
print trough) and the P2 grid on top, forming a capacitor whose electrodes are connected to bond
pads via serpentine springs. The mechanical Q ( 2) is governed by the size and distribution of holes
in the grid and the resonance frequency (19 kHz) by the mass of the P1 plate and stiffness of the
three beams.
Acelerómetros Figure 7.
Scanning electron micrograph of the all-surface-micromachined “tent” microphone made at the MCNC foundry.
determined by the size and tension of the membrane
but by the tunable length of the beams. The assembly
is accomplished in one step by pulling upwards with a
micropipette from the vertex as shown in Figure 8.
Several self-assembly techniques have also been tried
but measurements have not yet been made on these
devices. A sound pressure difference between the
interior and exterior of the chamber forces the membrane to move and the change in capacitance is
detected by a charge sensitive amplifier.
The main construction steps for the “tent” microphone are shown in Figure 8. Here one can see that
the assembly requires the pulling of the apex up out
of the plane and the pushing in from the two sides
to form the tetrahedron. Sealing of the hinge was
194
Hinges
Figure 8.
Main MEMS “tent” microphone construction steps.
Bell Labs Technical Journal
11 Historia Breve (e incompleta) •  1975 -­‐ 1st disposi8vo analí8co en miniatura (cromatograLa) -­‐ Fabricación: grabado en silicon. (Stanford; Terry y otros) •  1990 A. Manz introduce la idea de μTAS (Micro-­‐Total-­‐Analysis-­‐Systems) Se fabrican disposi8vos •  2000 Se introduce la idea de “sor-­‐lithography”. Se simplifica y populariza la fabricación de dis8ntos sistemas Se amplia el concepto de μTAS a Lab-­‐o-­‐a-­‐chip •  2010 Empiezan a surgir ideas para simplificar aun mas la fabricación: “Paper-­‐based microfluidics”; “CD-­‐microfluidics” y otros Impresoras 3D con resolución ~ 100 micrones. 12 Popularidad Microfluidic lab-­‐on-­‐a-­‐chip plavorms: requirements, characteris8cs and applica8ons D. Mark, S. Haeberle , G. Roth , F. von Stefen and R. Zengerle Chem. Soc. Rev., 2010, 39, 1153-­‐1182 Imposible mantenerse al dia!! 13 Microfluidica: desarrollo de tecnología μTAS & Lab-­‐on-­‐a-­‐chip Información y cálculo: Automa8zación Integración Miniaturización 14 Microfluidica: desarrollo de tecnología μTAS & Lab-­‐on-­‐a-­‐chip Información y cálculo: Automa8zación Integración Miniaturización Procesos y análisis químicos: Tubos de ensayo… Automa8zación Integración Automa8zación Miniaturización Integración 15 Microfluidica: desarrollo de tecnología μTAS & Lab-­‐on-­‐a-­‐chip Información y cálculo: Automa8zación Integración Miniaturización Tubos de ensayo… Automa8zación Integración Miniaturización Automa8zación Integración 16 μTAS & Lab-­‐on-­‐a-­‐chip Que ventajas 8ene? más chico; más rápido; más simple, más economico, …mejor!! • 
• 
• 
• 
• 
• 
• 
• 
• 
Portá8l Menos volumen de químicos Mayor seguridad Reduce la contaminación Bajo costo y producción masiva Más rápido Análisis en paralelo Usos novedosos (implantes?) Métodos novedosos ? 17 Microfluídica: Areas de mayor uso y crecimiento Química analí8ca; control de reacciones químicas; detección y muestreo; ensayos químicos en paralelo; Ej. Desarrollo de técnicas y disposi8vos de separación 18 Microfluídica: Areas de mayor uso y crecimiento Ventajas: Bioquímica: Numero grande de estudios simultáneos; Biología: Células: Control preciso de los esbmulos/condiciones Ej. Respuesta de células Madre a la falta de oxigeno 19 Desarrollo de medicamentos; ingeniería de tejidos; gené8ca; ensayos bioquímicos, celulares; Microfluídica: Materiales 2508
2508
D Quéré
Figure 12. Substrate decorated with posts (the bar indicates 1 µm). If coated wi
fluorinated silanes, this substrate is found to be super-hydrophobic [37].
Other important observations can be deduced from the Kao experim
hydrophilic and hydrophobic cases can be asymmetric—we see in figure 10 th
angle jumps to a much larger value as soon we enter the hydrophobic
20 domain. (b
hand, the variation of the contact angle is continuous in the hydrophilic part, bu
(both linear) seem to be successively followed. (c) It is impossible to induce ei
Microfluídica: Salud INSIGHT REVIEW
NATURE|Vol 442|27 July 2006|doi:10.1038/nature05064
Microfluidic diagnostic technologies for
global public health
Paul Yager1, Thayne Edwards1, Elain Fu1, Kristen Helton1, Kjell Nelson1, Milton R. Tam2 & Bernhard H. Weigl3
The developing world does not have access to many of the best medical diagnostic technologies; they
were designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of
calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of
samples. Microfluidic systems allow miniaturization and integration of complex functions, which could move
sophisticated diagnostic tools out of the developed-world laboratory. These systems must be inexpensive,
but also accurate, reliable, rugged and well suited to the medical and social contexts of the developing world.
Microfluidic systems can be designed to obtain and process measurements from small volumes of complex fluids with efficiency and speed,
and without the need for an expert operator; this unique set of capabilities is precisely what is needed to create portable point-of-care (POC)
medical diagnostic systems1,2. Fortunately for the microfluidics field, the
military has always had a need to practise medicine in challenging and
resource-limited environments, and so has long been trying to acquire
robust medical technologies that add an absolute minimum to the burden of those people and machines transporting them. It was for this
reason that microfluidics research in the United States was given a great
boost in the 1990s by funding from the US Defense Advanced Research
Projects Agency (DARPA). The technologies developed with DARPA’s
Infectious disease DALYs
3% 6%
Lower respiratory infections
24%
9%
HIV/AIDS
Diarrhoeal diseases
6%
Malaria
12%
23%
17%
Measles
Tuberculosis
Pertussis
Others
21 Microfluídica: Medicina 22