IOP PUBLISHING JOURNAL OF MICROMECHANICS AND MICROENGINEERING

J. Micromech. Microeng. 17 (2007) S103–S115 doi:10.1088/0960-1317/17/7/S07

The centrifugal microfluidic Bio-Disk

platform
Jens Ducrée1,2, Stefan Haeberle1, Sascha Lutz1, Sarah Pausch2,
Felix von Stetten2 and Roland Zengerle1,2
1
HSG-IMIT, Wilhelm-Schickard-Str.10, D-78052 Villingen-Schwenningen, Germany
2
IMTEK, Department of Microsystems Engineering, Georges-Koehler-Allee 106,
D-79110 Freiburg, Germany
E-mail: jens.ducree@hsg-imit.de

Received 19 February 2007, in final form 17 April 2007

Published 28 June 2007
Online at stacks.iop.org/JMM/17/S103

Abstract
This paper reviews the centrifugal ‘Bio-Disk’ platform which is based on
rotationally controlled, multi-scale liquid handling to fully integrate and
automate complex analysis and synthesis protocols in the life sciences. The
platform offers the crucial ingredients for a rapid development of
applications: a coherent library of fluidic unit operations, a device
technology for actuation, liquid interfacing and detection as well as a
developer toolbox providing experimental testing, rapid prototyping and
simulation capabilities. Various applications in the fields of life science,
in vitro diagnostics and micro-process engineering are demonstrated.
(Some figures in this article are in colour only in the electronic version)

Introduction systems [3] and hydrophobic venting [4]. This paper reviews
a centrifugal microfluidic Bio-Disk platform which has been
Microfluidic lab-on-a-chip technologies have experienced developed over the last years by IMTEK, HSG-IMIT and
a breathtaking surge over the last 10–15 years. The several partners [5].
field started out from mere analytical separations—mainly Compared to other lab-on-a-chip platforms, we will
chip-based chromatography and capillary electrophoresis as elaborate at various occasions throughout this paper that the
well as miniaturized (bio-)chemical sensors. However, centrifugal approach offers a unique way to integrate liquid
it was recognized very early that, apart from a mere handling for sample preparation and subsequent detection.
miniaturization, a comprehensive integration, automation The process integration on a single substrate eliminates the
and parallelization of upstream liquid handling is key for need for an off-chip liquid handling by costly and error prone
a successful commercialization of lab-on-a-chip systems.
pipetting robotics. It will further be shown that many unit
Therefore, different liquid handling platforms have been
operations can be devised to operate widely independent from
developed to implement unit operations such as sample
liquid properties such as viscosity, electrical conductivity,
take-up, sample preconditioning, reagent supply, metering,
thermal behavior and even surface tension over a broad
aliquoting, valving, routing, mixing, incubation, washing as
well as analytical or preparative separations. range of volumes. These unique features are particularly
Contrasting the huge variety component technologies, appealing to life science or in vitro diagnostic applications
techno-economically viable platforms typically have to where volumes to be processed in the same test, e.g. sample and
severely restrict the number of technologies used for substrate dilution buffer, often range on different orders of magnitude
fabrication, actuation and detection! The choice of the and the liquid properties are usually not exactly known and
technology platform is hence governed by finding the best strongly diverge, e.g. of from sample to sample.
compromise between the mere analytical or preparative Our developments started out from previous academic and
performance and issues such as liquid handling capabilities and commercial efforts in this field of centrifugal microfluidics
manufacturability. Various application platforms have been [6–24] which already came up with technologies featuring
proposed, among them electrokinetic systems [1], droplet- full-fledged workstations incorporating actuation, liquid
based electrowetting [2], large-scale integrated peristaltic interfacing and detection units as well as means for quality

0960-1317/07/070103+13$30.00 © 2007 IOP Publishing Ltd Printed in the UK S103

J Ducrée et al

control. Using proprietary substrate formats, these platforms

have primarily focused on general chemistry testing and
immunoassays using absorption, agglutination or fluorescence
detection. Also the preparation of protein samples for
subsequent analysis by MALDI-MS has been commercialized.
For the rapidly emerging field of nucleic acid testing, key
steps such as cell lysis, DNA isolation and thermocycling for
polymerase chain reaction (PCR) have been realized. In the
mid-term future, it seems feasible to integrate an entire process
chain comprising all steps between the take-up of real-world
samples to displaying the analytical result on a centrifugal
microfluidic nucleic acid workstation.
Another branch of centrifugal microfluidics forks into the
field of micro-process engineering. By making designated
use of the frequency-dependent artificial gravity conditions
Figure 1. Geometry and forces on a disk spinning at the angular
and the pseudo-forces on the rotating substrate, applications
pointing out of the paper plane toward the reader.
velocity vector ω
such as ultra-fast mixing at high discharges, e.g. for chemical The radial coordinate is given by r. The liquid plug of diameter d
reacting, have been established. Also the centrifugally induced and absolute length l extends between its inner and outer radial
generation of multiphase systems such as highly monodisperse positions r< and r>, respectively, with r = r> −r< and r̄ = 0.5
emulsions, segmented liquid–liquid and gas–liquid flow and (r< + r>). For a radially oriented plug, r = l, otherwise r < l.
The liquid traveling at a speed v
down the channel is exposed to the
air-to-liquid sampling has been shown [27].
centrifugal force density f
ω ∼ ω2 (1), the Euler force density
The first section of this paper introduces the simple
fE ∼ dω/dt (2) and to the Coriolis force density f
c ∼ v (3).
and robust centrifugo-hydrodynamic operating principles,
allowing a liquid handling widely independent of the
properties of the liquid. The next section surveys important
unit operations for centrifugal-microfluidic liquid handling
including the scope of so-far realized applications. After
describing further constituents of the centrifugal microfluidic
application platform, we conclude with a summary and
outlook.

Centrifugal hydrodynamics

Forces
A fluid of mass density ρ on a planar substrate rotating at
a distance r from a central axis at an angular velocity ω
experiences the centrifugal force (density) Figure 2. Sedimentation of a particle suspended in a liquid volume
fω = ρrω2 (1) under the impact of a centrifugal field fω (1). The volume of height
h is confined by the inner and outer radial boundaries r< and r>,
the Euler force (density)
respectively. The motion of the particle follows the buoyancy
dω corrected force fω accounting for the mass difference m between
fE = ρr (2)
dt the particle and the displaced liquid volume. The centrifugal motion
scaling with the rotational acceleration dω/dt and the Coriolis is counteracted by the viscous drag Fd.
force (density)
fC = 2ρωv (3) Centrifugal flow
scaling with the fluid velocity v in the plane of the substrate We consider the simplified case of a liquid plug in a straight
(figure 1). In a centrifugal microfluidic system, these three and round radial channel of length r and diameter d at a
forces can directly be controlled by the frequency of rotation mean radial position r̄ [24, 38, 42]. Under the impact of the
ω = 2πν. centrifugal force fω (1), a parabolic flow profile peaking at the
center of the tube with a mean velocity
Sedimentation and buoyancy ρ
v̄ = r̄d 2 ω2 (5)
32η
Due to the dependence of the centrifugal force on the density
ρ(1), suspended particles or gas bubbles displacing a volume establishes. Obviously, the overall discharge Q = v̄A ∼ d 4 is
with the mass deviating by m from the substituted liquid obtained from multiplying (5) with the channel cross section
experience a sedimentation or buoyancy force A ∼ d2.
The equivalent (external) pressure head
Fg = mrω2 (4)
according to the sign of m in the artificial gravity field pω = ρ r̄rω2 (6)
g = rω2 (figure 2). The motion of the particle is counteracted corresponds to the pressure difference required to pump a
by the viscous Stokes drag Fd. pressure-driven flow at a mean velocity (5) through the same

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Figure 3. (Left) A hydrophobic valve is made up of a geometrical constriction from the channel diameter dch to a narrow capillary of
diameter dcap  dch. The contact angles are cap > 90◦ > ch. The capability to stop the flow up to a certain frequency threshold (8) is
determined by the capillary pressure p scaling with the curvature d−1 as well as the inertia of the impinging flow. (Right) A hydrophilic
barrier is represented by a sudden expansion. While still within the constriction near the exit of the channel, the ‘pinning’ of the contact
angle as well as the constant channel width require a high transient curvature of the meniscus. This effect establishes an energetic barrier for
the flipping of the meniscus from a concave to a convex shape, thus blocking the protrusion of the meniscus into the expansion up to a
certain frequency of rotation.

channel. For the liquid with the characteristics of water the meniscus beyond sharp corner driven by the interfacial
(ρ ≈ 1000 kg m−3, η ≈ 1 mPa s), a plug length r = 2 cm, tension. While being pinned at the exit of the constriction,
a mean position r̄ = 3 cm and a channel diameter d = the surface tension counteracts a flipping from a concave to a
200 µm, a mean velocity v̄ of the order of 1 m s–1 (5) and a convex meniscus which would lower the energetic barrier for
pressure head pω of about 20 kPa = 0.2 atm can be generated passing the edge.
at a spinning frequency of 30 Hz (6). Note that the radial
pressure distribution in a typical centrifugal flow may feature Siphoning
a pronounced minimum near the center of the channel. The dip
originates from the centrifugally induced hydrostatic pressure High-pass valving can be accomplished by a siphon structure
increasing in the radial direction and the viscous pressure drop under the impact of the artificial gravity g = rω2 connected to
toward the outer end [24, 46]. the centrifugal field (figure 4). The siphon forwards the liquid
as soon as the meniscus at r> has passed the crest point at rcrest
Capillary priming and protruded further radially outward than the liquid level
in the reservoir at r<. In centrifugal-microfluidic systems,
In centrifugal-microfluidic systems, it is often desirable to the priming of the exit channel is commonly implemented by
transport liquid toward ‘back’ the center of rotation. This is capillary action while halting the rotation (7) or by adding a
usually implemented by capillary action in narrow hydrophilic ‘displacer liquid’ [13, 14]. The siphoning flow stops once the
channels. The formula liquid levels equilibrate hydrostatically at r< = r> or once the
4ηl 2 continuity of the liquid column is disrupted.
t= (7)
dσ cos 
expresses the time t it takes a liquid with a surface tension σ Sacrificial valves
a contact angle , and viscosity η to fill a capillary of length Destructible barrier layers are often employed to enable tasks
l and diameter d of the circumferentially completely wetted such as vapor-proof valves for long-term onboard liquid
capillary. storage. Liquids stored behind such sacrificial valves may
be released by an external trigger working independent of
Capillary valving the centrifugal field, e.g. by laser irradiation or mechanical
punching of a pouch [13, 14]. By placing a number
A common means to effectuate valving in centrifugal
of sacrificial valves at alternative outlet vias, microfluidic
microfluidics are narrow hydrophobic constrictions (figure 3,
networks can even be programmed on demand [21].
left). For the progression of the meniscus across a capillary
barrier, a burst frequency

Centrifugal-microfluidic networks
1 σ |cos |
ν (Hz) = (8) The paradigm of liquid handling in most centrifugal-
π ρ r̄rd
microfluidic systems concerns stepwise transitions between
must be surpassed which is mainly governed by the surface hydrostatic equilibria under the impact of rotationally induced
tension of the liquid σ the contact angle  and the diameter artificial gravity. By opening a valve, the system becomes
d of the constriction [25, 26]. We roughly obtain ν ≈ 20 Hz unbalanced to seek a new hydrostatic equilibrium where the
for the liquid characteristics of water (σ ≈ 10−1 N m−1), the center of gravity of the rotated liquid has advanced in radial
above specified plug (r̄ = 3 cm, r = 2 cm), d = 20 µm and direction.
 = 120◦ (similar to water on Teflon). A capillary barrier can Highly dynamic break-up phenomena which are common,
be regarded as a high-pass valve with respect to the frequency for instance, in contact-free liquid dispensers, are quite
of rotation ω. uncommon in centrifugal microfluidic networks. This means
Also sudden expansions of hydrophilic channels work as that the liquid handling performance can be made widely
capillary valves (figure 3, right). This is because the steep independent of the flow properties, in particular the viscosity
increase in the bending pressure dominates the creeping of of the processed liquid. Within the chambers, centrifugally

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r=0
displacer liquid

crest point
rcrest

siphon channel
r<

r̄ reservoir ∆r ∆p ω = r̄∆ ω 2

capillary priming
r> outlet

vent

liquid
fω
retracting
r vent meniscus
capillary ∆r
filling fω
ν = 50 Hz ν =0 ν 30 Hz ν 30 Hz

Figure 4. A siphon structure consists of a reservoir and an outlet which are connected by a completely liquid-filled tube passing the crest
point rcrest. The radial boundaries of the liquid volume are r< and r>. For r = r> − r< > 0, a flow propelled by the hydrostatic pressure
pω ∼ r (6) drains from the reservoir over the crest point to the outlet without an external pump. The siphon can either be triggered by a
displacer liquid with subsequent rotation or by capillary priming of the hydrophilic channel at rest.

induced buoyancy efficiently supports the removal of gas Centrifugal microfluidic operations
bubbles from the liquid bulk.
Furthermore, the ability to supersede capillary and In this section, we outline the library of unit operations which
surface-tension-related forces by raising the frequency of can be concatenated on our novel centrifugal platform in
rotation ω also means that undesirable effects can virtually order to implement integrated and automated liquid handling
be ‘switched off’. This refers the transient suppression of protocols.
unwanted capillary filling as, for example, implemented by a
hydrophilically primed siphon (figure 4). Also the bending
of surfaces in capillaries may be compensated by a strong Volume metering
centrifugal field, thus allowing us to shape flat menisci.
The liquid-handling performance may hence be made widely Centrifugally induced liquid handling operations depend on
independent of the surface tension σ . the geometry (e.g. r) and the position (e.g. r̄) of the processed
Another ubiquitous topic in lab-on-a-chip technology is liquid. An accurate volume metering is therefore not only
the parallelization of processes. The centrifugal field suggests essential for quantitative chemical analysis or synthesis, but
to replicate identical structures according to the rotational also for a reproducible flow control in centrifugal microfluidic
symmetry in a spoke–wheel-like pattern. While such highly technologies.
symmetric layouts have also been used in pressure-driven Volume metering is predominantly realized by
approaches with a single pump pressurizing a central feed conceptually simple overflow principles (figure 5). The
channel, only the actuation by the centrifugal volume force working principle can also be understood by picturing a filled
suppresses ‘hydrodynamic cross talk’ between the parallel bucket of known geometry. By drilling a first hole in the
channels, e.g. the increase of the flow rate in a given channel upper section of the bucket, gravity expels liquid until the
due to the clogging of a neighboring channel. meniscus reaches the lower edge of the hole. Another hole
In summary, the quasi-hydrostatic implementation of introduced into the lower section now issues a metered volume
liquid handling under the impact of the frequency-controlled defined by the positions of the two lower edges. In centrifugal
centrifugal field bears the potential to make liquid handling microfluidics, the first hole is usually an overflow to a waste
protocols widely independent of the liquid properties. The while the second hole is represented by one of the previously
symmetry as well as the volume force nature of the centrifugal introduced passive valving schemes, e.g. hydrophobic
field also pave the road for a well-controllable parallelization (figure 3, left) and hydrophilic barriers (figure 3, right) as
of processes. well as siphons (figure 4) [28].

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synchronous ‘cutting’ of the liquid column at the upper

edges.

Batch-mode mixing
Mixing problems arise in microfluidic systems when the
completion of diffusive mixing processes takes too long for
a given application. For our rotating platform, we engineered
an active mixing scheme complying with the modularity of
our setup which is made up of two main units. The first unit is
a disposable cartridge with passive components, the second is
a device accommodating stationary components and a rotating
Figure 5. Metering by an overflow connected at a radially inward
engine which rests in the lab frame [30].
position r<. As long as the valve blocking the exit channel at r> is Mixing can be induced in a rotating chamber by
closed, excess liquid depletes via the overflow to a waste. After the rapid changes of the spinning frequency, i.e., a rotational
liquid surface has lowered to r<, the lower valve is opened and a acceleration dω/dt. The resulting Euler force fE (2) leads
volume geometrically defined by r = r> − r< is forwarded via the to advective currents which appreciably speed up mixing
outlet to downstream structures. The valve can, for instance, be
represented by a hydrophobic constriction (figure 3) or a hydrophilic
(figure 7, left). The efficiency of the mixing process is
siphon (figure 4). primarily governed by the steepness of the frequency ramps
ω(t) as well as by the geometry and the volume of the chamber.
Due to the competition between favorable inertial effects
Volume splitting and counteracting viscous dampening, chambers exceeding
a height above 500 µm and displaying aspect ratios near unity
In case an initial volume has to be split into several (metered) are preferable for this ‘shake-mode’ mixing.
aliquots, a hydrophilic zigzag structure with hydrophobic By introducing paramagnetic beads which are deflected
patches confining the conduits connected to each jag has by stationary permanent magnets aligned with alternating
been proposed (figure 6) [10, 29]. The upper jags are polarization along the orbit of the chamber, even a ‘magnetic
vents assuring pressure balance during the exit phase of the stirring’ can easily be realized (figure 7, left). Compared
liquid. The outward pointing jags forward the geometrically to previous magneto-hydrodynamic mixing schemes using
defined volume retained in each ‘V’ to the downstream magnetic stirrer bars [31–33] or microparticles [34, 35] in
areas. Key factors for a proper functioning are a complete an oscillating magnetic field, our scheme uses a stationary
capillary priming of the zigzag, the compensation of boundary magnetic field with a rotating mixing chamber containing the
effects at the two laterally outermost ‘Vs’, as well as actuators.

Figure 6. (Top) Schematic of the structure for parallel metering comprising a zigzag channel which features hydrophobically blocked
valves and vents (functional principle described in [29]). (Bottom) By elevating the rotational frequency ω above the burst frequency of the
outer hydrophobic barriers, the volume contained in each ‘V’ is released into attached test units. The precision of metering is linked to the
symmetry of the break-up process.

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Figure 7. (Top left) Concept of the rotating microfluidic disk and the forces acting on a paramagnetic bead (adapted from [30]). A set of
permanent magnets is aligned in the lab-frame at radial positions which are positioned inbound and outbound relative to the mean orbit
followed by the rotating mixing chamber (dashed circle). Thus, a confined magnetic bead experiences an alternating radial force FB
deflecting the bead and induces advection via the viscous drag force Fd. The centrifugal force Fω constantly points away from the center of
rotation. Rapid changes of the sense of rotation lead to a Euler for FE (2) on the bead and the liquid. (Bottom left) Flow patterns induced in
the mixing chamber. (Right) Lateral spreading of two concurrent centrifugal flows A (clear) and B (dark) due to the Coriolis force fC (3) for
an angular frequency ω = 300 rad s−1 in a rectangular radial channel of length l = 2.1 cm, height h = 65 µm and width x = 320 µm
starting at r< = 3 cm (adapted from [38, 39]). The right-hand side shows a top-view photography of the lateral spreading in the
corresponding experiment. (Note that different length scales apply to the x- and y-axis.)

Mixing of flows sample, wash and elution buffers have to be directed to the
In case large ‘macroscopic’ volumes have to be mixed waste or a receiving vessel after passing a common stationary
which cannot be contained in a single chamber or when phase. While different strategies such as flow focusing
the volumes are too small for implementing mixing effects concepts have been pursued for lab-on-a-chip systems, we
based on the Euler force fE (2), continuous-flow mixing here address concepts connected to the rotational motion of
schemes are applied. The aim is to contact the reagents centrifugal microfluidic systems.
with a large interfacial contact surface and short diffusion In the first approach in figure 8 (left), the incoming liquid
distances. A plethora of schemes to optimize micromixing stream disintegrates at the orifice on the upper left side of a
between concurrent streams has been presented in the literature large chamber [17, 41]. The individual droplets preferentially
for pressure-driven flows [36, 37]. These schemes have
stick to the left-hand wall where the centrifugal field guides
often been enhanced by imposing secondary, transversal flow
them toward a hydrophobic patch at the entry of the first
components or turbulent flow, e.g. via bends, impeller walls,
grooves or stationary phases. The particular choice depends on outlet channel. At high frequencies of rotation ω, the droplets
parameters like the Reynolds number during operation and the overcome the capillary barrier. At lower frequencies ω, the
constraints on the manufacturability and the required durability interfacial force supersedes the centrifugal field to deflect the
of the system. droplet toward the second outlet on the right-hand side of
Due to the similarity of the flow profiles, most of the chamber.
these passive, continuous-flow schemes can, in principle, Another routing scheme presented in figure 8 (right) is
also be adopted for centrifugally driven flows. In addition, primarily based on the Coriolis force fC (3). In an inverse
the availability of the Coriolis pseudo-force fC (3) offers
Y-channel geometry, the common radial inlet splits into two
an intrinsic means for the generation transversal flow
symmetric outlets [42, 43]. As the Coriolis force fC prevails
components, even in straight radial channels exhibiting a
constant cross section (figure 7, right). It can be shown that the centrifugal force fω toward elevated frequencies of rotation
the scaling of the force ratio fω/fC follows ω−1 [38, 39], such ω a critical frequency ω∗ exists above which mere digital
that the Coriolis-force induced mixing is most efficient toward switching occurs. Ideally, individual droplets pass the chamber
high frequencies of rotation ω. This allows us to combine interspersed between the inlet and the outlets in a free flight.
high mixing quality with high flow rates of the order of The performance of this ‘Coriolis switch’ is tightly linked
1 ml s−1! Also options for an online flow control have been to the dimensions and surface properties of the channels and
demonstrated [40]. the chamber. Attachment to the upper and lower walls by
capillary forces tends to deteriorate the performance of binary
Routing switching. Note that a similar switching behavior could also
The routing of a sequence of discrete volumes to designated be achieved by (solely or additionally) using the Euler force
outlets is a common task, e.g. in preparative protocols where fE (2).

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 The centrifugal microfluidic Bio-Disk platform

Figure 8. Liquid routers. (Left) Liquid is introduced via the upper left inlet and follows the left-hand chamber walls toward a hydrophobic
region at the entrance of the first outlet (working principle introduced by Gyros AB [17] in [41]). Depending on the centrifugal field and
thus the frequency ω, the droplet can either pass the capillary barrier or proceed to the second outlet. (Right) Flow through a symmetric,
inverse Y-structure (adapted from [42, 43]). (Right) At low frequencies ω where the Coriolis force fC (1) is still negligible compared to
fω (2), the flow is symmetrically split between both outlets. As the Coriolis force fC dominates beyond a critical frequency ω∗, it diverts
100% of the flow into an outlet addressed by the sense of rotation.

Figure 9. Course of liquid break-off at the hydrophobic outlet of the drain channel in a structure designed to stabilize the flow rate Q (5).
The liquid tears off into a waste reservoir. This way, the outer radial position of the liquid plug r> is kept constant. The variation of inner
plug position r< is minimized by the large lateral extension of the upstream chamber.

Control of flow rate of the flow rate Q may be required. Using Q ∼ d 4 (5),
pω ∼ r (6) and a hydrodynamic resistance proportional
The centrifugally driven flow rate is governed by the mean
to the channel length l, we can also reduce the quotient
radial position r̄ ∼ [r< + r>] (5) of the liquid volume and the
rd 4 / l to throttle the flow rate. This geometric factor
frequency of rotation ω. In typical assay protocols, a metered
reflects the ratio of the hydrostatic pressure head (∼r) to
volume such as a reagent or a wash buffer is driven from an
the hydrodynamic resistance (∼l/d 4 ). So a radially shallow
upstream chamber by the centrifugal force through a stationary
channel with a high tilt angle between the channel axis and the
phase such as a biosensitive layer immobilized on the channel
radial direction, i.e. r  l, diminishes Q. A further reduction
wall, aggregated beads or a membrane.
of Q can be accomplished by increasing the flow resistance,
In many cases, the variation of the flow velocity due to e.g. by a narrow, meander-like flow channel with an embedded
changes in r̄ during the depletion of the upstream chamber stationary phase.
ought to be minimized to homogenize incubation times.
Looking at (5), the flow velocity can be stabilized by an online
adjustment of ω. Such a dynamic adjustment of ω either Centrifugo-magnetic pumping
requires a very well reproducible flow behavior or a closed The production and handling of liquid–gas systems is a
loop control of r̄, e.g. via continuous tracking of the transient common task of multiphase lab-on-a-chip systems. The
positions of the menisci r< and r>. surface-tension stabilized bubbles are often employed as
An alternative to the adjustment of ω is to pinpoint r< and spacers between different droplets in so-called plug-flow
r> as far as possible during the flow interval. Regarding the schemes. However, for the introduction of the gas phase in a
downstream end at r>, the continuous liquid column can, for liquid stream requires a differential pressurization of the gas.
example, be disrupted at a hydrophobic orifice leading into a We therefore developed a centrifugo-magnetic pumping
large receiving vessel (figure 9). The fixed radial position of scheme which well complies with the modular paradigm
the orifice then coincides with r>. For the upstream meniscus, of the rotating system (figure 10). Two flat and round
the radial change of the inner meniscus r> can be minimized magnetic plates are incorporated into an elastomer sealing
by maximizing the lateral dimensions of the issuing reservoir. above a valve chamber and an adjacent pump chamber [44].
For other applications such as the simultaneous This actuation scheme resembles the previously introduced
sedimentation at large ω see below, the overall minimization ‘magnetic PDMS’ membranes deflected by electromagnets for

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(a) (b)

(c) (d)

Figure 10. Functional principle of the gas micropump (reprinted from [44]). The pump chamber orbits above a stationarily mounted
permanent magnet. The two steel plates within the PDMS lid are spaced at a defined azimuthal distance to induce a sequence of
displacements during rotation for pressurizing the gas. After the magnet has passed, the chambers are primarily replenished by ambient gas
through the inlet of the valve chamber.

Figure 11. Centrifugal droplet generation ([46], with permission from Springer Science and Business Media). The dispersed phase is
contacted from both sides with the continuous phase at the junction of a flow-focusing structure. The main impact parameters are the three
incoming flow rates, the angle at which the side flows impact the central stream and the radial position of the intersection. The droplet
generation is characterized by the droplet diameter, the droplet spacing, and the droplet rate.

static setups [45]. While rotating, the magnets in our rotary artificial gravity field virtually ‘pulling out’ the droplet from
scheme are sequentially deflected upon passing a stationary the nozzle.
permanent magnet positioned at the orbit to differentially As the rotational motion is even stabilized by the inertia of
pressurize the gas. The pumping is impacted statically by the rotor, these centrifugal schemes are intrinsically pulse-free
the chamber geometry, the elastic modulus of the sealing and and thus highly reproducible. We could experimentally show
the magnetic force as well as dynamically by the spinning rate the production of highly monodisperse emulsions.
corresponding to the actuation frequency.

Particle sedimentation
Droplet generation
Several means to generate liquid droplets by centrifugal An initially homogeneous particle suspension separates in the
microfluidic technologies have been investigated. In a first presence of a centrifugal field. The speed of sedimentation
concept, a liquid plug is issued at a central orifice and cut off is governed by the difference of the masses of the particle
by two constricting flows exhibiting transversal components and the displaced liquid m as well as the Stokes drag Fd
(figure 11) [46]. scaling with the radius, the viscosity and the velocity of the
The other scheme is based on a dispenser delivering particle (figure 2). A phase boundary, the so-called shock
individual droplets from a nozzle through an intermediate interface travels from the inner liquid interface toward the outer
air spacer into a receiving liquid (see later in figure 16, perimeter of the vessel. As the rotary drive offers the function
left) [47]. While conventional dispensing schemes such as of a customary centrifuge, also sedimentation processes can
inkjet technologies require a highly dynamic ejection for be enforced. Thus is, for instance, implemented by the cell
surpassing the surface tension and viscosity, the centrifugal volume fraction in whole blood (hematocrit) measurement
droplet generation is associated with the frequency-scalable displayed in figure 12 [48, 49].

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Figure 12. Centrifugal hematocrit determination [48, 49] (adapted

from [48], [49] reproduced with permission from Springer Science Figure 13. Flow scheme of a decanting structure for plasma
and Business Media). (Left) After an unmetered volume of whole separation from whole blood (adapted from [50]). A metered
blood is applied to the inlet reservoir, the capillary is primed and a volume of the blood sample is defined between hydrophobic stop
precise volume of whole blood is metered during rotation. (Center) and overflow channel. Upon breaking the outlet valve, a metered
Following sedimentation, the absolute hematocrit can be determined volume flows via the drain channel into the decant structure. A
with the calibrated scale imprinted along the channel. (Right) It has shock interface separating plasma from the cellular pellet builds out
been demonstrated that this test can even be performed on a in all parts of the network and proceeds radially outward at a speed
standard CDROM-drive. udrift. The filling height of the decant chamber rises at counter-
current speed udec before the plasma overflows into the plasma
collection chamber. The speed udec of the filling height in the cell
However, in typical applications based on centrifugal reservoir is adjusted by the hydrodynamic resistance of the drain
microfluidics, the sedimentation only constitutes one upstream channel so that only purified plasma advances to the plasma
unit step in an integrated process chain to which the reservoir.
supernatant (or the concentrated pellet) has to be forwarded.
Figure 13 shows an integrated sedimentation structure based injection molding [58]. This epoxy casting approach saves
on hydrophobic valving for the initial, overflow-based time and costs compared to traditional, high-performance
metering. Next, a radially flat and narrow transfer channel processes based on LIGA [59].
throttles the flow such that the suspension has sufficient After the structuring of the bulk material, postprocessing
time to sediment in the separation chamber before pure such as surface modification (e.g. hydrophilic, hydrophobic,
supernatant is passed on to the plasma chamber [50]. From biosensitive, anti-fouling), sealing (e.g. thermal bonding,
there, the plasma can, e.g., be forwarded to downstream gluing), integration of stationary phases (e.g. aggregated
structures by a hydrophilic capillary while halting the beads, membranes) and reagent loading (e.g. lyophilized,
rotation. The alternative siphon-based, batch-mode metering liquid storage in pouch) may be required.
and sedimentation structure in figure 14 works without
hydrophobic surface patterning and without a long throttle
Device technology
channel to save precious on-disk space [28].
We also explored a centrifugal sedimentation of particles The modular approach of our centrifugal microfluidic platform
under the impact of a transversal dielectrophoretic (DEP) consists of a multi-purpose device which operates the passive
deflection [51–53]. The DEP force field is built up by microfluidic disk. The device is equipped with a set of
onboard electrodes, electronics and batteries, thus allowing lab-frame components to realize a comprehensive group of
a two-dimensional separation according to the density and applications (figure 15, left). A frequency-controlled motor
dielectrophoretic properties of the particle, e.g. a sorting of and a holder for the rotating substrates (e.g. disks) constitute
dead and viable cells into distinct exit channels [54]. the core elements of the device. Depending on the application,
liquid, optical and possibly electrical interfacing between
Polymer microfabrication rotating ‘on-board’ components and stationary ‘lab-frame’
components such as contact-free dispensers or detection units
We established a polymer prototyping chain for the structuring, can be incorporated. A process control software synchronizes
surface modification and sealing of the substrates [55]. events such as liquid handling or optical readout to the periodic
The method is closely derived from the well-known ‘soft motion of the substrate.
lithography’ approach elaborated by the Whitesides group
[56]. For subsequent polymer mass fabrication, various Rotor and cartridge formats
technologies are available such as injection molding are
available [57]. First, an intermediate master is made by multi- Due to its rotational symmetry, the generic format for a
layer SU-8 or dry etching technology using laser-printed foils. centrifugal microfluidic substrate is a disk. However, the
This original mold is then transferred by PDMS casting into a disk shape may for various reasons not fit to the envisioned
flexible and thus easily demoldable master for hot embossing application. This may be due to the established standard
(‘soft embossing’). substrate in the application field which complies with up-
Alternatively, the casting into an epoxy material has or downstream instrumentation. Also cost reasons may
proven to supply a sufficiently stable master for small lot interfere with the disk shape, e.g. when a one-test-per-substrate

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Figure 14. Section view of the plasma extraction structure (adapted from [28]). (1) After injection through the inlet, a droplet of raw blood is
metered by the overflow channel. Three menisci can be identified in the inlet and both outlets. (2) The cells settle towards the bottom of the
reservoir as the shock interface separating pure plasma and cellular blood proceeds. Once the shock interface is below the inlet of the plasma
extraction channel, the disk is stopped and the extraction channel is filled by the capillary pressure pθ . (3) A net radial offset r < 0 induces
centrifugal pressure pω to pump the plasma through the extraction channel. The extraction process ceases at the point when air is sucked into
the plasma extraction channel. This point is reproducibly defined (CV < 1%) by the centrifugally supported flattening of the meniscus
towards high spinning frequencies. The extracted plasma is collected in a reservoir attached to the extraction channel for further use.

Figure 16. Different rotor and substrate formats for centrifugal

microfluidic technologies. (Left) Liquid droplets are issued in a
Figure 15. (Left) Bio-Disk analyzer. (Right) Absorption contact-free fashion from the side surface of the cartridge into a
measurement by optical beam guidance using total internal standard reaction tube aligning according to the centrifugal field
reflection at substrate-integrated V-grooves on the Bio-Disk (adapted from [47]). (Right) Rotor accommodating standard
analyzer (adapted from [61, 62]). microscope (microarray) slides (adapted from [60]).

paradigm is mandatory in diagnostic applications to avoid Optical detection

cross-contamination.
We have constructed different rotors for the Bio-Disk Most common detection methods, such as qualitative test strips
technology to assure compatibility with established formats. or highly sensitive fluorescent measurements, in analytical or
Figure 16 (left) shows a rotor which has been adapted for the diagnostic assays are based on optical techniques. Among
purification and extraction of nucleic acid on the analogy of other detection concepts, these contact-free optical principles
common spin-column protocols [47]. A sequence of sample are also most compatible with the modular paradigm of the
and different buffer solutions is loaded to the disk and routed centrifugal platform. This section reviews several optical
by the Coriolis force to a distinct outlet selected by the sense of detection schemes which have already been successfully
rotation (figure 8, left). To allow a seamless integration into the implemented on the Bio-Disk platform.
process flow in the lab, the purified DNA is expelled in a free
jet through orifices in the side surface of the disk into standard
Visual inspection. The simplest, ‘detector-free’ scheme
Eppendorf tubes. The receiving tubes are accommodated in a
is visual inspection. Combining microstructures with
‘flying bucket’ extension of the rotor to freely align according
designated frequency protocols, we successfully demonstrated
to the ratio of gravity and the centrifugal force in order to avoid
the implementation of hematocrit (cell volume ratio in whole
spill over.
blood) and agglutination-based blood-group testing on a
Another example is the centrifugal microarray processor
simple disk centrifuge or even on an ordinary CDROM-drive
illustrated in figure 16 (right) [60]. The novel rotor can be
(figure 12) [48, 49].
loaded with four standard microarray slides which are clamped
against an elastomeric PDMS inlay featuring microfluidic
structures. Using the shake-mode protocol (figure 7, left), Absorption measurements. In clinical chemistry, the
incubation and washing of the microarray can be performed detection of many blood parameters is based on optical
very efficiently in a flat flow chamber above the microarray. absorption. Toward decreasing optical densities, the
A siphon structure (figure 4) at the outlet of the chamber obtainable sensitivity is limited by the short optical path
allows a well-controlled displacement of a processing buffer lengths immanent to microscopic volumes. In addition, the
by the subsequent buffer into a waste reservoir such that the volumes are commonly contained in flat chambers which can
microarrays never run dry. only be probed through the flat top side.

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To tackle this problem, we elaborated an optical guidance action (hydrophilic/hydrophobic) and fluidic structures on
based on the total internal reflection at polymer–air interface of the micro- to milli-scale. The paramount features of our
V-grooves incorporated the backside of the substrate (figure 15, centrifugal technology are as follows.
right) [61–63]. Under perpendicular incidence, the beam is
• Modular setup:
deflected by 90◦ into the plane of the substrate to probe the
measurement chamber. Another V-groove then redirects the – centrifuge drive—passive microfluidic substrate,
attenuated beam toward the stationary detector. This way, – easy exchange of disposable cartridge,
the optical path length through the flat measurement chamber – flexibility of substrate formats (disk, slide, etc).
and thus the performance of the measurements are massively • Centrifugal field:
enhanced compared to direct (perpendicular) beam incidence. – pulse-free pumping,
The achieved sensitivity has proven to be comparable to – no pressure-tight interfaces needed,
standard colorimetric, cuvette-based assays such as alcohol, – low pressure load on lids,
glucose and hemoglobin levels in serum and whole blood – standard operation in sample prep,
[64, 65]. It has also been shown that several different – robust liquid handling widely decoupled from
parameters can be measured at the same run on the same disk viscosity and surface tension,
in parallel to form so-called disease panels. – intrinsic, buoyancy-based bubble removal,
– Coriolis force manipulates flows,
Chemiluminescence measurements. We implemented a – many laboratory protocols rely on centrifugation,
parallel readout technique for running common • Rotational symmetry:
chemiluminescent assay formats on our centrifugal – replication of identical process channels,
microfluidic platform [66]. The pilot application was a – simultaneous processing of parallel channels,
panel of cardiac markers. Antigens indicating an acute – sequential channel-by-channel processing,
myocardial infarction (AMI) were captured by a bead-based – excellent temperature homogeneity.
chemiluminescent ELISA procedure conducted under rotation • Full process integration and automation.
on a polymer disk and detected by a photomultiplier (PMT).
Parallel channel structures allow the quasi-simultaneous Note that most conventional lab-on-a-chip technologies
screening for different markers. However, a clear may, in principle, be transferred to the ‘lab-on-a-disk’, in
disadvantage of the readout under rotation is the immanent particular when they are active only while halting the rotation.
discontinuity of photon acquisition. The above-listed benefits have to be carefully weighed against
potential drawbacks.
Fluorescence detection. We also evaluated schemes for • Interfacing with lab-frame components:
bead-based fluorescence detection [67–69]. On the one – pipettes and dispensers,
hand, the detection on a bead phase allows us to introduce – quality control units,
the sensitive capture molecules after the sealing of the – detection units.
substrate, possibly requiring thermally and/or chemically • On-board components:
harsh conditions. This also makes the disk reconfigurable.
– exposure to centrifugal force,
On the other hand, the flow through a stationary phase allows
– need for mechanical balancing,
rapid and tightly controlled reaction conditions. Furthermore,
– difficult wiring, e.g. for electrical power, liquids and
detection in a single channel can be multiplexed, e.g. by a
signal transmission,
color-encoding of off-disk prepared beads. The color encoding
can, for instance, be implemented by incorporation of quantum which are primarily associated with the rotating motion of the
dots or dyes into the beads. substrate.
Several companies have, had or are slated to have
Test and development stand commercial activities based on centrifugal microfluidic
technologies [14, 17, 19–21]. It is expected that researchers
For the development of centrifugal microfluidic technologies, will continue to further augment the level of process
it is very useful to capture the dynamic processes during high- integration, automation, parallelization and miniaturization.
speed rotation. We devised a stroboscopic measurement setup Multi-purpose workstations which can run a set of different
comprising a microscope mounted CCD camera with a short applications, each represented by a designated substrate (disk),
exposure time and a flash light which are synchronized to will certainly be a strong selling point. The largest markets
the rotational motion as well as a GUI for setting frequency for centrifugal microfluidic technologies are expected for
protocols and frame grabbing parameters [70]. decentralized systems for high-sensitivity medical diagnostics
and (bio-)chemical analysis as well as research tools for
Summary and outlook pharmaceutical drug discovery.
Apart from reliability, sensitivity, interfacing with
In this paper, we have outlined the simple, robust established standards and regulatory issues, the main hurdle
and well-controllable operational principles of centrifugal to pass for a successful commercialization is clearly the price
microfluidics. Most liquid handling functions can be per assay or preparation compared to presently established
implemented by the interplay between frequency-controllable or other emerging technologies. This concerns the polymer
inertia (centrifugal force, Euler force, Coriolis force), capillary substrate as well as the device for which important lessons

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may, for instance, be learnt from the massive cost erosion of [22] Sakurai T, Uchida K, Kuno N and Nagaoka Y 2005
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