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Novel Magnetic Mixer for Magnetic Bead-Based

Microfluidic Bioassays
Miguel Berenguel1*, Xavier Granados2, Jordi Faraudo2, Julin Alonso1 and Mar Puyol1
Sensors & Biosensors Group, Universitat Autnoma de Barcelona, Bellaterra 08193 (Spain)
2
Institut de Cincia dels Materials de Barcelona (ICMAB-CSIC), Campus UAB, Bellaterra 08193 (Spain)
* Miguel.Berenguel@uab.cat
1

G B

Grup de
Sensors i
Biosensors

Introduction

Simulation of the Magnet Configurations

Microfluidic bead-based bioassays are a very powerful technique,


with potential applications in fields ranging from medical diagnosis to environmental analysis and food safety. Nevertheless,
these microanalytical systems are limited by the long incubation
times required for the molecules to interact by diffusion, being
worth noticing that the reaction with the magnetic beads (MB) is
heterogeneous.

Three different configurations


of magnets were studied (Fig.
3) taking into account the following criteria: simplicity for
their integration in the rotating unit; magnets dimensions
for the accurate movement of
the MBs; and expected magnetic field strength.

Herein, we propose a magnetic actuator composed of a mobile


set of magnets, which enhances the reaction performance by actively mixing the MBs with the reagents dissolved in the medium.
The magnetic actuator would also enable the control of the MBs
within the microfluidic system, thus making it possible to move
them from one chamber to another depending on the needs of
the assay.

Research Goals
Design and study of a magnetic actuator to control the MBs and
enhance the kinetics of a reaction by actively mixing on-chip

As a general trend, Fig. 3


shows that the magnitude of
Figure 3. Sketches of the three magnet configurations with the corresponding magnetic field (color
the flux density of the field is
map), the magnetization of the particles (black arrows) and the acting force (white arrows). A) single
magnet, B) two magnets antiferromagnetic-like coupled, in order to enhance the magnetic gradient,
larger for the couple of magand C) the same magnet couple including a static third magnet for creating a bias magnetizing field,
nets (Fig. 3 B and C) than for
which produces an out of plane magnetization.
the single magnet (Fig. 3 A),
due to the overlapping of the stray field with the flux in the poles, as well as an increase of the gradient of the magnetic field in between both magnets, when they are coupled. The static magnet (Fig. 3
C) increases the bias magnetizing field, enhancing the force over the MBs. However, the static magnet
would only have an effect when the magnetization of the MBs was not saturated, as it already appears
to happen in the simulation of configuration B (Fig. 3 B).

Application of the actuator to the detection of E. Coli O157

Thus, Configuration B was chosen for the experimental setup, as it fulfills the criteria of simplicity,
magnetic field strength (saturation of the MBs) and appropiate size.

Microfluidic Device Fabrication

Results

The microfluidic device is fabricated using the thermoplastic Cyclic Olefin Co-polymer (COC). Its design is very simple for this first
stage of the research. It consists of two main microfluidic elements, namely the reaction chamber, to carry out the reactions of
the bioassay, and the optical detection chamber, for the fluorescence measurements. The fabrication process is shown in Fig. 1.

E. Coli O157 Immunoassay

As a proof of concept, a MB-based immunoassay


is designed for the detection of E. Coli O157. The
formation of the immunocomplex was carried
out off-chip and subsequently injected into the
microfluidic device to carry out the enzymatic reaction. In this way, we focused on evaluating the
enhancement provided by the magnetic actuator
for a MB-based reaction on-chip.

Off-Chip

On-Chip

Figure 4. Analytical concept of the immunoassay. The anti-E. Coli O157


MBs (Invitrogen) react successively with the bacteria and the alkaline phosphatase labelled antibody. Then the immunocomplex is injected in the chip
and the substrate 4-MUP is added to generate the fluorescent product.

MB-based enzymatic reaction on-chip


Figure 1. Fabrication process of the microfluidic device schematically represented. A) CAD design,
B) CNC micromilling machine, C) alignment of the layers and bonding, and D) final device.

Magnetic Actuator
A

Detector

Rotation Axis

The reaction product was measured with a miniaturized fluorescence detection system (see Fig. 5).
The movement of MBs can be tuned by changing the rotation speed of the magnetic actuator, and it
enhances the reaction kinetics due to the mixing. The optimal movement velocity was found to be 1.7
mm/s (see Fig. 6). The calibration curves show a 2.7-fold sensitivity enhancement (see Fig. 7) when
using the magnetic actuator. Concentrations of E. Coli as low as 600 cfu/mL have been determined.

Optical Filter

Magnetic
Beads

Insertion Port

Rotation
Axis

Microfluidc Chip
LED

Magnets

Figure 5. Detection system used for the fluorescence on-chip measurements

D
0

90

180

270

90

180

Figure 6. Signal obtained at different movement velocities of the MBs. The dashed line
indicates the relative signal at 0 mm/s.

Figure 7. Calibration curves for the immunoassay performed without mixing (0 mm/s) and
at two different mixing speeds.

270

Conclusions and Future Work


A magnetic actuator has been designed and studied by means of COMSOL simulations and experimentally by an enzymatic reaction using commercial MBs.
Figure 2. Schematic representation of the magnetic actuator. A) and B) show schematically the
magnetic actuator from different perspectives. Notice that the rotation axis and the center of the
magnets circumference are not the same. C) Scheme of the MBs movement while the actuator rotates. D) Pictures of the MBs movement.

Different concentrations of E. Coli O157 have been determined using a fluorescence immunoassay.
The magnetic actuator showed a 2.7-fold sensitivity enhancement over the retention-only systems.
Further research must address the integration of all the immunoassays reactions on-chip.

Watch how it works!

Acknowledgements

Scan this QR code with your smartphone to see a video of the


magnetic actuator moving the MBs. You can also have a look at the
poster online, or check out our website and see what else we are
working on.

The authors acknowledge the financial support of the Government of Catalonia (FI program), MICINN (project CTQ2012-36165),
co-funded by FEDER, and MEC (Consolider Nanoselect, MAT200801022).

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