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Department of Chemistry, Imperial College London, South Kensington, London SW7 2AY, UK
b
Department of Chemistry, The University of Hull, Cottingham Road, Hull HU6 7RX, UK
c
BIOS/Lab-on-a-Chip Group, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
d
Institute for Analytical Sciences (ISAS), Bunsen-Kirchhoff Strasse 11, 44139 Dortmund, Germany
Received 17 January 2006
Available online 12 May 2006
Abstract
The complete separation of mixtures of magnetic particles was achieved by on-chip free-ow magnetophoresis. In continuous ow,
magnetic particles were deected from the direction of laminar ow by a perpendicular magnetic eld depending on their magnetic
susceptibility and size and on the ow rate. 2.8 and 4.5 mm superparamagnetic particles with magnetic susceptibilities of 1.1 104 and
1.6 104 m3 kg1, respectively, could be completely separated from each other reproducibly. The separated particles were detected by
video observation and also by on-chip laser light scattering. Potential applications of this separation method include sorting of magnetic
micro- and nanoparticles as well as magnetically labelled cells.
r 2006 Elsevier B.V. All rights reserved.
PACS: 75.50.T
Keywords: Magnetic separation; Magnetic microparticles; Microuidics; Magnetophoresis
1. Introduction
Magnetic microparticles are widely used in biomedical
sciences as a solid support surface for immunoassays,
DNA sequencing and cell analysis [1,2]. The use of
magnetic labels greatly facilitates the separation of the
desired biomaterial from the bulk of a reaction mixture
simply by application of an external magnetic eld.
Conventionally, such magnetic separations are carried
out in a test tube which is brought in close proximity to
a magnet that traps the magnetic particles whilst the
remainder of the reaction mixture is pipetted off. Such
conventional separation methods are quite labour intensive
and time consuming. Recently there has therefore been an
interest in continuous ow separation of magnetic particles
Corresponding author. Department of Chemistry, The University of
Hull, Cottingham Road, Hull HU6 7RX, UK. Tel.: +44 1482 465027; fax:
+44 1482 466416.
E-mail address: n.pamme@hull.ac.uk (N. Pamme).
0304-8853/$ - see front matter r 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jmmm.2006.04.008
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,
6pZr
6pZr
(2)
(3)
3. Experimental section
3.1. Microchip fabrication
Microchips were fabricated from sodalime glass [11]. The
design is shown in Fig. 2. The separation chamber of
6 mm 6 mm was supported by 13 square posts of
200 mm 200 mm. 16 buffer inlet channels and one sample
inlet channel were all 100 mm wide and evenly spaced. The
junction between the inlet channels and the separation
(1)
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Fig. 3. Photograph of the setup showing the microuidic glass chip with
buffer and sample inlet reservoirs as well as the connection to the syringe
pump for application of negative pressure. To generate a magnetic eld
gradient over the separation chamber, assemblies of small NdFeB magnets
were used.
239
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Fig. 5. Flow visualisation with black ink in the sample reservoir: (a) for a
uid cell design with 901 junctions between the channels and the
separation chamber some of the sample stream was observed to leave
via exit number 2 and (b) for the design with tapered 451 junctions, all
uid from the sample stream was found to leave via exit number 1.
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Table 1
The deection of 2.8 and 4.5 mm Dynabeads observed at different ow
rates
Flow rate (mL h1)
200
300
400
500
600
3
23
23
2
12
Intermittent ow
Intermittent ow
35
34
3
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Fig. 7. Photograph sequence of the separation of a mixture of 2.8 and 4.5 mm magnetic particles at (a) 400 mL h1 and (b) 500 mL h1.
Table 2
Estimated force on magnetic particles based on the observed deection
Particle
diameter (mm)
Flow rate
(mL h1)
Fmag (pN)
2.8
2.8
4.5
4.5
400
500
400
500
0.030.05
0.040.05
0.100.12
0.100.12
0.81.3
1.11.3
4.35.1
4.35.1
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Fig. 9. Signals detected by both optical bres for a mixture of 2.8 and
4.5 mm particles at the respective outlets.
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