Magnetic particle dosing and size separation in a microfluidic channel

Separation of functional magnetic particles or magnetically labeled entities is a key feature for bioanalytical or biomedical applications and therefore also an important component of lab-on-a-chip devices for biological applications. We present a novel integrated microfluidic magnetic bead manipulation device, comprising dosing of magnetic particles, controlled release and subsequent magnetophoretic size separation with high resolution. The system is designed to meet the requirements of specific bioassays, in particular of on-chip agglutination assays for the detection of rare analytes by particle coupling as doublets. Integrated soft-magnetic microtips with different shapes provide the magnetic driving force of the bead manipulation protocol. The magnetic tips that serve as field concentrators of an external electromagnetic field, are positioned in close contact to a microfluidic channel in order to generate high magnetic actuation forces. Mixtures of 1.0 μm and 2.8 μm superparamagnetic beads have been used to characterize the system. Magnetophoretic size separation with high resolution was performed in static conditions and in continuous flow mode. In particular, we could demonstrate the separation of 1.0 μm single beads and doublets in a sample flow.

Rana Afshar Ghasemlouy, Martinus Gijs, Thomas Lehnert, Yves Moser

Separation of functional magnetic particles or magnetically labeled entities is a key feature for bioanalytical or biomedical applications and therefore also an important component of lab-on-a-chip devices for biological applications. We present a novel integrated microfluidic magnetic bead manipulation device, comprising dosing of magnetic particles, controlled release and subsequent magnetophoretic size separation with high resolution. The system is designed to meet the requirements of specific bioassays, in particular of on-chip agglutination assays for the detection of rare analytes by particle coupling as doublets. Integrated soft-magnetic microtips with different shapes provide the magnetic driving force of the bead manipulation protocol. The magnetic tips that serve as field concentrators of an external electromagnetic field, are positioned in close contact to a microfluidic channel in order to generate high magnetic actuation forces. Mixtures of 1.0 mu m and 2.8 mu m superparamagnetic beads have been used to characterize the system. Magnetophoretic size separation with high resolution was performed in static conditions and in continuous flow mode. In particular, we could demonstrate the separation of 1.0 mu m single beads and doublets in a sample flow. (C) 2009 Elsevier B.V. All rights reserved.

2011

Separation and Focusing of Magnetic Beads for Agglutination Tests

Rana Afshar Ghasemlouy

Functional magnetic micro- and nanoparticles are used in bioanalytical applications as solid carriers for capture, transport and detection of biomolecules or magnetically labeled cells. Colloidal suspensions of such particles provide a large specific surface for chemical binding and therefore allow highly efficient interactions with target molecules in a sample solution. Controlled actuation and manipulation of these mobile substrates in the microfluidic format offers interesting new opportunities for on-chip bioassays with previously unmatched properties. Separation of functional magnetic particles or magnetically labeled entities is therefore a key feature for bioanalytical or biomedical applications and also an important component of lab-on-a-chip devices for biological applications. In this thesis we present two novel integrated microfluidic magnetic bead manipulation devices. The first system consists of dosing of magnetic particles, controlled release and subsequent magnetophoretic size separation with high resolution. On-chip integrated soft-magnetic microtips with different shapes provide the magnetic driving force for the bead manipulation. The system is designed to meet the requirements of specific bioassays, in particular of on-chip agglutination assays for the detection of rare analytes, in which the latter can be quantified via the counting of the particle doublets. In a second approach, magneto-microfluidic three-dimensional (3D) focusing of microparticles has been developed. In this system, magnetic microparticles from a dense plug are released into a single streamline with longitudinal inter-particle spacing. Plug formation is induced by a high-gradient magnetic field generated at the sidewall of a microchannel by a micromachined magnetic tip that is connected to an electromagnet. Controlled release of the microparticles is achieved using an exponential damping protocol of the magnetic retention force in the presence of an applied flow. Carefully balancing the relative strengths of the drag force imposed by the flow and the magnetic retention force moreover allows in-flow size separation of the microparticles. Adding subsequently a lateral sheath flow microchannel focuses the microparticles into a single stream situated within 0plusmn; 5 µm from the channel center axis. Our system for 3D focusing and in-flow separation of magnetic microparticles has been used for performing an immuno-agglutination assay on-chip. 3D focusing was of the basis of reliable in-flow counting of singlets and agglutinated doublets. We demonstrated the potential of the agglutination assay in a microfluidic format using a streptavidin/biotinylated-bovine serum albumin (bBSA) model system. A bBSA detection limit of about 400 pg/mL (6 pM) is achieved.

EPFL2011

Separation and Focusing of Magnetic Beads for Agglutination Tests

Rana Afshar Ghasemlouy

EPFL2011