Magnetic separation filters for microfluidic devices
Inventors
Issadore, David Aaron • WOLDEMARIAM, MELAKU MULUNEH
Assignees
University of Pennsylvania Penn
Publication Number
US-12370547-B2
Publication Date
2025-07-29
Expiration Date
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Abstract
A magnetic separation device has a membrane having a plurality of pores, a magnetically soft material layer disposed on the membrane, and a passivation layer disposed on the magnetically soft material layer. The magnetic separation device may be part of a microfluidic device having a lateral flow channel and a vertical flow magnetic separation filter. The magnetic separation device may be used to separate magnetically tagged particles, such as cells.
Core Innovation
A magnetic separation device comprises a membrane having a plurality of pores, a layer comprising a magnetically soft material, and a passivation layer. The magnetic separation device may be part of a microfluidic device having a lateral flow channel and a vertical flow magnetic separation filter. The magnetic separation device may be used to separate magnetically tagged particles, such as cells.
One aspect of the present invention relates to a flexible magnetic separation device comprising a membrane including a plurality of pores, wherein the pores have an average diameter ranging from about 100 nm to 100 μm, a layer of magnetically soft material adjacent said membrane, and a passivation layer adjacent said layer of magnetically soft material. Another aspect relates to a microfluidic device comprising at least one lateral flow channel and at least one vertical flow magnetic separation filter in fluidic communication with the at least one lateral flow channel, wherein the at least one vertical flow magnetic separation filter comprises a membrane comprising a plurality of pores, a layer of magnetically soft material disposed on said membrane, and a passivation layer disposed on said layer of magnetically soft material.
The background identifies a need for magnetic separation devices that have improved sorting efficiencies and/or greater throughput, which can be produced inexpensively and incorporated into microfluidic devices. The invention addresses this need by providing track-etched polycarbonate membranes coated with a thin layer of soft magnetic material and a passivation layer, and by configuring vertical flow magnetic separation filters to generate strong, highly localized magnetic field gradients and large flow channel area to achieve high enrichment at high flow rates.
Claims Coverage
The patent includes four independent claims. The inventive features relate to composite layered magnetic separation filters with discrete continuous pores, external magnetic field interaction, microfluidic integration with lateral flow channels, and a method of capturing and releasing magnetically tagged particles.
Composite layer of membrane, magnetically soft material, and passivation layer
A composite layer that includes (i) a membrane, (ii) a layer of magnetically soft material; and (iii) a passivation layer.
Discrete continuous pores extending through all layers
A plurality of discrete, continuous pores extend through the membrane, the layer of magnetically soft material, and the passivation layer of the composite layer.
External magnetic field source configured to interact with magnetically soft material
An external magnetic field source configured to magnetically interact with the magnetically soft material.
Layer arrangement with magnetically soft material adjacent membrane and passivation adjacent magnetically soft material
A composite layer with the layer of magnetically soft material adjacent the membrane and the passivation layer adjacent the layer of magnetically soft material, and a plurality of discrete, continuous pores that extend through these layers.
Microfluidic device with lateral flow channel and magnetic separation filter in fluidic communication
A microfluidic device comprising at least one lateral flow channel and at least one magnetic separation filter in fluidic communication with the at least one lateral flow channel.
Magnetic separation filter composite with adjacent layers and through-pores
The at least one magnetic separation filter comprises (i) a membrane, (ii) a layer of magnetically soft material adjacent the membrane, and (iii) a passivation layer adjacent the layer of magnetically soft material, wherein a plurality of discrete, continuous pores extend through the membrane, the passivation layer adjacent the membrane, and the layer of magnetically soft material of the at least one magnetic separation filter.
Magnetic capture and release via external magnetic field
A method comprising flowing a suspension comprising the magnetically tagged particles through the magnetic separation device of claim 1; capturing the magnetically tagged particles by exposing the magnetic separation device to an external magnetic field; and releasing the magnetically tagged particles by removing the external magnetic field.
The claims are directed to a composite layered magnetic separation device with a membrane, a layer of magnetically soft material, and a passivation layer with discrete continuous pores through the layers; incorporation of an external magnetic field source configured to magnetically interact with the magnetically soft material; integration of such filters into microfluidic devices with lateral flow channels in fluidic communication with vertical flow filters; and a method of capturing and releasing magnetically tagged particles by applying and removing an external magnetic field.
Stated Advantages
Strong forces can be applied without the need for a power supply or moving parts, making these devices well suited for use in practical settings outside of the laboratory.
Magnetic sorting can be performed directly on unprocessed clinical samples and environmental samples due to the lack of magnetic susceptibility of biological materials.
Flexibility of the magnetic separation device can be beneficial in the construction of microfluidic devices.
Polycarbonate track-etched membranes can be produced over large areas for little cost, enabling highly efficient isolation (ξ>104) at extremely high flow rates (Θ>10 ml/hr).
The passivation layer may protect the magnetically soft material from undesired interaction or reaction with fluids, for example oxidation.
Low magnetic remanence of Ni20Fe80 allows the magnetic force to disappear when the external magnet is removed, facilitating efficient release of trapped cells.
Documented Applications
Isolation of rare biological targets, such as circulating tumor cells (CTCs), pathogenic bacteria, or circulating microvesicles (CμVs), from biological fluids.
Separating magnetically tagged particles, such as cells, molecules, nucleic acids, and proteins.
Integration of vertical flow magnetic separation filters (e.g., TEMPO filters) into microfluidic devices comprising at least one lateral flow channel and flow converters to redirect lateral flow to vertical flow.
Immunomagnetic capture and isolation of immunomagnetically labeled E. coli from a suspension of similarly sized bacteria for downstream analysis.
Sorting magnetic from non-magnetic polystyrene beads to quantify enrichment and purity.
Isolation of circulating tumor cells from a background of leukocytes using TEMPO filters.
Sorting magnetically labeled bacteria from complex backgrounds including oral lavage and river water to demonstrate background insensitivity.
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