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Lab-on-a-chip microdevices for manipulation and separation of microparticles using dielectrophoresis

Ming Li

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Abstract

The development of lab-on-a-chip (LOC) over the past decade, has attracted more and more interest, and aims to achieve the miniaturisation, integration, automation, and parallelisation of biological and chemical assays. One of the applications, the ability to effectively and accurately manipulate and separate micro and nano-scale particles in an aqueous solution is quite appealing in biological, chemical and medical fields. Among the technologies developed and implemented in microfluidic microsystems (i.e. mechanical, inertial, hydrodynamic, acoustic, optical, magnetic, and electrical methodologies), dielectrophoresis (DEP) may prove to be the most popular method for manipulating and separating particles. This is because of its great advantages, such as label-free nature, compatibility with LOC devices, ability to manipulate neutral bio-particles, easy and direct interface with electronics, and analyse with high selectivity and sensitivity. The required spatial electric nonuniformities for the DEP effect could be generated by applying alternating current (AC) fields to microelectrodes (either 2D or 3D) embedded within microchannels, or placing insulating obstacles within a microchannel and curving microchannels, while direct current (DC) or DC-biased AC fields are applied via external electrodes located at the inlet and outlet reservoirs. The major objective of this work is to develop methods of micro-fabrication and DEP-based microdevices to manipulate and separate particles.\nA novel method for fabricating dielectrophoretic microdevices with top-bottom patterned microelectrodes has been proposed, which utilised a laser-patterned polydimethylsiloxane (PDMS) layer which acts as both a working and bonding layer. This method is simple and cost-effective because it eliminates the demand for a template and the corresponding fabrication process, facilities, and consumables in high-standard clean rooms. Another method has been developed to fabricate DEPbased microsystems with arc-shaped extruded microelectrodes on channel sidewalls using metal alloy microspheres. This fabrication method offers many advantages such as good conductivity, simplicity, low cost, and an improvement in the design of topological electrodes. The capabilities of these methods were demonstrated by fabricating and testing DEP-based microfluidic chips with either top-bottom or sidewall patterned microelectrodes functioning as a micro-concentrator/separator.\nTwo DEP-based microsystems with bi-layer microelectrode configurations were designed and constructed using the proposed fabrication method. The structure of the first 3D electrode structure consists of a funnel-shaped focusing unit, a parallel aligning unit and a crescent-shaped trapping unit in series, which improves the integrated functionalities as concentration of single particle population in a continuous flow, separation of particle-particle mixture according to size, and separation of particle-cell mixture according to their dielectric properties. The second microdevice consists of 13 individual microchannels fixed in a radial direction and top-bottom patterned arrowhead-shaped microelectrodes, which aims to collect and separate particles in a high-throughput manner. The performance was demonstrated by dielectrophoretically collecting polystyrene (PS) particles, yeast cells, and E. coli, and separating live and dead yeast cells.\nUnlike electrode-based DEP microdevices, insulator-based ones are mechanically robust, chemically inert, and simple to fabricate. A waved microchannel consisting of consecutive curved S-shaped channels in series was developed for continuous particle focusing. How the effects of applied electric field, particle size, and medium concentration affect the focusing performance was studied both experimentally and numerically by continuously focusing polystyrene particles of various sizes, and yeast cells. In addition, a curved S-shaped microchannel embedded with multiple round hurdles was developed to manipulate and separate particles. It combines the effect of obstacle and curvature for spatial electric non-uniformities, allowing greater control of electric field distribution and hence the particle motion. Both experiments and numerical simulations were conducted to demonstrate the controlled trajectories of particles, and the separation of polystyrene particles according to size by adjusting the voltages applied at the inlet and outlets. It is anticipated that the proposed designs will integrate with different components and functionalities into a single LOC device for widespread use in the field of biology, chemistry, and medicine.

About this research paper

What this paper is about

The development of lab-on-a-chip (LOC) over the past decade, has attracted more and more interest, and aims to achieve the miniaturisation, integration, automation, and parallelisation of biological and chemical assays. One of the applications, the ability to effectively and accurately manipulate and separate micro and nano-scale particles in an aqueous solution is quite appealing in biological, chemical and medical fields. Among the technologies developed and implemented in microfluidic microsystems (i.e. mechanical, inertial, hydrodynamic, acoustic, optical, magnetic, and electrical methodologies), dielectrophoresis (DEP) may prove to be the most popular method for manipulating and separating particles. This is because of its great advantages, such as label-free nature, compatibility with LOC devices, ability to manipulate neutral bio-particles, easy and direct interface with electronics, and analyse with high selectivity and sensitivity. The required spatial electric nonuniformities for the DEP effect could be generated by applying alternating current (AC) fields to microelectrodes (either 2D or 3D) embedded within microchannels, or placing insulating obstacles within a microchannel and curving microchannels, while direct current (DC) or DC-biased AC fields are applied via external electrodes located at the inlet and outlet reservoirs. The major objective of this work is to develop methods of micro-fabrication and DEP-based microdevices to manipulate and separate particles.\nA novel method for fabricating dielectrophoretic microdevices with top-bottom patterned microelectrodes has been proposed, which utilised a laser-patterned polydimethylsiloxane (PDMS) layer which acts as both a working and bonding layer. This method is simple and cost-effective because it eliminates the demand for a template and the corresponding fabrication process, facilities, and consumables in high-standard clean rooms. Another method has been developed to fabricate DEPbased microsystems with arc-shaped extruded microelectrodes on channel sidewalls using metal alloy microspheres. This fabrication method offers many advantages such as good conductivity, simplicity, low cost, and an improvement in the design of topological electrodes. The capabilities of these methods were demonstrated by fabricating and testing DEP-based microfluidic chips with either top-bottom or sidewall patterned microelectrodes functioning as a micro-concentrator/separator.\nTwo DEP-based microsystems with bi-layer microelectrode configurations were designed and constructed using the proposed fabrication method. The structure of the first 3D electrode structure consists of a funnel-shaped focusing unit, a parallel aligning unit and a crescent-shaped trapping unit in series, which improves the integrated functionalities as concentration of single particle population in a continuous flow, separation of particle-particle mixture according to size, and separation of particle-cell mixture according to their dielectric properties. The second microdevice consists of 13 individual microchannels fixed in a radial direction and top-bottom patterned arrowhead-shaped microelectrodes, which aims to collect and separate particles in a high-throughput manner. The performance was demonstrated by dielectrophoretically collecting polystyrene (PS) particles, yeast cells, and E. coli, and separating live and dead yeast cells.\nUnlike electrode-based DEP microdevices, insulator-based ones are mechanically robust, chemically inert, and simple to fabricate. A waved microchannel consisting of consecutive curved S-shaped channels in series was developed for continuous particle focusing. How the effects of applied electric field, particle size, and medium concentration affect the focusing performance was studied both experimentally and numerically by continuously focusing polystyrene particles of various sizes, and yeast cells. In addition, a curved S-shaped microchannel embedded with multiple round hurdles was developed to manipulate and separate particles. It combines the effect of obstacle and curvature for spatial electric non-uniformities, allowing greater control of electric field distribution and hence the particle motion. Both experiments and numerical simulations were conducted to demonstrate the controlled trajectories of particles, and the separation of polystyrene particles according to size by adjusting the voltages applied at the inlet and outlets. It is anticipated that the proposed designs will integrate with different components and functionalities into a single LOC device for widespread use in the field of biology, chemistry, and medicine.

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Available abstract

The development of lab-on-a-chip (LOC) over the past decade, has attracted more and more interest, and aims to achieve the miniaturisation, integration, automation, and parallelisation of biological and chemical assays. One of the applications, the ability to effectively and accurately manipulate and separate micro and nano-scale particles in an aqueous solution is quite appealing in biological, chemical and medical fields. Among the technologies developed and implemented in microfluidic microsystems (i.e. mechanical, inertial, hydrodynamic, acoustic, optical, magnetic, and electrical methodologies), dielectrophoresis (DEP) may prove to be the most popular method for manipulating and separating particles. This is because of its great advantages, such as label-free nature, compatibility with LOC devices, ability to manipulate neutral bio-particles, easy and direct interface with electronics, and analyse with high selectivity and sensitivity. The required spatial electric nonuniformities for the DEP effect could be generated by applying alternating current (AC) fields to microelectrodes (either 2D or 3D) embedded within microchannels, or placing insulating obstacles within a microchannel and curving microchannels, while direct current (DC) or DC-biased AC fields are applied via external electrodes located at the inlet and outlet reservoirs. The major objective of this work is to develop methods of micro-fabrication and DEP-based microdevices to manipulate and separate particles.\nA novel method for fabricating dielectrophoretic microdevices with top-bottom patterned microelectrodes has been proposed, which utilised a laser-patterned polydimethylsiloxane (PDMS) layer which acts as both a working and bonding layer. This method is simple and cost-effective because it eliminates the demand for a template and the corresponding fabrication process, facilities, and consumables in high-standard clean rooms. Another method has been developed to fabricate DEPbased microsystems with arc-shaped extruded microelectrodes on channel sidewalls using metal alloy microspheres. This fabrication method offers many advantages such as good conductivity, simplicity, low cost, and an improvement in the design of topological electrodes. The capabilities of these methods were demonstrated by fabricating and testing DEP-based microfluidic chips with either top-bottom or sidewall patterned microelectrodes functioning as a micro-concentrator/separator.\nTwo DEP-based microsystems with bi-layer microelectrode configurations were designed and constructed using the proposed fabrication method. The structure of the first 3D electrode structure consists of a funnel-shaped focusing unit, a parallel aligning unit and a crescent-shaped trapping unit in series, which improves the integrated functionalities as concentration of single particle population in a continuous flow, separation of particle-particle mixture according to size, and separation of particle-cell mixture according to their dielectric properties. The second microdevice consists of 13 individual microchannels fixed in a radial direction and top-bottom patterned arrowhead-shaped microelectrodes, which aims to collect and separate particles in a high-throughput manner. The performance was demonstrated by dielectrophoretically collecting polystyrene (PS) particles, yeast cells, and E. coli, and separating live and dead yeast cells.\nUnlike electrode-based DEP microdevices, insulator-based ones are mechanically robust, chemically inert, and simple to fabricate. A waved microchannel consisting of consecutive curved S-shaped channels in series was developed for continuous particle focusing. How the effects of applied electric field, particle size, and medium concentration affect the focusing performance was studied both experimentally and numerically by continuously focusing polystyrene particles of various sizes, and yeast cells. In addition, a curved S-shaped microchannel embedded with multiple round hurdles was developed to manipulate and separate particles. It combines the effect of obstacle and curvature for spatial electric non-uniformities, allowing greater control of electric field distribution and hence the particle motion. Both experiments and numerical simulations were conducted to demonstrate the controlled trajectories of particles, and the separation of polystyrene particles according to size by adjusting the voltages applied at the inlet and outlets. It is anticipated that the proposed designs will integrate with different components and functionalities into a single LOC device for widespread use in the field of biology, chemistry, and medicine.

Key concepts: Dielectrophoresis, Lab-on-a-chip, Nanotechnology, Chip, Microsphere, Separation (statistics), Materials science, Microfluidics

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