Continuous separation of nanoparticles by type via localized DC-dielectrophoresis using asymmetric nano-orifice in pressure-driven flow
Graphical abstract
Introduction
Microfluidic Lab-on-Chip (LOC) technologies use the microfluidic platforms to achieve miniaturization, automation, and integration of the complicated chemical and biological analysis in the fields of chemical, biological and medical research [1], [2]. The manipulation of particles in the LOC systems is crucial in varieties of biological and clinical applications such as trapping, sorting, separation and characterization of micro and nanoparticles, cells, viruses, bacteria and DNA [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]. Compared with various techniques that have been applied in the microfluidic systems for the manipulation of particles by optical, mechanical, magnetic, chemical, acoustic and electrical means [14], [15], [16], [17], [18], [19], dielectrophoresis (DEP) may be one of the most popular methods due to its advantages such as label-free and low consumption of samples [20], [21], ability to analyze particles selectively and sensitively [22], [23], and capability of separating bioparticles with high efficiency and throughput [24].
Dielectrophoresis is the induced movement of the polarizable particles due to the dielectric differences between the particles and suspending medium in non-uniform electrical fields. The non-uniform electric field is conventionally generated by applying AC electric fields to an array of microelectrodes embedded inside the microchannel. The non-uniform electric field can also be induced by applying DC electric fields via the external electrodes across the locally constricted structures inside a microchannel (e.g., hurdles or obstacles) which are made of electrically insulating materials [6], [25]. Since the magnitude of the DEP force is proportional to the particle size, the manipulation and separation of particles and cells by size is straightforward [26]. However, for the particles of similar sizes, the separation by DEP based on the electrical properties of the particle and medium requires discrete processes[27], [28], [29], [30], [31], [32], [33], [34], [35], [36] and becomes challenging. Since each kind of particle or cell has a unique dielectric property, AC-DEP is implemented to identify particles or to sort and detect cells by adjusting the frequency of the electric field [2]. The polystyrene particles and E. coli, and the live and dead yeast cell were separated based on their different polarizabilities and DEP behaviors by AC-DEP in an AgPDMS electrode-based 3D electric field [26]. The isolation and detection of cfc-DNA nanoparticulate biomarkers and the virus were conducted by an array of circular microelectrodes under a 10 kHz AC electric field [37]. Traditionally, the electrode-based AC-DEP microfluidic devices can generate strong non-uniform electrical field by applying low electrical voltage and avoid electrokinetic flow over the whole microchannel. However, these devices suffer from the adhesion of the particles on the microelectrodes surface [38], fabrication complexity [20], [21], and chemical reactions on the surface of electrodes [39].
The above-mentioned problems are not encountered in the insulator-based DC-DEP microfluidic systems. Chen et al. [13] demonstrated an insulator tree structure for the concentration of 900 nm fluorescent microspheres in DC fields. The white blood cells and breast cancer cells were separated by DC-DEP in a triangular hurdle-based microchannel [6]. DC-DEP methods can be used not only for the particles manipulation by size but also for separating particles by their electrical properties. A circular insulating post based microfluidic device was investigated to selectively release live and dead E. coli by applying DC electric fields [8]. Song et al. [40] showed the separation of 5 μm polystyrene particles and marine P. subcapitata algae by different DEP forces with a hurdle inside the channel. Overall, the insulator-based DC-DEP approach requires simple fabrication, avoids the electrochemical reaction on the electrodes, and provides a chemically inert platform. However, sufficiently high DC electric field is required for effective performance of these DC-DEP devices. The locally amplified electric fields around the constricted structures inside the microchannel may induce significant Joule heating, and cause large transmembrane voltages and shear stresses on the biological cells [41]. Furthermore, these microfluidic devices are prone to fouling because of particle clogging [42]. In addition, due to the limitation of the conventional soft lithography techniques and microfabrication methods, the smallest gap in most microchannels is approximately 10 μm, and thus the insulator-based DC-DEP devices cannot generate sufficiently strong non-uniform electrical fields and hence cannot separate smaller micron particles and nanoparticles with similar sizes. Generally, the DC-DEP separation of particles as reported in the literature cannot separate particles with a size difference smaller than a few microns and particles smaller than 500 nm [8], [40], [43], [44], [45].
In this work, a novel microfluidic device is developed for the DC dielectrophoretic separation of nanoparticles with similar size in a pressure-driven flow. In such a microfluidic chip, there is no constriction and hurdles or obstacles in the channel; the localized strong gradient of the electric field is generated by a pair of asymmetrical orifices on the channel sidewalls. By applying a DC electrical field over the asymmetrical orifices, i.e., a small orifice on one side of the channel wall and a large orifice on the opposite side of the channel wall, to generate the non-uniform electric field, the above mentioned negative effects associated with DEP chips (e.g., complexed fabrication of arrays of the embedded microelectrodes, electrodes fouling, and particles clogging) are avoided. Moreover, as the liquid flow is driven by the hydraulic pressure in the channel, the particles are exposed to the non-uniform electric field only when they move through the vicinity of the DEP separation region and hence the adverse effects caused by the electric field, such as Joule heating, are significantly reduced. By choosing an appropriate electrical conductivity of the suspending medium enables one kind of particles to experience positive DEP and another to experience negative DEP, thus, it becomes possible to separate microparticles or nanoparticles with similar sizes by the dielectric property. In this paper, the fabrication of the microfluidic chip with the small orifice, and the generation of the flow field and the non-uniform electric field are presented. The DEP behaviors, i.e., the Clausius-Mossotti factors of the particles as a function of the electrical conductivity of the suspending medium, are discussed. Finally, the experimental separation of two pairs of microparticles and two pairs of nanoparticles are demonstrated.
Section snippets
Separation of particle by dielectrophoresis
Dielectrophoresis refers to the motion of polarized particles in a dielectric suspending medium under non-uniform electric fields. The DEP force acting on a spherical particle of radius a, suspended in a dielectric medium with permittivity εm, in a non-uniform electric field E is given by [46]where is the gradient of the square of the electric field, and is the real part of the Clausius-Mossotti (CM) factor which describes the relative polarizability
Simulation of the electric field and the flow field
Fig. 3 shows the flow field and the distribution of the electric field in the vicinity of the small orifice which is calculated by using COMSOL 4.3b. The non-uniform electric field is generated by applying DC electric field across the microchannel via the external electrodes placed in wells C and D, and the strongest gradients of the electric field exist near the small orifice. As shown in Fig. 3(A), the focusing flow from channel B forces the stream carrying the particle mixture from channel A
Conclusion
A new DC-DEP microfluidic device is developed for continuously separating particles with similar size but different electric conductivities. This microfluidic chip employs a pair of asymmetric orifices on the opposite sidewalls of the microchannel to induce a strong gradient of the non-uniform electric field and sufficient DEP effect under a locally applied low voltage difference. With the pressure-driven flow, the mixed particles are forced to move along the strong DEP effect region in the
Acknowledgement
The authors wish to thank the Natural Sciences and Engineering Research Council (NSERC) of Canada for financial support through a research grant to Dr. Li.
Mr. Kai Zhao received the B.S. degree in marine engineering from Dalian Maritime University, Dalian, China, in 2012 and the M.S. degree in marine engineering from Dalian Maritime University, Dalian, China, in 2015, now he is a Ph.D. candidate in Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, Canada. His research focuses on the Lab-on-a-chip, and micro- and nanofluidics, now he is doing research work on the dielectrophoretic manipulation and separation
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2023, Journal of Colloid and Interface ScienceCitation Excerpt :DEP forces induce the movement of dielectric particles owing to the polarization effects between the particles and the suspending medium in a non-uniform electric field [25–27]. Generally, an alternating current (AC) inhomogeneous electric field can be generated via an array of micro-electrodes with patterned configurations, which are embedded in a microchannel [28,29], while inhomogeneous direct current (DC) electric fields are typically obtained by larger external electrodes in the presence of patterns of insulating obstacles within the channel [30–32]. Since the magnitude and direction of the dielectrophoretic forces rely on the particles’ size and dielectric properties, which depend on their morphology and composition, DEP enables selective and sensitive particle analysis [33–35].
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Mr. Kai Zhao received the B.S. degree in marine engineering from Dalian Maritime University, Dalian, China, in 2012 and the M.S. degree in marine engineering from Dalian Maritime University, Dalian, China, in 2015, now he is a Ph.D. candidate in Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, Canada. His research focuses on the Lab-on-a-chip, and micro- and nanofluidics, now he is doing research work on the dielectrophoretic manipulation and separation of nanoparticles and microdroplets.
Dr. Dongqing Li is a professor at the University of Waterloo. His research is in the area of electrokinetic-based microfluidics, nanofluidics and lab-on-a-chip technology. He was the Editor-in-Chief of an international journal—Microfluidics and Nanofluidics from 2004 to 2012, and the Editor-in-Chief of the Encyclopedia of Microfluidics and Nanofluidics (1st edition and 2nd edition). He has published over 290 papers in top international journals, 31 book chapters and 3 books. The Google Scholar citation number of his publication is over 17300. The H-index of him is 65.