Using wettability and interfacial tension to handle droplets of magnetic beads in a micro-chemical-analysis system
Introduction
Micro-electro-mechanical-systems (MEMS) technologies can be used to integrate many types of mechanical and electrical elements on the same chip and are therefore expected to open the door for the development of new types of fluidic systems. Many types of micro-chemical-analysis systems for biological applications have been proposed, but most of them need complicated micro-mechanical components for handling the solution. For example, they require such micro-devices as micro-valves and micro-pumps for driving the liquid through the system. These systems are therefore large, and their fabrication costs are high even if the fluid channels and reaction devices are integrated onto microchips [1], [2]. Systems on portable microchips, such as those used for chemical analysis in the field, are also costly. Although electrical droplet manipulation is in principle rather simple and can be used for solution fusion and separation [3], [4], [5], [6], [7], condensing and diluting the target samples is difficult using electrical droplet manipulation.
We propose a micro-chemical-analysis system based on a mechanism for handling bead droplets. We developed a reliable system for handling droplets containing magnetic beads and also developed mechanisms for extracting and fusing sample magnetic beads.
Section snippets
Principle of magnetic handling of bead droplets
We use magnetic beads as sample carriers and disperse them in a buffer solution. We use a permanent magnet to collect and handle them. As illustrated in Fig. 1, buffer solution containing magnetic beads is dropped into silicone oil on a glass plate, which is made hydrophobic by applying a surface treatment. The droplets that form in the solution are suspended in the oil because of the differences in surface tension between the two liquids and the superior wettability of the oil to the plate. As
Experimental confirmation of separation and fusion principle
We confirmed the principle of the proposed bead-droplet-handling mechanism experimentally using beads made of a ferromagnetic material. The specifications of the three kinds of beads we used are listed in Table 1. Each bead – 5.9, 18.8, or 32.7 μm in diameter – was composed of Fe3O4 particles 20 nm in diameter that were bound together by a phenol resin. Water containing the beads was dropped into silicone oil to form the droplet. The viscosity of the oil was 1.3 cP.
Fig. 3 shows the experimental
Magnetic driving force
As explained in Section 2, we use magnetic force for extracting the bead cluster from the droplet and handling the bead-cluster droplet after the extraction. We estimated the magnetic force acting on the magnetic-bead cluster usingwhere F, I, and H are, respectively, the force (N/m3), the magnetization of the magnetic material (Wb/m2), and the magnetic field strength (A/m). By partially differentiating (1.1), we can write driving force Fx (N/m3) in the x-direction as
Conclusion
We have developed a bead-droplet-handling mechanism for micro-chemical-analysis systems. Magnetic bead droplets are magnetically handled by exploiting differences in wettability and surface tension between different liquids. We also developed mechanisms for extracting and diluting sample beads and confirmed that beads can be collected and rinsed effectively using extraction and dilution units. We obtained the following results:
- (1)
The system needs a magnetic pulling force of only a few mN.
- (2)
The total
Acknowledgement
We would like to thank Dr. Nanao Horiishi, Toda Kogyo Corp., for his useful suggestions and his help in the experiments.
Mitsuhiro Shikida received BS and MS degrees in electrical engineering from Seikei University, Tokyo, in 1988 and 1990, respectively. He received a PhD from Nagoya University in 1998. From 1990 to 1995, he worked at Hitachi, Ltd., Tokyo. In 1995, he joined the Department of Micro-System Engineering at Nagoya University as a research associate. He was an assistant professor from 1998 to 2004 and has been an associate professor since 2004. He joined the Research Center for Advanced Waste and
References (8)
- et al.
A novel fabrication of in-channel 3-D micromesh structure using maskless multi-angle exposure and its microfilter application
- et al.
A disposable, dead-volume-free and leak-free monolithic pdms microvalve
- et al.
Towards digital microfluidic circuits: creating, transporting, cutting and merging liquid droplets by electrowetting-based actuationdkjdot
- et al.
Enhancement of mixing by droplet-based microfluidics
Cited by (86)
Microscale immiscible phase magnetic processing for bioanalytical applications
2023, TrAC - Trends in Analytical ChemistryCitation Excerpt :Other materials include silicone rubber [5,63], aluminum [38], wax [19,20], polypropylene [10,18,30,36,70,72], polystyrene [26,58–60], polycarbonate [9,14,37], polymethylmethacrylate [49,51,67], various resins [7,24,25,32,33], glass [31] and Tygon [6,68] and fluorinated ethylene-propylene [28,29,44,45] tubing. Some devices were hydrophobically coated with Teflon [39–41], parylene [5,38] or PDM silane [9] prior to their use, whilst others required priming and blocking with BSA solutions [23,55,74]. Platforms utilizing microscale immiscible phases and paramagnetic particles have demonstrated great potential to integrate workflows and streamline bioanalytical assays.
External-field-induced directional droplet transport: A review
2021, Advances in Colloid and Interface ScienceMagnetic particle transport through organogel – an application to DNA extraction –
2020, Analytical BiochemistryGold nanoparticle conjugated magnetic beads for extraction and nucleation based signal amplification in lateral flow assaying
2020, Sensors and Actuators, B: ChemicalCitation Excerpt :Therefore, efforts have been devoted to improve performance of such assays by adopting sample extraction or preconcentration protocols for removal of analogues and interferents present in complex matrices that yield false responses [6,11,12]. Polystyrene magnetic beads (MB) have been utilized for extraction of target biomolecules such as proteins or nucleic acids from complex matrices [13–15]. These MBs are homogeneous, stable in suspension and have been utilized as reporters for detection of several biomolecules [13,16,17].
Integrated droplet microfluidic device for magnetic particles handling: Application to DNA size selection in NGS libraries preparation
2020, Sensors and Actuators, B: Chemical
Mitsuhiro Shikida received BS and MS degrees in electrical engineering from Seikei University, Tokyo, in 1988 and 1990, respectively. He received a PhD from Nagoya University in 1998. From 1990 to 1995, he worked at Hitachi, Ltd., Tokyo. In 1995, he joined the Department of Micro-System Engineering at Nagoya University as a research associate. He was an assistant professor from 1998 to 2004 and has been an associate professor since 2004. He joined the Research Center for Advanced Waste and Emission Management at Nagoya University in 2001 and joined the EcoTopia Science Institute at Nagoya University in 2004. His research interests include integration of micro-sensors and actuators for intelligent systems, micro-fabrication of 3D microstructures for medical applications, and micro-total analysis systems for biotechnologies. Dr. Shikida is a member of the Institute of Electrical Engineers of Japan and the Japan Society of Mechanical Engineers.
Kentaro Takayanagi received a BS degree in mechanical engineering from Nagoya University, Japan, in 2004. He is currently working on an MS degree in micro–nano systems engineering at Nagoya University. His research interests include micro-total analysis systems for biotechnologies.
Kohta Inouchi received a BS degree in mechanical engineering and an MS degree in micro-system engineering from Nagoya University, Japan, in 2002 and 2004, respectively. He is currently working at Hitachi, Ltd. His research interests include handling of micro-beads by magnetic force.
Hiroyuki Honda received BS, MS, and PhD degrees in chemical engineering from Nagoya University in 1983, 1985, and 1988, respectively. He worked as an assistant professor at Nagoya University from 1988 to 1990 and at the Tokyo Institute of Technology from 1990 to 1992. He was an associate professor from 1993 to 2004 and became a professor in April 2004. His research interests include bioengineering, medical engineering, bioinformatics, and biomolecule sensing. Dr. Honda is a member of the Society of Biotechnology, Japan, the Society of Chemical Engineers, Japan, the Chemical Society of Japan, the Japanese Cancer Association, the Japan Bioindustry Association, the Japan Society of Bioscience, Biotechnology, and Agrochemistry, and the Japanese Society for Bioinformatics.
Kazuo Sato received a BS degree in mechanical engineering from Yokohama National University in 1970 and a PhD from the University of Tokyo in 1982. In 1970, he joined Hitachi, Ltd., Tokyo. He has been studying micro-machining technologies and their application since 1983 and has been a professor at Nagoya University since 1994. Dr. Sato is a member of the Japan Society of Mechanical Engineers, the Japan Society for Precision Engineering, the Institute of Electrical Engineers of Japan, and the Japan Society for Technology of Plasticity.