Optimal micromanipulator design for gathering magnetic beads

In this study, we evaluated the optimal geometry for collecting magnetic beads. As a result of making a square shaped coil in the previous research, it was confirmed that magnetic beads were collected at the center and the corner. However, this result was not satisfactory. Because we did not intend for magnetic beads to be collected at the corner of the coil. Therefore, in order to evaluate the shape of the optimal layout, we made and evaluated round, square, and triangular coils, respectively. As a result, it was confirmed that the round coil had the property of collecting magnetic beads in the center more efficiently than the other coils.


Introduction
as DNA, proteins, viruses, and cells, as well as in drug delivery systems for transporting drugs to affected areas and in hyperthermia for cancer [1]. Furthermore, fluorescent labeling of fluorescent magnetic beads makes it possible to construct multiplexed detection systems with optical detection [2]. Recently, the development of high-speed and high-sensitivity immunoassay systems that combine a magnetic collection of fluorescent magnetic beads and fluorescence measurement has been required in the medical field [3]. However, the ELISA method currently used for immunoassay using fluorescent magnetic beads is large and expensive [4]. In our laboratory, we have developed a filter-less spectrometer using a compact and inexpensive integrated circuit by installing a sensor for fluorescence detection and a manipulator for magnetic bead collection on an IC chip (Lab on a chip) [5,6]. Figure 2 shows an image of a photodiode with magnetic manipulator. The manipulator works to gather the beads for efficiently sensing. In the previous study, it was already confirmed that the magnetic beads were collected at the center of the coil by the coil, but the beads dropped at the corner of the coil did not collect at the center of the coil and stayed there [6]. In this study, we evaluated the optimal shape for magnetic beads to be collected. By doing so, we thought it would be possible to collect and detect the object to be measured with a single chip.
In this paper, we evaluate and report the optimal manipulator geometry for collecting magnetic beads.

Purpose
The purpose of this study is to fabricate and evaluate a manipulator with an optimal shape for collecting magnetic beads.
A coil is used to collect the beads, and by considering the shape of the coil, the beads can be efficiently collected at the intended location. In order to achieve the above objectives, this study evaluates the comparison of the collection characteristics of the corner of the round, square and triangular coils.  Figure 3 shows the overall layout of the IC chip with the magnetic manipulator that is using a 0.8 µm one-poly-three-metal (1P3M) CMOS design rule. The chip size is 1.8mm×1.8mm. There are three type layout that are triangle, square and round shape.              Figure 13 shows the fabricated IC chip with the dam that is using a 0.8 µm one-poly-three-metal (1P3M) CMOS design process.

Experiment
The dam depth, area and volume are 500µm, 1.4mm1.4mm and 0.98 mm 3 respectively.  "Dynabeads protein A" was adopted as the magnetic beads used in this experiment. These magnetic beads have a particle size of 2.6μm and a weight of about 1.1×10 -8 mg/particle. The beads were suspended in phosphate-buffered saline (PBS) and diluted to about 15 times with pure water to make the concentration easy to observe with a microscope.   In both Fig.15 and Fig.16, magnetic beads are gathered in the center of the coil, but many magnetic beads are also gathered in the corner surrounded by the yellow oval. Figure 17 shows the round shape coil with magnetic beads. Fig. 17. Round shape coil with magnetic beads.

Collection characteristics of round coil
By eliminating the corners, the magnetic beads moved toward the center of the coil from all directions, rather than gathering locally.
In addition, the number of beads decreased at distances up to about 10 µm from the edge of the coil. In this experiment, it took about 300 seconds for the magnetic beads to be induced to the center of the coil. Therefore, we can see that round-shaped coil can efficiently collect magnetic beads in the center of the coil.

Conclusions
The purpose of this study is to evaluate the optimal geometry for collecting magnetic beads. Therefore, we fabricated round, square, and triangular coils on the IC chip. From the simulation results, it was confirmed that the magnetic flux density of the round coil was concentrated in the center of the coil compared to the coil with corners. Also, from the actual measurement results, by eliminating the corners of the coil and making it round, the magnetic beads gathered efficiently in the center of the coil.
Therefore, the round shape was found to be the best shape.