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Matsuura 2016
Matsuura 2016
Matsuura 2016
with three- or four magnetic poles has also been proposed[8]-[11]. force exertion
Downward only Arbitrary Arbitrary
direction
D. Matsuura is with Department of Mechanical Sciences and Engineering, Hazard for Heating by
Tip contamination None
Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo bio-specimen trapping laser
152-8552 Japan (corresponding author to provide phone and Fax:
Capability of
+81-3-5734-2177; e-mail: matsuura@mech.titech.ac.jp). N.A. N.A. Available
intra-cellular
H. Aoki is with Department of Mechanical Sciences and Engineering, probe steering
Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo
152-8552 Japan (e-mail: aoki.h.ai@m.titech.ac.jp). Fine spatial Transparency &
Ease of particle
Y. Takeda is with Department of Mechanical Sciences and Engineering, Advantage resolution and non-harmfulness of
trapping
Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo high force strength magnetic force
152-8552 Japan (e-mail: takeda@mech.titech.ac.jp).
1,..., 6 T Φ Nc K I I (1)
Ra
By using superposition principle, a magnetic field where and V are permeability and volume of the particle,
generated by the six magnetic charges can be written as respectively, and the magnetic force due to this magnetization
is written as
6 qj
B km 2
uj , (3) written as
j 1 rj
1 3V 0
where km = μ0/4π = 1.0×107 [N/A2], rj and uj are the distance F m B B B k Q FQ , (5)
2 2 0 2 o
between the j-th charge and the particle, and its directional
unit vector. Since a magnetization of a particle is proportional The above equation can be written in quadratic form as
to the external magnetic field, it can be written as
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u j uk Namely, an approximate solution of eq. (13) is written as
5 6 6
FQ B B q k 2 2 Q T LQ , (6)
km
2 rˆ rˆ ( Fˆcx , Fˆcy , Fˆcz ) ( Fˆx 8 x, Fˆ y 8 y, Fˆz 32 z ) . (14)
j 1 k 1
j k
where rˆ r / h is a normalized distance. By substituting eq. From eqs. (10) and (14), linearized inverse model is finally
(2) in eq. (6), the direct model in quadratic form is obtained as obtained as
2 3 Fˆ 8 x 4 3 Fˆ 8 x 4
N Iˆ1 x Iˆ2 x
F kQ c I T K I LK I I
T
4 6 9 4 6 9
0 Ra . (15)
, (7) ˆ 3 y ˆ
F 8 y 4 3 ˆ
F 8 y 4
N
2
3I Iˆ y
4 6 9 4 9
4
kQ c I T NI k I I T NI 6
0 Ra 3 Fˆ 32 z 16 ˆ 3 Fˆz 32 z 16
Iˆ5 z I 6
where kI = kQ[Nc/(0Ra)]2 is a lumped coefficient related to the 8 6 9 8 6 9
property of the particle and the magnetic circuit. A
normalized input current with saturation current, Imax, III. IMPLEMENTATION
simplifies eq. (7) as
A. Design of a 3D-MT with pole positioning mechanisms
F k I I NI k I I T 2
max Iˆ T NIˆ k Iˆ Fˆ In the above theoretical modeling of the magnetic tweezer,
. (8) the magnetic charges were aligned onto the three axes of the
Fˆ x , y , z Iˆ T N x , y , z Iˆ actuation coordinate system. To minimize the difference
between the actual setup and the theoretical model, the tips of
Here, a constraint condition that summation of the six input the magnetic poles should be precisely aligned onto a target
currents is always zero is introduced to limit the possible circle on the top and bottom layers respectively as shown in
solutions and further simplification of the forward model as Fig.3(b), and the shapes of the tips should be identical to each
other. In order to make the actual assembly as close to this
Fˆcx 6( Iˆ1 Iˆ2 ), Fˆcy 6( Iˆ3 Iˆ4 ), Fˆcz 6( Iˆ5 Iˆ6 ) , (9)
2 2 2 2 2 2
ideal condition as possible, positioning mechanisms were
implemented in the base block of each magnetic pole.
where Fˆc Fˆcx , Fˆcy , Fˆcz is a normalized force at the center of the
Fig. 4(a) shows the composition of the developed MT. Each
working space. Since a linear solution which satisfies eq.(9) is magnetic pole unit is composed of four pieces, a base block, a
written as moving block, a rocker pin and a magnetic pole as shown in
1/ 8 0 0 1/ 3 Fig.4(b). This composition is common between the three
0 1 / 8 0 1/ 3 upper units and the three lower units. In-between the base
block and the moving block, a couple of micrometer heads are
1 / 8 0 0 1/ 3
ˆI DFˆ E , where D , E . (10) attached. By using them, the tip of the magnetic pole can be
c
0 1/ 8 0 1/ 3 turned around the rocker pin and can be fed forward or
0 0 1 / 16 2 / 3 backward as shown in Fig.4(c). By using this mechanism, the
0 0 1 / 16 2 / 3 tips of the poles can be aligned onto a target circle. The height
of each pole was aligned by inserting a few sheets of shim
Substituting Eq. (10) to Eq. (8) gives a normalized force as between the baseplate and the pole block before doing
Fˆ x Fˆ cT N 2 x Fˆ c N 1x Fˆ c N 0 x N 2 x, y, z D T N x, y, z D
horizontal alignment.
ˆ
F y Fˆ c N 2 y Fˆ c N 1 y Fˆ c N 0 y , where N 1x , y , z 2 E N x , y , z D . (11)
T T
In order to evaluate many specimens quickly, introducing a
Fˆ Fˆ T N Fˆ N Fˆ N N specimen holders should be easily done while the alignment of
0 x, y , z E N x, y, z E
T
z c 2z c 1z c 0z
the pole tips is guaranteed. To satisfy this requirement, the
First order Taylor expansion of F̂x in two dimensions near upper poles are fixed to the yoke ring so that they can be easily
removed from the bottom unit. In order to guarantee the fine
Fˆ cx0 0 0 0 and probe position P 0 0 0 can be
T 0 T
alignment between the lower three poles and upper three poles,
derived as Three of coupled v-groove and hemisphere convex were made
on the bottom surface of the yoke ring and on the top of base
Fˆx y , z blocks respectively. Since each couple of v-groove and
Fˆx y , z Fˆc , P Fx y , z Fc0 , P 0 P
P P 0
(12) convex is fit when the yoke ring is placed onto the bottom base
Fc0 , P 0 block, alignment can be well guaranteed, and removal of the
Fˆx y , z N 0 x y , z upper poles together with the yoke ring can be easily done as
Fc
Fˆ F
c c
0
P
P N1x y , z
P0
Fˆc shown in Fig. 5. The fabricated prototype is shown in Fig. 6,
Fc0 , P 0 P0 and the close-up image of the six pole tips when they were
aligned around a circle of 900μm, which was equivalent to a
By substituting N1x,y,z and N0x,y,z into eq. (12), inverse force spatial gap distance of 1.1mm, is shown in Fig. 7. In this figure,
model can be expressed as three poles with fine focus are located on the upper side, and
three blurred poles are on the lower side. During a 20 cycles
( Fˆx , Fˆ y , Fˆz ) ( Fˆcx 8 x, Fˆcy 8 y, Fˆcz 32 z ) . (13)
removal and placement of the yoke and upper pole assembly,
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the alignment error of the upper pole tips against an exact
target position were no larger than 20μm. Upper positioning unit
measurement was done by using a calibration-based algorithm (b) Composition of the lower unit (c) Tip rotation and translation
corresponding to the micrometer operation
as shown in Fig.8. As the first process of the out-of-plane
position measurement, images with respect to known Figure 4. 3D-CAD drawing of the pole positioning mechanism
out-of-plane displacements should be recorded. In order to
give a known Z displacement to the probe, a piezo driven
flexure stage shown in Fig. 9 was fabricated and mounted V-groove
under the objective lens. The flexure mechanism of the stage
magnifies the piezo actuator’s input stroke 5 times to achieve
200μm stroke. Displacement of this stage was measured by a Semi spherical convex
capacitance sensor having sub-micrometer resolution to
establish a PI feedback position control. Fig.10 plots an
obtained result during a calibration process in which a stepped Replace
command trajectory within +/-40μm was given. During the
calibration process, positioning error was within +/-0.1μm.
Although it can be seen that positioning error has a ripple
spiky peak of approximately 100nm amplitude, that only
occurred when the target position of the stage was stepped.
Figure 5. Alignment mechanism for specimen replacement
The image acquisition for the calibration was done when the
target position remained stable, and the positioning error of the
stage was under 20nm at that time.
By substituting the measured probe position and the target
force calculated by the PI feedback controller into eq. (15), a
visual servo system can be established. In the current
implementation, the control frequency of the visual servo is
approximately 300 FPS.
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Figure 8. Out-of-plane visual measurement algorithm utilizing a
calibration of off-focus blurred image
Figure 11. A result of a trajectory tracking experiment
Lens mount
(M25 x 0.75mm thread) Lens displacement
Figure 10. Commanded trajectory for the objective lens stage (right
upward slope) and positioning error (spiky line) during a calibration
1749
The reason of the imbalance between the two layers needs [5] F. J. Alenghat, B. Fabry, K. Y. Tsai, W. H. Goldmann and D. E. Ingber,
to be further investigated and solved. Saturation of Analysis of Cell Mechanics in Single Vinculin-Deficient Cells using a
Magnetic Tweezer, Biochemical and Biophysical Research
magnetization of the pole tip, magnetic conductivity between
Communications, Vol. 277, No. 1, pp. 93-99, 2000.
the gaps of the magnetic pole, pole support block and yoke [6] M. Weicheng, F Niu, X. Li, H. Ji, J. Yang and D. Sun, Automated
ring and the unbalance of excitation coil characteristics, e.g. Manipulation of Magnetic Micro Beads with Electromagnetic Coil
resistance and inductance, are currently under investigated. It System, Proc. of the 7th IEEE Intr. Conf. on Nano/Molecular Medicine
is also necessary to take the nonlinearity of the magnetization and Engineering, pp. 47-50, 2013.
phenomena against the excitation current, e.g. saturation and [7] D. Kilinc and G. U. Lee, Advances in magnetic tweezers for single
hysteresis, into account either theoretical or experimental. molecule and cell biophysics, Integrative Biology, Vol. 6, No. 1, pp.
27-34, 2014.
After solving these problems, the setup will become capable
[8] F. Amblard, B. Yurke, A. Pargellis and S. Leibler, A Magnetic
of generating several hundred pico-newton force by reducing Manipulator for Studying Local Rheology and Micromechanical
the gap distance in between each pole by using the adjustment Properties of Biological Systems, Review of Scientific Instruments,
mechanism. Regarding the strength of the magnetic force, Vol. 67, pp. 818-827, 1996.
large-size particles would be suitable to achieve it easily. [9] A. H. B. de Vries, B. E. Krenn, R. van Driel, and J. S. Kanger, “Micro
However, when the bead diameter becomes too large, magnetic tweezers for nanomanipulation inside live cells,” Biophys. J.,
vol. 88, no. 3, pp. 2137-2144, 2005.
gravitational force and inertial force will become too large to
[10] F. Niu, X. Li, H. K. Chu, J. Yang, H. Ji and D. Sun, Modeling and
be ignored, and it will also influence the resolution of the Development of a Magnetically Actuated System for Micro-particle
Z-position measurement since the measurement is utilizing the Manipulation, Proc. of the 14th IEEE Intr. Conf. on Nanotechnology,
blur of the particle image with respect to the displacement on pp. 127-130, 2014.
Z axis. The capability of the usage of various-size particles for [11] Z. Zhang, and C. H. Menq, Design and Modeling of a 3-D Magnetic
making it possible to select an optimum diameter particle for Actuator for Magnetic Microbead Manipulation, IEEE/ASME Trans.
each experimental plan is an important engineering problem to on Mechatronics, Vol. 16, No. 3, pp. 421-430, 2011.
make the MT system more practical. [12] D. Matsuura, Z. Zhang, C. H. Menq, Development of Noncontact
Micro Particle Manipulation System Using Three-Dimensional
Magnetic Tweezer and Three Axis Piezo Stage, Proc. of the 15th Intr.
V. CONCLUSIONS Conf. on Mechatronics Technology. pp. 514-519, 2011.
[13] Z. Zhang and C. H. Menq, Three-Dimensional Particle Tracking with
In the present paper, development of a prototype 3D Subnanometer Resolution using Off-Focus Images, Applied Optics,
magnetic tweezer (MT), which aims to establish non contact Vol 47, No. 13, pp. 2361-2370, 2008.
precise manipulation of a probe’s position and the exerted
force on it has been discussed. All essential components
including the MT, the inverted microscope for 3D visual
measurement with a piezo objective stage and the
measurement/control software were developed. Especially, a
pole positioning mechanism was implemented in each pole
support block to minimize the undesirable effect of pole
misalignment. By using the developed prototype, the bead
steering experiment to trace a spatial trajectory tracking was
successfully demonstrated. In case of horizontal tracking, the
tracking error was almost less than 500nm. The homogeneity
of the six magnetic poles for generation of magnetomotive
force was evaluated by exerting a constant current on each
coil one by one. From the obtained results, it can be said that
poles located on the same level established sufficiently close
strength, but the imbalance between the poles in different
layers needs to be solved. After further investigation and
improvement, the developed prototype will provide position
and force control for bioengineering experiments and other
micro-manipulation tasks.
REFERENCES
[1] K. C. Neuman and A. Nagy, Single-Molecule Force Spectroscopy:
Optical Tweezers, Magnetic Tweezers and Atomic Force Microscopy,
National Institute of Health (NIH) Public Access, Vol. 5, No. 6, pp.
491-505, 2008.
[2] G. T. Gillies, R. C. Ritter, W. C. Broaddus, M. S. Grady, M. A. Howard
and R. G. McNeil, Magnetic Manipulation Instrumentation for Medical
Physics Research, Review of Scientific Instruments, Vol. 65, pp.
533-562, 1994.
[3] A. R. Bausch, W. Moller and E. Sackmann, Measurement of Local
Viscoelasticity and Forces in Living Cells by Magnetic Tweezers,
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[4] C. Haber and D. Wirtz, “Magnetic tweezers for DNA
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