Scanning probe electromagnetic tweezers

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APPLIED PHYSICS LETTERS
VOLUME 79, NUMBER 12
17 SEPTEMBER 2001
Scanning probe electromagnetic tweezers
Mladen Barbic,a) Jack J. Mock, Andrew P. Gray, and S. Schultz
Department of Physics, University of California–San Diego, La Jolla, California 92093-0319
共Received 26 March 2001; accepted for publication 16 July 2001兲
We present a micromanipulation technique that utilizes integrated microcoils and magnetic
microtips for localized positioning of micron-sized magnetic objects. Forces of 10 pN, and
submicron positioning control are demonstrated on the 2.8 ␮m diameter superparamagnetic beads.
The technique also implements an optical illumination scheme that provides a clear viewing of the
magnetically trapped objects without including the scattering background from the magnetic
manipulator tip. This simple instrument provides a noninvasive, low cost alternative to the optical
trapping techniques normally used in micromanipulation. Among the possible advantages are the
negligible heating of the manipulated sample, effective decoupling of the manipulation component
of the experiment from the optical studies of the systems of interest, and the ability to perform
studies in a variety of fluids. © 2001 American Institute of Physics. 关DOI: 10.1063/1.1402963兴
Progress in nanotechnology critically depends on the advances in instrumentation for characterization and manipulation of objects ranging in size from atomic to micrometer
dimensions. Scanning tunneling microscopy1 and atomic
force microscopy2 have allowed imaging with atomic resolution, as well as atomic manipulation3 at a low temperature
and ultrahigh vacuum. The optical trapping methods4,5 have
become routine for manipulating latex micron-sized balls attached to objects of biological interest at room temperature.
In addition, various microelectromechanical systems are being utilized for the physical tweezing of the micro-objects.6
There is also a significant interest in the manipulation of
magnetic objects. Magnetic tweezers have found wide uses
in biological applications, such as investigations of the
physical properties of the cytoplasm,7,8 mechanical properties of cell surfaces,9 and elasticity and transport of single
DNA molecules.10,11 For the cell studies, most of these techniques rely on the micromanipulation of a magnetic particle
positioned inside a cell wall or bound on the surface of a cell,
while the single molecule investigations involve linking the
magnetic particle to one end of the molecule strand. In all of
these studies, micromanipulation is performed by a magnetic
manipulator consisting of permanent or soft coil-wound
magnets with macroscopic dimensions.12,13 Typical forces
available through these techniques are in the range of 0.1–10
pN.
In this letter, we describe a technique that implements a
scanning probe version of a magnetic manipulator allowing
forces of similar magnitude to be applied to magnetic particles. Manipulation of micron-sized magnetic objects is performed by an electromagnetic device that integrates a microcoil and a soft ferromagnetic microtip. This simple device
can remotely manipulate magnetic objects with submicron
resolution, while operating at a distance of more than 40 ␮m,
and showing negligible heating of the manipulated object. In
addition, the manipulation technique is performed in parallel
with the viewing technique that decouples the optical illumia兲
The author has changed the last name from Todorovic to Barbic in 1999;
electronic mail: mladen@ucsd.edu
nation of the manipulated objects from the illumination of
the manipulator. This has the advantage of allowing optical
investigation of the samples to not be obscured by the light
scattering from the manipulation component of the experiment.
The scanning probe electromagnetic tweezers device is
shown in Fig. 1. The device is fabricated by winding a 25
␮m diameter copper magnet wire around a 50 ␮m diameter
soft-ferromagnetic wire.14 The usual winding design consists
of two coil layers with six to eight turns each. Similar microcoils have previously been used in the studies of the
Aharonov–Bohm effect,15 propagation of magnetic domain
walls,16 high-sensitivity detection of electron17,18 and nuclear
spin resonance,19,20 and in the application of high gradient
magnetic fields in the high-sensitivity force magnetometry.21
In order to create high field gradients, soft-ferromagnetic
wire is electrochemically etched into a sharp probe in aqueous 40% sulfuric acid solution at 3 V. The tip is then positioned in the vicinity of the coil, as seen in Fig. 1, in order to
be maximally magnetized by the coil fields. Uses for ferromagnetic tips of this form have been found in magnetic force
FIG. 1. Photograph of the micromagnetic manipulator. Magnet wire, 25 ␮m
in diameter, is wound over a 50 ␮m diameter soft-ferromagnetic wire. The
wire is electrochemically etched into a sharp tip and positioned inside the
microcoil. Small tip and microcoil dimensions maximize the magnetic fields
and field gradients, thus maximizing the forces applied to the magnetic
particles.
0003-6951/2001/79(12)/1897/3/$18.00
1897
© 2001 American Institute of Physics
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1898
Barbic et al.
Appl. Phys. Lett., Vol. 79, No. 12, 17 September 2001
FIG. 2. Block diagram of the scanning probe electromagnetic tweezers.
microscopy,22 magnetic resonance imaging microscopy,23
and microfluidic pumping.24 The microcoils and ferromagnetic microtips are both preferred for the application of sufficient magnetic forces in the tweezers applications, since the
forces on the magnetic bead depend on the field dependent
magnetization of the bead and the magnetic field gradient at
the bead:25
Fbead⫽ 共 mbead共 H兲 "ⵜ)H.
共1兲
Since the magnetic field from a coil is inversely proportional
to the coil diameter, and the field gradient from a ferromagnetic tip is inversely proportional to the tip dimensions, minimization of both of these parameters in the design of our
magnetic microtweezers is advantageous.
The described device is part of a complete micromanipulation instrument, as described in the block diagram of Fig.
2. The system is placed on a Nikon Diaphot inverted optical
microscope mounted on a vibration isolation stage. The microtweezers tip is placed on a mechanical stage for positioning the tip above the viewing lens of the microscope. We
normally implement a 40⫻ Plan objective lens, but other
lenses can also be used. The coil component of the manipulator is connected to a programmable constant current source
for the tunable operation of the device. Since the coil resistance is on the order of 1 ohm, we do not observe any sample
heating during operation up to 250 mA of operating current
through the coil, although currents of ⬍100 mA are sufficient for the work reported in this letter. The nonheating
feature of the instrument might be an advantage compared to
the optical trapping methods used for manipulation of beads
in biological applications.
The samples to be manipulated are placed inside a rectangular cross section quartz capillary tube. The tube is 500
␮m in width, with a 50 ␮m inner diameter, and 40 ␮m capillary wall thickness. The capillary tube is fastened to a
sample positioning stage of the microscope, and white light
illumination is coupled to the quartz capillary tube from a 1
mm diameter optical fiber connected to a Xenon white light
source 共Oriel兲. The manipulator tip is positioned mechanically at the center of the optical axis of the viewing lens prior
FIG. 3. Sequence of images demonstrating the positioning capability of the
magnetic micromanipulator. Two 1-␮m-diameter nonmagnetic polystyrene
beads are placed inside a capillary tube. A magnetic bead, 2.8 ␮m in diameter, is manipulated to trace out a figure eight with respect to the two nonmagnetic beads, as shown by the dashed white curve of the first image.
to instrument operation. The capillary tube containing the
magnetic particles is placed between the tip and the lens, and
the microtip is positioned within several microns of the outside capillary tube surface. In this design, the manipulated
object is always in the center of the viewing location, and
during the operation the capillary tube is moved with respect
to the manipulator tip.
This relative sample–tip placement method creates several important advantages in the operation of the instrument
and in the observation of the manipulated samples. Because
of the differences in the index of refraction of the capillary
tube and the air, light is confined to the capillary tube and
does not illuminate the manipulator tip. This presents a significant advantage during the instrument operation since
there is no spurious light scattering from the tip that would
obscure the light scattered from the sample of interest. The
capillary tube wall separating the tip and the sample also
prevents the particles from coming into contact with the manipulator tip. Since the samples of interest are normally inside a liquid solution, the capillary tube also provides a convenient container for a variety of host solutions for biological
applications. We note that we have also manipulated objects
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Barbic et al.
Appl. Phys. Lett., Vol. 79, No. 12, 17 September 2001
on top of the microscope glass slides. However, such a manipulation method limited us to solutions 共such as glycerol兲
that sustained a thin film form on the slides, and did not bead
up or evaporate during the experiment. Additionally, this
method presented us with problems due to light scattering
from the manipulator tip. It is worth mentioning that the
surface tension of the sample host liquid prevented the magnetic particle from coming into contact with the manipulator
tip positioned outside of the liquid layer in those experiments.
In order to demonstrate the manipulation of samples using the scanning probe electromagnetic tweezers, we placed
2.8 ␮m superparamagnetic beads26 into the capillary tube,
and added 1 ␮m polystyrene beads into the same solution.
We found an area where there were two closely spaced nonmagnetic beads and, using the manipulator with 100 mA microcoil current, we cleared the area by removing all of the
magnetic beads. We then selected one of the magnetic beads
for performing the manipulation demonstration. Figure 3
shows a collection of successive images of the magnetic
bead manipulated so as to trace out a ‘‘figure eight’’ around
the nonmagnetic beads. The nonmagnetic polystyrene beads
in Fig. 3 are 10 ␮m apart, and we were able to achieve
submicron positioning resolution. We note that the ferromagnetic tip behaves as a soft magnet, and we observe nonhysteretic magnetic behavior of the tip returning to zero field
state when no current is passed through the microcoil. One
should also note the high dark background contrast in Fig. 3
due to the illumination method used in the micromanipulation technique. Although the tip of the micromanipulator is
very close to the particle, there is no observable scattered
light from the manipulator tip due to the total internal reflection at the outside capillary surface.
In addition to the demonstration of the magnetic micromanipulation, an estimation of the magnetic forces on the
beads is presented. Although there are several experimental
techniques that attempt to characterize fields from sharp ferromagnetic tips,27,28 it is difficult to directly measure the
magnetic field and the magnetic field gradient at the bead
position. We used an alternative method of estimating the
exerted force on the magnetic bead by calculating the force
required to overcome the force of gravity on the magnetic
bead 共minus the buoyancy兲 in order to raise the bead from
the bottom inside surface to the top inside surface of the
capillary tube. This estimation gives approximately 0.5 pN of
force per 10 mA current through the microcoil of the manipulator. This means that we could potentially exert 10 pN
of force on the beads with a 200 mA current to the coil, a
value that did not degrade the operation of the device. In
principle, it is possible to apply even stronger forces on the
beads by using the methods of pulsed currents through the
microcoil, winding additional coil turns, or using thinner
capillary tube walls.
1899
In summary, we have described and demonstrated a
magnetic micromanipulation tool for positioning magnetic
objects of micron dimensions with submicron resolution. The
instrument provides an alternative to the optical tweezers
methods often used to manipulate objects in biological studies. The technique offers several advantageous features such
as negligible heating, decoupling of the optical investigation
from the manipulation component of the experiment, and the
ability to completely remove the light scattered by a manipulator that is positioned within tens of microns from the
sample of interest. The device may also find uses in medical
applications of magnetic manipulation29 since the complete
device 共without leads兲 is less than 1 mm3 in size.
The authors thank Miriam Katz for careful reading of the
manuscript. This work was supported by grants from NSF
DMR 9724535, NIH PHS H601959-02, and ONR 共DARPA兲
N00014-00-1-0632.
1
G. Bennig, H. Rohrer, C. Gerber, and E. Weibel, Phys. Rev. Lett. 50, 120
共1983兲.
2
G. Benning, C. F. Quate, and C. Gerber, Phys. Rev. Lett. 56, 930 共1986兲.
3
D. M. Eigler and E. K. Schweizer, Nature 共London兲 344, 524 共1990兲.
4
A. Ashkin, Phys. Rev. Lett. 24, 156 共1970兲.
5
A. Ashkin and J. M. Dziedzic, Science 235, 1517 共1987兲.
6
P. Kim and C. M. Lieber, Science 286, 2148 共1999兲.
7
F. H. C. Crick and A. F. W. Hughes, Exp. Cell Res. 1, 37 共1950兲.
8
P. A. Valberg, Science 224, 513 共1984兲.
9
N. Wang, J. P. Butler, and D. E. Ingber, Science 260, 1124 共1993兲.
10
S. B. Smith, L. Finzi, and C. Bustamante, Science 258, 1122 共1992兲.
11
D. Wirtz, Phys. Rev. Lett. 75, 2436 共1995兲.
12
F. Ziemann, J. Radler, and E. Sackmann, Biophys. J. 66, 2210 共1994兲.
13
F. Amblard, B. Yurke, A. Pargellis, and S. Leibler, Rev. Sci. Instrum. 67,
818 共1996兲.
14
Magnet wire and nickel alloy 120 soft-ferromagnetic wire are available
from the California Fine Wire Company, Grover Beach, California.
15
G. Mollenstedt and W. Bayh, Phys. Bl. 18, 299 共1962兲.
16
R. W. DeBlois, J. Appl. Phys. 29, 459 共1958兲.
17
J. Sanny and W. G. Clark, Rev. Sci. Instrum. 52, 539 共1981兲.
18
H. Mahdjour, W. G. Clark, and K. Baberschke, Rev. Sci. Instrum. 57, 1100
共1986兲.
19
D. L. Olson, T. L. Peck, A. G. Webb, R. L. Magin, and J. V. Sweedler,
Science 270, 1967 共1995兲.
20
J. A. Rogers, R. J. Jackman, G. M. Whitesides, D. L. Olson, and J. V.
Sweedler, Appl. Phys. Lett. 70, 2464 共1997兲.
21
M. Todorovic and S. Schultz, Appl. Phys. Lett. 73, 3595 共1998兲.
22
D. Rugar, H. J. Mamin, P. Guethner, S. E. Lambert, J. E. Stern, I. McFadyen, and T. Yogi, J. Appl. Phys. 68, 1169 共1990兲.
23
J. A. Sidles, J. L. Garbini, K. J. Bruland, D. Rugar, O. Zuger, S. Hoen, and
C. S. Yannoni, Rev. Mod. Phys. 67, 249 共1995兲.
24
J. Joung, J. Shen, and P. Grodzinski, IEEE Trans. Magn. 36, 2012 共2000兲.
25
F. H. C. Crick, Exp. Cell Res. 1, 505 共1950兲.
26
Dynal, Inc., Lake Success, New York.
27
D. G. Streblechenko, M. R. Scheinfein, M. Mankos, and K. Babcock,
IEEE Trans. Magn. 32, 4124 共1996兲.
28
A. Thiaville, L. Belliard, D. Majer, E. Zeldov, and J. Miltat, J. Appl. Phys.
82, 3182 共1997兲.
29
G. T. Gillies, R. C. Ritter, W. C. Broaddus, M. S. Grady, M. A. Howard
III, and R. G. McNeil, Rev. Sci. Instrum. 65, 533 共1994兲.
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