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 Downloaded 24 Jul 2006 to 129.240.250.61. Redistribution subject to AIP license or copyright, see http://apl.aip.org/apl/copyright.jsp 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 Downloaded 24 Jul 2006 to 129.240.250.61. Redistribution subject to AIP license or copyright, see http://apl.aip.org/apl/copyright.jsp 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. 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