601 © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com small 2011, 7, No. 5, 601–605 Nanomotors DOI: 10.1002/smll.201001559 In biological systems, nanoscale molecular motors can gen- erate forces from spontaneous reactions of energy-rich molecules, mostly adenosine triphosphate (ATP), to convert chemical energy into mechanical movement. These motors are roughly 10 nm in size, take steps of a few nanometers, and can exert forces in the piconewton range. [1,2] However, to efficiently design and construct nanoscale motors in the laboratory, two key requirements must be satisfied: 1) the generation of forces sufficient to power nanomachines or nanodevices and 2) the exertion of precise control over the motion produced. Accomplishing these objectives begins with DNA, which is the ideal building block for nanostruc- tures. In addition, DNA can also be used to create dynamic molecules that replicate machine functions including tweezers, [3] gears, [4] walkers, [5] and motors. [6] DNA nano- motors, which can be operated with high efficiency for sev- eral cycles, require exergonic reactions, such as hydrolysis of the DNA backbone, [5a,5b,6c] hydrolysis of ATP, [5c] and DNA hybridization. [7,8] However, operating such DNA nanomotors requires the addition and removal of fuels and waste strands for motor function. This mode of operation is accompanied by the accumulation of waste products, which results in decreased motor efficiency.Therefore, coupling the nanomotors to clean alternative energy sources would both eliminate the accumulation of waste products and produce a practical high-efficiency device. Single molecules can be manipulated through magnetic forces by attaching them to magnetic par- ticles and applying an external magnetic field. Using a mag- netic field to control the movement of molecules can also avoid molecular damage from photonic flux. Therefore, the application of a magnetic field could be of great interest as an alternative energy source for DNA nanomotors and could also satisfy the design requirements enumerated above. Magnetically Driven Single DNA Nanomotor Suwussa Bamrungsap, Joseph A. Phillips, Xiangling Xiong, Youngmi Kim, Hui Wang, Haipeng Liu, Arthur Hebard, and Weihong Tan* A DNA nanomotor has been designed that is fueled by an oscillating magnetic field gradient. The nanomotor consists of DNA hairpins that are immobilized on a glass surface inside a microchannel and subsequently conjugated to magnetic particles. An external magnetic field gradient is then used to apply a force on the magnetic particles per- pendicular to the glass surface, thereby opening the DNA hairpins. The separation of the 5’ and 3’ ends of the DNA hairpin during opening is interpreted as the power stroke of this nanomotor and the hybridization of the hairpin as the recovery stroke. The movement of the hairpin mol- ecule can be monitored by fluorescence resonance energy transfer (FRET) between a fluorophore and a quencher on the stem ends. [9–11] Compared with other DNA nanomotor systems, in which the cycles involve the addition of sev- eral DNA strands, the magnetic hairpin DNA nanomotor can be operated by the simple application of an external magnetic field gradient. As such, this magnetically driven hairpin DNA nanomotor adds no DNA fuels and gener- ates no DNA waste products after each cycle, in addition to which it can be operated at room temperature with a low salt concentration. The DNA hairpins and biotinylated linker are summa- rized in Table 1 . Specifically, DNA hairpin structures were selected because they can be switched from the “closed” (contracted) state to the “open” (extended) state. Each DNA hairpin has 20 thymidine (T) bases in the loop and 6, 9, or 12 base pairs (6ds, 9ds, or 12ds) in the stem part. In order to visualize movement between the two states, a fluorophore (Fluorescien, FAM) is attached to one arm of the stem and a quencher (Dabcyl, DAB) on the other arm of the stem. Poly T (20 bases) was used as the spacer between the DNA hair- pins and the magnetic beads at the 3’ end, and 15 bases were incorporated at the 5’ end to hybridize with a DNA linker that was immobilized on a glass surface. It is necessary to point out that the FRET pair is not needed for motor func- tion but gives a convenient way to monitor the motion of the motor. The fluorescence intensity is related to the distance between the FRET pair in the stem ends, which indicates the state (closed or open) of the DNA nanomotor move- ment. [9–11] As shown in Figure 1 , an external magnetic field attracts the magnetic beads, which are conjugated to the 5’ end of the DNA molecular probes, to trigger the opening and closing of DNA hairpins. In order to control the movement, the 3’ end is tethered to a glass surface. In the absence of the magnetic field, the DNA hairpins are in the contracted state and the fluorophore is quenched by FRET. When the external magnetic field is applied, the magnetic beads are attracted to S. Bamrungsap, Dr. J. A. Phillips, X. Xiong, Dr. Y. Kim, H. Wang, Dr. H. Liu, Dr. W. Tan Center for Research at the Bio/nano Interface Department of Chemistry and Department of Physiology and Functional Genomics Shands Cancer Center University of Florida Gainesville, FL 32611–7200, USA E-mail: tan@chem.ufl.edu Dr. A. Hebard Department of Physics University of Florida Gainesville, FL 32611–7200, USA