Macromolecular rotary motor driven by AC field

Abstract

The invention relates to a nucleic acid nanomotor. The invention also relates to a system comprising a nanomotor and a control unit configured to generate an alternating current for rotating the nanomotor. The invention also relates to a method of rotating a rotor of a nanomotor relative to a stator of the nanomotor. Furthermore, the present invention relates to the use of a nanomotor or system as a turbine, a propeller, a fluid mixer, an energy storage device, a machine for applying mechanical forces, for example on a system coupled to said nanomotor and / or in chemical synthesis.

Description

Technical Field

[0001] The present invention relates to a nucleic acid nanomotor. The present invention also relates to a system comprising a nanomotor and a control unit, the control unit being configured to generate an alternating current for rotating the nanomotor. The present invention also relates to a method for rotating a rotor of a nanomotor relative to a stator of the nanomotor. In addition, the present invention relates to the use of a nanomotor or a system as a turbine, a propeller, a fluid mixer, an energy storage device, a machine for applying mechanical force, for example on a system coupled to the nanomotor and / or in chemical synthesis. Background Art

[0002] The development of the steam engine sparked the Industrial Revolution, and today, a world without motors is almost unimaginable. Given the rapid progress in creating increasingly miniaturized integrated systems in fields ranging from semiconductors to synthetic biology, it is clear that nanoscale motor units have the potential to create truly revolutionary opportunities for nanoscale science and technology. Indeed, biological molecular motors, such as the famous F1F0 ATPase, have inspired visions of a future in which artificial molecular motors will be designed and used for mechanically driven chemical synthesis, chemotaxis, and other tasks such as directional molecular transport. However, the design of nanomotors is very complex.

[0003] To endow molecular-scale mechanisms with directionality of motion, one must overcome and exploit the ubiquitous random thermal forces at such small scales and in liquid solutions at ambient temperature. Furthermore, directed motion cannot be sustained in equilibrium without energy supply without violating the laws of thermodynamics. Directed biased motion can be achieved in the theoretical framework of the Brownian ratchet, a spatially periodic diffusion mechanism that breaks inversion symmetry when operating under conditions far from thermodynamic equilibrium, in the spirit of the Curie principle. Simple forms of energy supply, resulting in periodic or random modulation of the energy barrier, can be sufficient to drive autonomous directed motion, making the Brownian ratchet framework particularly attractive for applications. The Brownian ratchet has been successfully applied to microscale systems, but the use of this concept to fabricate artificial nanoscale motors is still in its infancy. In particular, progress has been made in the prototype of artificial molecular motors (AMMs) fabricated by organic chemical synthesis. In parallel, DNA nanotechnology and DNA origami have yielded a variety of nanoscale mechanical switch-like systems, including pivots, hinges, crank sliders, and rotary mechanisms made from DNA molecules. Some of these objects can be switched through different configurations by using strand displacement reactions (SDRs) or by changing environmental parameters such as pH, ionic strength, temperature, and external fields. While many of these developments are conceptually based on intuition borrowed from how motors work at larger scales, there are also theoretical developments on how to make random artificial swimmers and motors by combining viscous and low Reynolds number dynamics with inherent randomness using appropriate laws governing nanoscale physics. However, nanomotors, such as autonomous nanomotors, have not yet been successfully realized.

[0004] At the molecular scale in liquid solutions, the motion of molecules can be described as diffusion in a free energy landscape. The basic physical requirements for imposing directionality on molecular motion to counteract random thermal forces include specially sculpted energy landscapes and dynamic modulation of features such as energy barriers and minima. Said modulation allows the molecular motion to be biased along a user-defined path in a process called ratcheting. These Brownian ratchet concepts include flash ratchets, where the transition barrier height is modulated in a random or periodic manner; information ratchets, where the energy landscape is dynamically updated depending on the state the motor is in - which, incidentally, seems to be the main working principle of biological motors -; and rocking ratchets, where the energy landscape tilts back and forth under alternating forces as the average time vanishes. Small artificial molecular machines (AMMs) have been previously synthesized with an eye toward implementing such ratchet-like mechanisms, resulting in molecules whose motion can be biased by chemical fuels, light, and other stimuli. Previous achievements include autonomously operating chemical fuel-powered artificial molecular motors that can operate until the fuel is exhausted, taking about 12 hours to complete each 360-degree rotation. There are also several examples of artificial molecular motors powered by light fuels, with the fastest observed rotational speeds being in the range of minutes per revolution. Some of these impressive previous achievements have been recognized with the 2016 Nobel Prize in Chemistry, however, molecular motors with the properties and performance that make them suitable for practical applications have yet to be created.

[0005] While AMMs generated by chemical synthesis tend to contain around 100 atoms, DNA nanostructures (particularly DNA origami objects) can advantageously be much larger and contain hundreds of thousands of atoms. In addition to AMMs, DNA nanotechnologists have created a range of nanoscale mechanical devices, including pivots, hinges, slider cranks, and rotary mechanisms, which dynamically reconfigure using strand displacement reactions (SDRs) or by changing environmental parameters such as pH, ionic strength, and temperature. For example, a nanoscale rotary device has been described that performs a rotational random walk around the central axis of a bearing [1].

[0006] Existing systems are slow, complex, have low assembly yields, or are unable to apply appreciable forces to external loads. There remains a need for nanomotors and systems containing nanomotors that allow directional rotation. In addition, there remains a need for nanomotors and systems containing nanomotors that can rotate at high speeds (especially directional rotation). There is also a need for autonomous nanoscale motors and systems containing autonomous nanomotors. In addition, there remains a need for nanomotors and systems containing nanomotors that can apply forces to external loads. Summary of the invention

[0007] The elements of the present invention will be described below. These elements are listed together with specific embodiments, but it should be understood that they can be combined in any way and in any number to create other embodiments. The various described examples and preferred embodiments should not be interpreted as limiting the present invention to only the embodiments clearly described. This description should be understood to support and cover embodiments that combine two or more clearly described embodiments or one or more clearly described embodiments with any number of disclosed and / or preferred elements. In addition, unless the context otherwise indicates, any arrangement and combination of all description elements in this application should be deemed to be disclosed by the description of this application.

[0008] In a first aspect, the present invention relates to a nucleic acid nanomotor, comprising a nucleic acid rotor and a nucleic acid stator.

[0009] wherein the stator comprises a first surface and a rotor docking point,

[0010] wherein the rotor comprises a stator docking site configured to connect with the rotor docking site of the stator,

[0011] wherein the rotor has at least one longitudinal extension, preferably at least two longitudinal extensions, extending from the stator docking site along a longitudinal axis, wherein the longitudinal axis has a direction substantially parallel to the first surface of the stator,

[0012] wherein the rotor is rotatable about an axis of rotation substantially perpendicular to the longitudinal axis,

[0013] The rotor is electrically charged.

[0014] In one embodiment, the longitudinal extension of the rotor, if present, each of the two longitudinal extensions of the rotor, has a length of at least 1 nm, preferably at least 10 nm, more preferably at least 30 nm.

[0015] In one embodiment, the longitudinal extension of the rotor, if present, the two longitudinal extensions of the rotor, have a total length in the range of 20nm to 1000nm, preferably in the range of 30nm to 700nm, even more preferably in the range of 50nm to 600nm.

[0016] In one embodiment, the rotor has a rod-like shape and / or a T-like shape.

[0017] In one embodiment, the stator comprises at least one protrusion extending towards the rotor, preferably towards the rotor such that the rotor interacts with the protrusion at least once during a rotation of 360° relative to the rotation axis.

[0018] In one embodiment, the nanomotor is configured such that the rotor is rotatable within an energy landscape having at least one energy minimum.

[0019] In one embodiment, the nanomotor is configured such that the rotor is rotatable within an energy landscape defined by a graph of free energy versus rotor angle θ, wherein the rotor angle θ is the rotor angle of the longitudinal axis of the rotor relative to an axis perpendicular to the rotation axis, wherein the energy landscape has at least one energy minimum.

[0020] In one embodiment, the rotor docking site and the stator docking site are directly connected, connected via a nucleic acid hinge and / or connected via a nucleic acid torsion spring.

[0021] In another aspect, the present invention relates to a system comprising

[0022] - a nanomotor comprising a rotor and a stator, wherein the stator comprises a first surface and a rotor docking site, wherein the rotor comprises a stator docking site, the stator docking site being configured to connect with the rotor docking site of the stator,

[0023] wherein the rotor has a longitudinal extension extending from the stator docking site along a longitudinal axis, wherein the longitudinal axis has a direction substantially parallel to the first surface of the stator,

[0024] wherein the rotor is rotatable about an axis of rotation substantially perpendicular to the longitudinal axis,

[0025] wherein the rotor is electrically charged;

[0026] wherein, optionally, the nanomotor is a nanomotor as defined herein; and

[0027] - a control unit configured to generate an alternating current for rotating the nanomotor, wherein the control unit preferably comprises at least two electrodes;

[0028] The stator of the nanomotor has a fixed direction relative to the control unit.

[0029] In one embodiment, the stator comprises at least one protrusion extending towards the rotor, preferably towards the rotor such that the rotor interacts with the protrusion at least once during a rotation of 360° relative to the rotation axis.

[0030] In one embodiment, the nanomotor, the nucleic acid rotor, the nucleic acid stator, the longitudinal extension of the rotor, the rotor docking site and the stator docking site are as defined herein.

[0031] In another aspect, the present invention relates to a method of rotating, preferably directionally rotating, a rotor of a nanomotor relative to a stator of the nanomotor, comprising:

[0032] i) providing a nanomotor comprising a rotor and a stator, wherein the stator comprises a first surface and a rotor docking site, wherein the rotor comprises a stator docking site configured to couple with the rotor docking site of the stator,

[0033] wherein the rotor has a longitudinal extension extending from the stator docking site along a longitudinal axis, wherein the longitudinal axis has a direction substantially parallel to the first surface of the stator,

[0034] wherein the rotor is rotatable about an axis of rotation substantially perpendicular to the longitudinal axis,

[0035] wherein the rotor is electrically charged;

[0036] wherein, optionally, the nanomotor is a nanomotor as defined herein; and

[0037] ii) applying an alternating current to the nanomotor.

[0038] In one embodiment, the stator comprises at least one protrusion extending towards the rotor, preferably towards the rotor such that the rotor interacts with the protrusion at least once during a rotation of 360° relative to the rotation axis.

[0039] In one embodiment, the frequency of the alternating current is in the range of 0.1 Hz to 1000 Hz, preferably in the range of 0.5 Hz to 100 Hz, even more preferably in the range of 1 Hz to 10 Hz, such as about 5 Hz.

[0040] In one embodiment, the voltage of the alternating current is in the range of 1V to 200V, preferably in the range of 5V to 100V, and more preferably in the range of 20V to 60V.

[0041] In one embodiment, the rotor and / or the stator comprises or consists of nucleic acids, peptides, proteins and / or small molecules; wherein, preferably, the rotor and / or the stator comprises or consists of DNA.

[0042] In one embodiment, the nanomotor, the rotor, the stator, the longitudinal extension of the rotor, the rotor docking site, and the stator docking site are as defined herein.

[0043] In another aspect, the present invention relates to the use of a nanomotor as defined herein or a system as defined herein as a turbine, a propeller, a fluid mixer, an energy storage device, a machine for applying mechanical force, for example on a system coupled to said nanomotor and / or in chemical synthesis.

[0044] In another aspect, the invention relates to a nanomotor as defined herein or a system as defined herein, for use in medicine.

[0045] In another aspect, the invention relates to a nanomotor as defined herein or a system as defined herein for use in preventing or treating a disease selected from cancer, an infectious disease, an inflammatory disease, an autoimmune disease and a neurodegenerative disease.

[0046] In another aspect, the present invention relates to a method for preventing or treating a disease comprising administering a nanomotor as defined herein to a patient in need thereof.

[0047] In one embodiment, the disease is selected from the group consisting of cancer, infectious diseases, inflammatory diseases, autoimmune diseases, and neurodegenerative diseases.

[0048] In another aspect, the present invention relates to the use of a nanomotor as defined herein for the manufacture of a medicament.

[0049] In one embodiment, the medicament is a medicament for preventing or treating a disease selected from cancer, infectious diseases, inflammatory diseases, autoimmune diseases, and neurodegenerative diseases.

[0050] Detailed description

[0051] DNA nanotechnology offers design opportunities to rationally engineer molecular implementations of practical Brownian ratchet mechanisms. Due to the inherent modularity of DNA-based objects, such motors can be easily integrated into a variety of environments to do practical useful work, such as turbines, propulsion, fluid mixers, energy storage devices, machines for applying mechanical forces, such as on systems coupled to said nanomotor and / or in chemical synthesis. Herein, the inventors describe the design and experimental realization of an artificial rotary nanomotor built from DNA. Based on the concept of a Brownian flash ratchet, the inventors designed the motor and energy landscape from first principles, creating a directional motor that, surprisingly, can rotate at speeds up to about 250 revolutions per minute, with a drive mechanism that is unexpectedly very easy to implement.

[0052] Advantageously, the rotary nanomotor of the present invention rotates continuously and autonomously. Without being bound by any theory, the inventors believe that the ratchet effect originates from the coupling between the symmetry-breaking features in the energy landscape of the motor (for example, by providing a protrusion to the stator of the motor so that the energy landscape has at least one energy minimum) and the barrier-modulated AC field. Each motor breaks the time reversal symmetry individually, and the inventors have demonstrated this by verifying the fluctuation relationship that detects its irreversibility. Advantageously, the motor can generate torque against external loads, which can be demonstrated by their continued rotation against viscous drag in solution and their ability to roll up molecular torsion springs. When the barrier modulation is turned off, the mechanical energy stored in the spring can drive the motor to move in the opposite direction. Therefore, the nanomotor, system and method of the present invention are highly advantageous in that it provides directional rotation. With a rotation speed of up to about 250 revolutions per minute and a torque of up to 10 pN*nm, the mechanical properties of the motor are surprisingly close to those that have so far only come from well-known biological motors such as F1F0 ATPase. The inventors' discovery opens up the prospect of creating a large number of nanomotors based on simply designed molecular components that can convert easily accessible energy supplies into useful work.

[0053] The inventors show here that three-dimensional realizations of ratchet-like motor mechanisms can be rationally designed using DNA nanotechnology methods. In particular, using DNA origami, means can be included for direct experimental tracking of motor motion in real time, which has proven difficult to achieve with smaller chemically synthesized AMMs. De novo designed DNA origami motors are formed by sequence-programmable self-assembly. For successful designs, the sequence information or design as provided herein can be simply passed on to other users, who can then easily replicate and build their own motors using DNA molecules obtained from commercial sources, and can produce them on a large scale, which is very attractive for future technological applications.

[0054] In one embodiment, the term "nanomotor" as used herein relates to a nanoscale machine designed to convert one or more forms of energy (preferably provided by alternating current) into mechanical energy. In one embodiment, the nanomotor of the present invention is an electric motor that uses electrical energy to generate mechanical energy, preferably powered by alternating current. In one embodiment, the nanomotor is an autonomously rotating motor. In one embodiment, the nanomotor of the present invention is different from a nanorotor in that it rotates autonomously, for example, autonomously in the presence of alternating current. The advantage of a nanomotor is that once a system comprising a nanomotor and an alternating current is established, no external changes (such as switching the direction of the direct current or changing the pH value) need to be applied to cause the nanomotor to rotate in a directional manner. Instead, the nanomotor rotates autonomously and directionally, especially in the presence of alternating current. The nanomotor of the present invention rotates directionally in the presence of alternating current. In particular, the nanomotor and system of the present invention unexpectedly provide directional rotation, although the alternating field is zero on the time average. This is in contrast to the rotor in the presence of direct current, because in the presence of direct current, the direction of rotation is imposed on the rotor by the field arrangement.

[0055] The advantage of the nanomotor of the present invention is that it is autonomous to a certain extent, that is, no external control system is required to update the external energy input according to the state of the motor. In one embodiment, the nanomotor is configured so that the rotor is movable, in particular rotatable, relative to the stator. In one embodiment, the nanomotor is characterized in that the rotor and the stator are connected so that all relative movements of the rotor and the stator are restricted, except for the rotation of the rotor in a plane substantially parallel to the first surface of the stator. For example, this connection can be configured by direct connection, nucleic acid hinges and / or nucleic acid torsion springs. In one embodiment, this connection can additionally or alternatively include a mechanical interlock of the rotor and the stator. In one embodiment, the nanomotor is characterized in that it includes a rotor and a stator, the stator is preferably a nanostructure having a first surface or a platform such as a substrate surface, wherein the rotor and the stator are connected so that all relative movements of the rotor and the stator are restricted, except for the rotation of the rotor in a plane substantially parallel to the first surface of the stator. In a preferred embodiment, the rotor and the stator are both nucleic acid nanostructures.

[0056] In one embodiment, the nanomotor is characterized in that any dimension of the rotor and / or stator is less than 1000nm. In one embodiment, the nanomotor is configured so that the rotor is rotatable within an energy landscape defined by a graph of free energy and rotor angle θ, wherein the rotor angle θ is the rotor angle of the longitudinal axis of the rotor relative to an axis perpendicular to the rotation axis, wherein the energy landscape has at least one energy minimum. In one embodiment, the nanomotor is configured so that the rotor is rotatable within an energy landscape defined by a graph of free energy and rotor angle θ, wherein the rotor angle θ is the rotor angle of the longitudinal axis of the rotor relative to an axis perpendicular to the rotation axis, wherein the energy landscape has at least one energy minimum, and wherein the energy landscape is configured by providing the stator with at least one protrusion. In one embodiment, the rotor angle is the rotor angle of the longitudinal axis of the rotor relative to the direction of the alternating current. In one embodiment, the rotor angle is the rotor angle of the longitudinal axis of the rotor relative to the axis of the field of the alternating current. In one embodiment, the protrusion is configured so that at least a portion of the protrusion extends parallel to the rotation axis. In one embodiment, the nanomotor is configured so as to provide an energy landscape comprising at least one energy minimum for the rotor, for example by providing the nanomotor (preferably the stator) with protrusions; by providing the stator and / or the rotor with a rough surface; and / or by providing the nanomotor such that there is a rotational imbalance in the rotation of the rotor. In one embodiment, the stator comprises two or more protrusions, preferably a plurality of protrusions.

[0057] In one embodiment, a rotor rotatable within an energy landscape passes through the energy landscape and / or is subjected to energy within the energy landscape. In one embodiment, the term "free energy" relates to Gibbs free energy. Gibbs free energy is defined as G(p, T)=H-TS, where p is pressure (SI unit: Pascal), T is temperature (SI unit: Kelvin), H is enthalpy (SI unit: Joule), and S is entropy (SI unit: Joule / Kelvin). In one embodiment, the first surface of the stator is a rough surface, which is configured to provide an energy landscape having at least one energy minimum for the rotor. In one embodiment, the nanomotor, in particular the stator, is configured to provide an energy landscape so that the rotor is more likely to rotate in one direction (e.g., clockwise or counterclockwise) rather than randomly rotating.

[0058] The term "nucleic acid nanomotor" as used herein relates to a nanomotor comprising or consisting of nucleic acids. For example, such a nucleic acid nanomotor may comprise a rotor comprising or consisting of nucleic acids and / or may comprise a stator comprising or consisting of nucleic acids. In one embodiment, the nanomotor comprises a rotor comprising or consisting of nucleic acids, and a stator, the stator being a substrate, such as a glass substrate. In a preferred embodiment, the nanomotor comprises a rotor comprising or consisting of nucleic acids and a stator comprising or consisting of nucleic acids.

[0059] In a preferred embodiment, the nucleic acid nanomotor includes or consists of one or more nucleic acid nanostructures. In one embodiment, the term "nanostructure" used herein relates to a nucleic acid nanostructure, preferably a DNA origami structure consisting of one or more DNA origami subunits (entities). In one embodiment, the nanostructure is a DNA origami nanostructure. Existing nucleic acid nanostructure technology (e.g., DNA origami technology, which involves an assembly procedure that is relatively simpler than standard nanofabrication technology) can be used to manufacture the nanostructure. In one embodiment, the nanostructure is at least partially manufactured using DNA origami technology. Due to the self-assembly of DNA origami structures and the ready-made software for designing corresponding scaffold chains and staple chains, this may be a relatively simple manufacturing process compared to standard nanofabrication technology. In one embodiment, the nanostructure is a DNA origami structure. In one embodiment, the DNA origami structure comprises at least one scaffold chain and a plurality of single-stranded oligonucleotide staple chains. In one embodiment, the scaffold chain constitutes and / or traverses a major portion of a DNA origami structure and / or a DNA origami subunit ("entity"). In one embodiment, the entity is a DNA origami subunit. The term "tack chain" used in the present invention refers to a single-stranded oligonucleotide molecule that is at least partially complementary to the scaffold chain. Typically, staple chains can be used to introduce, for example, coupling sites into DNA origami structures and / or DNA origami subunits ("entities"), such as coupling sites of rotor docking sites and stator docking sites. In a preferred embodiment, the stator and the rotor are each DNA origami structures and / or are composed of DNA origami structures. A nanostructure, such as a DNA origami nanostructure, may include at least one scaffold chain, i.e., a single-stranded polynucleotide scaffold DNA with a known sequence. The DNA origami structure may further include a plurality of single-stranded oligonucleotide staple chains, wherein each staple chain may be at least partially complementary to at least one scaffold chain. Further, each staple chain may be configured to bind to the at least one scaffold chain, wherein the at least one scaffold chain may be folded and / or arranged so as to form a desired nanostructure. The term "chain" used herein relates to nucleic acid chains, such as DNA and / or RNA chains. This three-dimensional nanostructure can be implemented using DNA origami technology, i.e., by combining scaffold chains and staple chains to form the desired parts and the entire device. For example, software such as caDNAno can be used to perform such designs. That is, in some embodiments, a nanostructure comprising multiple parts can be made from one scaffold chain, while in other embodiments, each part of the nanostructure can be constructed using multiple scaffold chains. In one embodiment, the nanomotor comprises any of the following sequences:

[0060] - any of the following stator sequences, such as stator first domain sequences,

[0061] SEQ ID NO.1 (support of base), SEQ ID NO.2 (core_01), SEQ ID NO.3 (core_02), SEQ ID NO.4 (core_03), SEQ ID NO.5 (core_04), SEQ ID NO.6 (core_05), SEQ ID NO.7 (core_06), SEQ ID NO.8 (core_07), SEQ ID NO.9 (core_08), SEQ ID NO.10 (core_09), SEQ ID NO.11 (core_10), SEQ ID NO.12 (core_11), SEQ ID NO.13 (core_12), SEQ ID NO.14 (core_13), SEQ ID NO.15 (core_14), SEQ ID NO.16 (core_15), SEQ ID NO.17 (core_16), SEQ ID NO.18 (core_17), SEQ ID NO.19 (core_18), SEQ ID NO.20 (core_19), SEQ ID NO.21 (core_20), SEQ ID NO.22(Core_21),SEQ ID NO.23(Core_22),SEQ ID NO.24(Core_23),SEQ ID NO.25(Core_24),SEQ ID NO.26(Core_25),SEQ ID NO.27(Core_26),SEQ ID NO.28(Core_27),SEQ ID NO.29(Core_28),SEQ ID NO.30(Core_29),SEQ ID NO.31(Core_30),SEQ ID NO.32(Core_31),SEQ ID NO.33(Core_32),SEQ ID NO.34(Core_33),SEQ ID NO.35(Core_34),SEQ ID NO.36(Core_35),SEQ ID NO.37(Core_36),SEQ ID NO.38(Core_37),SEQ ID NO.39(Core_38),SEQ ID NO.40(Core_39),SEQ ID NO.41(Core_40),SEQ ID NO.42(Core_41),SEQ ID NO.43(Core_42),SEQ ID NO.44(Core_43),SEQ ID NO.45(Core_44),SEQ ID NO.46(Core_45),SEQ ID NO.47(Core_46),SEQ ID NO.48(Core_47),SEQ ID NO.49(Core_48),SEQ ID NO.50(Core_49),SEQ ID NO.51(Core_50),SEQ ID NO.52(Core_51),SEQ IDNO.53(Core_52),SEQ ID NO.54(Core_53),SEQ ID NO.55(Core_54),SEQ ID NO.56(Core_55),SEQ ID NO.57(Core_56),SEQ ID NO.58(Core_57),SEQ ID NO.59(Core_58),SEQ IDNO.60(Core_59),SEQ ID NO.61(Core_60),SEQ ID NO.62(Core_61),SEQ ID NO.63(Core_62),SEQ ID NO.64(Core_63),SEQ ID NO.65(Core_64),SEQ ID NO.66(Core_65),SEQ IDNO.67(Core_66),SEQ ID NO.68(Core_67),SEQ ID NO.69(Core_68),SEQ ID NO.70(Core_69),SEQ ID NO.71(Core_70),SEQ ID NO.72(Core_71),SEQ ID NO.73(Core_72),SEQ IDNO.74(Core_73),SEQ ID NO.75(Core_74),SEQ ID NO.76(Core_75),SEQ ID NO.77(Core_76),SEQ ID NO.78(Core_77),SEQ ID NO.79(Core_78),SEQ ID NO.80(Core_79),SEQ IDNO.81(Core_80),SEQ ID NO.82(Core_81),SEQ ID NO.83(Core_82),SEQ ID NO.84(Core_83),SEQ ID NO.85(Core_84),SEQ ID NO.86(Core_85),SEQ ID NO.87(Core_86),SEQ IDNO.88(Core_87),SEQ ID NO.89(Core_88),SEQ ID NO.90(Core_89),SEQ ID NO.91(Core_90),SEQ ID NO.92(Core_91),SEQ ID NO.93(Core_92),SEQ ID NO.94(Core_93),SEQ IDNO.95(Core_94),SEQ ID NO.96(Core_95),SEQ ID NO.97(Core_96),SEQ ID NO.98(Core_97),SEQ ID NO.99(Core_98),SEQ ID NO.100(Core_99),SEQ ID NO.101(core_100), SEQ ID NO.102(core_101), SEQ ID NO.103(core_102), SEQ ID NO.104(core_103), SEQ ID NO.105(core_104), SEQ ID NO.106(core_105), SEQ ID NO.107(core_106), SEQ ID NO.108(core_107), SEQ ID NO.109(core_108), SEQ ID NO.110(core_109), SEQ ID NO.111(core_110), SEQ ID NO.112(core_111), SEQ ID NO.113(top_01), SEQ ID NO.114(top_02), SEQ ID NO.115(top_03), SEQ ID NO.116(top_04), SEQ ID NO.117(top_05), SEQ ID NO.118(top_06), SEQ ID SEQ ID NO.119(top_07),SEQ ID NO.120(top_08),SEQ ID NO.121(top_09),SEQ ID NO.122(top_10),SEQ ID NO.123(top_11),SEQ ID NO.124(top_12),SEQ ID NO.125(top_13),SEQ ID NO.126(top_14),SEQ ID NO.127(top_15),SEQ ID NO.128(top_16),SEQ ID NO.129(top_17),SEQ ID NO.130(top_18),SEQ ID NO.131(top_19),SEQ ID NO.132(top_20),SEQ ID NO.133(top_21),SEQ ID NO.134(top_22),SEQ ID NO.135(top_23),SEQ ID NO.136(top_24),SEQ ID NO.137(top_25),SEQ ID NO.138 (top_26), SEQ ID NO.139 (top_27), SEQ ID NO.140 (top_28), SEQ ID NO.141 (top_29), SEQ ID NO.142 (top_30), SEQ ID NO.143 (top_31), SEQ ID NO.144 (top_32), SEQ ID NO.145 (top_33), SEQ ID NO.146 (top_34), SEQ ID NO.147 (top_35), SEQ ID NO.148 (top_36), SEQ ID NO.149 (top_37), SEQ ID NO.150 (top_38), SEQ ID NO.151 (top_39), SEQ ID NO.152 (top_40), SEQ ID NO.153 (top_41), SEQ ID NO.154 (top_42), SEQ ID NO.155 (top_43), SEQ ID NO.156 (bottom_01), SEQ ID NO.157 (bottom_02), SEQ ID NO.158 (bottom_03), SEQ ID NO.159 (bottom_04), SEQ ID NO.160 (bottom_05), SEQ ID NO.161 (bottom_06), SEQ ID NO.162 (bottom_07), SEQ ID NO.163 (bottom_08), SEQ ID NO.164 (bottom_09), SEQ ID NO.165 (bottom_10), SEQ ID NO.166 (bottom_11), SEQ ID NO.167(bottom_12),SEQ ID NO.168(bottom_13),SEQ ID NO.169(bottom_14),SEQ ID NO.170(bottom_15),SEQ ID NO.171(bottom_16),SEQ ID NO.172(bottom_17),SEQ ID NO.173(bottom_18),SEQ ID NO.174(bottom_19),SEQ ID NO.175(bottom_20),SEQ ID NO.176(bottom_21),SEQ ID NO.177(bottom_22),SEQ ID NO.178(bottom_23),SEQ ID NO.179(bottom_24),SEQ ID NO.180(bottom_25),SEQ ID NO.181(bottom_26),SEQ ID NO.182(bottom_27),SEQ ID NO.183(bottom_28),SEQ ID NO.184(bottom_29),SEQ ID NO.185(bottom_30),SEQ ID NO.186(bottom_31),SEQ ID NO.187(bottom_32),SEQ ID NO.188(bottom_33),SEQ ID NO.189(bottom_34),SEQ ID NO.190(bottom_35),SEQ ID NO.191(bottom_36),SEQ ID NO.192 (bottom_37), SEQ ID NO.193 (bottom_38), SEQ ID NO.194 (bottom_39), SEQ ID NO.195 (bottom_40), SEQ ID NO.196 (bottom_41), SEQ ID NO.197 (bottom_42), SEQ ID NO.198 (connected to triangle_01), SEQ ID NO.199 (connected to triangle_02), SEQ ID NO.200 (connected to triangle_03), SEQ ID NO.201 (connected to triangle_04), SEQ ID NO.202 (connected to triangle_05), SEQ ID NO.203 (connected to triangle_06), SEQ ID NO.204 (connected to triangle_07), SEQ ID NO.205 (connected to triangle_08), SEQ ID NO.206 (connected to triangle_09), SEQ ID NO.207 (connected to triangle_10), SEQ ID NO.208 (connected to triangle_11), SEQ ID NO.209 (connected to triangle_12), SEQ ID NO.210 (for biotin anchor_01), SEQ ID NO.211 (for biotin anchor_02), SEQ ID NO.212 (for biotin anchor_03), SEQ ID NO.213 (for biotin anchor_04), SEQ ID NO.214 (for biotin anchor_05), SEQ ID NO.215 (for biotin anchor_06), SEQ ID NO.216 (for biotin anchor_07), SEQ ID NO.217 (for biotin anchor_08), SEQ ID NO.218 (for biotin anchor_09), SEQ ID NO.219 (rotor arm docking_01), SEQ ID NO.220 (rotor arm docking_02), SEQ ID NO.221 (rotor arm docking_03), SEQ ID NO.222 (rotor arm docking_04), SEQ ID NO.223 (rotor arm docking_05), SEQ ID NO.224 (rotor arm docking_06),.

[0062] - any of the following stator sequences, such as stator second domain sequences,

[0063] SEQ ID NO.225 (side 1_01), SEQ ID NO.226 (side 1_02), SEQ ID NO.227 (side 1_03), SEQ ID NO.228 (side 1_04), SEQ ID NO.229 (side 1_05), SEQ ID NO.230 (side 1_06), SEQ ID NO.231 (side 1_07), SEQ ID NO.232 (side 1_08), SEQ ID NO.233 (side 1_09), SEQ ID NO.234 (side 1_10), SEQ ID NO.235 (side 1_11), SEQ ID NO.236 (side 1_12), SEQ ID NO.237 (side 1_13), SEQ ID NO.238 (side 1_14), SEQ ID NO.239 (side 1_15), SEQ ID NO.240 (side 1_16), SEQ ID NO.241 (side 1_17), SEQ ID SEQ ID NO.242 (side 1_18), SEQ ID NO.243 (side 1_19), SEQ ID NO.244 (side 1_20), SEQ ID NO.245 (side 1_21), SEQ ID NO.246 (side 1_22), SEQ ID NO.247 (side 1_23), SEQ ID NO.248 (side 1_24), SEQ ID NO.249 (side 1_25), SEQ ID NO.250 (side 1_26), SEQ ID NO.251 (side 1_27), SEQ ID NO.252 (side 1_28), SEQ ID NO.253 (side 1_29), SEQ ID NO.254 (side 1_30), SEQ ID NO.255 ​​(side 1_31), SEQ ID NO.256 (side 1_32), SEQ ID NO.257 (side 1_33), SEQ ID NO.258 (side 1_34), SEQ ID NO.259 (side 1_40), SEQ ID NO.260 (side 1_41), SEQ ID NO.261 (side 1_42), SEQ ID NO.262 (side 1_43), SEQ ID NO.263 (side 1_44), ID NO.259 (side 1_35), SEQ ID NO.260 (side 1_36), SEQ ID NO.261 (side 1_37), SEQ ID NO.262 (side 1_38), SEQ ID NO.263 (side 1_39), SEQ ID NO.264 (side 1_40), SEQ ID NO.265 (side 1_41), SEQ ID NO.266 (side 1_42), SEQ ID NO.267 (side 1_43), SEQ ID NO.268 (side 1_44), SEQ ID NO.269 (side 1_45), SEQ ID NO.270 (side 1_46), SEQ ID NO.271 (side 2_01), SEQ ID NO.272 (side 2_02), SEQ ID NO.273 (side 2_03), SEQ ID NO.274 (side 2_04), SEQ ID NO.275 (side 2_05), SEQ ID NO.276 (side 2_06), SEQ ID NO.277 (side 2_07), SEQ ID NO.278 (side 2_08), SEQ ID NO.279 (side 2_09), SEQ ID NO.280 (side 2_10), SEQ ID NO.281 (side 2_11), SEQ ID NO.282 (side 2_12), SEQ ID NO.283 (side 2_13), SEQ ID NO.284 (side 2_14), SEQ ID NO.285 (side 2_15), SEQ ID NO.286 (side 2_16), SEQ ID NO.287 (side 2_17), SEQ ID NO.288 (side 2_18), SEQ ID NO.289 (side 2_19), SEQ ID NO.290 (side 2_20), SEQ ID NO.291 (side 2_21), SEQ ID NO.292 (side 2_22), SEQ ID NO.293 (side 2_23), SEQ ID NO.294 (side 2_24), SEQ ID NO.295 (side 2_25), SEQ ID NO.296 (side 2_26), SEQ ID NO.297 (side 2_27), SEQ ID NO.298 (side 2_28), SEQ ID NO.299 (side 2_29), SEQ ID NO.300 (side 2_30), SEQ ID NO.301 (side 2_31), SEQ ID NO.302 (side 2_32), SEQ ID NO.303 (side 2_33), SEQ ID NO.304 (side 2_34), SEQ ID NO.305 (side 2_35), SEQ ID NO.306 (side 2_36), SEQ ID NO.307 (side 2_37), SEQ ID NO.308 (side 2_38), SEQ ID NO.309 (side 2_39), SEQ ID NO.310 (side 2_40), SEQ ID NO.311 (side 2_41), SEQ ID NO.312 (side 2_42), SEQ ID NO.313 (side 2_43), SEQ ID NO.314 (side 2_44), SEQ ID NO.315 (side 2_45), SEQ ID NO.316 (side 2_46), SEQ ID NO.317 (side 2_47), SEQ ID NO.318 (side 3_01), SEQ ID NO.319 (side 3_02), SEQ ID NO.320 (side 3_03), SEQ ID NO.321 (side 3_04), SEQ ID NO.322 (side 3_05), SEQ ID NO.323 (side 3_06), SEQ ID NO.324 (side 3_07), SEQ ID NO.325 (side 3_08), SEQ ID NO.326 (side 3_09), SEQ ID NO.327 (side 3_10), SEQ ID NO.328 (side 3_11), SEQ ID NO.329 (side 3_12), SEQ ID NO.330 (side 3_13), SEQ ID NO.331 (side 3_14), SEQ ID NO.332 (side 3_15), SEQ ID NO.333 (side 3_16), SEQ ID NO.334 (side 3_17), SEQ ID NO.335 (side 3_18), SEQ ID NO.336 (side 3_19), SEQ ID NO.337 (side 3_20), SEQ ID NO.338 (side 3_21), SEQ ID NO.339 (side 3_22), SEQ ID NO.340 (side 3_23), SEQ ID NO.341 (side 3_24), SEQ ID NO.342 (side 3_25), SEQ ID NO.343 (side 3_26), SEQ ID NO.344 (side 3_27), SEQ ID NO.345 (side 3_28), SEQ ID NO.346 (side 3_29), SEQ ID NO.347 (side 3_30), SEQ ID NO.348 (side 3_31), SEQ ID NO.349 (side 3_32), SEQ ID NO.350 (side 3_33), SEQ ID NO.351 (side 3_34), SEQ ID NO.352 (side 3_35), SEQ ID NO.353 (side 3_36), SEQ ID NO.354 (side 3_37), SEQ ID NO.355 (side 3_38), SEQ ID NO.356 (side 3_39), SEQ ID NO.357 (side 3_40), SEQ ID NO.358 (side 3_41), SEQ ID NO.359 (side 3_42), SEQ ID NO.360 (side 3_43), SEQ ID NO.361 (side 3_44), SEQ ID NO.362 (side 3_45), SEQ ID NO.363 (side 3_46), SEQ ID NO.364 (side 3_47), SEQ ID NO.365 (side 3_48), SEQ ID NO.366 (angle 3_1_01), SEQ ID NO.367 (angle 3_3.1_02),SEQ ID NO.368(Corner_3.1_03),SEQ ID NO.369(Corner_3.1_04),SEQ ID NO.370(Corner_3.1_05),SEQ ID NO.371(Corner_3.1_06),SEQ ID NO.372(Corner_3.1_07),SEQ ID NO.373(Corner_3.1_08),SEQ ID NO.374(Corner_3.1_09),SEQ ID NO.375(Corner_3.1_10),SEQ ID NO.376(Corner_3.1_11),SEQ ID NO.377(Corner_3.1_12),SEQ ID NO.378(Corner_3.1_13),SEQ ID NO.379(Corner_3.1_14),SEQ ID NO.380(Corner_3.1_PAINT_pos_01),SEQ ID NO.381(Corner_3.1_PAINT_pos_02),SEQ ID NO.382(Corner_3.1_PAINT_pos_03),SEQ ID NO.383(Corner_1.2_01),SEQ IDNO.384(Corner_1.2_02),SEQ ID NO.385(Corner_1.2_03),SEQ ID NO.386(Corner_1.2_04),SEQ IDNO.387(Corner_1.2_05),SEQ ID NO.388(Corner_1.2_06),SEQ ID NO.389(Corner_1.2_07),SEQ IDNO.390(Corner_1.2_08),SEQ ID NO.391(Corner_1.2_09),SEQ ID NO.392(Corner_1.2_10),SEQ IDNO.393(Corner_1.2_11),SEQ ID NO.394(Corner_1.2_12),SEQ ID NO.395(Corner_1.2_PAINT_pos_01),SEQ ID NO.396(Corner_1.2_PAINT_pos_02),SEQ ID NO.397(Corner_1.2_PAINT_pos_03),SEQ ID NO.398(Corner_2.3_01),SEQ ID NO.399(Corner_2.3_02),SEQ ID NO.400(Corner_2.3_03),SEQ IDNO.401(Corner_2.3_04),SEQ ID NO.402(Corner_2.3_05),SEQ ID NO.403(Corner_2.3_06),SEQ ID NO.404 (Corner_2.3_07), SEQ ID NO.405 (Corner_2.3_08), SEQ ID NO.406 (Corner_2.3_09),SEQ ID NO.407(angle_2.3_10),SEQ ID NO.408(angle_2.3_11),SEQ ID NO.409(angle_2.3_12),SEQ ID NO.410(angle_2.3_13),SEQ ID NO.411(angle_2.3_14),SEQ ID NO.412(angle_2.3_18),SEQ ID NO.413(angle_2.3_PAINT_pos_01),SEQ ID NO.414(angle_2.3_PAINT_pos_02),SEQ ID NO.415(angle_2.3_PAINT_pos_03),SEQ ID NO.416(obstacle 1_01),SEQ ID NO.417 (obstacle 1_02), SEQ ID NO.418 (obstacle 1_03), SEQ ID NO.419 (obstacle 1_04), SEQ ID NO.420 (Obstacle 1_05), SEQ ID NO.421 (Obstacle 1_06), SEQ ID NO.422 (Obstacle 1_07), SEQ ID NO.423 (Obstacle 1_08), SEQ ID NO.424 (Obstacle 1_09), SEQ ID NO.425 (Spacer 1_01), SEQ ID NO.426 (Spacer 1_02), SEQ ID NO.427 (Obstacle 2_01), SEQ ID NO.428 (Obstacle 2_02), SEQ ID NO.429 (Obstacle 2_03), SEQ ID NO.430 (Obstacle 2_04), SEQ ID NO.431 (Obstacle 2_05), SEQ ID NO.432 (Obstacle 2_06), SEQ ID NO.433 (Obstacle 2_07), SEQ ID NO.434 (Obstacle 2_08), SEQ ID NO.435 (Obstacle 2_09), SEQ ID NO.436 (Obstacle 2_10), SEQ ID NO.437 (Spacer 2_01), SEQ ID NO.438 (Spacer 2_02), SEQ ID NO.439 (Obstacle 3_01), SEQ ID NO.440 (Obstacle 3_02), SEQ ID NO.441 (Obstacle 3_03), SEQ ID NO.442 (Obstacle 3_04), SEQ ID NO.443 (Obstacle 3_05), SEQ ID NO.444 (Obstacle 3_06), SEQ ID NO.445 (Obstacle 3_07), SEQ ID NO.446 (Obstacle 3_08), SEQ ID NO.447 (Obstacle 3_09), SEQ ID NO.448 (spacer 3_01), SEQ ID NO.449 (spacer 3_02), SEQ ID NO.450 (spacer_complement_01), SEQ ID NO.451 (spacer_complement_02), SEQ ID NO.452 (corner_3.1_for PAINT_01), SEQ ID NO.453 (corner_3.1_for PAINT_02), SEQ ID NO.454 (corner_3.1_for PAINT_03), SEQ ID NO.455 (corner_3.1_for PAINT_04), SEQ ID NO.456 (corner_1.2_for PAINT_01), SEQ ID NO.457 (corner_1.2_for PAINT_02), SEQ ID NO.458 (corner_1.2_for PAINT_03), SEQ ID NO.459 (corner_1.2_for PAINT_04), SEQ ID NO.460 (angle_1.2_for PAINT_05), SEQ ID NO.461 (angle_2.3_for PAINT_01), SEQ ID NO.462 (angle_2.3_for PAINT_02), SEQ ID NO.463 (angle_2.3_for PAINT_03), SEQ ID NO.464 (angle_2.3_for PAINT_04), SEQ ID NO.465 (PAINT_Atto655_imager),.

[0064] - Any of the following rotor sequences

[0065] SEQ ID NO.466(Core_01),SEQ ID NO.467(Core_02),SEQ ID NO.468(Core_03),SEQ ID NO.469(Core_04),SEQ ID NO.470(Core_05),SEQ ID NO.471(Core_06),SEQ IDNO.472(Core_07),SEQ ID NO.473(Core_08),SEQ ID NO.474(Core_09),SEQ ID NO.475(Core_10),SEQ ID NO.476(Core_11),SEQ ID NO.477(Core_12),SEQ ID NO.478(Core_13),SEQ ID NO.479(Core_14),SEQ ID NO.480(Core_15),SEQ ID NO.481(Core_16),SEQID NO.482(Core_17),SEQ ID NO.483(Core_18),SEQ ID NO.484(Core_19),SEQ IDNO.485(Core_20),SEQ ID NO.486(Core_21),SEQ ID NO.487(Core_22),SEQ ID NO.488(Core_23),SEQ ID NO.489(Core_24),SEQ ID NO.490(Core_25),SEQ ID NO.491(Core_26),SEQ ID NO.492(Core_27),SEQ ID NO.493(Core_28),SEQ ID NO.494(Core_29),SEQID NO.495(Core_30),SEQ ID NO.496(Core_31),SEQ ID NO.497(Core_32),SEQ IDNO.498(Core_33),SEQ ID NO.499(Core_34),SEQ ID NO.500(Core_35),SEQ ID NO.501(Core_36),SEQ ID NO.502(Core_37),SEQ ID NO.503(Core_38),SEQ ID NO.504(Core_39),SEQ ID NO.505(Core_40),SEQ ID NO.506(Core_41),SEQ ID NO.507(Core_42),SEQ ID NO.508(Core_43),SEQ ID NO.509(Core_44),SEQ ID NO.510(Core_45),SEQ IDNO.511(Core_46),SEQ ID NO.512(Core_47),SEQ ID NO.513(Core_48),SEQ ID NO.514(Core_49),SEQ ID NO.515(Core_50),SEQ ID NO.516(Core_51),SEQ ID NO.517(Core_52),SEQ ID NO.518(Core_53),SEQ ID NO.519(Core_54),SEQ ID NO.520(Core_55),SEQID NO.521(Core_56),SEQ ID NO.522(Core_57),SEQ ID NO.523(Core_58),SEQ IDNO.524(Core_59),SEQ ID NO.525(Core_60),SEQ ID NO.526(Core_61),SEQ ID NO.527(Core_62),SEQ ID NO.528(Core_63),SEQ ID NO.529(Core_64),SEQ ID NO.530(Core_65),SEQ ID NO.531(Core_66),SEQ ID NO.532(Core_67),SEQ ID NO.533(Core_68),SEQ ID NO.534(Core_69),SEQ ID NO.535(Core_70),SEQ ID NO.536(Core_71),SEQ IDNO.537(Core_72),SEQ ID NO.538(Core_73),SEQ ID NO.539(Core_74),SEQ ID NO.540(Core_75),SEQ ID NO.541(Core_76),SEQ ID NO.542(Core_77),SEQ ID NO.543(Core_78),SEQ ID NO.544(Core_79),SEQ ID NO.545(Core_80),SEQ ID NO.546(Core_81),SEQ ID NO.547(Core_82),SEQ ID NO.548(Core_83),SEQ ID NO.549(Core_84),SEQ IDNO.550(Core_85),SEQ ID NO.551(Core_86),SEQ ID NO.552(Core_87),SEQ ID NO.553(Core_88),SEQ ID NO.554(Core_89),SEQ ID NO.555(Core_90),SEQ ID NO.556(Core_91),SEQ ID NO.557(Core_92),SEQ ID NO.558(Core_93),SEQ ID NO.559(Core_94),SEQID NO.560(Core_95),SEQ ID NO.561(Core_96),SEQ ID NO.562(Core_97),SEQ IDNO.563(Core_98),SEQ ID NO.564(Core_99),SEQ ID NO.565(Core_100),SEQ ID NO.566(Core_101),SEQ ID NO.567(Core_102),SEQ ID NO.568(Core_103),SEQ ID NO.569(Core_104),SEQ ID NO.570(Core_105),SEQ ID NO.571(Core_106),SEQ ID NO.572(Core_107),SEQ ID NO.573(Core_108),SEQ ID NO.574(Core_109),SEQ ID NO.575(Core_110),SEQ ID NO.576(Core_111),SEQ ID NO.577(Core_112),SEQ ID NO.578(Core_113),SEQ ID NO.579(Core_114),SEQ ID NO.580(Core_115),SEQ ID NO.581(Core_116),SEQ IDNO.582(Core_117),SEQ ID NO.583(Core_118),SEQ ID NO.584(Core_119),SEQ IDNO.585(Core_120),SEQ ID NO.586(Core_121),SEQ ID NO.587(Core_122),SEQ IDNO.588(Core_123),SEQ ID NO.589(Core_124),SEQ ID NO.590(Core_125),SEQ IDNO.591(core_126),SEQ ID NO.592(core_127),SEQ ID NO.593(core_128),SEQ IDNO.594(core_129),SEQ ID NO.595(core_130),SEQ ID NO.596(core_131),SEQ IDNO.597(core_132),SEQ ID NO.598(core_133),SEQ ID NO.599(core_134),SEQ IDNO.600(core_135),SEQ ID NO.601(core_136),SEQ ID NO.602(core_137),SEQ IDNO.603(core_138),SEQ ID NO.604(core_139),SEQ ID NO.605(core_140),SEQ IDNO.606(core_141),SEQ ID NO.SEQ ID NO.607 (core_142), SEQ ID NO.608 (core_143), SEQ ID NO.609 (core_144), SEQ ID NO.610 (core_145), SEQ ID NO.611 (core_146), SEQ ID NO.612 (core_147), SEQ ID NO.613 (core_148), SEQ ID NO.614 (core_149), SEQ ID NO.615 (core_150), SEQ ID NO.616 (core_151), SEQ ID NO.617 (core_152), SEQ ID NO.618 (core_153), SEQ ID NO.619 (core_154), SEQ ID NO.620 (core_155), SEQ ID NO.621 (core_156), SEQ ID NO.622 (core_157), SEQ ID NO.623 (core_158), SEQ ID NO.624 (core_159), SEQ ID NO.630 (core_160), SEQ ID NO.631 (core_161), SEQ ID NO.632 (core_162), SEQ ID NO.633 (core_163), SEQ ID NO.634 (core_164), SEQ ID NO.635 SEQ ID NO.624 (core_159), SEQ ID NO.625 (core_160), SEQ ID NO.626 (core_161), SEQ ID NO.627 (core_162), SEQ ID NO.628 (core_163), SEQ ID NO.629 (core_164), SEQ ID NO.630 (core_165), SEQ ID NO.631 (core_166), SEQ ID NO.632 (core_167), SEQ ID NO.633 (core_168), SEQ ID NO.634 (core_169), SEQ ID NO.635 (core_170), SEQ ID NO.636 (core_171), SEQ ID NO.637 (core_172), SEQ ID NO.638 (core_173), SEQ ID NO.639 (core_174), SEQ ID NO.640 (core_175), SEQ ID NO.641 (core_176), SEQ ID NO.642 (core_177), SEQ ID NO.643 (core_178), SEQ ID NO.644 (core_179), SEQ ID NO.645 (core_180), SEQ ID NO.646 (core_181), SEQ ID NO.647 (core_182), SEQ ID NO.648 (core_183), SEQ ID NO.649 (core_184), SEQ ID NO.650 (core_185), SEQ ID NO.651 (core_186), SEQ ID NO.652 (core_187), SEQ ID NO.653 (core_188), SEQ ID NO.654 (core_189), SEQ ID NO.655 (rotor end_01), SEQ ID NO.656 (rotor end_02), SEQ ID NO.657 (rotor end_03), SEQ ID NO.658 (rotor end_04), SEQ ID NO.659 (rotor end_05), SEQ ID NO.660 (rotor end_06), SEQ ID NO.661 (rotor end_07), SEQ ID NO.662 (connected to base_01), SEQ ID NO.663 (connected to base_02), SEQ ID NO.664 (connected to base_03), SEQ ID NO.665 (connected to base_04), SEQ ID NO.666 (connected to base_05), SEQ ID NO.667 (connected to base_06), SEQ ID NO.668 (connected to base_07), SEQ ID NO.669 (connected to base_08), SEQ ID NO.670 (connected to base_09), SEQ ID NO.671 (connected to base_01 with spring), SEQ ID NO.672 (connected to base_02 with spring), SEQ ID NO.673 (connected to base_03 with spring), SEQ ID NO.674 (connected to base_04 with spring), SEQ ID NO.675 (connected to base_05 with spring), SEQ ID NO.676 (connected to base_06 with spring), SEQ ID NO.677 (connected to base_07 with spring), SEQ ID NO.678 (connected to base_08 with spring), SEQ ID NO.679 (connected to base_09 with spring), SEQ ID NO.680 (core_01), SEQ ID NO.681 (core_02), SEQ ID NO.682 (core_03), SEQ ID NO.683 (core_04), SEQ ID NO.684 (core_05), SEQ ID NO.685 (core_06), SEQ ID NO.686 ​​(core_07), SEQ ID NO.687 (core_08), SEQ ID NO.688 (core_09), SEQ ID NO.689 (core_10), SEQ ID NO.690 (core_11), SEQ ID NO.691 (core_12), SEQ ID NO.692 (core_13), SEQ ID NO.693 (core_14), SEQ ID NO.694 (core_15), SEQ ID NO.695(Core_16),SEQ ID NO.696(Core_17),SEQ IDNO.697(Core_18),SEQ ID NO.698(Core_19),SEQ ID NO.699(Core_20),SEQ ID NO.700(Core_21),SEQ ID NO.701(Core_22),SEQ ID NO.702(Core_23),SEQ ID NO.703(Core_24),SEQ ID NO.704(Core_25),SEQ ID NO.705(Core_26),SEQ ID NO.706(Core_27),SEQID NO.707(Core_28),SEQ ID NO.708(Core_29),SEQ ID NO.709(Core_30),SEQ IDNO.710(Core_31),SEQ ID NO.711(Core_32),SEQ ID NO.712(Core_33),SEQ ID NO.713(Core_34),SEQ ID NO.714(Core_35),SEQ ID NO.715(Core_36),SEQ ID NO.716(Core_37),SEQ ID NO.717(Core_38),SEQ ID NO.718(Core_39),SEQ ID NO.719(Core_40),SEQID NO.720(Core_41),SEQ ID NO.721(Core_42),SEQ ID NO.722(Core_43),SEQ IDNO.723(Core_44),SEQ ID NO.724(Core_45),SEQ ID NO.725(Core_46),SEQ ID NO.726(Core_47),SEQ ID NO.727(Core_48),SEQ ID NO.728(Core_49),SEQ ID NO.729(Core_50),SEQ ID NO.730(Core_51),SEQ ID NO.731(Core_52),SEQ ID NO.732(Core_53),SEQID NO.733(Core_54),SEQ ID NO.734(Core_55),SEQ ID NO.735(Core_56),SEQ IDNO.736(Core_57),SEQ ID NO.737(Core_58),SEQ ID NO.738(Core_59),SEQ ID NO.739(Core_60),SEQ ID NO.740(Core_61),SEQ ID NO.741(Core_62),SEQ ID NO.742(Core_63),SEQ ID NO.743(Core_64),SEQ ID NO.744(Core_65),SEQ ID NO.745(Core_66),SEQ ID NO.746(Core_67),SEQ ID NO.747(Core_68),SEQ ID NO.748(Core_69),SEQ IDNO.749(Core_70),SEQ ID NO.750(Core_71),SEQ ID NO.751(Core_72),SEQ ID NO.752(Core_73),SEQ ID NO.753(Core_74),SEQ ID NO.754(Core_75),SEQ ID NO.755(Core_76),SEQ ID NO.756(Core_77),SEQ ID NO.757(Core_78),SEQ ID NO.758(Core_79),SEQID NO.759(Core_80),SEQ ID NO.760(Core_81),SEQ ID NO.761(Core_82),SEQ IDNO.762(Core_83),SEQ ID NO.763(Core_84),SEQ ID NO.764(Core_85),SEQ ID NO.765(Core_86),SEQ ID NO.766(Core_87),SEQ ID NO.767(Core_88),SEQ ID NO.768(Core_89),SEQ ID NO.769(Core_90),SEQ ID NO.770(Core_91),SEQ ID NO.771(Core_92),SEQID NO.772(Core_93),SEQ ID NO.773(Core_94),SEQ ID NO.774(Core_95),SEQ IDNO.775(Core_96),SEQ ID NO.776(Core_97),SEQ ID NO.777(Core_98),SEQ ID NO.778(Core_99),SEQ ID NO.779(Core_100),SEQ ID NO.780(Core_101),SEQ ID NO.781(Core_102),SEQ ID NO.782(Core_103),SEQ ID NO.783(Core_104),SEQ ID NO.784(Core_105),SEQ ID NO.785(Core_106),SEQ ID NO.786(Core_107),SEQ ID NO.787(Core_108),SEQID NO.788(Core_109),SEQ ID NO.789(Core_110),SEQ ID NO.SEQ ID NO.790 (core_111), SEQ ID NO.791 (core_112), SEQ ID NO.792 (core_113), SEQ ID NO.793 (core_114), SEQ ID NO.794 (core_115), SEQ ID NO.795 (core_116), SEQ ID NO.796 (core_117), SEQ ID NO.797 (core_118), SEQ ID NO.798 (core_119), SEQ ID NO.799 (core_120), SEQ ID NO.800 (core_121), SEQ ID NO.801 (core_122), SEQ ID NO.802 (core_123), SEQ ID NO.803 (core_124), SEQ ID NO.804 (core_125), SEQ ID NO.805 (core_126), SEQ ID NO.806 (core_127), SEQ ID NO.807(Core_128),SEQ ID NO.808(Core_129),SEQ ID NO.809(Core_130),SEQ ID NO.810(Core_131),SEQ ID NO.811(Core_132),SEQ ID NO.812(Core_133),SEQ ID NO.813(Core_134),SEQ ID NO.814(Core_135),SEQ ID NO.815(Core_136),SEQ ID NO.816(Core_137),SEQ ID NO.817(Core_138),SEQ ID NO.818(Core_139),SEQ ID NO.819(Core_140),SEQ ID NO.820(Core_141),SEQ ID NO.821(Core_142),SEQ ID NO.822(Core_143),SEQ ID NO.823(Core_144),SEQ SEQ ID NO.824 (core_145), SEQ ID NO.825 (core_146), SEQ ID NO.826 (core_147), SEQ ID NO.827 (core_148), SEQ ID NO.828 (core_149), SEQ ID NO.829 (core_150), SEQ ID NO.830 (core_151), SEQ ID NO.831 (core_152), SEQ ID NO.832 (core_153), SEQ ID NO.833 (core_154), SEQ ID NO.834 (core_155), SEQ ID NO.835 (core_156), SEQ ID NO.836(Core_157),SEQ ID NO.837(Core_158),SEQ ID NO.838(Core_159),SEQ ID NO.839(Core_160),SEQ ID NO.840(Core_161),SEQ ID NO.841(Core_162),SEQ ID NO.842(Core_163),SEQ ID NO.843(Core_164),SEQ ID NO.844(Core_165),SEQ ID NO.845(Core_166),SEQ ID NO.846(Core_167),SEQ ID NO.847(Core_168),SEQ ID NO.848(Core_169),SEQ ID NO.849(Core_170),SEQ ID NO.850(Core_171),SEQ IDNO.851(Core_172),SEQ ID NO.852(Core_173),SEQ ID NO.853 (core_174), SEQ ID NO.854 (core_175), SEQ ID NO.855 (core_176), SEQ ID NO.856 (core_177), SEQ ID NO.857 (core_178), SEQ ID NO.858 (core_179), SEQ ID NO.859 (core_180), SEQ ID NO.860 (core_181), SEQ ID NO.861 (core_182), SEQ ID NO.862 (core_183), SEQ ID NO.863 (core_184), SEQ ID NO.864 (core_185), SEQ ID NO.865 (core_186), SEQ ID NO.866 (core_187), SEQ ID NO.867 (core_188), SEQ ID NO.868 (core_189), SEQ ID NO.869 (core_190), SEQ ID NO.870 (core_191), SEQ ID NO.871 (core_192), SEQ ID NO.872 (core_193), SEQ ID NO.873 (core_194), SEQ ID NO.874 (core_195), SEQ ID NO.875 (core_196), SEQ ID NO.876 (core_197), SEQ ID NO.877 (tip dye_01), SEQ ID NO.878 (tip dye_02), SEQ ID NO.879 (tip dye_03), SEQ ID NO.880 (tip dye_04), SEQ ID NO.881 (tip dye_05), SEQ ID NO.882 (tip dye_06), SEQ ID NO.883 (tip dye_07), SEQ ID NO.884 (tip dye_08), SEQ ID NO.885 (tip dye_09), SEQ ID NO.886 (tip dye_10), SEQ ID NO.887 (connection between rotor arms_01), SEQ ID NO.888 (connection between rotor arms_02), SEQ ID NO.889 (connection between rotor arms_03), SEQ ID NO.890 (connection between rotor arms_04), SEQ ID NO.891 (connection between rotor arms_05), SEQ ID NO.892 (connection between rotor arms_06), and / or.

[0066] - any of the following stator sequences, e.g. a stator with a torsion spring sequence,

[0067] SEQ ID NO.893(Core_01),SEQ ID NO.894(Core_02),SEQ ID NO.895(Core_03),SEQ ID NO.896(Core_04),SEQ ID NO.897(Core_05),SEQ ID NO.898(Core_06),SEQ IDNO.899(Core_07),SEQ ID NO.900(Core_08),SEQ ID NO.901(Core_09),SEQ ID NO.902(Core_10),SEQ ID NO.903(Core_11),SEQ ID NO.904(Core_12),SEQ ID NO.905(Core_13),SEQ ID NO.906(Core_14),SEQ ID NO.907(Core_15),SEQ ID NO.908(Core_16),SEQID NO.909(Core_17),SEQ ID NO.910(Core_18),SEQ ID NO.911(Core_19),SEQ IDNO.912(Core_20),SEQ ID NO.913(Core_21),SEQ ID NO.914(Core_22),SEQ ID NO.915(Core_23),SEQ ID NO.916(Core_24),SEQ ID NO.917(Core_25),SEQ ID NO.918(Core_26),SEQ ID NO.919(Core_27),SEQ ID NO.920(Core_28),SEQ ID NO.921(Core_29),SEQID NO.922(Core_30),SEQ ID NO.923(Core_31),SEQ ID NO.924(Core_32),SEQ IDNO.925(Core_33),SEQ ID NO.926(Core_34),SEQ ID NO.927(Core_35),SEQ ID NO.928(Core_36),SEQ ID NO.929(Core_37),SEQ IDNO.930(Core_38),SEQ ID NO.931(Core_39),SEQ ID NO.932(Core_40),SEQ ID NO.933(Core_41),SEQ ID NO.934(Core_42),SEQID NO.935(Core_43),SEQ ID NO.936(Core_44),SEQ ID NO.937(Core_45),SEQ IDNO.938(Core_46),SEQ ID NO.939(Core_47),SEQ ID NO.940(Core_48),SEQ ID NO.941(Core_49),SEQ ID NO.942(Core_50),SEQ ID NO.943(Core_51),SEQ ID NO.944(Core_52),SEQ ID NO.945(Core_53),SEQ ID NO.946(Core_54),SEQ ID NO.947(Core_55),SEQID NO.948(Core_56),SEQ ID NO.949(Core_57),SEQ ID NO.950(Core_58),SEQ IDNO.951(Core_59),SEQ ID NO.952(Core_60),SEQ ID NO.953(Core_61),SEQ ID NO.954(Core_62),SEQ ID NO.955(Core_63),SEQ ID NO.956(Core_64),SEQ ID NO.957(Core_65),SEQ ID NO.958(Core_66),SEQ ID NO.959(Core_67),SEQ ID NO.960(Core_68),SEQID NO.961(Core_69),SEQ ID NO.962(Core_70),SEQ ID NO.963(Core_71),SEQ IDNO.964(Core_72),SEQ ID NO.965(Core_73),SEQ ID NO.966(Core_74),SEQ ID NO.967(Core_75),SEQ ID NO.968(Core_76),SEQ ID NO.969(Core_77),SEQ ID NO.970(Core_78),SEQ ID NO.971(Core_79),SEQ ID NO.972(Core_80),SEQ ID NO.973(Core_81),SEQ ID NO.974(Core_82),SEQ ID NO.975(Core_83),SEQ ID NO.976(Core_84),SEQ IDNO.977(Core_85),SEQ ID NO.978(Core_86),SEQ ID NO.979(Core_87),SEQ ID NO.980(Core_88),SEQ ID NO.981(Core_89),SEQ ID NO.982(Core_90),SEQ ID NO.983(Core_91),SEQ ID NO.984(Core_92),SEQ ID NO.985(Core_93),SEQ ID NO.986(Core_94),SEQ ID NO.987(Core_95),SEQ ID NO.988(Core_96),SEQ ID NO.989(Core_97),SEQ ID NO.990(Core_98),SEQ ID NO.991(Core_99),SEQ ID NO.992(Core_100),SEQ ID NO.993(Core_101),SEQ ID NO.994(Core_102),SEQ ID NO.995(Core_103),SEQ ID NO.996(Core_104),SEQ ID NO.997(Core_105),SEQ ID NO.998(Core_106),SEQ ID NO.999(Core_107),SEQ ID NO.1000(Core_108),SEQ ID NO.1001(Core_109),SEQ ID NO.1002(Core_110),SEQ ID NO.1003(Core_111),SEQ ID NO.1004(Core_112),SEQ ID NO.1005(core_113),SEQ ID NO.1006(core_114),SEQ ID NO.1007(core_115),SEQ ID NO.1008(core_116),SEQ ID NO.1009(top_01),SEQ ID NO.1010(top_02),SEQ ID NO.1011(top_03),SEQ ID NO.1012(top_04),SEQ ID NO.1013(top_05),SEQ ID NO.1014(top_06),SEQ ID NO.1015(top_07),SEQ ID NO.1016(top_08),SEQ ID NO.1017(top_09),SEQ ID NO.1018(top_10),SEQ ID NO.1019(top_11),SEQ ID NO.1020(top_12),SEQ ID NO.1021(top_13),SEQ ID NO.1022 (top_14), SEQ ID NO.1023 (top_15), SEQ ID NO.1024 (top_16), SEQ ID NO.1025 (top_17), SEQ ID NO.1026 (top_18), SEQ ID NO.1027 (top_19), SEQ ID NO.1028 (top_20), SEQ ID NO.1029 (top_21), SEQ ID NO.1030 (top_22), SEQ ID NO.1031 (top_23), SEQ ID NO.1032 (top_24), SEQ ID NO.1033 (top_25), SEQ ID NO.1034 (top_26), SEQ ID NO.1035 (top_27), SEQ ID NO.1036 (top_28), SEQ ID NO.1037 (top_29), SEQ ID NO.1038 (top_30), SEQ ID NO.1039 (top_31), SEQ ID NO.1040 (top_32), SEQ ID NO.1041 (top_33), SEQ ID NO.1042 (top_34), SEQ ID NO.1043 (top_35), SEQ ID NO.1044 (top_36), SEQ ID NO.1045 (top_37), SEQ ID NO.1046 (top_38), SEQ ID NO.1047 (top_39), SEQ ID NO.1048 (top_40), SEQ ID NO.1049 (top_41), SEQ ID NO.1050(top_42),SEQ ID NO.1051(top_43),SEQ ID NO.1052(top_44),SEQ ID NO.1053(bottom_01),SEQ ID NO.1054(bottom_02),SEQ ID NO.1055(bottom_03),SEQ ID NO.1056(bottom_04),SEQ ID NO.1057(bottom_05),SEQ ID NO.1058(bottom_06),SEQ ID NO.1059(bottom_07),SEQ ID NO.1060(bottom_08),SEQ ID NO.1061(bottom_09),SEQ ID NO.1062(bottom_10, SEQ ID NO.1063(bottom_11), SEQ ID NO.1064(bottom_12), SEQ ID NO.1065(bottom_13), SEQ ID NO.1066(bottom_14), SEQ ID NO.1067(bottom_15),SEQ ID NO.1068(bottom_16),SEQ ID NO.1069(bottom_17),SEQ ID NO.1070(bottom_18),SEQ ID NO.1071(bottom_19),SEQ ID NO.1072(bottom_20),SEQ ID NO.1073(bottom_21),SEQ ID NO.1074 (bottom_22), SEQ ID NO.1075 (bottom_23), SEQ ID NO.1076 (bottom_24), SEQ ID NO.1077 (bottom_25), SEQ ID NO.1078 (bottom_26), SEQ ID NO.1079(bottom_27),SEQ ID NO.1080(bottom_28),SEQ ID NO.1081(bottom_29),SEQ ID NO.1082(bottom_30),SEQ ID NO.1083(bottom_31),SEQ ID NO.1084(bottom_32),SEQ ID NO.1085(bottom_33),SEQ ID NO.1086(bottom_34),SEQ ID NO.1087(bottom_35),SEQ ID NO.1088(bottom_36),SEQ ID NO.1089(bottom_37),SEQ ID NO.1090(bottom_38),SEQ ID NO.1091(bottom_39),SEQ ID NO.1092(bottom_40),SEQ ID NO.1093(bottom_41),SEQ ID NO.1094(bottom_42),SEQ ID NO.1095(bottom_43),SEQ SEQ ID NO.1096 (bottom_44), SEQ ID NO.1097 (bottom_45), SEQ ID NO.1098 (bottom_46), SEQ ID NO.1099 (connected to triangle_01), SEQ ID NO.1100 (connected to triangle_02), SEQ ID NO.1101 (connected to triangle_03), SEQ ID NO.1102 (connected to triangle_04), SEQ ID NO.1103 (connected to triangle_05), SEQ ID NO.1104 (connected to triangle_06), SEQ ID NO.1105 (connected to triangle_07), SEQ ID NO.1106 (connected to triangle_08), SEQ ID NO.1107 (connected to triangle_09), SEQ ID NO.1108 (connected to triangle_10), SEQ ID NO.1109 (connected to triangle_11), SEQ ID NO.1110 (connected to triangle_12), SEQ ID NO.1111 (for biotin anchor_01), SEQ ID NO.1112 (for biotin anchor_02), SEQ ID NO.1113 (for biotin anchor_03), SEQ ID NO.1114 (for biotin anchor_04), SEQ ID NO.1115 (for biotin anchor_05), SEQ ID NO.1116 (for biotin anchor_06), SEQ ID NO.1117 (for biotin anchor_07), SEQ ID NO.1118 (for biotin anchor_08), SEQ ID NO.1119 (for biotin anchor_09), SEQ ID NO.1120 (rotor arm docking_01), SEQ ID NO.1121 (rotor arm docking_02), SEQ ID NO.1122 (rotor arm docking_03), SEQ ID NO.1123 (rotor arm docking_04), SEQ ID NO.1124 (rotor arm docking_05), and SEQ ID NO.1125 (rotor arm docking_06);.

[0068] or any combination thereof.

[0069] The term "DNA origami structure" as used herein relates to a nanostructure comprising DNA as a building material to form a nanoscale shape. The preparation of DNA origami involves the use of multiple rationally designed "tack" DNA chains, for example, by self-assembly, to fold one or more "scaffold" DNA chains into a specific shape. The scaffold chain is usually longer than the staple chain. The nucleic acid sequence of the staple chain is designed so that the staple chain hybridizes with a specific part of the scaffold chain, and a nanostructure of a specific shape is obtained due to the hybridization. In one embodiment, the term nucleic acid "handle" refers to an extension of a nucleic acid sequence that can be combined with a part, for example, a staple chain with an extension that can be combined with a part (for example, a nucleic acid sequence connected to a targeting agent). In a preferred embodiment, the nanomotor, stator and / or rotor is a DNA origami structure and / or consists of a DNA origami structure. In a preferred embodiment, the nanomotor includes or consists of one or more DNA origami structures, for example, a stator for a DNA origami structure, a rotor for a DNA origami structure, and optionally, a protrusion for a DNA origami structure. In a preferred embodiment, the nanomotor is a nucleic acid nanomotor, particularly a DNA origami structure. In one embodiment, the nanomotor comprises one or more sequences selected from SEQ ID NO. 1-1125, preferably a plurality of sequences.

[0070] The term "rotor" as used herein relates to a moving component of a nanomotor (e.g., a nanomotor of the present invention). In one embodiment, the rotor is configured so that it is rotatably connected to the stator of the nanomotor. Preferably, the rotor and the stator are connected so that all relative motions of the rotor and the stator are restricted, except for the rotation of the rotor in a plane substantially parallel to the first surface of the stator. In one embodiment, the rotor is configured so that it can rotate around a rotation axis substantially perpendicular to the longitudinal axis of the rotor. In one embodiment, the rotor is charged, for example, negatively charged. In one embodiment, the rotor has a rod-like shape and / or a T-like shape. For example, the rotor can have a rod-like shape, wherein the rod includes a stator docking site connected to the stator. In a preferred embodiment, the rotor is a nucleic acid rotor. The term "nucleic acid rotor" used herein refers to a rotor comprising or consisting of nucleic acids. In one embodiment, the rotor comprises or consists of a nucleic acid nanostructure, particularly a DNA origami structure. In one embodiment, the rotor comprises one or more sequences selected from SEQ ID NO.466-892. In one embodiment, the rotor has a first domain and a second domain, for example a first arm and a second arm. In one embodiment, the first domain and the second domain of the rotor each extend along a longitudinal extension of the rotor, wherein the first domain extends along the first longitudinal extension and the second domain extends along the second longitudinal extension. In one embodiment, the first domain of the rotor, such as the first domain extending along the first longitudinal extension of the rotor, comprises one or more sequences selected from SEQ ID NO.466-679. In one embodiment, the second domain of the rotor, such as the second domain extending along the first and / or second longitudinal extension of the rotor, comprises one or more sequences selected from SEQ ID NO.680-892.

[0071] In one embodiment, when referring to the rotation of the rotor "in a plane substantially parallel to the first surface of the stator", such expression is meant to be understood to refer to the situation where the rotor is in a plane substantially parallel to the first surface for most of the time and / or most of the angles of such rotation; however, such expression also includes the situation where the rotor is out of the plane for a small amount of time and / or a small amount of angles of such rotation, such as when interacting with and / or bypassing a protrusion that prevents the rotor from staying in the plane. For example, rotation "in the plane" means that the rotation occurs in the plane for at least about 50% of the time of the rotation, preferably at least about 60% of the time of the rotation, and more preferably at least about 70% of the time. For example, rotation "in the plane" means that the rotation occurs in the plane for at least a total of about 180° of a 360° rotation, preferably at least a total of about 220° of a 360° rotation, and more preferably at least a total of about 250° of a 360° rotation. In one embodiment, such "total" degrees (e.g., a total of about 180° degrees) relate to the sum of the degrees during the rotation and may be interrupted by intermediate out-of-plane rotations.

[0072] The term "stator" as used herein relates to the stationary part of a nanomotor (preferably a nanomotor of the present invention). The stator can be a substrate, such as an immobilized substrate, such as a glass substrate, and / or a nanostructure, such as a nucleic acid nanostructure. In a preferred embodiment, the stator is a nucleic acid nanostructure, such as an immobilized nucleic acid nanostructure. In one embodiment, the stator comprises at least one protrusion extending toward the rotor, preferably extending toward the rotor so that the rotor interacts with the protrusion at least once when rotating 360° relative to the rotation axis. In one embodiment, the stator is configured so as to provide an energy landscape having at least one energy minimum, for example by providing the stator with protrusions and / or appropriate roughness of the first surface of the stator. The energy landscape having at least one energy minimum advantageously promotes the directionality of the rotor rotation. In one embodiment, the stator comprises or consists of a nucleic acid nanostructure, in particular a DNA origami structure. In one embodiment, the stator comprises one or more sequences selected from SEQ ID NO.1-465 and 893-1125. In one embodiment, the stator comprises one or more sequences selected from SEQ ID NO.1-465 and 893-1125, preferably multiple sequences; and the rotor comprises one or more sequences selected from SEQ ID NO.466-892, preferably multiple sequences. In one embodiment, the first domain of the stator comprises one or more sequences selected from SEQ ID NO.1-224. In one embodiment, the second domain of the stator comprises one or more sequences selected from SEQ ID NO.225-465. In one embodiment, the stator is provided with a torsion spring, wherein, preferably, the stator with the torsion spring comprises one or more sequences selected from SEQ ID NO.893-1125.

[0073] In one embodiment, the stator comprises a first domain and a second domain. In one embodiment, the stator comprises a first domain and a second domain; wherein the first domain of the stator comprises one or more sequences selected from SEQ ID NO.1-224, preferably multiple sequences, and / or the second domain of the stator comprises one or more sequences selected from SEQ ID NO.225-465, preferably multiple sequences. In one embodiment, the first domain and the second domain comprise or consist of a nucleic acid nanostructure, in particular a DNA origami structure. In one embodiment, the first domain and the second domain are directly connected (e.g., covalently coupled), coupled by a joint, mechanically interlocked, and / or connected by a nucleic acid hinge. For example, any sequence in SEQ ID NO.198-209, 662-679, 887-892, and 1099-1110 can be used to connect the first domain and the second domain, such as a first domain in the form of a base and a second domain in the form of a triangle. In one embodiment, the stator comprises a first domain and a second domain, wherein the first domain comprises the rotor docking site; wherein, preferably, the second domain comprises at least one protrusion extending toward the rotor, so that the rotor contacts the protrusion at least once when rotating 360° relative to the rotation axis. In one embodiment, the second domain has a triangular shape, a rod shape, a star shape and / or an elliptical shape, preferably a triangular shape. In one embodiment, the stator comprises a first domain and a second domain, wherein the second domain comprises at least one protrusion. The term "nucleic acid stator" used herein refers to a stator comprising or consisting of nucleic acids, preferably a stator as defined herein. In a preferred embodiment, the stator is a nucleic acid stator. In one embodiment, the size of the first domain is about 10-60nm×10-80nm, for example, about 30nm×about 40nm. In one embodiment, the size of the second domain is about 5-30nm×10-80nm, for example, about 13nm×60nm. In one embodiment, the stator is fixed on, for example, a glass surface. In one embodiment, the stator is fixed on a surface, for example, a glass surface, by any one of biotin, streptavidin and neutravidin.

[0074] In one embodiment, the term "protrusion" as used herein relates to a nanostructure or domain contained in a stator (e.g., a stator of a nanomotor of the present invention), for example, a nucleic acid nanostructure. In one embodiment, such a protrusion extends from the stator toward the rotor, for example, from the first surface of the stator toward the rotor. In a preferred embodiment, the protrusion extends from the stator toward the rotor so that the rotor interacts with the protrusion at least once when rotating 360° relative to the rotation axis, for example, the rotor interacts with the protrusion by contacting the protrusion (e.g., physically contacting the protrusion), the rotor interacts with the protrusion by electrostatic repulsion or electrostatic attraction, the rotor moves around the protrusion out of plane, and combinations thereof. This interaction may cause the rotor to temporarily leave and re-enter a plane in which the rotor mainly rotates and is substantially parallel to the first surface of the stator. In one embodiment, at least one protrusion extends to a plane in which the rotor mainly rotates and is substantially parallel to the first surface of the stator. In one embodiment, at least one protrusion extends to a plane in which the longitudinal extension of the rotor extends. In one embodiment, at least one protrusion extends to a plane in which the longitudinal extension of the rotor extends. In one embodiment, at least one protrusion extends to a plane in which the longitudinal axis of the rotor extends. In one embodiment, the protrusion is an obstacle to the rotor and / or the rotation of the rotor. In one embodiment, the protrusion is an obstacle that interacts with the rotor at least once when the rotor undergoes a 360° rotation.

[0075] In one embodiment, the stator, such as the second domain of the stator, includes at least one protrusion extending toward the rotor, so that the rotor interacts with the protrusion at least once when rotating 360° relative to the rotation axis. In one embodiment, this interaction between the protrusion and the rotor includes the rotor contacting the protrusion (e.g., physically contacting the protrusion), the rotor interacting with the protrusion by electrostatic repulsion or electrostatic attraction, the rotor bypassing any of the protrusions with an out-of-plane motion, and combinations thereof. In one embodiment, the terms "interaction" and "contact" are used interchangeably. In one embodiment, at least one protrusion is configured so that it modifies the energy landscape of the rotor rotation so that the energy landscape includes at least one minimum. Providing at least one protrusion to the stator has the advantage of being conducive to directional rotation.

[0076] The term "first surface" as used herein relates to the surface of the stator. In one embodiment, the first surface can be in the form of an area, a line, an edge, an angle, a DNA helix flat end, DNA and / or a point, preferably in the form of an area, such as an area substantially parallel to the longitudinal extension of the rotor. In one embodiment, the surface has an arbitrary topological structure. In one embodiment, the first surface is a rough surface. In one embodiment, a rough surface is a surface that provides at least one energy minimum for the rotor, thereby allowing a directional rotation of the rotor. In one embodiment, the surface is a two-dimensional or three-dimensional surface. In one embodiment, the first surface is an area, such as a substantially flat area, which includes at least one protrusion. In one embodiment, the first surface of the stator is a substantially flat area, optionally including a protrusion. In one embodiment, in the context of the stator including a protrusion, the expressions "the stator includes" and "the stator includes a protrusion" mean that the stator (e.g., the first surface of the stator) presents at least a portion of the protrusion and / or at least a portion of the protrusion is accessible from the stator (e.g., from the first surface of the stator). In one embodiment, the term "accessible" as used herein means capable of interacting with the rotor. In one embodiment, the first surface of the stator is a surface of the stator facing the rotor, preferably a surface facing the longitudinal extension of the rotor. In one embodiment, the first surface of the stator is a region of the stator facing the rotor, preferably a region facing the longitudinal extension of the rotor.

[0077] The term "rotor docking site" as used herein relates to a site of the stator that is configured so that the rotor can be connected thereto, such as by nucleic acid base pairing, by a connector, such as a polymer connector or a nucleic acid connector, and / or by mechanical interlocking. In one embodiment, the rotor docking site of the stator is configured to be connected to the stator docking site of the rotor. For example, the rotor docking site may include or consist of a sequence of a single-stranded nucleic acid, which may be connected to a stator docking site that includes or consists of a complementary sequence of the single-stranded nucleic acid by nucleic acid base pairing. For example, the rotor docking site and the stator docking site may be connected using any sequence in SEQ ID NO.198-209, 662-679, 887-892, and 1099-1110. In one embodiment, the rotor docking site and / or the stator docking site comprises or consists of any of SEQ ID NOs. 198-209, 219-224, 662-679, 887-892, 1099-1110 and 1120-1125.

[0078] The term "stator docking site" as used herein relates to a site of the rotor that is configured so that a stator can be connected thereto, such as by nucleic acid base pairing, by a joint, such as a polymer joint or a nucleic acid joint, and / or by mechanical interlocking. In one embodiment, the stator docking site of the rotor is configured to be connected to the rotor docking site of the stator. In one embodiment, the rotor docking site and the stator docking site are directly connected (e.g., by nucleic acid base pairing in a nucleic acid hinge or a nucleic acid torsion spring), or indirectly connected by a joint (e.g., a polymer joint), or by mechanically interlocking the rotor and the stator. The nanomotor can be used as an energy storage device by configuring a torsion spring connecting the rotor docking site and the stator docking site on the nanomotor, thereby allowing energy to be stored by the torsion spring. In one embodiment, the nucleic acid hinge and / or the nucleic acid torsion spring include a nucleic acid sequence of about 1 to 200 nucleotides, preferably about 1 to 100 nucleotides. For example, the nucleic acid hinge may include or consist of three nucleotides (e.g., a CAT sequence). For example, the torsion spring may include or consist of a sequence comprising 50 to 90 nucleotides (e.g., about 75 nucleotides). The rotor and stator can also be connected by mechanically interlocking the rotor and stator. In one embodiment, the stator docking site includes or consists of a groove present on the rotor, wherein the groove can be connected to the rotor docking site of the stator by mechanically interlocking the rotor docking site and the stator docking site, by nucleic acid base pairing and / or by covalent coupling. In one embodiment, the rotor docking site includes or consists of a docking protrusion present on the stator, wherein the docking protrusion can be connected to the stator docking site of the rotor by mechanically interlocking the rotor docking site and the stator docking site, by nucleic acid base pairing and / or by covalent coupling.

[0079] In one embodiment, the term "longitudinal extension" used herein relates to the longitudinal extension of the rotor. The rotor has at least one longitudinal extension extending along the longitudinal axis, preferably extending from the stator docking site. For example, the rotor can extend from the stator docking site in one direction or in two opposite directions along the longitudinal axis. The stator docking site can be any site on the rotor that is connected to the stator, especially the rotor docking site of the stator. For example, the stator docking site can be a nucleic acid of the rotor connected to a joint or a nucleic acid of the rotor docking site of the stator, and the rotor docking site can be a nucleic acid of the stator connected to a joint or a nucleic acid of the stator docking site of the rotor. In one embodiment, at least one longitudinal extension of the rotor is at least 1m, preferably at least 10m, more preferably at least 30m. In one embodiment, the rotor includes at least two longitudinal extensions extending from the stator docking site, wherein at least one of the at least two longitudinal extensions, preferably at least two, has a length of at least 1nm, preferably at least 10nm, more preferably at least 30nm. In one embodiment, the rotor includes at least two longitudinal extensions extending from the stator docking site along at least one longitudinal axis.

[0080] In one embodiment, the longitudinal extension of the rotor, if present, each of the two longitudinal extensions of the rotor, has a length of at least 1 nm, preferably at least 10 nm, more preferably at least 30 nm. In one embodiment, the rotor has at least two longitudinal extensions extending from the stator docking site along at least one longitudinal axis, and the length of each of the longitudinal extensions is at least 1 nm, preferably at least 10 nm, more preferably at least 30 nm. In one embodiment, the longitudinal extension of the rotor, if present, each of the two longitudinal extensions of the rotor, has a total length in the range of 20 nm to 1000 nm, preferably in the range of 30 nm to 700 nm, even more preferably in the range of 50 nm to 600 nm. In one embodiment, in the case where at least two longitudinal extensions extend from the stator docking point along the longitudinal axis, for example in the case where the rotor is T-shaped, the total length of each of the two longitudinal extensions or the total length of the two longitudinal extensions, preferably the total length of the two longitudinal extensions, is in the range of 20nm to 1000nm, preferably in the range of 30nm to 700nm, even more preferably in the range of 50nm to 600nm. In one embodiment, the length of the first of the at least two longitudinal extensions is at least 1nm, preferably at least 10nm, more preferably at least 30nm, and the length of the second of the at least two longitudinal extensions is at least 1nm, preferably at least 10nm, more preferably at least 30nm. In one embodiment, such at least two longitudinal extensions (preferably from the stator docking point) extend along the same longitudinal axis or along different longitudinal axes. In one embodiment, the length of the first longitudinal extension of the at least two longitudinal extensions is at least 1 nm, preferably at least 10 nm, more preferably at least 30 nm, and the length of the second longitudinal extension of the at least two longitudinal extensions is at least 10 nm, preferably at least 30 nm, for example, the length of the first longitudinal extension is about 50 nm and the length of the second longitudinal extension is about 500 nm. For example, the length of the first longitudinal extension can be about 50 nm and the length of the second longitudinal extension can be about 500 nm, so that the total length of the longitudinal extension of the rotor is about 550 nm. In one embodiment, the first longitudinal extension and the second longitudinal extension of the at least two longitudinal extensions have the same length or different lengths. For example, the length of the first longitudinal extension can be about 10 nm and the length of the second longitudinal extension can be about 20 nm, thus providing a total length of about 30 nm.

[0081] In one embodiment, the term "longitudinal axis" as used herein relates to a line passing through the longitudinal extension, preferably the maximum longitudinal extension, and / or a line passing through the length of the rotor, preferably the maximum length of the rotor. In one embodiment, the first surface of the stator lies in a plane substantially parallel to the longitudinal axis of the rotor.

[0082] In one embodiment, the term "substantially parallel direction" as used herein relates to the direction of the longitudinal axis of the rotor, which is substantially parallel to the first surface of the stator, wherein the first surface is a surface facing the rotor, preferably facing the longitudinal extension of the rotor. For example, the longitudinal axis may be substantially parallel to the first surface of the stator, the first surface of the stator being an area facing the rotor, which optionally includes one or more protrusions. In one embodiment, the term "substantially perpendicular to the longitudinal axis" as used herein relates to the direction of the rotation axis of the rotor relative to the longitudinal axis of the rotor. In one embodiment, the rotation axis of the rotor passes through the stator docking site and / or the rotor docking site. In one embodiment, the rotation axis is substantially perpendicular to the axis passing through the maximum longitudinal extension of the rotor. In one embodiment, the rotation axis passes through the stator docking site, optionally further through the rotor docking site, and is substantially perpendicular to the axis passing through the maximum longitudinal extension of the rotor, in particular substantially perpendicular to the longitudinal axis.

[0083] In one embodiment, a system comprising a nanomotor and a control unit configured to generate alternating current, as defined herein, is a device or component comprising said nanomotor and said control unit configured to generate alternating current. In one embodiment, the system of the present invention is a device or component comprising:

[0084] - a nanomotor comprising a rotor and a stator, wherein the stator comprises a first surface and a rotor docking site, wherein the rotor comprises a stator docking site, the stator docking site being configured to connect with the rotor docking site of the stator,

[0085] wherein the rotor has a longitudinal extension extending from the stator docking site along a longitudinal axis, wherein the longitudinal axis has a direction substantially parallel to the first surface of the stator,

[0086] wherein the rotor is rotatable about an axis of rotation substantially perpendicular to the longitudinal axis,

[0087] wherein the rotor is electrically charged;

[0088] wherein, optionally, the nanomotor is a nanomotor as defined herein; and

[0089] - a control unit configured to generate an alternating current for rotating the nanomotor, wherein the control unit preferably comprises at least two electrodes;

[0090] The stator of the nanomotor has a fixed direction relative to the control unit.

[0091] In one embodiment, the control unit comprises two or more electrodes, preferably two electrodes. In one embodiment, the system comprises two or more electrodes, preferably two electrodes. In one embodiment, the system comprises less than four electrodes. Advantageously, the system of the present invention allows the use of alternating current to provide directional rotation. In particular, in the presence of alternating current, the system of the present invention allows directional rotation even when the system comprises only two electrodes / one electrode pair. In contrast, in systems using direct current, more than two electrodes (e.g., four electrodes) are required to provide directional rotation, in particular directional rotation by changing the direction of the electric field. In systems using direct current, nanostructures can only be rotated by arranging the nanostructures in an electric field. Therefore, in order to achieve directional rotation of nanostructures using direct current, the electric field must rotate in the direction of rotation of the nanostructure. In contrast, advantageously, the system of the present invention is particularly effective if the stator comprises at least one protrusion extending toward the rotor, so that the rotor interacts with the protrusion at least once when rotating 360° relative to the rotation axis, allowing the nanomotor to be directional rotated in the presence of alternating current. The inventors found that, surprisingly, the system of the present invention allows the nanomotor to be directional rotated without the need for a rotating electric field. Advantageously, the system of the present invention overcomes the disadvantage of other systems, in particular systems involving direct current, that the electric field must be rotated in order to rotate the nanostructure (e.g., nanomotor). The inventors have found that, surprisingly, a system comprising alternating current and / or a control unit configured to generate alternating current and comprising a nanomotor allows for efficient rotation of the nanomotor, in particular the rotor of the nanomotor, in a target direction. The inventors have found that the efficiency of the directional rotation is even further improved if the stator of the nanomotor comprises at least one protrusion extending towards the rotor, so that the rotor interacts with the protrusion at least once when rotating 360° relative to the rotation axis. As used herein, the expressions "directional rotation", "directional rotation", "directional movement" and "rotation in a target direction" are used interchangeably. Advantageously, by using alternating current to rotate the nanomotor, the complexity of the system can be reduced, in particular the number of electrodes can be reduced, for example, from four electrodes (if direct current is used) to two electrodes (if alternating current is used). The disadvantage of a system comprising direct current is that the rotation of the nanostructure requires more than two electrodes and the electric field must be rotated. By using alternating current for directional rotation of the nanomotor, the complexity of the system is reduced compared to a system involving direct current. For example, because the system of the present invention requires only two electrodes, the fluid channel system that can contain the nanomotor is much simpler than the fluid channel system of a system involving a direct current setup with four electrodes.

[0092] In one embodiment, the stator of the device comprises at least one protrusion extending towards the rotor, preferably extending towards the rotor so that the rotor interacts with the protrusion at least once when rotating 360° relative to the rotation axis. In one embodiment, the stator comprises the at least one protrusion, and the at least one protrusion is configured so that it provides an energy minimum at about 30° to 60°, preferably about 45°, relative to the field axis of the alternating current. Advantageously, such a stator facilitates efficient rotation of the nanomotor in a target direction.

[0093] In one embodiment, the system is configured such that the rotor is rotatable within an energy landscape defined by a graph of free energy versus rotor angle θ, wherein the rotor angle θ is the rotor angle of the longitudinal axis of the rotor relative to an axis perpendicular to the axis of rotation, wherein the energy landscape has at least one energy minimum. In one embodiment, the rotor angle is the rotor angle of the longitudinal axis of the rotor relative to the direction of the alternating current generated by a control unit. In one embodiment, the rotor angle is the rotor angle of the longitudinal axis of the rotor relative to the axis of the field of the alternating current generated by the control unit. In one embodiment, the protrusion is configured such that at least a portion of the protrusion extends parallel to the axis of rotation. In one embodiment, the system is configured such that an energy landscape containing at least one energy minimum is provided for the rotor, for example by providing a nanomotor (preferably a stator) with protrusions; by providing a rough surface for the stator and / or the rotor; and / or by providing a nanomotor such that there is a rotational imbalance in the rotation of the rotor. By providing an energy landscape with at least one energy minimum for the nanomotor / system, for example by providing the stator with the protrusions, the efficiency of the directional rotation is greatly improved. Advantageously, the directional rotation is possible even if the input signal, in particular alternating current, is non-directional.

[0094] In one embodiment, the system is configured such that the stator comprises at least one protrusion, wherein the protrusion is located at the stator such that the angle between the field axis of the alternating current and the axis connecting the protrusion and the rotor docking point is about 30° to 60°, preferably about 45°. In one embodiment, the system is configured such that the stator comprises at least one protrusion, wherein the protrusion is located at the stator such that an energy minimum is provided at about 30° to 60°, preferably about 45°, relative to the field axis of the alternating current. With such a configuration, efficient rotation in a target direction can be achieved.

[0095] In one embodiment, the control unit is configured to generate an alternating current with a frequency in the range of 0.1 Hz to 1000 Hz, preferably in the range of 0.5 Hz to 100 Hz, even more preferably in the range of 1 Hz to 10 Hz, for example about 5 Hz. In one embodiment, the control unit is configured to generate an alternating current with a voltage in the range of 1 V to 200 V, preferably in the range of 5 V to 100 V, more preferably in the range of 20 V to 60 V. In one embodiment, the system comprises an alternating current; wherein, preferably, the frequency of the alternating current is in the range of 0.1 Hz to 1000 Hz, preferably in the range of 0.5 Hz to 100 Hz, even more preferably in the range of 1 Hz to 10 Hz, for example about 5 Hz, and / or its voltage is in the range of 1 V to 200 V, preferably in the range of 5 V to 100 V, more preferably in the range of 20 V to 60 V.

[0096] In one embodiment, the system comprises more than one nanomotor, preferably a plurality of nanomotors. In one embodiment, the system comprises more than one nanomotor, preferably a plurality of nanomotors, wherein each of the nanomotors is configured such that the rotor of the nanomotor is rotatable within an energy landscape defined by a graph of free energy versus rotor angle θ, wherein the energy landscapes of the nanomotors are the same or different. Advantageously, by configuring the energy landscapes of two or more nanomotors differently, the nanomotor can be directionally rotated in different directions using the same input signal, particularly using alternating current.

[0097] In one embodiment, the rotation method includes providing a nanomotor as defined herein and / or a system as defined herein. In one embodiment, the nanomotor is a nucleic acid nanostructure comprising a nucleic acid stator and / or a nucleic acid rotor. In one embodiment, in the context of the method of the present invention, the term "providing a nanomotor" or "providing a nucleic acid nanostructure" includes providing an assembled nucleic acid nanostructure and / or providing building materials for a nucleic acid nanostructure, such as a support chain and one or more staple chains. In one embodiment, step i) of the rotation method according to the present invention includes providing a nanomotor of the present invention and / or includes providing a nanomotor included in the system of the present invention. For example, the nanomotor, rotor and / or stator can be such a nucleic acid nanostructure. In one embodiment, preparing a nanostructure includes the steps of self-assembling the nanostructure and purifying the self-assembled nanostructure. In one embodiment, self-assembly includes mixing at least one support chain and one or more staple chains, optionally further including adjusting the ionic strength, for example by adding MgCl2 to 20mM, and / or further including using a temperature scheme running a series of temperatures. In one embodiment, the purification includes removing the remaining excess staple chains, for example by precipitation (e.g., PEG precipitation), filtration and / or liquid chromatography. In one embodiment, the step of self-assembly and / or self-assembly comprises a denaturation step and a cooling step. In one embodiment, the denaturation step is carried out at a temperature of 50°C to 80°C, preferably 60°C to 70°C, for example, about 65°C, for a duration of 1 minute to 45 minutes, preferably 10 to 20 minutes, for example, about 15 minutes. In one embodiment, the cooling step is carried out at a temperature of 0°C to 70°C, preferably 20°C to 60°C, for example, about 50°C to 58°C. In a preferred embodiment, the cooling step is carried out in a gradually cooling manner, preferably at a temperature of about 58°C to about 50°C, decreasing by 1°C per hour. It is understood by those skilled in the art that the scheme of self-assembly depends on the design of the nanostructure and / or the nucleic acid sequence, and can be adjusted according to known schemes for preparing nanostructures. In one embodiment, the nanostructure is configured to have a scaffold sequence that does not contain a sequence that forms a secondary structure. In one embodiment, the self-assembling nanostructure has one or more vacancies, such as a single-stranded nucleic acid sequence that can form a rotor docking site or a stator docking site. In one embodiment, the nanomotor, stator and / or rotor is a nucleic acid nanostructure. In one embodiment, the nanomotor comprises a nucleic acid nanostructure as a stator and / or a nucleic acid nanostructure as a rotor, which are optionally directly connected, for example, by a nucleic acid hinge or a nucleic acid torsion spring, or by a joint or mechanical interlocking. In one embodiment, the nucleic acid stator and the nucleic acid rotor are connected by a covalent bond, by nucleic acid base pairing, by a nucleic acid hinge and / or by a nucleic acid torsion spring to form a nucleic acid nanomotor. In one embodiment, the nanomotor included in the system of the present invention is a nucleic acid nanomotor as defined above.In one embodiment, the nanomotor provided in the rotation method of the present invention is a nucleic acid nanomotor as defined above. In one embodiment, step ii) of the rotation method of the present invention comprises providing an alternating current and applying the alternating current to the nanomotor. In one embodiment, step ii) of the rotation method of the present invention comprises providing two or more electrodes, preferably two electrodes, which are configured to generate an alternating current and apply the alternating current to the nanomotor. In one embodiment, step ii) of the rotation method of the present invention comprises generating an alternating current using a control unit configured to generate an alternating current, and applying the alternating current to the nanomotor. In one embodiment, step i) of the rotation method of the present invention comprises providing a nanomotor comprised by the system of the present invention, and step ii) of the rotation method of the present invention comprises applying the alternating current generated by the control unit of the system to the nanomotor.

[0098] The rotation method of the present invention is very advantageous because the directionality of rotation can be achieved, for example, by providing the stator with the said protrusions, by applying an alternating current with a frequency in the range of 0.1 Hz to 1000 Hz, preferably in the range of 0.5 Hz to 100 Hz, and even more preferably in the range of 1 Hz to 10 Hz, and / or by applying an alternating current with a voltage in the range of 1 V to 200 V, preferably in the range of 5 V to 100 V, and more preferably in the range of 20 V to 60 V.

[0099] The frequency and voltage of the alternating current can be adjusted by a technician. For example, the shorter the total length of the longitudinal extension of the rotor, the higher the frequency of the alternating current used. In one embodiment, the frequency of the applied alternating current is related to 1 / tau, where tau is the duration of a 180° rotation of the rotor with a friction constant gamma.

[0100] In one embodiment, the use of a nanomotor as defined above or a system as defined above as a turbine, a propeller, a fluid mixer, an energy storage device, a machine for applying mechanical force, for example on a system coupled to the nanomotor and / or in chemical synthesis, comprises rotating the rotor of the nanomotor. In one embodiment, when the nanomotor or system is used as a machine for applying mechanical force, the nanomotor or system is used to pull a molecular tether.

[0101] As used herein, the terms "[the] invention," "according to the present invention," "according to the present invention" and the like are intended to refer to all aspects and embodiments of the present invention described and / or claimed herein.

[0102] The term "comprising" as used herein should be interpreted as covering both "including" and "consisting of", both of which are clearly indicated, and are therefore embodiments disclosed separately according to the present invention. Wherein "and / or" as used herein should be regarded as a specific disclosure of each of the two specified features or components (with or without the other). For example, "A and / or B" should be regarded as a specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each were listed separately in this article. In the context of the present invention, the terms "about" and "approximately" represent the accuracy interval understood by those skilled in the art to ensure the technical effect of the discussed feature. The term generally indicates a deviation of ±20%, ±15%, ±10%, such as ±5% from the numerical value shown. As will be understood by those skilled in the art, this specific deviation of the numerical value of a given technical effect will depend on the nature of the technical effect. For example, natural or biotechnological effects may generally have greater such deviations than artificial or engineered technical effects. When referring to a singular noun, an indefinite article or a definite article is used, such as "one", "a kind of" or "the", unless otherwise expressly stated, this includes the plural form of the noun. BRIEF DESCRIPTION OF THE DRAWINGS

[0103] The present invention will now be further described with reference to the following drawings.

[0104] All methods mentioned in the following description of the figures are carried out according to the detailed description in the embodiments.

[0105] Figure 1 Motor design and experimental setup are shown. (a, b) Schematic representation of the base and triangular platform, respectively. The cylinder represents the DNA double helix. (c) Schematic representation of the motor assembly steps. (d, e) Rotor arm assembly. (f) Left: Schematic representation of the experimental setup used to observe motor dynamics in an inverted TIRF microscope. The base is immobilized on a microscope coverslip via multiple biotin-neutravidin linkages. Stars at the tips of the rotor arms: Cy5 dye. Stars at the vertices of the triangles: marker positions of the DNAPAINT imager strands. Right: Two platinum electrodes are inserted into the liquid chamber from above and connected to a function generator that produces a square-wave alternating current to generate fixed-axis energy modulation acting on all motors.

[0106] Figure 2Structural analysis of a DNA origami motor is shown. (a) Different views of the 3D electron density map of the motor block determined by single-particle cryo-electron microscopy. (b) Detail of a cryo-electron microscopy map of the motor block depicted at different density thresholds, where three obstacles and the rotor docking site can be discerned. Inset: Schematic diagram showing the six preferred residence sites of the rotor arms. (c) Exemplary negative stain TEM image of a motor variant with long rotor arms attached. Scale bar = 50 nm. (d) Exemplary single particle fluorescence image. Scale bar = 500 nm. The image shows the standard deviation of the mean intensity per pixel calculated from all frames of the recorded TIRF movie. (e) DNAPAINT image showing the position of the rotor arm tip relative to the triangular platform. Scale bar = 500 nm.

[0107] Figure 3 Motor dynamics are shown. (a) Example single-particle trajectory showing the cumulative angular displacement of the rotor arm tip with the AC field turned off during the first 10 seconds. Blue, orange: example motors rotating clockwise and counterclockwise, respectively. Unless otherwise stated, the AC field was a 5 Hz square wave with an amplitude of 20 V. (b) Histogram of angular velocity of a single particle with the field turned off (left, N=557) and the field turned on (right, N=1078). (c) Example single-motor trajectory showing the effect of the AC field axis direction on the motor velocity. The AC field axis was rotated stepwise in 5° increments. The dashed lines indicate the time points when the field direction was updated. (d) Phase-corrected angular velocity scatter plot for different AC field axes (N=75). The box plots show the 25th and 75th percentiles, while the whiskers indicate the 10th and 90th percentiles. The line inside the box indicates the median. (e) Solid line: Example single-particle trajectory seen during an AC frequency sweep showing counterclockwise and clockwise rotating motors. The dashed line gives the effective angular velocity in revolutions per field period. (f) Solid line: Example single particle trajectory seen during a voltage sweep showing counterclockwise and clockwise rotating motors. The dashed line gives the directional bias efficiency as shown in (e). (g) Scatter plot of absolute angular velocity per AC field period for different frequencies (left, N=156) and different voltages (right, N=28). Box and whisker plots are shown as in (d).

[0108] Figure 4The motor mechanism, fluctuation analysis, and winding of the main axis are shown. (a) Solid line: Schematic diagram of the internal energy landscape of a simplified model motor with two minima. Dashed and dotted lines: Energy contribution of the external AC field applied along the 0°-180° axis. The inset on the right gives the energy function in polar coordinates. (b) Solid line: Snapshot of the effective energy landscape (i.e., the sum of the internal motor energy and the field contribution). The dashed line gives the expected trajectory of the rotor arm when the field direction is reversed. The initial position of each field half-cycle is represented by a dot. (c) The effective energy landscape of the hypothetical 2-minimum motor from (a, b), plotted as a 2D space-time surface, and three exemplary orientations of the motor relative to the field axis are calculated (see inset). The field axis is along the 0°-180° direction. Dots: Exemplary single-particle trajectories simulated by Langevin dynamics. (d) Cumulative angular displacement distribution after two, four, and six AC field cycles summarized from the simulated Langevin dynamics trajectories. The prominent peaks at 180° intervals are due to the twofold symmetry in the simulated energy landscape. (e) Irreversibility analysis of the simulated motor. Shown are population averages of 20 simulated motors evaluated at different displacement values ​​and time intervals of two, four, and six AC cycles, as indicated by gray shading. The motor contains a twofold symmetry, as shown in (a), where a motor orientation of 45° relative to the field is used in the tilted scheme and a symmetry orientation (0°) is used in the horizontal scheme. Solid lines are added as sight guides to emphasize trends or lack thereof. (f) Experimentally observed irreversibility analysis of motor particles. The shading of the distributions indicates the time intervals, as shown in (e). To account for the variation in rotational speed, the linear trend for each rotor was renormalized to unit slope before calculating the distributions shown. A line with slope unit is added as sight guide. (g) Left: Schematic of a motor variant containing a torsion spring at the pivot point, implemented by an ssDNA loop. Right: Example experimentally observed single-particle trajectory showing the accumulated angular displacement of the motor. Phase 1: AC field off, spring relaxed. Phase 2: AC field on, spring rolled up. Phase 3: AC field off, spring unrolled and driving motion.

[0109] Figure 5 The experimental setup is shown with electrodes for applying an AC field. (a) Schematic cross-section of the sample chamber with the plug inserted. (b) Illustration of the top view of the assembled sample chamber and schematic of the resulting channel shape and electrode wiring (main electrode pair in black, second optional electrode pair in gray). (c) Dimensions of the sample chamber top assembly (left) and tape using one (middle) and two (right) electrode pairs. (d) Schematic top view of the rotor attached to a microscope coverslip with one electrode pair for a single-axis AC field. (e) Schematic top view of the rotor attached to a microscope coverslip with two electrode pairs to allow rotation of the AC field axis.

[0110] Figure 6The motor mechanism is shown. (a, c, e) Solid lines: Schematic representation of the internal energy landscape of a simplified model motor with one (a), two (c), and six (e) minima. Dashed, dotted lines: Energy contribution of an external AC field applied along the 0°-180° axis. The inset on the right gives the energy function in polar coordinates. (b, d, f) Solid lines: Snapshots of the effective energy landscape (i.e., the sum of the internal motor energy and the field contribution) of a motor with one (b), two (d), and six (f) minima. The dashed lines give the expected trajectory of the rotor arms when the field direction is reversed. The initial position of each field half-cycle is indicated by a dot.

[0111] Figure 7 Gel electrophoresis analysis of motor assembly is shown. Laser scanning image of a 1.5% agarose gel containing 5.5 mM MgCl2, run at 100 V in a water bath for 165 minutes, where the following samples were electrophoresed: L, 1 kb ladder; 1, triangular platform; 2, base; 3, first part of rotor arm; 4, second part of rotor arm (extension); 5, dimer of triangular platform and base; 6: dimer of rotor arm; 7 fully assembled tetramer. P: pocket, Tet: tetramer, Dim1: dimer of triangular platform and base, Dim2: dimer of rotor arm.

[0112] Figure 8 An exemplary single image showing the standard deviation of fluorescence intensity in a single particle TIRF movie. Scale bar = 500 nm. The image shows the standard deviation of the mean intensity per pixel calculated from all frames of the recorded TIRF movie.

[0113] Fig. 9 Displays a single frame TIRF image. (ac) Figure 2 Montage of the first 76 individual frames of the particle given in ((a) left, (b) middle, (c) right particle). First square: average intensity over the entire movie. Second square: standard deviation of the average intensity per pixel calculated over the entire movie.

[0114] Fig.10 An exemplary DNAPAINT image is shown, showing the position of the rotor arm tip (outer trace) relative to the triangular platform (inner trace). Scale bar = 500 nm.

[0115] Fig.11 An exemplary single particle trajectory is shown, showing the effect of the AC field axis direction on the motor rotation. The AC field axis is rotated stepwise in increments of 5° every 1.6 seconds. The dashed lines indicate the time points at which the field direction is updated.

[0116] Fig.12The assembly of a rotating device with a torsion spring is shown. (a) Laser scanning image of a 1.5% agarose gel containing 5.5 mM MgCl2, run at 100 V in a water bath for 165 minutes, where the following samples were electrophoresed: L, 1 kbladder; 1, triangular platform; 2, base; 3, first part of the rotor arm; 4, second part of the rotor arm (extension); 5, dimer of triangular platform and base; 6: dimer of rotor arm; 7 fully assembled tetramer. P: pocket, Tet: tetramer, Dim1: dimer of triangular platform and base, Dim2: dimer of rotor arm. (b) Example negative stain TEM image of the complete motor assembly with attached rotor arm, imaged using a Philips CM100 microscope. Scale bar = 100 nm. DETAILED DESCRIPTION

[0117] Hereinafter, reference will be made to examples which are intended to illustrate the present invention rather than to limit the present invention.

[0118] Example

[0119] Example 1: Materials and Methods

[0120] Design of DNA origami nanostructures

[0121] All structures were designed using cadnano0.2. The base is folded from a linearized custom scaffold of 7585 bases, while the base with torsion springs is folded from a scaffold of 8064 bases, as are the two rotor arms. The triangular platform is folded from a scaffold of 9072 bases [2].

[0122] Custom Scaffold Preparation

[0123] The circular scaffolds of 8064 bases in length were prepared in a 2 L stirred bioreactor. The circular scaffolds of 9072 bases in length and the circular precursors of the linear scaffolds of 7585 bases in length were prepared in shake flask cultures as previously described [2]. To linearize the scaffolds, they were zinc digested.

[0124] Folding of DNA origami nanostructures

[0125] All folding reaction mixtures contained a final scaffold concentration of 50 nM and 500 nM (for triangular platform) or 200 nM (for other structures) of each oligonucleotide chain (Integrated DNA Technologies (IDT)). The folding reaction buffer contained 5 mM TRIS-HCl, 1 mM EDTA, 5 mM NaCl and 10 mM (rotor arm), 15 mM (two base variants) or 20 mM (triangular platform) MgCl2. The folding solution was thermally annealed using a TETRAD (MJ Research, now Biorad) thermal cycler. The reaction was maintained at 65°C for 15 minutes, followed by a thermal annealing gradient from 60°C to 44°C (1°C / hour). The folded structures were stored at room temperature until further sample preparation steps. All DNA sequences can be found in the attached sequence list.

[0126] Purification and concentration of DNA origami nanostructures

[0127] All folded structures were purified from excess oligonucleotides by PEG precipitation (rotor arm and base variants) or by physical extraction from agarose gels (triangular platform). Gel-purified monomers were concentrated using ultracentrifugation. PEG-purified rotor arm extensions were additionally incubated with a set of linked oligonucleotide chains at 10 mM MgCl2 for 1 h at 30 °C, followed by another PEG precipitation. All procedures were performed as previously described [3].

[0128] Assembly of the rotating device

[0129] As a first step, two dimers, the triangular platform and base (dimer 1) and the two rotor arm parts (dimer 2), were assembled by mixing 1:1 solutions of the respective monomers at a final MgCl2 concentration of 40 mM (dimer 1) and 5 mM (dimer 2) and kept at 40 °C for at least 16 h. Dimer 1 was then PEG-precipitated and the buffer was exchanged to a final MgCl2 concentration of 5 mM. Both dimers were mixed and incubated at 10 mM MgCl2 for at least 16 h.

[0130] Agarose gel analysis of DNA origami nanostructures

[0131] The folded and assembled DNA nanostructures were electrophoresed on 1.5% or 2% agarose gels containing 0.5× TBE and 5.5 mM MgCl2 in a water-cooled gel box at a bias voltage of 90 V or 100 V for 1.5-3 h. The agarose gels after electrophoresis were stained with ethidium bromide and scanned using a Typhoon FLA9500 laser scanner (GE Healthcare) at a resolution of 50 μm / pixel.

[0132] Negative stain transmission electron microscopy

[0133] 5ul of sample was adsorbed onto glow-discharged Cu grids with carbon support (in-house production and scientific services, Munich) and stained with 2% aqueous uranyl formate containing 25mM NaOH. Samples were incubated for different lengths of time depending on the concentration. In general, structures with concentrations of tens of nM were incubated for 30s, while samples with lower concentrations (5nM or less) were incubated for 5 to 10 minutes. Images were acquired using a Philips CM100 operating at 100kV.

[0134] Cryo-electron microscopy sample preparation

[0135] The purified and concentrated samples were applied to glow-discharged C-Flat 2 / 14C (EMS) grids (Protochips) and flash frozen using a Vitrobot MarkV (FEI, now Thermo Scientific) under the following settings: temperature 22 °C, humidity 90%, waiting time 0 s, blotting time 3 s, blotting force -1, drainage time 0 s.

[0136] Cryo-electron microscopy image acquisition

[0137] Data were collected using EPU software (Thermo Scientific) on a Titan Krios G2 electron microscope equipped with a Falcon 3 direct detector, operating at 300 kV. The total exposure time was 3.3 s, with a dose of 44 e / Angstom^2 in 11 fractions.

[0138] Cryo-electron microscopy image processing

[0139] Image processing was performed in Relion 3.0. Motion correction and contrast transfer function estimation were performed on the micrographs using MotionCor2 and CTFFIND4.1, respectively. Particles were picked using Cryolo. Automatically picked particles were extracted from the micrographs and classified by 2, and a round of 2D and 3D classification was performed to remove wrongly picked grid contamination and damaged particles and to account for structural heterogeneity. A refined 3D map was reconstructed using a low-resolution initial model created in Relion. A total of 38,649 particles were used for the final reconstruction. The map was post-processed using a low-pass filter mask to calculate the FCS and estimate the global resolution to be 16 Å, with a manually set B-factor of -500.

[0140] Sample preparation for fluorescence measurements

[0141] Monomers were folded, purified, and assembled as previously described. Biotinylated oligonucleotides were incubated with 32× excess of neutravidin (Thermo Fisher Scientific) and then added to the polymer at ~10× excess for the binding site for 1-2 hours at room temperature. The resulting reaction mixture was gel purified by extracting only the tetramer species. The sample concentration was ~100 pM. If necessary, a set of two spacer oligonucleotide chains were added to the sample at ~100× excess to mount the obstacles on the triangular platform. All samples were stored at room temperature until imaging under the microscope, with a shelf life of up to several weeks.

[0142] Total Internal Reflection Fluorescence Microscopy (TIRFM) Movie Acquisition Using AC Field

[0143] Biotin-PEG coverslip preparation, flow chamber fabrication, and TIRFM setup were as described previously. The sample was diluted to less than 100 pM in imaging buffer (FMB 500) containing 500 mM NaCl, 100 mM TRIS-HCl, and 2 mM EDTA, added to the sample chamber, and immobilized on the glass surface via biotin-streptavidin-biotin linkage. After approximately 5 minutes, it was rinsed with FMB 500 to remove unbound structures. The sample chamber was then rinsed twice with the final imaging buffer (FMB 1.5), which contained 150 mM TRIS-HCl, 1 mM EDTA, 1.5 M NaCl and included an oxygen scavenging system (OSS) containing 2 mM Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), 0.8% D-glucose, 2000 U / ml catalase, and 165 U / ml glucose oxidase. For torsion spring measurements, 30% sucrose was added and the final NaCl concentration was reduced to 1 M. Enzymes, Trolox, and glucose were purchased from SigmaAldrich. Finally, the sample chamber was completely filled with FMB 1.5 and a custom plug was attached to the top of the flow chamber, which held a 0.2 mm thick platinum wire to which the operating voltage was applied. The applied voltage was controlled by a custom LabView routine that provided a control voltage to a custom op amp to produce the final output voltage. Movies ranging from 40 to 64 seconds were acquired at a frame rate of 250 frames / second, with an applied uniaxial AC field of 0-60V and a frequency of 1-100Hz.

[0144] Total Internal Reflection Fluorescence Microscopy Movie Processing

[0145] The moving particles were manually positioned, Gaussian fitted, and picked using Picasso software. All subsequent steps were performed using custom MATLAB scripts. The accumulated angular displacement was obtained by tracking the position of the rotor arm tip. In addition, the angular velocity (Ω) was calculated according to the following formula:

[0146]

[0147] in is the angle of each frame (the first and last frame of a cycle with or without an external AC field), and Δt represents the time difference between these two frames. A histogram of angular velocity is calculated.

[0148] Total internal reflection fluorescence microscopy experiment of DNAPAINT

[0149] For DNA-PAINT super-resolution imaging, three transient DNA-PAINT binding sites were labeled at all three corners of the triangular platform. After acquiring rotor diffusion data, the FMB 1.5 imaging buffer containing OSS was exchanged with a DNA-PAINT imaging solution consisting of 1× TAE, 12mM MgCl2, 0.05% TWEEN20, and 20nM P1 imaging strand. Before acquiring DNA-PAINT data, the rotor fluorophores were bleached by increasing exposure to 642nm excitation. Videos were recorded for 7,000 frames with 400ms exposure and 70mW of 642nm excitation laser output. The “Localize” function of the Picasso software package was used to spot detect imager binding events and Gaussian fit the point spread function. Subsequently, the resulting event list was visualized using the “Render” function and the DNA-PAINT super-resolution data were correlated with the rotor diffusion measurement data.

[0150] Langevin dynamics simulation

[0151] For the simulation, the inventors considered the rotor arms as a time-dependent one-dimensional energy landscape Brownian particles in the . This allows us to write the first-order equation

[0152]

[0153] The damping constant λ and the noise term η satisfy <η(t)η(t')>=2k B Tλδ(t-t'). This can be simulated using the well-known Euler-Maruyama method.

[0154] The energy landscape consists of the time-independent rotor intrinsic contribution and the AC external electric field

[0155]

[0156] in

[0157]

[0158] represents the AC external electric field with an oscillation period of T. The parameters a, b, and c represent the relative strength of the electric field, the inherent rotor landscape, and the width of the local energy minimum, respectively. In addition, Describes the angle between the rotor and the field axis, with energy minima separated by Note that to ensure a connection back to rotational dynamics, must be a simple fraction of 2π. To enhance numerical stability, it helps to use a differential energy landscape, so the inventors make an approximation for some larger N.

[0159]

[0160] Statistical drift analysis

[0161] The data are described in the text and presented in Figure 4 Given a time interval Δt, calculate the time series All pairs in Among them The angular position of the rotor is measured, including the previous full rotation.

[0162] Based on these data, the inventors used probability distribution The Gaussian kernel of is estimated by kernel density, indicating that arrive Using this distribution, the inventors Take the average value to calculate

[0163]

[0164] The analysis of each rotor k produces the function The function follows an approximately linear trend that is independent of t. Figure 4 (e) and (f) show the estimated distributions of these functions for the simulated and experimental rotors, respectively. The average slope of the resulting trend is proportional to the rotational bias. To account for the significant variation in the rotational bias among the different experimental rotors, panels Figure 4 All trends in f are renormalized to unit slope. This renormalization step becomes ill-defined for the unbiased statistic, so the unbiased statistic is excluded.

[0165] Example 2: Motor Working Principle

[0166] Consider a rotating arm rotating around a stator, constrained to rotate along a single axis in the horizontal plane ( Figure 6 ). The rotating arm can then be described as moving in a one-dimensional energy landscape on a closed circle with angular directions as coordinates. The inventors' motor concept is based on an energy landscape containing one or more energy minima, such as Figure 6c. To drive the motor, an alternating electric field of frequency f is applied via two electrodes mounted at a distance from the motor. In the electrolyte, the field drives the ionic current to flow along the field lines. Without wishing to be bound by any theory, the inventors assume that the field lines point in a vertical direction and that the rotating arms are negatively charged. The alternating field adds an energy contribution in both half-cycles of the field period, as shown in the example Figure 6 f, bottom, where the AC field has a rectangular waveform. Thus, under a non-zero AC field, the motor moves in a dynamically modulated energy environment and tends to fill a global energy minimum during each field half-cycle. However, depending on the orientation of the energy minimum in the motor relative to the direction of the electric field, the symmetry can be broken and the motor can be driven to move in a preferred rotational direction. Figure 6 In the example shown in d, the motor will first be located at the global minimum at 45° ( Figure 6 d top left). Once the field is reversed, it will escape from the local minimum, but it will prefer to move clockwise towards the global minimum at 225°, because the counterclockwise direction is energetically disadvantaged by the energy barrier in a Boltzmann-weighted manner. For each field reversal, clockwise motion will be kinetically favored. Therefore, as AC cycles accumulate, the motor will run clockwise at a certain average speed. More generally, in the motor concept, the effective directionality of the motor depends on the location of the minimum in the motor energy landscape relative to the field axis, which can be determined by inspecting the effective energy landscape in the presence of a non-zero field plotted as a function of angular coordinates and time ( Figure 4 c) to understand, taking into account that the motor will find the minimum energy state over time driven by Brownian diffusion.

[0167] Without being bound by any theory, the inventors believe that simply switching the direction of the field by 90°, for example using a second set of electrodes, can reverse the asymmetry in the energy landscape and thus reverse the direction of rotation of the motor. Regarding the effect of field amplitude and AC frequency on rotor speed, the stronger the field, the greater the dynamic asymmetry, which will increase the directional bias and thus increase the average rotational speed. However, at very high field amplitudes, the symmetry-breaking characteristics of the energy landscape may become negligible and the directional bias may decrease. In the limit of very low AC frequencies, the average rotational speed will be lower because the maximum possible rpm is given by the AC frequency at the limit of the preferred directional bias.

[0168] Example 3: Experimental Demonstration

[0169] The inventors designed and fabricated several motor prototypes using a multilayer DNA origami approach, as described in Example 1. Objects are negatively charged by default, since DNA carries one negative elementary charge per base at the pH used in the experiments. The inventors encoded their candidate designs in DNA sequences and self-assembled the designs in a one-pot reaction mixture using previously described methods. The inventors used gel electrophoretic mobility shift analysis and negative stain transmission electron microscopy (TEM) imaging to assess the quality of the self-assembly. The inventors also analyzed selected prototypes using single-particle cryo-EM. To reveal the motion of the motors in real time, the inventors acquired movies using single-particle total internal reflection fluorescence microscopy. To this end, each stator was firmly attached to a microscope glass coverslip using multiple biotin-neutravidin bonds, and the inventors attached multiple fluorescent dyes to the tips of the rotating lever arms to allow their orientation to be determined using super-resolution center of mass tracking. The setup also included a set of platinum electrodes for applying the electric field.

[0170] One motor variant consists of a 40nm-high, 30nm-wide base, to which the inventors fixed an equilateral triangular platform with an edge length of 60nm and a thickness of 13nm. Figure 1 a, b). A portion of the base protrudes from the central cavity of the triangular platform. The inventors fixed a 550 nm long rotor arm to the base at a pivot point near the midpoint of the triangular platform ( Figure 1 c). The pivot point is a stretch of single-stranded DNA with the sequence CAT. The rotor arms consist of ten DNA double helices arranged in a honeycomb lattice pattern. The persistence length of this helical bundle is in the range of several micrometers. Therefore, the rotor arms can be regarded as rigid but elastic rods. The rotor arms protrude on either side to the pivot point outside the range of the triangular platform. With this design, the rotor arms are spatially constrained to a uniaxial rotation about the pivot point in the plane of the triangle. In order to create a ratchet-like energy landscape with multiple minima, the inventors installed physical obstacles ( Figure 1 b). The obstacles consist of 18 nm long rectangular plates protruding from the surface of the triangular platform at an inclination of approximately 50°. The plates are firmly fixed at this angle using a set of double-helical spacers. When sweeping across the triangular platform, the rotor arms must bend upwards to overcome the obstacles. The bending constitutes an energy barrier that can trap the rotor between the obstacles in a Boltzmann-weighted manner. The 3D shape of the rotor platform was verified using a 3D density map determined by the inventors using single-particle cryo-EM ( Figure 2 a, b).

[0171] In the absence of any driving field, single-particle TIRF movies collected by the inventors from this motor design reveal rotating particles where the rotor arms prefer to stay in six discrete positions ( Figure 2d). These positions correspond to orientations where the rotor arms are trapped on either side of a protruding obstacle, as determined by the inventors using two-color DNAPAINT imaging ( Figure 2 e, PAINT IMAGES). The DNA-PAINT images also provide a strong illustration of the relative sizes of the triangular platform and the rotor arms.

[0172] At first glance, the six preferred directions seem unexpected, since the inventors installed only three protruding obstacles on the platform. However, the inventors can use Figure 2 This behavior can be understood from the simple schematic diagram shown in b: the lever arm is trapped at both ends, with one end in front of the steep slope of an obstacle and the other end in front of the slight side of another obstacle. This orientation occurs exactly six times, explaining the six resting positions observed in the experiment.

[0173] Example 4: Driving motor, controlling speed and direction.

[0174] Under zero field, the motor particle exhibits unbiased random Brownian rotational motion, and the accumulated angular displacement vanishes ( Figure 3 AU=0V). However, when the inventors applied an AC field in the vertical direction, the inventors observed that many particles were obviously rotating with a strong unidirectional bias ( Figure 3 aU=20V). The effective rotation speed depends on the AC frequency ( Figure 3 e - Example trace frequency sweep, Figure 3 gleft - absolute angular velocity vs. frequency). The directional bias disappears at high AC frequencies (about 100 Hz). The velocity can also be controlled by the AC field amplitude ( Figure 3 f, Example trace voltage sweep, Figure 3 g right - absolute angular velocity vs. voltage). The maximum effective rotation speed recorded by the inventors was 246 rpm.

[0175] Without wishing to be bound by any theory, the inventors believe that the directionality and strength of the bias depends on the position of the energy minimum relative to the field axis. The inventors deposited the motor particles on a microscope cover glass in random orientations, so the inventors expected that there would be roughly equal numbers of particles running clockwise and counterclockwise - which is exactly what the inventors observed ( Figure 3 b right). Without wishing to be bound by any theory, the inventors hypothesized that the direction of rotation of the motor can be reversed simply by switching the field axis by 90°. To test this hypothesis, the inventors used a second set of electrodes to rotate the AC field axis by 180° in 5° steps. The inventors indeed observed a sinusoidal dependence of the motor speed on the field direction, including a direction reversal ( Figure 3 c). The inventors compared the angular velocity to the field direction data and calculated the mean and standard deviation of the angular velocity for a collection of 75 motor particles, thus providing an impression of the motor-to-motor velocity variability ( Figure 3d). An overall sinusoidal trend becomes apparent, with maximum angular velocities in both the clockwise and counter-clockwise directions being observed when the AC field axis is rotated 90° - as the inventors explained above with the illustrative embodiment of a motor with two energy minima.

[0176] To test the generality of the drive mechanism, the inventors also analyzed the dynamics of several other motor variants, including a highly simplified motor prototype consisting only of the above-mentioned rotor arm, which was attached directly to the coverslip glass surface via single-stranded DNA. This configuration provides little control over the details of the energy landscape over which the motor moves. Instead, the energy landscape of rotation will be created by the local details of the glass surface environment to which the rotor arm is anchored. Despite this, this motor and all other variants tested by the inventors also showed directional rotation after applying an AC field. Interestingly, the variant in which the inventors anchored the rotor arm directly to a base without a triangular platform showed the lowest tendency to rotate unidirectionally, which may reflect that in this design the rotor moves on a substantially flat energy landscape.

[0177] Example 5: Discussion

[0178] The motors of the present invention offer familiar control options from macroscopic rotational motors: users can turn them on and off at will, they react quickly, and the speed and direction of rotation can be adjusted. On the other hand, the motors can also be considered autonomous to a certain extent, because they move directionally according to their inherent mechanical properties, which means that the user does not need to monitor the state of the motor to actually control the movement. This autonomy is also reflected in the fact that the motors are not synchronized. Our system can be contrasted with previously demonstrated non-autonomous nanoelectromechanical rotors and DNA robotic arms, which are manipulated directly by the action of periodically rotating electric fields. These systems move in response to direct actions of the user, but do not yet possess the inherent properties necessary for directional movement driven by a wave-induced ratchet.

[0179] The working principle of the motor proposed by the inventors can be understood within the theoretical framework of the rocking ratchet concept, in which alternating additional forces with vanishing time averages act on particle diffusion in a periodic, asymmetric energy landscape. In the inventors' rocking ratchet, when the negatively charged rotor points toward the anode, the field-induced torque vanishes, the torque is maximum in the direction perpendicular to the anode, and a metastable state exists in the direction of the cathode.

[0180] The motor working concept is general and can be applied to many other systems. In addition to DNA origami, protein-based rotating assemblies with charged residues can also be designed and driven to rotate with a directionally biased rotation by AC fields. At a smaller scale, charged small molecules produced by chemical synthesis can also be anchored to the surface and driven directionally by AC fields. In addition, in addition to electric fields, other perturbations that alternate in directionality can be used. For example, an alternating magnetic field can drive a Brownian rotor with a magnetic moment, while an alternating fluid or gas flow can drive a directional rotation by a periodically alternating drag force.

[0181] From a practical point of view, the motor concept is very easy to implement. The motors rotate reliably and at speeds several orders of magnitude higher than previously made synthetic DNA motors. They can be produced by anyone with standard wet lab equipment. Large-scale production is also possible. Due to the modularity of the DNA origami components, the inventors expect that the motors can also be easily modified, adapted, and integrated into other environments for use as pumps or nano-turbines to drive fluid flows. In addition, it has recently been described how DNA-based nanostructures can be placed and oriented on solid surfaces in a programmable manner. These methods can be used to build motor arrays with controlled stator orientation relative to the field axis. Based on the microscopic reversibility, it is also possible to envision using directed motion to drive uphill chemical synthesis, using more complex synthetic mechanisms with coordinated reciprocating motion - just as the F1F0 ATP synthase synthesizes ATP through rotational motion driven by ion flow.

[0182] Example 6: Further experiments

[0183] The inventors used a multilayer DNA origami approach to design and fabricate a prototype of a ratchet motor. The motor consists of a 40nm high and 30nm wide base, to which is fixed an equilateral triangular platform with an edge length of 60nm and a thickness of 13nm ( Figure 1 ). A portion of the base that protrudes through the central cavity of the triangular platform includes the docking site for the rotor arm. The rotor docking portion is fixed to the base by a pivot point consisting of three unpaired nucleotides near the midpoint of the triangular platform. The rotor arm consists of two rigid rod modules (each module is a separate DNA origami) connected end to end ( Figure 1 d, e), with a total length of 550 nm. This length was chosen to enable real-time tracking of angular orientation changes of individual motors and to slow down angular motion in diffraction-limited fluorescence microscopy, inspired by classic experiments by Kinosita et al. that revealed the rotation of individual F-actin-tagged F1 ATPase motors. The rod-shaped module consists of ten DNA double helices arranged in a honeycomb lattice pattern ( Figure 1d, e). Such helical bundles have previously been shown to have persistent lengths in the multi-micrometer range. The rotor arms can therefore be viewed as rigid but elastic rods. The rotor arms protrude from both sides to a pivot point outside the confines of the triangular platform. With this design, the rotor arms are spatially constrained to a uniaxial rotation about a pivot point within the plane of the triangle.

[0184] To create a rippled energy landscape, physical barriers were installed on the three edges of the triangular platform ( Figure 1 b). The obstacles consist of 18 nm long rectangular plates protruding from the surface of the triangular platform at an inclination of approximately 50°. The plates are firmly fixed at this angle using a set of double-helical spacers. When sweeping across the triangular platform, the rotor arms must bend upward to overcome the obstacles. The bend constitutes an energy barrier that can trap the rotor between the obstacles in a Boltzmann-weighted manner. The motor design also includes functional modifications such as biotin moieties and fluorescent dyes ( Figure 1 F) to enable experimental observation of the motion of individual motor particles. The biotin moiety allows the stators to be firmly attached to a microscope glass coverslip via multiple biotin-neutravidin bonds per stator, while multiple fluorescent dyes at the tip of the rotating arm allow their orientation to be determined using center of mass tracking relative to the position of an individually labeled triangular platform ( Figure 1 F).

[0185] By operating the motor as a Brownian ratchet and driving a directed rotational motion, the system may be out of thermal equilibrium. This symmetry can be broken during time reversal to achieve a ratcheting effect. The inventors found that this can be achieved in a very simple way: simply apply an irrotational AC field using two electrodes immersed in a liquid chamber ( Figure 1 F, Figure 5 ). The field causes an alternating ionic current (AC) to flow through the sample chamber in a fixed direction, dynamically modulating the energy landscape of each motor's movement. Note that this external modulation produces a time-averaged net force of zero, and its curl is zero. Thus, there is no information provided by the external modulation that could indicate motor rotation. Instead, in the presence of modulation as described below, directed, autonomous rotational motion arises from the intrinsic details of the motor mechanism.

[0186] The inventors encoded their design in a DNA sequence (SEQ ID NO. 1-1125) and self-assembled the motor in a one-pot reaction mixture using a previously described procedure. The inventors assessed the quality of the self-assembly using gel electrophoretic mobility shift analysis ( Figure 7 ), and the inventors used single-particle cryo-electron microscopy (cryo-EM) to determine the 3D electron density map to verify the three-dimensional shape of the motor complex including the base, triangular platform and rotor docking part ( Figure 2a, b). Within the resolution range, the electron density map shows all the required major structural features, including the barriers and the rotor docking part. The inventors also verified the correct assembly of the complete motor complex with full-length rotor arms by using negative stain transmission electron microscopy (TEM) imaging ( Figure 2 c).

[0187] Next, the inventors used single-particle total internal reflection fluorescence (TIRF) microscopy of surface-immobilized motor particles to study the diffusive motion of the motor. Single-particle TIRF movies collected in the absence of any driving field showed randomly rotating particles, with the rotor arms preferring to stay in six discrete positions ( Figure 2 d. Figure 8 These positions correspond to the orientations of the rotor arms trapped on either side of the protruding obstacle, as determined by the inventors using DNAPAINT imaging ( Figure 2 e. Fig.10 ). The DNA-PAINT images also provide a strong illustration of the relative sizes of the triangular platform and the longer rotor arms. Thus, the motor complex implements a diffusive rotation mechanism with multiple energy minima and transition barriers separating the minima.

[0188] Importantly, in the absence of external energy supply, i.e. when the field is turned off, the motor particle exhibits an unbiased random rotational motion and the accumulated angular displacement vanishes, as expected from equilibrium fluctuations in the energy landscape ( Figure 3 a). In contrast, when we turned on the AC field (e.g., fixed in the vertical direction), we observed that many motor particles immediately switched from random, undirected rotation to continuous rotation with a strong directional bias ( Figure 3 a). The maximum angular velocity recorded by the inventors is about 250 full revolutions per minute ( Figure 3 b). When the field is on, the inventors observed that approximately equal numbers of motors run continuously in clockwise and counterclockwise directions, respectively ( Figure 3 b).

[0189] The inventors then describe the dynamic characteristics of a single motor as a function of the AC field frequency, amplitude, and field axis. The effective angular velocity of the motor depends strongly on the AC frequency, and is optimal at a drive frequency of around 5 Hz ( Figure 3 e. Figure 3 g left). The directional bias of the rotation is absent in the DC field and is reduced at high AC frequencies (about 100 Hz). Similarly, the angular velocity of the motor can be controlled by the AC field amplitude, showing the best effective angular velocity within the amplitude band between 20 V and 60 V ( Figure 3 f. Figure 3g right). Moreover, the direction of rotation and the effective angular velocity can be controlled by the static orientation of the AC field relative to the particle: the inventors studied the same set of motor particles with the field turned off and with a uniaxial AC field pointing horizontally and then vertically (with respect to coordinates defined by the TIRF microscope field of view). For a subset of particles, the direction of rotation of individual motors follows a sinusoidal dependence of the motor speed on the field orientation, including a reversal of direction when rotating the AC field axis ( Figure 3 c, d). For all motor particles, it is clear that the orientation of the motor relative to the field axis is the key factor in determining the actual direction and speed of the rotation performed.

[0190] Based on the recorded data, the inventors can estimate the torque and work generated by the motor on the environment. Figure 3 In the experiment, this work is dissipated in the form of friction between the long rotor arm and the solvent. The rotational friction coefficient of the rotor arm (ζ r =πηL 3 ) is about 4*10 -22 N*m*s. Based on the observed maximum angular velocity of ~25 rad / s (~1500° / s), the inventors derived a maximum torque of about 10 pN*nm, which can be compared to the 50 pN*nm that the F1F0 ATPase can produce. The maximum power dissipated in friction by the motor is estimated to be about 250 pN*nm / s (62k B T / s), which is equivalent to the free energy transferred by the hydrolysis of about 2.5 ATP molecules per second under cellular conditions.

[0191] The trajectory and angular velocity of the motor are symmetrically distributed ( Figure 3 a, b). By viewing Figure 4 c, which are exemplarily calculated for different stator-field orientations of a simplified dual-minimal rotary motor. Langevin dynamics simulations in these energy landscapes lead to rotational trajectories with clockwise, counterclockwise, and no directional bias, respectively, depending on the relative orientation of the motor energy landscape to the field axis. The asymmetry required for net directional selection (bias) is provided by the interaction between the background static potential landscape provided by the motor body and the external modulating field and its initial phase. In other words, depending on the orientation of the stator relative to the field axis, time reversal symmetry can be broken and the motor will ratchet in a preferred rotational direction. Moreover, the predicted effective motor speed depends on the degree of dynamical asymmetry between clockwise and counterclockwise motion induced by the AC field, which in turn depends on how the stator is oriented relative to the field axis. Since we randomly deposited the motor particles on a microscope coverslip, we obtained a nearly uniform sampling of stator orientations relative to the field axis, and thus obtained a sampling of motors that move continuously clockwise or counterclockwise at various speeds ( Figure 3 b).

[0192] The inventors have now demonstrated the irreversibility of the mechanism at the level of a single motor by analyzing the fluctuation characteristics of the single motor in the context of stochastic thermodynamics. If the inventors compile the distribution of the displacement angle as a function of time (in multiples of the AC field period T), the inventors will observe that the rotor will naturally move randomly in the direction of the bias, and also move against the bias direction ( Figure 4 d; see also Figure 3 a). Stochastic thermodynamics allows us to probe the extent of entropy generation in nonequilibrium systems with finite trajectories from the ratio between upstream and downstream transition rates. Denoting P(θ0+Δθ,t|θ0,0) as the probability of rotating through an angle Δθ from an initial position θ0 within a period t, the inventors contemplate a fluctuation relationship that probes irreversibility by extracting the average entropy generation Δs in the nanomotor over a period t=nT (an integer multiple of the AC field period), expressed in the following form.

[0193]

[0194] where ω eff and D eff represents the effective angular velocity and diffusion coefficient of the nanomotor during random ratcheting dynamics. Note that this relationship is independent of time t = nT. This relationship holds true in the simulations performed by the inventors ( Figure 4 e), and importantly, also holds true in experimental data for precessing rotary motors ( Figure 4 f), which can be seen by collapsing all plots into a line of unity slope by rescaling the slopes in the non-equilibrium case. Non-equilibrium actuation can also be probed in the mean square displacement (MSD), showing a crossover from diffusive to ballistic behavior.

[0195] The inventors also directly demonstrated that the motor can be driven directionally and produce torque to resist additional external loads. To this end, the inventors designed additional motor variants that include a torsion spring at the pivot point ( Figure 4 g, Fig.12 ). The torsion spring consists of a single-stranded DNA loop, fixed at one end to the base and at the other end to the rotor arm. Rotor rotation will therefore cause the loop to wrap around the rotor pivot connection as an entropy spring. The torsion spring will act as a harmonic potential and provide a restoring force, eventually stalling the motor once the torque generated by the tightened spring balances the maximum torque delivered by the motor. The thus tightened spring acts as an energy reservoir that can drive the rotor in the opposite direction when the external energy supply is turned off, until the spring relaxes again. This predicted behavior is exactly what the inventors observed: a single particle with a torsion spring exhibits continuous rotation until stalling when the AC field is turned on, and then begins to rotate continuously in the opposite direction immediately after the AC field is turned off ( Figure 4 g).

[0196] In summary, the system provides a solution to a long-standing challenge in the field of nanotechnology: the inventors have built an autonomous macromolecular rotary motor that, unexpectedly, can do work on the environment against an external load, and that achieves rotational speeds and torques approaching those of powerful natural molecular machines such as ATP synthase. Advantageously, due to the inherent mechanical properties, the motor can move directionally and autonomously, powered by simple external energy modulation, without requiring any feedback or information from the user to guide the motor. Despite its autonomy, the motors advantageously still offer the control options familiar to macroscopic motors: users can turn them on and off at will, they react quickly, and the speed and direction of rotation can be adjusted.

[0197] From a practical point of view, the motors described herein are very easy to implement. Simply insert two wires into a liquid solution and apply an AC voltage. Advantageously, the motors can be produced and operated by anyone with standard wet lab equipment. In addition, a major advantage of the nanomotor of the present invention is that the required DNA molecules can be mass-produced. Due to the modularity of the DNA origami components, the motors can also be easily modified, adjusted, and integrated into other environments. It has recently been described how to place and orient DNA origami objects on patterned solid surfaces in a programmable manner. These methods can be used to construct motor arrays with controlled stator orientation relative to the field axis to achieve synchronization of rotation direction.

[0198] The motor design and operation concepts are also applicable to other systems beyond DNA origami. For example, protein-based rotary assemblies with charged residues can be designed de novo and driven to rotate with a directional bias by an AC field. Furthermore, in addition to electric fields, other energy supplies that alternate in direction, such as AC fluid flow, can be used. Directed motor motion can be exploited to drive uphill chemical synthesis, using more complex synthetic mechanisms with coordinated reciprocating motion - just as the F1F0 ATP synthase drives mechanical ATP synthesis through rotational motion.

[0199] Example 7: Sequence

[0200] SEQ ID NO.1: Bracket sequence for base (first domain of stator)

[0201] SEQ ID NO.2-224: Base sequence (first domain of stator)

[0202] SEQ ID NO. 2-224 are nucleic acid sequences encoding the following: core_01, core_02, core_03, core_04, core_05, core_06, core_07, core_08, core_09, core_10, core_11, core_12, core_13, core_14, core_15, core_16, core_17, core_18, core_19, core_20, core_21, core_22, core_23, core_24, core_25, core_26, core_27, core_28, core_29, core_30, core_31, core_32, core_33, core_34, core_35, core_36, core_37, core_38 ,core_39,core_40,core_41,core_42,core_43,core_44,core_45,core_46,core_47,core_48,core_49,core_50,core_51,core_52,core_53,core_54,core_55,core_56,core_57,core_58,core_59,core_60,core_61,core_62,core_63,core_64,core_65,core_66,core_67,core_68,core_69,core_70,core_71,core_72,core_73,core_74,core_75,core_76,core_77,core_78,core_79,core heart_80,core_81,core_82,core_83,core_84,core_85,core_86,core_87,core_88,core_89,core_90,core_91,core_92,core_93,core_94,core_95,core_96,core_97,core_98,core_99,core_100,core_101,core_102,core_103,core_104,core_105,core_106,core_107,core_108,core_109,core_110,core_111,top_01,top_02,top_03,top_04,top_05,top_06,top_07,top_ 08,top_09,top_10,top_11,top_12,top_13,top_14,top_15,top_16,top_17,top_18,top_19,top_20,top_21,top_22,top_23,top_24,top_25,top_26,top_27,top_28,top_29,top_30,top_31,top_32,top_33,top_34,top_35,top_36,top_37,top_38,top_39,top_40,top_41,top_42,top_43,bottom_01,bottom_02,bottom_03,bottom_04,bottom_05,bottom_06,bottom_07,bottom_08,bottom_09,bottom_10,bottom_11,bottom_12,bottom_13,bottom_14,bottom_15,bottom_16,bottom_17,bottom_18,bottom_19,bottom_20,bottom_21,bottom_22,bottom_23,bottom_24,bottom_25,bottom_26,bottom_27,bottom_28,bottom_29,bottom_30,bottom_31,bottom_32,bottom_33,bottom_34,bottom_35,bottom_36,bottom_37,bottom_38,bottom_39,bottom_40,bottom_41,bottom_42,connect to triangle_01,connect to triangle_02,connect to triangle triangle_03, connected to triangle_04, connected to triangle_05, connected to triangle_06, connected to triangle_07, connected to triangle_08, connected to triangle_09, connected to triangle_10, connected to triangle_11, connected to triangle_12, for biotin anchor_01, for biotin anchor_02, for biotin anchor_03, for biotin anchor_04, for biotin anchor_05, for biotin anchor_06, for biotin anchor_07, for biotin anchor_08, for biotin anchor_09, rotor arm docking_01, rotor arm docking_02, rotor arm docking_03, rotor arm docking_04, rotor arm docking_05, and rotor arm docking_06. ,

[0203] SEQ ID NO.225-465: Sequence for triangle (optional stator second domain)

[0204] SEQ ID NOs. 225-465 are nucleic acid sequences encoding the following, respectively: side 1_01, side 1_02, side 1_03, side 1_04, side 1_05, side 1_06, side 1_07, side 1_08, side 1_09, side 1_10, side 1_11, side 1_12, side 1_13, side 1_14, side 1_15, side 1_16, side 1_17, side 1_18, side 1_19, side 1_20, side 1_21, side 1_22, side 1_23, side 1_24, side 1_25, side 1_26, side 1_27, side 1_28, side 1_29, side 1_30, side 1_31, side 1_32, side 1_33, side 1_34, side 1_35, side 1_36, side 1_37, side 1_38 _38, side 1_39, side 1_40, side 1_41, side 1_42, side 1_43, side 1_44, side 1_45, side 1_46, side 2_01, side 2_02, side 2_03, side 2_04, side 2_05, side 2_06, side 2_07, side 2_08, side 2_09, side 2_10, side 2_11, side 2_12, side 2_13, side 2_14, side 2_15, side 2_16, side 2_17, side 2_18, side 2_19, side 2_20, side 2_21, side 2_22, side 2_23, side 2_24, side 2_25, side 2_26, side 2_27, side 2_28, side 2_29, side 2_30, side 2_31, side 2_32, side 2_3 3, side 2_34, side 2_35, side 2_36, side 2_37, side 2_38, side 2_39, side 2_40, side 2_41, side 2_42, side 2_43, side 2_44, side 2_45, side 2_46, side 2_47, side 3_01, side 3_02, side 3_03, side 3_04, side 3_05, side 3_06, side 3_07, side 3_08, side 3_09, side 3_10, side 3_11, side 3_12, side 3_13, side 3_14, side 3_15, side 3_16, side 3_17, side 3_18, side 3_19, side 3_20, side 3_21, side 3_22, side 3_23, side 3_24, side 3_25, side 3_26, side 3_27 , side 3_28, side 3_29, side 3_30, side 3_31, side 3_32, side 3_33, side 3_34, side 3_35, side 3_36, side 3_37, side 3_38, side 3_39, side 3_40, side 3_41, side 3_42, side 3_43, side 3_44, side 3_45, side 3_46, side 3_47, side 3_ 48,corner_3.1_01,corner_3.1_02,corner_3.1_03,corner_3.1_04,corner_3.1_05,corner_3.1_06,corner_3.1_07,corner_3.1_08,corner_3.1_09,corner_3.1_10,corner_3.1_11,corner_3.1_12,corner_3.1_13,corner_3.1_14,corner_3.1_PAINT_pos_01,corner_3.1_PAINT_pos_02,corner_3.1_PAINT_pos_03,corner_1.2_01,corner_1.2_02,corner_1.2_03,corner_1.2_04,corner_1.2_05,corner_1.2_06,corner_1.2_07,corner_1.2_08,corner_1.2_09,corner_1.2_10,corner_1.2_11,corner_1.2_12,corner_1.2_PAINT_pos_01,corner_1.2_PAINT_pos_02,corner_1.2_PAINT_pos_03,corner_2.3_01,corner _2.3_02,angle_2.3_03,angle_2.3_04,angle_2.3_05,angle_2.3_06,angle_2.3_07,angle_2.3_08,angle_2.3_09,angle_2.3_10,angle_2.3_11,angle_2.3_12,angle_2.3_13,angle_2.3_14,angle_2.3_18,angle_2.3_PAINT_pos_01,angle_2.3_PAINT_pos_02,angle_2.3_PAINT_pos_03,obstacle1_01,obstacle1_02,obstacle1_03,obstacle1_04,obstacle1_05,obstacle1_06,obstacle1_07 ,obstacle1_08,obstacle1_09,spacer1_01,spacer1_02,obstacle2_01,obstacle2_02,obstacle2_03,obstacle2_04,obstacle2_05,obstacle2_06,obstacle2_07,obstacle2_08,obstacle2_09,obstacle2_10,spacer2_01,spacer2_02,obstacle3_01,obstacle3_02,obstacle3_03,obstacle3_04,obstacle3_05,obstacle3_06,obstacle3_07,obstacle3_08,obstacle3_09,spacer3_01,spacer3_02,spacercomplement_01,spacercomplement_02,corner_ 3.1_for PAINT_01, 3.1_for PAINT_02, 3.1_for PAINT_03, 3.1_for PAINT_04, 1.2_for PAINT_01, 1.2_for PAINT_02, 1.2_for PAINT_03, 1.2_for PAINT_04, 1.2_for PAINT_05, 2.3_for PAINT_01, 2.3_for PAINT_02, 2.3_for PAINT_03, 2.3_for PAINT_04, and PAINT_Atto655_Imager.

[0205] SEQ ID NO.466-679: Rotor Arm I Series

[0206] SEQ ID NOs. 466-679 are nucleic acid sequences encoding: core_01, core_02, core_03, core_04, core_05, core_06, core_07, core_08, core_09, core_10, core_11, core_12, core_13, core_14, core_15, core_16, core_17, core_18, core_19, core_20, core_21, core_22, core_23, core_24, core_25, core_26, core_27, core_28, core_29, core_30, core_31, core_32, core_33, core_34, core_35, core_36, core_37, core_38 _38,core_39,core_40,core_41,core_42,core_43,core_44,core_45,core_46,core_47,core_48,core_49,core_50,core_51,core_52,core_53,core_54,core_55,core_56,core_57,core_58,core_59,core_60,core_61,core_62,core_63,core_64,core_65,core_66,core_67,core_68,core_69,core_70,core_71,core_72,core_73,core_74,core_75,core_76,core_77,core_78,core_ 79, core_80, core_81, core_82, core_83, core_84, core_85, core_86, core_87, core_88, core_89, core_90, core_91, core_92, core_93, core_94, core_95, core_96, core_97, core_98, core_99, core_100, core_101, core_102, core_103, core_104, core_105, core_106, core_107, core_108, core_109, core_110, core_111, core_112, core_113, core_114, core_115, core_116, core_117 7, core_118, core_119, core_120, core_121, core_122, core_123, core_124, core_125, core_126, core_127, core_128, core_129, core_130, core_131, core_132, core_133, core_134, core_135, core_136, core_137, core_138, core_139, core_140, core_141, core_142, core_143, core_144, core_145, core_146, core_147, core_148, core_149, core_150, core_151, core_152,core_153,core_154,core_155,core_156,core_157,core_158,core_159,core_160,core_161,core_162,core_163,core_164,core_165,core_166,core_167,core_168,core_169,core_170,core_171,core_172,core_173,core_174,core_175,core_176,core_177,core_178,core_179,core_180,core_181,core_182,core_183,core_184,core_185,core_186,core_187,core_188,core _189, end_01, end_02, end_03, end_04, end_05, end_06, end_07, connected to base_01, connected to base_02, connected to base_03, connected to base_04, connected to base_05, connected to base_06, connected to base_07, connected to base_08, connected to base_09, connected to base_01 with spring, connected to base_02 with spring, connected to base_03 with spring, connected to base_04 with spring, connected to base_05 with spring, connected to base_06 with spring, connected to base_07 with spring, connected to base_08, and connected to base_09 with spring. ,

[0207] SEQ ID NO.680-892: Rotor Arm II Series

[0208] SEQ ID NOs. 680-892 are nucleic acid sequences encoding the following: core_01, core_02, core_03, core_04, core_05, core_06, core_07, core_08, core_09, core_10, core_11, core_12, core_13, core_14, core_15, core_16, core_17, core_18, core_19, core_20, core_21, core_22, core_23, core_24, core_25, core_26, core_27, core_28, core_29, core_30, core_31, core_32, core_33, core_34, core_35, core_36, core_37, core_38 _38,core_39,core_40,core_41,core_42,core_43,core_44,core_45,core_46,core_47,core_48,core_49,core_50,core_51,core_52,core_53,core_54,core_55,core_56,core_57,core_58,core_59,core_60,core_61,core_62,core_63,core_64,core_65,core_66,core_67,core_68,core_69,core_70,core_71,core_72,core_73,core_74,core_75,core_76,core_77,core_78,core_ 79, core_80, core_81, core_82, core_83, core_84, core_85, core_86, core_87, core_88, core_89, core_90, core_91, core_92, core_93, core_94, core_95, core_96, core_97, core_98, core_99, core_100, core_101, core_102, core_103, core_104, core_105, core_106, core_107, core_108, core_109, core_110, core_111, core_112, core_113, core_114, core_115, core_116, core_117 7, core_118, core_119, core_120, core_121, core_122, core_123, core_124, core_125, core_126, core_127, core_128, core_129, core_130, core_131, core_132, core_133, core_134, core_135, core_136, core_137, core_138, core_139, core_140, core_141, core_142, core_143, core_144, core_145, core_146, core_147, core_148, core_149, core_150, core_151, core_152,core_153,core_154,core_155,core_156,core_157,core_158,core_159,core_160,core_161,core_162,core_163,core_164,core_165,core_166,core_167,core_168,core_169,core_170,core_171,core_172,core_173,core_174,core_175,core_176,core_177,core_178,core_179,core_180,core_181,core_182,core_183,core_184,core_185,core_ 186, core_187, core_188, core_189, core_190, core_191, core_192, core_193, core_194, core_195, core_196, core_197, tip dye_01, tip dye_02, tip dye_03, tip dye_04, tip dye_05, tip dye_06, tip dye_07, tip dye_08, tip dye_09, tip dye_10, connection between rotor arms_01, connection between rotor arms_02, connection between rotor arms_03, connection between rotor arms_04, connection between rotor arms_05, and connection between rotor arms_06. ,

[0209] SEQ ID NO.893-1125: Base with torsion spring

[0210] SEQ ID NOs. 893-1125 are nucleic acid sequences encoding the following, respectively: core_01, core_02, core_03, core_04, core_05, core_06, core_07, core_08, core_09, core_10, core_11, core_12, core_13, core_14, core_15, core_16, core_17, core_18, core_19, core_20, core_21, core_22, core_23, core_24, core_25, core_26, core_27, core_28, core_29, core_30, core_31, core_32, core_33, core_34, core_35, core_36, core_37, core_38 heart_38,core_39,core_40,core_41,core_42,core_43,core_44,core_45,core_46,core_47,core_48,core_49,core_50,core_51,core_52,core_53,core_54,core_55,core_56,core_57,core_58,core_59,core_60,core_61,core_62,core_63,core_64,core_65,core_66,core_67,core_68,core_69,core_70,core_71,core_72,core_73,core_74,core_75,core_76,core_77,core_78,core _79,core_80,core_81,core_82,core_83,core_84,core_85,core_86,core_87,core_88,core_89,core_90,core_91,core_92,core_93,core_94,core_95,core_96,core_97,core_98,core_99,core_100,core_101,core_102,core_103,core_104,core_105,core_106,core_107,core_108,core_109,core_110,core_111,core_112,core_113,core_114,core_115,core_116,top_0 1,top_02,top_03,top_04,top_05,top_06,top_07,top_08,top_09,top_10,top_11,top_12,top_13,top_14,top_15,top_16,top_17,top_18,top_19,top_20,top_21,top_22,top_23,top_24,top_25,top_26,top_27,top_28,top_29,top_30,top_31,top_32,top_33,top_34,top_35,top_36,top_37,top_38,top_39,top_40,top_41,top_42,top_43,top_44,bottom_01,bottom_02,bottom_03,bottom_04,bottom_05,bottom_06,bottom_07,bottom_08,bottom_09,bottom_10,bottom_11,bottom_12,bottom_13,bottom_14,bottom_15,bottom_16,bottom_17,bottom_18,bottom_19,bottom_20,bottom_21,bottom_22,bottom_23,bottom_24,bottom_25,bottom_26,bottom_27,bottom_28,bottom_29,bottom_30,bottom_31,bottom_32,bottom_33,bottom_34,bottom_35,bottom_36,bottom_37,bottom_38,bottom_39,bottom_40,bottom_41,bottom_42,bottom_43,bottom_44, bottom_45, bottom_46, connected to triangle_01, connected to triangle_02, connected to triangle_03, connected to triangle_04, connected to triangle_05, connected to triangle_06, connected to triangle_07, connected to triangle_08, connected to triangle_09, connected to triangle_10, connected to triangle_11, connected to triangle_12, for biotin anchor_01, for biotin anchor_02, for biotin anchor_03, for biotin anchor_04, for biotin anchor_05, for biotin anchor_06, for biotin anchor_07, for biotin anchor_08, for biotin anchor_09, rotor arm docking_01, rotor arm docking_02, rotor arm docking_03, rotor arm docking_04, rotor arm docking_05, and rotor arm docking_06. ,

[0211] References

[0212] [1] P. Ketterer, EM Willner, H. Dietz, Nanoscale rotary apparatus formed from tight-fitting 3D DNA components. SciAdv 2, e1501209 (2016).

[0213] [2]FAEngelhardt et al., Custom-size, functional, and durable DNAorigami with design-specific scaffolds. ACS nano 13, 5015-5027 (2019)

[0214] [3]KFWagenbauer et al.,How we make DNA origami.ChemBioChem 18,1873-1885405(2017).

[0215] The features of the invention disclosed in the description, the claims and / or the drawings may, alone or in any combination thereof, be material for realizing the invention in various forms.

Claims

1. A nucleic acid nanomotor comprising a nucleic acid rotor and a nucleic acid stator, wherein the stator comprises a first surface and a rotor docking point, wherein the rotor comprises a stator docking site configured to connect with the rotor docking site of the stator, wherein the rotor has at least one longitudinal extension, preferably at least two longitudinal extensions, extending from the stator docking site along a longitudinal axis, wherein the longitudinal axis has a direction substantially parallel to the first surface of the stator, wherein the rotor is rotatable about an axis of rotation substantially perpendicular to the longitudinal axis, The rotor is electrically charged.

2. The nucleic acid nanomotor of claim 1, wherein the longitudinal extension of the rotor, if any, each of the two longitudinal extensions of the rotor, has a length of at least 1 nm, preferably at least 10 nm, and more preferably at least 30 nm.

3. The nucleic acid nanomotor according to claim 1 or 2, wherein the longitudinal extension of the rotor, if present, the two longitudinal extensions of the rotor, have a total length in the range of 20 nm to 1000 nm, preferably in the range of 30 nm to 700 nm, even more preferably in the range of 50 nm to 600 nm.

4. The nucleic acid nanomotor according to any one of the preceding claims, wherein the rotor has a rod-like shape and / or a T-like shape.

5. A nucleic acid nanomotor according to any of the preceding claims, wherein the stator comprises at least one protrusion extending towards the rotor, preferably extending towards the rotor so that the rotor interacts with the protrusion at least once when the rotor rotates 360° relative to the rotation axis.

6. A nucleic acid nanomotor according to any of the preceding claims, wherein the nanomotor is configured such that the rotor is rotatable within an energy landscape defined by a graph of free energy versus rotor angle θ, wherein the rotor angle θ is the rotor angle of the longitudinal axis of the rotor relative to an axis perpendicular to the rotation axis, wherein the energy landscape has at least one energy minimum.

7. A nucleic acid nanomotor according to any of the preceding claims, wherein the rotor docking site and the stator docking site are directly connected, connected via a nucleic acid hinge and / or connected via a nucleic acid torsion spring.

8. A system comprising: - a nanomotor comprising a rotor and a stator, wherein the stator comprises a first surface and a rotor docking site, wherein the rotor comprises a stator docking site, the stator docking site being configured to connect with the rotor docking site of the stator, wherein the rotor has a longitudinal extension extending from the stator docking site along a longitudinal axis, wherein the longitudinal axis has a direction substantially parallel to the first surface of the stator, wherein the rotor is rotatable about an axis of rotation substantially perpendicular to the longitudinal axis, wherein the rotor is electrically charged; Wherein, optionally, the nanomotor is a nanomotor according to any one of claims 1-7; and - a control unit configured to generate an alternating current for rotating the nanomotor, wherein the control unit preferably comprises at least two electrodes; The stator of the nanomotor has a fixed direction relative to the control unit.

9. The system of claim 8, wherein the stator comprises at least one protrusion extending towards the rotor, preferably extending towards the rotor such that the rotor interacts with the protrusion at least once during a 360° rotation relative to the rotation axis.

10. A method of rotating, preferably directionally rotating, a rotor of a nanomotor relative to a stator of the nanomotor, comprising: i) providing a nanomotor comprising a rotor and a stator, wherein the stator comprises a first surface and a rotor docking site, wherein the rotor comprises a stator docking site configured to couple with the rotor docking site of the stator, wherein the rotor has a longitudinal extension extending from the stator docking site along a longitudinal axis, wherein the longitudinal axis has a direction substantially parallel to the first surface of the stator, wherein the rotor is rotatable about an axis of rotation substantially perpendicular to the longitudinal axis, wherein the rotor is electrically charged; Wherein, optionally, the nanomotor is a nanomotor according to any one of claims 1-7; and ii) applying an alternating current to the nanomotor.

11. Method according to claim 10, wherein the stator comprises at least one protrusion extending towards the rotor, preferably towards the rotor such that the rotor interacts with the protrusion at least once during a 360° rotation relative to the rotation axis.

12. The method according to claim 10 or 11, wherein the frequency of the alternating current is in the range of 0.1 Hz to 1000 Hz, preferably in the range of 0.5 Hz to 100 Hz, even more preferably in the range of 1 Hz to 10 Hz, for example about 5 Hz.

13. The method according to any one of claims 10 to 12, wherein the voltage of the alternating current is in the range of 1V to 200V, preferably in the range of 5V to 100V, and more preferably in the range of 20V to 60V.

14. The method according to any one of claims 10 to 13, wherein the rotor and / or the stator comprises or consists of nucleic acids, peptides, proteins and / or small molecules; wherein, Preferably, the rotor and / or the stator comprises or consists of DNA.

15. Use of the nanomotor of any one of claims 1 to 7 or the system of any one of claims 8 to 9 as a turbine, a propeller, a fluid mixer, an energy storage device, a machine for applying mechanical force, for example, on a system coupled to the nanomotor and / or in chemical synthesis.

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