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BIO-NANOROBOTICS & ITS MEDICAL APPLICATIONS

Submitted by

T.Anton Bright BE-II Year,ECE bright91anton@gmail.com, Mobile:9842815400

R.Arumugam BE-II year, EEE 6face4u@gmail.com Mobile: 9791992571

BIO-NANOROBOTICS
Living organisms are naturally-existing, fabulously complex systems of molecular nanotechnology."

of actuation, sensing, signaling, information processing, intelligence, swarm behavior at nano scale. Nano Devices and Components Protein based molecular machines o ATP Synthase a true nano rotary motor o The Kinesin,Myosin,Dynein and Flagella molecular motors DNA based molecular machines o THE DNA tweezers Inorganic (chemical) molecular machines o The Rotaxenes o The Catenanes o Other inorganic molecular machines Other Protein based motors under development o VPLM(Viral Protein linear Motors ) o SCPM(Synthetic Contractile Polymer Motors ) The ATPase Motor ATP Synthase is the process within the mitochondria of a cell by which a rotary engine uses the potential difference across the bilipid layer to power a chemical transformation of ADP into ATP. The process, though as complicated as it sounds, can be simplified into a few steps and two pieces. Mitochondria, the powerhouses of cells, exist in a fluid within the human body. They have a wall (a "bilipid layer") which bounds them on all sides. Because of a difference in sodium and potassium ion concentrations a potential can be created. The potential can even be altered to a desired value by changing the ion concentrations. This process is one which uses that difference in potential to the cells' advantage.

Abstract: This paper focuses on the state of the art in the field of Bio -Nano robotics by describing various molecular level systems and associated design and control issues. Nano-robots are
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controllable machines at the nano (10 ) meter or molecular scale that are composed of nano-scale components. With the modern scientific capabilities, it has become possible to attempt the creation of nanorobotic devices and interface them with the macro world for control. There are countless such machines that exist in nature and there is an opportunity to build more of them by mimicking nature. Even if the field of nanorobotics is fundamentally different than that of macro robots due to the differences in scale and material, there are many similarities in design and control techniques that eventually could be projected and applied. A roadmap towards the progression of this field is proposed and some design concept and philosophies are illustrated. Two types of control mechanisms are given with examples and further hybrid mechanisms are proposed. There are many applications for nanorobotic systems and its biggest impact would be in the area of medicine. Introduction: Nanotechnology, is the study of the controlling of matter on an atomic and molecular scale. Generally nanotechnology deals with structures of the size 100 nanometers or smaller in at least one dimension, and involves developing materials or devices within that size. A Bio nanorobot (bio-nanorobot implies nanorobots made up of bio components) is essentially a controllable machine at the nano meter or molecular scale that is composed of nano-scale components. Nano robots would constitute any passive or active structure (nano scale) capable 2

Kinesin and Myosin Kinesins are a large family of proteins with diverse structures. Mammalian cells have atleast 40 different kinesin genes. Kinesin are referred to as kinesin related proteins (KRPs) or kinesin I. Kinesin I has a structure somewhat analogous to but distinct from that of myosin. There are 2 copies each of a heavy chain and a light chain. Each heavy chain includes a globular ATPbinding motor domain at the N-terminus.

The positive ions try to move to a lower potential, and the negative ions try to move to a higher one, thus creating a force which is used to spin the rotor. As shown in one of the movies below, as the rotor spins the bottom section opens and closes special sections which do the actual work. When they open they take in ADP (Adenosine Di-Phosphate), and a phosphate group. As the rotor continues to turn the section closes and the phosphate is chemically bound to the ADP to form ATP (Adenosine TriPhosphate). ATP is what your body uses (especially in muscle cells) to store energy and the process of breaking it up into ADP and phosphate is what releases that energy. More technically, the diphosphate state is at a lower energy, so when the body breaks off the extra phosphate group in ATP it releases energy which the body can then use. The rotor combines an extra phosphate group with the lower energy ADP using the cell wall's potential as the driving force...

Stalk domais of the heavy chain interact in an ahelical coiled coil that extends from the heavy chain neck to the tail.The coiled coil is interrupted by a few hinge regions that give flexibility to the otherwise stiff stalk domain.

N-termini of the two light chains associate with the two heavy chains near the tail. The diagram above is over simplified. Light chains at the Nterminus include a series of hydrophobic heptad repeats that are predicted to interact with similar repeats in heavy chains near the tail region, in a 4-helix coiled coil. C-terminal tail domains of kinesin light chains include several "tetratrico peptide repeats" (TPRs). The 34 amino acid TPRs mediate protein-protein interactions. Kinesin light chain TPR repeats are involved in binding of kinesins to cargo. C terminal domains of heavy chains may also participate in binding some kinesins to cargo.

The Flagella Motors Escherichia coli and similar organisms are equipped with a set of rotary motors only 45 nm in diameter. Each motor drives a long, thin, helical filament that extends several cell body lengths out into the external medium. In addition to rotary engines and Propellers, E. colis standard accessories include particle counters, rate meters, and gearboxese train system, complete with tracks, loading docks and a control system. Since motor proteins are a thousand times smaller than any man-made motor, they aim to utilize them in a synthetic environment as engines powering the nanotrains a static wheel, Inorganic (chemical) based motors: Rotaxanes are organic compounds consisting of a dumbbell-shaped component that incorporates one or more recognition sites in its rod section and is terminated by bulky stoppers, encircled by one or more ring components. The possibility of manufacturing specific forms of rotaxane and creating molecular motors capable of guided rotary motion and the possibility of fueling such a motor bylight, electrons and chemical energy has been proposed [Schalley e, 2001]. Molecular shuttles have been reported using cyclodextrin a parent of rotaxanes and catenanes [Harada, 2001]. A light-driven monodirectional rotor made of helical alkene, with rotation around a central carbon-carbon covalent bond due to chirality has been reported [Koumura et al, 1999].

induced transition between the B and Z DNA morphologies acts as a moving nanoscale device. A method for localized element-specific motion control was seen in the reversible transition between four stranded topoisomeric DNA motifs (PX and JX2) thereby producing rotary motion [Yan et al, 2002]. A very important, though simple DNA machine that resembles a pair of tweezers has been successfully created [Seeman1998], whose actuation (opening and closing) is also fueled by adding additional DNA fuel strands.

Power sources for nanorobots: The powering of the nanorobots can be done by metabolising local glucose and oxygen for energy. In a clinical environment, another option would be externally supplied acoustic energy. Other sources of energy within the body can also be used to supply the necessary energy for the devices. They will have simple onboard computers capable of performing around 1000 or fewer computations per second. This is because their computing needs are simple. Communication with the device can be achieved by broadcast-type acoustic signalling. A navigational network may be installed in the body, with station keeping navigational elements providing high positional accuracy to all passing nanorobots that interrogate them, wanting to know their location. This will enable the physician to keep track of the various devices in the body. These nanorobots will be able to distinguish between different cell types by checking their surface antigens (they are different for each type of cell). This is accomplished by the use of chemotactic sensors keyed to the specific antigens on the target cells. When the task of the nanorobots is completed, they can be retrieved by allowing them to exfuse themselves via the usual human excretory channels. They can also be removed by active scavenger systems. This feature is designdependent.

DNA-Based Molecular Nanomachines, Joints and Actuators DNA is small, relatively simple and homogeneous, and its structure and function is well understood. The predictable selfassembling nature of the double helix makes it an attractive candidate for engineered nanostructures. This property has been exploited to build several complex geometric structures, including knots, cubes and various polyhedral [Seeman, 1998]. A dynamic device providing atomic displacements of 2-6 nm was proposed in [Mao et al, 1999], wherein the chemically 4

Bio-Nano robotics Design and Control

(C) Bacteriorhodopsin could be used as a sensor or a power source. Step 2: Assembled Bio Nano Robots The next step involves the assembly of functionally stable bio-nano components into complex assemblies. Some examples of such complex assemblies or bio-nanorobots are shown in Fig.A shows a bio-nanorobot with its feet made of helical peptides and its body of carbon nano tubes, while the power unit is a biomolecular motor. Fig.B shows a conceptual representation of modular organization of a bionanorobot. The modular organization defines the hierarchy rules and spatial arrangements of various modules of the bio-nano-robots such as: the inner core (the brain / energy source for the robot); the actuation unit; the sensory unit; and the signaling and information processing unit.

Step 1: Bio Nano Components DNA and carbon nanotubes are being fabricated into various shapes, enabling possibilities of constructing newer and complex devices. These nano-structures are potential candidates for integrating and housing the bio-nano components within them. Proteins such as rhodopsin and bacteriorhodopsin are a few examples of such bio-nano components. Both these proteins are naturally found in biological systems as light sensors. They can essentially be used as solar collectors to gather abundant energy from the sun. This energy could either be harvested (in terms of proton motive force) for later use or could be consumed immediately by other components, such as the ATP Synthase nano rotary motor. The initial work is intended to be on the bio-sensors, such as, heat shock factor. These sensors will form an integral part of the proposed bio-nano assemblies, where these will be integrated within a nano structure and will get activated, as programmed, for gathering the required information at the nano scale. Tools and techniques from molecular modeling and protein engineering will be used to design these modular components. Understanding of basic biological components & controlling their functions as robotic components

(A) DNA which may be used in a variety of ways such as a structural element and a power source; (B) Hemagglutinin virus may be used as a motor;

By the beginning of this phase a library of bionano components will be developed, which will include various categories such as, actuation, energy source, sensory, signaling etc. Thereon, one will be able to design and develop such bionanosystems that will have enhanced mobile characteristics, and will be able to transport themselves as well as other objects to desired locations at nano scale. Furthermore, some bionanorobots will have the capability of assembling various bio-components and nanostructures from in situ resources to house fabrication sites and storage areas, while others will just manipulate existing structures by repairing damaged walls or making other renovations. There will also be robots that not only perform physical labor, but also sense the environment and react accordingly. There will 5

be systems that will sense an oxygen deprivation and stimulate other components to generate oxygen, creating an environment with stable homoeostasis.

Here work has to be performed towards control and programming of bio-nano swarms. This will evolve concepts like distributive intelligence in the context of bio nanorobots. Designing swarms of bio-nano robots capable of carrying out complex tasks and capable of computing and collaborating amongst the group will be the focus. Therefore, the basic computational architectures needs to be developed and rules need to be evolved for the bio-nanorobots to make intelligent decisions at the nano scale.

Fig.Describtion(B) Modular Organization concept for the bio-nano robots. Spatial arrangements of the various modules of the robots are shown. A single bio nano robot will have actuation, sensory and information processing capabilities.

Step 3: Distributive Intelligence, Programming and Control With the individual bio-nanorobots in full function, they will now need to collaborate with one another to further develop systems and colonies of similar and diverse nanorobots. This design step will lay the foundation to the concept of bio-nano swarms (distributive bionanorobots) (see Fig.A). Figure (A) shows Basic bio nano robot forming a small swarm of five robots. The spatial arrangement of the individual bio nano robot will define the arrangement of the swarm. Also, these swarms could be reprogrammed to form bindings with various other types of robots. The number of robots making a swarm will be dependent of the resulting capability required by the mission. Also the capability of attaching new robots at run time and replacing the non functional robots will be added.

To establish an interface with the macro world, the computers and electronic hardware have to be designed as well. From a location, humans should be able to control, monitor the behavior and action of these swarms. Also, the basic computational capabilities required for functioning of the swarms will be developed. A representative computational bio-nano cell, which will be deployed within a bio-nano-robot, is shown in Figure 16 B. This basic computational cell will initially be designed for data retrieval and storage at the nano scale.

Fig.A Figure 4A: An automatic fabrication floor layout. Different color represents different functions in automatic fabrication mechanisms. The arrows indicate the flow of components on the floor layout. Section 1 Basic stimuli storage Control expression; Section 2 Bio molecular component manufacturing (actuator / sensor); Section 3 Linking of bio-nano components; Section 4 Fabrication of bio-nano robots (assemblage of linked bio-nano components). Control of Nanorobotic systems The control of nano robotic systems could be classified in two categories: Step 4: Automatic Fabrication and Information Processing Machines For carrying out complex missions, such as sensing, signaling and storing, colonies of these bio-nanorobotic swarms needs to be created. The next step in nanorobotic designing would see the emergence of automatic fabrication methodologies (see Fig.4A) of such bio-nano robots in vivo and in vitro. Capability of information processing, which will involve learning and decision making abilities, will be a key consideration of this step. This would enable bio-swarms to have capability of self-evolving based on the environment they will be subjected to. These swarms could be programmed to search for alternate energy sources and would have an ability to adapt as per that resource. Energy management, self-repairing, and evolving will be some of the characteristics of these swarms. i. Internal control mechanisms ii. External control mechanisms The other category could be the hybrid of internal and external control mechanisms. Internal Control Mechanism Active and Passive This type of control depends upon the mechanism of bio chemical sensing and selective binding of various bio molecules with various other elements. This is a traditional method, which has been in use since quite sometime for designing bio molecules. Using the properties of the various bio molecules and combining with the knowledge of the target molecule that is to be influenced, these mechanisms could be effective. But again, this is a passive control mechanism where at run time these bio molecules cannot change their behavior. Once programmed for a particular kind of molecular interaction, these molecules stick to that. Here lies the basic issue in controlling the nanorobots which are supposed 7

This capability will enable us to program (within certain degrees of freedom) the swarm behavior in the bio-nano robots. We will further be able to get their sensory data (from nano world) back to the macro world through these storage devices. This programming capability would form the core essence of a bionano robotics system and hence enables them with immense power.

to be intelligent and hence programmed and controlled so that they could be effective in the ever dynamic environment. The question of actively controlling the nanorobots using internal control mechanism is a difficult one. We require an active control mechanism for the designed nanorobots such that they can vary their behavior based on situations they are subjected to, similar to the way macro robots perform. For achieving this internal control, the concept of molecular computers could be utilized. DNA computers (devised at University of Southern California) are used to solve a mathematical problem by utilizing DNA molecules. Biomolecular computer (devised at Israel's Weizmann Institute) which could be an excellent method for an internal active control mechanism for nanorobots. They have recently been successful in programming the biomolecular computer to analyze the biological information, which could detect and treat cancer (prostate and a form of lung cancer) in their laboratory . The molecular computer has an input and output module which acting together can diagnose a particular disease and in response produce a drug to cure that disease. It uses novel concept of software (made up of DNAs) and hardware (made up of enzymes) molecular elements. This molecular computer is in generalized form and can be used for any disease which produces a particular pattern of gene expression related to it. External Control Mechanism:

Other possibilities being explored are in the category of hybrid control mechanisms where the target is located and fixed by an external navigational system but the behavior of the nanorobot is determined locally through an active internal control mechanism. The use of nano sensors and evolutionary agents to determine the nanorobots behavior is suggested by the mentioned reference. Biomedical applications of Nanorobotics

The enormous potential in the biomedical capabilities of nanorobots and the imprecision and side effects of medical treatments today make nanorobots very desirable. Medical treatment today involves the use of surgery and drug therapy. Surgery is a direct, manual approach to fixing the body. However, no matter how highly trained the specialists may be, surgery can still be dangerous since anesthetics, infections, organ rejection, and missed cancer cells can all cause failure. Surgeons lack finescale control. From the perspective of a cell, a fine surgical scalpel is as crude as a blunt tool. Invasive surgery wounds peripheral tissue and causes unnecessary harm to the patient. Drug therapy affects the body at the molecular level. Drug molecules are dumped into the body where they are transported by the circulatory system. They may come into contact with untargeted parts of the body and lead to unwanted side effects. Nanomedical robots, however, will have no difficulty identifying cancer cells and will ultimately be able to track them down and destroy them wherever they ma~ be growing. This is why the medical profession is looking towards the use of biomedical, nanotechnological engineering to refine the treatment of diseases. Applications of nanorobots are expected to provide remarkable possibilities. An interesting utilization of nanorobots may be their attachment to transmigrating inflammatory cells or white blood cells, to reach inflamed tissues and assist in their healing process . Nanorobots will be applied in chemotherapy to combat 8

This type of control mechanism employs affecting the dynamics of the nanorobot in its work environment through the application of external potential fields. Researchers are actively looking at using MRI as an external control mechanism for guiding the nano particles. An MRI system is capable of generating variable magnetic field gradients which can exert force on the nanorobot in the three dimensions and hence control its movement and orientation.

cancer through precise chemical dosage administration, and a similar approach could be taken to enable nanorobots to deliver anti-HIV drugs. Such drug-delivery nanorobots have been termed pharmacytes. Nanorobots could be used to process specific chemical reactions in the human body as ancillary devices for injured organs. Monitoring and controlling nutrient concentrations in the human body , including glucose levels in diabetic patients will be a possible application of medical nanorobots. Nanorobots might be used to seek and break kidney stones. Another important possible feature of medical nanorobots will be the capability to locate atherosclerotic lesions in stenosed blood vessels, particularly in the coronary circulation, and treat them either mechanically, chemically or pharmacologically.

References:

1. Drexler Eric. K. 1992. Nanosystems: Molecular Machinery, Manufacturing and Computation: John Wiley & Sons. 2. Lubert S. 1995: Biochemistry, 4th edition: W.H Freeman and Company

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Niemeyer CM. 1999. Progress in "engineering up" nanotechnology devices utilizing DNA as a construction material. Applied Physics A: Materials Science and Processing 68: 119-24

Conclusion: All of these current developments in technology directs humans a step closer to nanorobots and simple, operating nanorobots is the near future. Nanorobots can theoretically destroy all common diseases of the 2lstcenturythereby ending much of the pain and suffering. It can also have (alternative, practical uses such as improved mouthwash and cosmetic creams that can expand the commercial market in biomedical engineering. People can envision a future where people can self-diagnose their own ailments with the help of nanorobot monitors in their bloodstream. Simple everyday illnesses can be cured without ever visiting the physician. Invasive surgery will be replaced by an operation carried out by nano-surgical robots. Although research into nanorobots is in its preliminary stages, the promise of such technology is endless.

4. Simmel FC, Yurke, B. DNA-based Nanodevices. http://www2.nano.physik.unimuenchen.de/publikationen/Preprints/in dex.htm

5. 5.Ummat A, Dubey A, Sharma G, Mavroidis C.-Nanorobotics

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