PAPER PRESENTATION

ON

NANO ROBOTICS
BY M.Pramodh Dev Jayanth Indian Institute of Technology Mandi (H.P)

List of contents
1. Introduction 2. Design and control 3. Present applications 4. Future potentials 5. Conclusions 6. References

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Introduction
What is NANOTECHNOLOGY?
The prefix nano in the word nanotechnology means a billionth (1 x l0^9). Nanotechnology deals with various structures of matter having dimensions of the Order of a billionth of a meter. Research and technology development aimed to understand and control matter at dimensions of approximately 1 - 100 nanometer the nanoscale As the modern day scientists put it, it is the: Ability to understand, create and use structures, devices and systems that have fundamentally new properties and functions because of their nanoscale structure. Ability to image, measure, model, and manipulate matter on the nanoscale to exploit those properties and functions. Ability to integrate those properties and functions into systems spanning from nano- to macro-scoped scales.

What are NANO-ROBOTICS?

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Nano-robots are 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 nano-robotic devices and interface them with the macro world for control.

Nano-robots would constitute any passive or active structure (nano scale) capable of actuation, sensing, signaling, information processing, intelligence, swarm behavior at nano scale. These functionalities could be illustrated individually or in combinations by a nano robot (swarm intelligence and co-operative behavior). So, there could be a whole genre of actuation and sensing or information processing nano robots having ability to interact and influence matter at the nano scale. Some of the characteristic abilities that are desirable for a nano-robot to function are: i. Swarm Intelligence decentralization and distributive intelligence ii. Cooperative behavior emergent and evolutionary behavior iii. Self assembly and replication assemblage at nano scale and nano maintenance iv. Nano Information processing and programmability for programming and controlling nano-robots (autonomous nanorobots) v. Nano to macro world interface architecture an architecture enabling instant access to the nano-robots and its control and maintenance

How can they be seen?

The nano-robots are invisible to naked eye, which makes them hard to manipulate and work with. Techniques like

Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) are being employed to establish a visual and haptic interface to enable us to sense the molecular structure of these nano scaled devices. Virtual Reality (VR) techniques are currently being explored in nano-science and bio-technology research as a way to enhance the operators perception (vision and haptics) by approaching more or

almost any way imaginable. These mutations can consist of anything from simple amino acid side-chain swapping, to amino acid insertions or deletions, incorporation of nonnatural amino acids, and even the combination of unrelated peptide domains into whole new structures. An excellent example of this approach is the engineering of the F 1

less a state of full immersion or tele-presence.

ATPase, which is able rotate a nano-propeller in the presence of ATP. A computational algorithm [190] was used to determine the mutations necessary to engineer an allosteric zinc-binding site into the F -ATPase using site1

Nano-robotics Design and Control

3.1 Design of nano robotic systems
Designing nanorobotic systems deal with vast variety of sciences, from quantum molecular dynamics, to kinematic analysis. The rules applicable to nano-robotics depend upon the nano material we intend to use. Nanomechanical robotic systems deal with science significantly different from the biological or inorganic nanorobotic systems. Eric Drexler, author of the famous book, Nanosystems: Molecular machinery, manufacturing and Computation, detailed on many areas of science which influences design of nano-mechanical systems. In this review chapter on various laws which govern the designing of nano-robotics, we will concentrate on biological systems. We will consider that the components that details a nanorobot is made of biological components, such as, proteins and DNAs. There doesnt exist any particular guideline or a prescribed manner which details the methodology of designing a bio-nano-robot (bio-nano-robot implies nanorobots made up of bio components) up to the date. There are many complexities which are associated with using bio components (such as protein folding, presence of aqueous medium), but the advantages of using these are also quite considerable. These bio components offer immense variety and functionality at a scale where creating a man made material with such capabilities would be extremely difficult. These bio components have been perfected by nature through millions of years of evolution and hence these are very accurate and efficient. As noted in the review section on Molecular Machines, F -ATP ase is known to work at
1

directed mutagenesis. The mutant F -ATPase was then

1

shown to rotate an act in filament in the presence of ATP with average torque of 34 pN nm. This rotation could be stopped with the addition of zinc, and restored with the addition of a chelator to remove the zinc from the allosteric binding site [191]. This type of approach can be used for the improvement of other protein-based nanocomponents. Hence, these bio components seem to be a very logical choice for designing nano-robots. Some of the core applications of nano-robots are in the medical field and using bio-components for these applications seems to be a good choice as they both offer efficiency and variety of functionality. This idea is clearly inspired by natures construction of nano-robots, bacteria and viruses which could be termed as intelligent organisms capable of movement, sensing and organized control. Hence our scope would be proposed which details the main steps towards the design and development of bio-nano-robots. 3.1.1 The Roadmap The roadmap for the development of bionanorobotic systems for future applications (medical, space and military) is shown in Fig.3.1.1. The roadmap progresses through the following main steps: Step 1: Bio Nano Components Development of bio-nano components from biological systems is the first step towards the design and development of an advanced bio-nano-robot, which could be used for future applications. Since the planned systems and devices will be composed of these components, we must have a sound understanding of how these behave and how could they be controlled. From the simple elements such as structural links to more advanced concepts such as motors, each component must be carefully studied and possibly manipulated to understand the functional limits of

efficiencies which are close to 100%. Such efficiencies, variety and form are not existent in any other form of material found today. Also, the other significant advantages in using protein-based bio nano components is the development and refinement over the last 30 years of tools and techniques that enable researchers to mutate proteins in

each one of them. DNA and carbon nano-tubes are being fabricated into various shapes, enabling possibilities of constructing newer and complex devices. These nanostructures 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.

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-nano-robots. Fig.3.2.1. shows a bio-nano-robot with its feet made of helical peptides and its body of carbon nano tubes, while the power unit is a bio-molecular motor. Fig.3.2.2. shows a conceptual representation of modular organization of a bionano-robot. 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. By the beginning of this phase a library of bio-nano 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 bionano-systems 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 bio-nano-robots will have the capability of assembling various bio-components and nano-structures 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 be systems that will sense an oxygen deprivation and stimulate other components to generate oxygen, creating an environment with stable homoeostasis.

Fig3.1.1

Fig3.2.1.

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. To establish an interface with the macro world, the computers and electronic hardware have to be designed as well. Fig. 17 shows the overall electronic communication architecture. 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. 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 bio-nano robotics system and hence enables them with immense power. 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. 18) 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 bioswarms 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.

Fig3.2.2 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 bio-nanorobots) (see Fig. 16A). 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

Present day applications.

MEDICAL NANOROBOTICS
The major development pathway of nano medicine molecular nanotechnology (MNT) or nano-robotics takes as its purview the engineering of complex nano-mechanical systems for medical applications. Just as biotechnology extends the range and efficacy of treatment options available from nano-materials, the advent of molecular nano technology will again expand enormously the effectiveness , precision and speed of future medical treatments while at the same time significantly reducing their risk, cost, and invasiveness.MNT will allow doctors to perform direct in vivo surgery on individual human cells. The ability to design, construct, and deploy large numbers of microscopic medical nano-robots will make this possible.

defense mechanisms need to be passed through such as the blood-brain barrier, the transit time and delivery challenges can be greatly different. Once a drug an-ives at its destination, it needs to be released at an appropriate rate for it to be effective. If the drug is released too rapidly it might not be completely absorbed, or it might cause gastrointestinal irritation and other side effects. The drug delivery system must positively impact the rate of absorption, distribution, metabolism, and excretion of the drug or other substances in the body. In addition, the drug delivery system must allow the drug to bind to its target receptor and influence that receptors signaling and action, as well as other drugs, which might also be active in the body. Drug delivery systems also have severe restrictions on the materials and production processes that can be used. The drug delivery material must be compatible and bind easily with the drug, and be bio-restorable (i.e. degrade into fragments after use which are either metabolized or eliminated via normal excretory routes). The production process must respect stringent conditions on processing and chemistry that wont degrade the drug, and still provide a cost effective product.

PRINCIPAL NANOROBOTIC APPLICATIONS

The availability of advanced nanomedical instrumentalities should not significantly alter the classical medical treatment methodology, although the patient experiences and outcomes will be greatly improved. Treatment in the nanomedical era will become faster and more accurate, efficient and effective. A. DRUG DELIVERY Nanotechnology provides a wide range of new technologies for developing customized solutions that optimize the delivery of pharmaceutical products. To be therapeutically effective, drugs need to be protected during their transit to the target action site in the body while maintaining their biological and chemicals properties. Some drugs are highly toxic and can cause harsh side effects and reduced therapeutic effect if they decompose during their delivery. Depending on where the drugs will be absorbed (i.e. colon, small intestine, etc), and whether certain natural

(Drug delivery system) Nanotechnology can offer new drug delivery solutions in the following areas. 1. Drug Encapsulation One major class of drug delivery systems is materials that encapsulate drugs to protect them during transit in the body. Drug encapsulation materials include liposomes and polymers (i.e. Polylactide (PLA) and Lactide-co-Glycolide (PLGA)) which are used as microscale particles. The materials form capsules around the drugs and permit timed drug release to occur as the drug diffuses through the encapsulation material. The drugs can also be released as the encapsulation material degrades or erodes in the body.

Nanoparticle encapsulation is also being investigated for the treatment of neurological disorders to deliver therapeutic molecules directly to the central nervous system beyond the blood-brain barrier, and to the eye beyond the blood-retina barrier. Applications could include Parkinsons, Huntingtons, Alzheimers, ALS and diseases of the eye. 2. Functional Drug Carriers Another class of drug delivery systems where nanotechnology offers interesting solutions is in the area of nanomaterjals that carry drugs to their destination sites and also have functional properties. Certain nanostrucfures can be controlled to link with a drug, a targeting molecule, and an imaging agent, then attract specific cells and release their payload when required. B. DRUG DISCOVERY Nano and micro technologies are part of the latest advanced solutions and new paradigms for decreasing the discovery and development times for new drugs, and potentially reducing the development costs. Traditional trial-anderror methods have contributed to a discovery process lasting 10 years or more for new drugs to reach the market. In recent years, a number of new and complementary technologies have been developed which considerably impact the drug discovery process. High-throughput arrays and ultra-sensitive labeling and detection technologies are being used to increase the speed and accuracy of identifying genes and genetic materials for drug discovery and development. These micro and nano technologies along with information technology solutions such as combinatorial chemistry, computational biology, computer-aided drug design, data mining, and data processing tools are addressing the challenges related to eliminating critical bottlenecks in drug discovery replacement. While most types of tissues repair the interaction of stem cells with chemical modulators, there are differences in the ways that various tissues heal. Hard tissues such as bone and teeth heal by reproducing tissues indistinguishable from the original. However in cases where a dental or artificial bone implant is required, the structural material used in the implant may trigger immune rejection, corrode in the body fluids, or no longer bond to the host bone. This can require additional surgery or result in the loss of the implants function. In many cases, the failure occurs at the tissue-implant interface,

which may be due to the implant material weakening its bond with the natural material. To overcome this, implants are often coated with a biocompatible material to increase their adherence properties and produce a greater surface area to volume ratio for the highest possible contact area between the implant and natural tissue. Soft tissues such as skin, muscle, nerves, blood vessels and ligaments repair damaged areas with fibrous tissue. Damaged tissue from various sources such as burns and ulcers can be self-repaired by the body, but can also result in scar formation. Graft material using artificial sheets can replace skin and other tissue with reasonable graft stability and cosmetic outcome. Nanotechnology can new offer new solutions for tissue repair and replacement in the following areas. C. IMPLANTABLE DEVICS Nanotechnology offers sensing technologies that provide more accurate and timely medical information for diagnosing disease, and miniature devices that can administer treatment automatically if required. Health assessment can require medical professionals, invasive procedures and extensive laboratory testing to collect data and diagnose disease. This process can take hours, days or weeks for scheduling and obtaining results. Some medical information is extremely time sensitive such as finding out if there is sufficient blood flow to an organ or tissue after transplant or reconstructive surgery, before irreversible damage occurs. Certain medical tests such as biopsies are subjective and can provide inconclusive or incorrect results. In a false negative result where a needle misses the tumor and then samples a normal tissue, the cancer nay go untreated and can impact a patients chances for long-term survival. Some tests such as diabetes blood sugar levels require patients to administer the test themselves to avoid the risk of their blood glucose falling to dangerous levels. Certain users such as children and the elderly may not be able to perform the test properly, timely or without considerable pain. People who are exposed to radiation or hazardous chemicals in their work environment are at a higher risk of illness. Occasional testing is typically done but may not detect a disease in its early stage. Early detection could initiate timely treatment with a higher chance of success,

and have a worker removed from the hazardous environment to prevent further damage. Nanotechnology can new offer new implantable and/or wearable sensing technologies that provide continuous and extremely accurate medical information. Complementary microprocessors and miniature devices can be incorporated with sensors to diagnose disease, transmit information and administer treatment automatically if required.

Robotic surgical systems are being developed to provide surgeons with unprecedented control over precision instruments. This is particularly useful for minimally invasive surgery. Instead of manipulating surgical instruments, surgeons use their thumbs and fingers to move joystick handles on a control console to maneuver two robot arms containing miniature instruments that are inserted into ports in the patient. The surgeons movements transform large motions on the remote controls into micromovements on the robot arms to greatly improve mechanical precision and safety. E DIAGNOSTIC TOOLS Genetic Testing Nano and micro technologies provide new solutions for increasing the speed and accuracy of identifying genes and genetic materials for drug discovery and development, and for treatment-lnked disease diagnostics products. Ultra-sensitive Labeling and Detection Technologies Several new technologies are being developed to improve the ability to label and detect unknown target genes. At Genicon, gold nanoparticle probes are being treated with chemicals that cling to target genetic materials and illuminate when the sample is exposed to light. Killing cancer cells. The device would circulate freely throughout the body, and would periodically sample its environment by determining whether the binding sites were or were not occupied. Occupancy statistics would allow determination of concentration. Todays monoclonal antibodies are able to bind to only a single type of protein or other antigen, and have not proven effective against most cancers. The cancer killing device suggested here could incorporate a dozen different binding sites and so could monitor the concentrations of a dozen different types of molecules. The computer could determine if the profile of concentrations fit a pre-programmed cancerous profile and would, when a cancerous profile was encountered, release the poison. Beyond being able to determine the concentrations of different compounds, the cancer killer could also determine local pressure. By using several macroscopic acoustic signal sources, the cancer killer could determine its location within the body much as a radio receiver on earth can use the transmissions from several satellites to determine its position (as in the widely used GPS system). .

(Implantation) Example applications are as follows. I Retina Implants Retinal implants are in development to restore vision by electrically stimulating functional neurons in the retina One approach being developed by various groups including a project at Argonne National Laboratory is an artificial retina implanted in the back of the retina. The artificial retina uses a miniature video camera. 2 Cochlear Implants A new generation of smaller and more powerful cochlear implants are intended to be more precise and offer greater sound quality. D. SURGICAL AIDS 1 Operating Tools Medical devices that contain nano and micro technologies will allow surgeons to perform familiar tasks with greater precision and safety, monitor physiological and biomechanical parameters more accurately, and perform new tasks that are not currently done. 2 Surgical Robotics

The cancer killer could thus determine that it was located in (say) the big toe. If the objective was to kill a colon cancer, the cancer killer in the big toe would not release its poison. Very precise control over location of the cancer killers activities could thus be achieved. The cancer killer could readily be reprogrammed to attack different targets (and could, in fact, be reprogrammed via acoustic signals transmitted while it was in the body). This general architecture could provide a flexible method of destroying unwanted structures (bacterial infestations, etc). Providing oxygen A second application would be to provide metabolic support in the event of impaired circulation. Poor blood flow, caused by a variety of conditions, can result in serious tissue damage. A major cause of tissue damage is inadequate oxygen. A simple method of improving the levels of available oxygen despite reduced blood flow would be to provide an artificial red blood cell of about a day by about a liter of small spheres. As oxygen is being absorbed by our artificial red blood cells in the lungs at the same time that carbon dioxide is being released, and oxygen is being released in the tissues when carbon dioxide is being absorbed, the energy needed to compress one gas can be provided by decompressing the other. The power system need only make up for losses caused by inefficiencies in this process. These losses could presumably be made small, thus albwing our artificial red blood cells to operate with little energy consumption conditions of temperature and pressure. Thus, our spheres are over 2,000 times more efficient per unit volume than blood; taking into account that blood is only about half occupied by red blood cells, our spheres are over 1,000 times more efficient than red blood cells. Artificial mitochondria While providing oxygen to healthy tissue should maintain metabolism, tissues already suffering from ischemic injury (tissue injury caused by loss of blood flow) might no longer be able to properly metabolize oxygen. In particular, the mitochondria will, at some point, fail. Increased oxygen levels in the presence of nonfunctional or partially functional mitochondria will be ineffective in restoring the tissue. However, more direct metabolic support could be provided. The direct release of ATP, coupled with selective release or absorption of critical metabolifes (using the kind of selective transport system mentioned earlier), should be effective in restoring cellular

function even when mitochondrial function had been compromised. The devices restoring metabolite levels, injected into the body, should be able to operate autonomously for many hours ~depending on power requirements, the storage capacity of the device and the release and uptake rates required to maintain metabolite levels).

Future potentials
Some possible applications using nano-robots are as follows: 1. To cure skin diseases, a cream containing nano-robots may be used. It could remove the right amount of dead skin, remove excess oils, add missing oils, apply the right amounts of natural moisturizing compounds, and even achieve the elusive goal of 'deep pore cleaning' by actually reaching down into pores and cleaning them out. The cream could be a smart material with smooth-on, peel-off convenience. 2. A mouthwash full of smart nano-machines could identify and destroy pathogenic bacteria while allowing the harmless flora of the mouth to flourish in a healthy ecosystem. Further, the devices would identify particles of food, plaque, or tartar, and lift them from teeth to be rinsed away. Being suspended in liquid and able to swim about, devices would be able to reach surfaces beyond reach of toothbrush bristles or the fibers of floss. As short-lifetime medical nano-devices, they could be built to last only a few minutes in the body before falling apart into materials of the sort found in foods (such as fiber). 3 .Medical nano-devices could augment the immune system by finding and disabling unwanted bacteria and viruses. When an invader is identified, it can be punctured, letting its contents spill out and ending its effectiveness. If the contents were known to be hazardous by themselves, then the immune machine could hold on to it long enough to dismantle it more completely. 4. Devices working in the bloodstream could nibble away at arteriosclerotic deposits, widening the affected blood vessels. Cell herding devices could restore artery walls and artery linings to health, by ensuring that the right cells and

supporting structures are in the right places. This would prevent most heart attacks.

References
1. Drexler Eric. K. 1992. Nano-systems: Molecular Machinery, Manufacturing and Computation: John Wiley & Sons. 2. Kinosita K, Jr., Yasuda R, Noji H, Adachi K. 2000: A rotary molecular motor that can work at near 100% efficiency. Philosophical Transactions: Biological Sciences 2000 Apr 29; 355(1396):473-89 3.http://www.nobel.se/chemistry/educational/poster/1997/b oyer-walker.html Copyright 2004 the Nobel Foundation. The
th

Conclusion
Manipulating matter at molecular scale and influencing their behavior (dynamics and properties) is the biggest challenges for the nano-robotic systems. This field is still in very early stages of development and still a lot has to be figured out before any substantial outcome is produced. The recent explosion of research in nanotechnology, combined with important discoveries in molecular biology have created a new interest in bio nanorobotic systems. The preliminary goal in this field is to use various biological elements whose function at the cellular level creates a motion, force or a signal as nanorobotic components that perform the same function in response to the same biological stimuli but in an artificial setting. In this way proteins and DNA could act as motors, mechanical joints, transmission elements, or sensors. If all these different components were assembled together they can form nano-robots and nano devices with multiple degrees of freedom, with ability to apply forces and manipulate objects in the nano-scale world, transfer information from the nano- to the macro-scale world and even travel in a nano-scale environment. Ability to determine the structure, behavior and properties of the nano components is the first step which requires focused research thrust. Only when the preliminary results on these nano components are achieved, steps towards actually building complex assemblies could be thought of. Still problems like protein (basic bio nano component folding, precise mechanism behind working of the molecular motors like ATP Synthase have still has to be solved. Active control of nano-robots has to be further refined. Hybrid control mechanisms, where in, a molecular computer and external (navigational) control system work in sync to produce the precise results seems very promising. Further, concepts like swarm behavior in context of nanorobotics is still have to be worked out. As it would require colonies of such nano-robots for accomplishing a particular task, concept of co-operative behavior, distributed intelligence has to be evolved.

Noble Prize in Chemistry 1997. April 10 2004. 4. http://www.life.uiuc.edu/crofts/bioph354/lect10.html Copyright 1996. Antony Crofts. Lecture 10, ATPSynthase. University of Illinois at UrbanaChampaign 5. Lubert S. 1995: Biochemistry, 4th edition: W.H Freeman and Company 6. Itoh H, Takahashi A, Adachi K, Noji H, Yasuda R, Yoshida M, Kinosita K, and Jr.2004: Mechanically driven ATP synthesis by F -ATPase. Nature 427: 465 468. 7. Howard J. 1997. Molecular motors: structural adaptations to cellular functions. Nature 389: 561-7 8. Vale R. 1996. Switches, latches, and amplifiers: common themes of G proteins and molecular motors. J. Cell Biol. 135: 291-302 9. Farrell CM, Mackey AT, Klumpp LM, Gilbert SP. 2002. The role of ATP hydrolysis for kinesin processivity. J Biol Chem 277: 17079-87 10. Vale RD, Milligan RA. 2000. The way things move: looking under the hood of molecular motor proteins. Science 288: 88-95
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