INTRODUCTIONBiomedical sciences being a life and dynamic subject continuously explores newfrontiers, though I must confess that it is very slow in incorporating this findings intoevery day practice. The reasons for the slow incorporation ~of new development intomedicine are basically three. As a subject dealing with humans, experimentations arestrictly controlled by ethical, moral and religious guidelines and respect for human life.The second reason is that training in medicine being through apprenticeship; younggraduates guard jealously what they’ve learnt from the masters” and rarely deviate fromthe norms set by the masters to avoid cristisms and back lash from the masters. Thirdly ittakes years of trial from animal to human subjects before it certified free from dangers.The fears of side effect and adverse out of new drugs are exemplified by the thousands ofbabies born with phocomelia following the use of thalidomide.Because of above reasons experimental medicine is almost light years ahead of clinicalpractice.Examination: The first step in any treatment process. It includes individual’s medicalhistory, personal function and structural baselines, and current complaints. In classicalmedicine interview and observation have long been the cornerstone of examination.Advancing technology has brought plethora of tests that contribute to accurate diagnosis.Diagnosis: The determination of the cause and nature of a disease in order to provide alogical basis for treatment and prognosis traditionally the diagnostic process begins witha thorough history taken from the patient and relevant physical examination. Often thissufficed to make a confident diagnosis, but the cause of some illnesses remaineduncertain without recourse to additional information such as blood tests or radiologicalexaminations.Prognosis and treatment: Prognosis Is a judgment or forecast, based upon a correctdiagnosis, of the future course of a disease or injury, and of the patients prospects forpartial or full recovery. But prognosis Is a function of treatment as well as disease. Fromthe post-Hippocratic era through the 18th century, treatments were almost purelyempirical and often did more harm than good. During the 19th and early 20th centuries,treatments were scientific but largely homeostatic—the medical intervention was rationalbut served mainly to assist the body in healing itself. Throughout the remainder of the20th century, truly curative treatments began to rescue some patients from conditionsfrom which their unaided bodies would not have been able to recover.Validation and prophylaxis: A proper therapeutic protocol will include a procedure forfollow-up to ensure that the prescribed treatment was correctly executed with goodresults. This step is often neglected in order to save costs and may be consideredunimportant by some practitioners because approximately 80%-90% of all illnesses,which take patients to the doctor, are self-curing or self-limiting. For example, thecommon cold, most infectious diseases and many minor injuries are problems thatusually will resolve on their own even with no treatment. In these cases the purpose oftreatment is not to provide a cure, but rather to speed the healing process, improvecomfort, and avoid complications. Prophylaxis is the prevention of disease, typicallyincluding patient education, immunization programs, amelioration of occupationalhazards, and other preventive and public health measures.
LIMITATIONS OF CURRENT MEDICINEWhen the body’s working, building, and battling goes awry, we turn to medicine fordiagnosis and treatment. Today’s methods, though, have obvious shortcomings.A. Crude Methods: Diagnostic procedures vary widely, from asking a patient questions,through looking at X-ray shadows, through exploratory surgery and the microscopic andchemical analysis of materials from the body. Doctors can diagnose many ills, but othersremain mysteries. Even a diagnosis does not imply understanding: doctors could diagnoseinfections before they knew about germs, and today can diagnose many syndromes withunknown causes. After years of experimentation and unfold loss of life, they can eventreat what they don’t understand a drug may help, though no one knows why.Leaving aside such therapies as heating, massaging, irradiating, and so forth, the twomain forms of treatment are surgery and drugs. From a molecular perspective, neither issophisticated.Surgery is a direct, manual approach to fixing the body, now practiced by highly trainedspecialists. Surgeons sew together torn tissues and skin to enable healing, cut out cancer,clear out clogged arteries, and even install pacemakers and replacement organs. It’sdirect, but if can be dangerous: anesthetics, infections, organ rejection, and missed cancercells can all cause failure. Surgeons lack fine-scale control. The body works by means ofmolecular machines, most working inside cells. Surgeons can see neither molecules norcells, and can repair neither.Drug therapies affect the body at the molecular level. Some therapies - like insulin fordiabetics - provide materials the body lacks. Most - like antibiotics for infections -introduce materials no human body produces. A drug consists of small molecules; in oursimulated molecular world, many would fit in the palm of your hand. These moleculesare dumped into the body (sometimes directed to a particular region by a needle or thelike), where they mix and wander through blood and tissue. They typically bump intoother molecules of all sorts in all places, but only stick to and affect molecules of certainkinds.Antibiotics like penicillin are selective poisons. They stick to molecular machines inbacteria and jam them, thus fighting infection. Viruses are a harder case because they aresimpler and have fewer vulnerable molecular machines. Worms, fungi, and protozoa arealso difficult, because their molecular machines are more like those found in the humanbody, and hence harder to jam selectively. Cancer is the most difficult of all. Cancerousgrowths consist of human cells, and attempts to poison the cancer cells typically poisonthe rest of the patient as well.Other drug molecules bind to molecules in the human body and modify their behavior.Some decrease the secretion of stomach acid, others stimulate the kidneys, many affectthe molecular dynamics of the brain. Designing drug molecules to bind to specific targetsis a growth industry today, and provides one of the many short-term payoffs that isspurring developments in molecular engineering.B. Limited Abilities: Current medicine is limited both by its understanding and by ifsfools. In many ways, it is still more an art than a science. Mark Pearson of Du Pont pointsout, “In some areas, medicine has become much more scientific, and in others not muchat all. We’re still short of what I would consider a reasonable scientific level. Many
people don’t realize that we just don’t know fundamentally how things work. It’s likehaving an automobile, and hoping that by taking things apart, we’ll understand somethingof how they operate. We know there’s an engine in the front and we know it’s under thehood, we have an idea that it’s big and heavy, but we don’t really see the rings that allowpistons to slide in the block. We don’t even understand that controlled explosions areresponsible for providing the energy that drives the machine.Better tools could provide both better knowledge and better ways to apply thatknowledge for healing. Today’s surgery can rearrange blood vessels, but is far too coarseto rearrange or repair cells. Today’s drug therapies can target some specific molecules,but only some, and only on the basis of type. Doctors today can’t affect molecules in onecell while leaving identical molecules in a neighboring cell untouched because medicinetoday cannot apply surgical control to the molecular level.NANOTECHNOLOGYThe possibility of nanorobotics and nanotechnology was first proposed by Nobel prizewinner Richard Feynman in his talk in 1959 titled“There is plenty of room at the bottom”.While many definitions of nanotechnology exist, the one most widely used is from theUS Government’s National Nanotechnology Initiative (NNI). According to the NNI,nanotechnology is defined as:“Research and technology development at the atomic, molecular and macromolecularlevels in the length scale of approximately 1 — 100 nanometer range, to provide afundamental understanding of phenomena and materials at the nanoscale and to createand use structures, devices and systems that have novel properties and functions becauseof their small and/or intermediate size.”More simply put, nanotechnology is the space at the nanoscale (i.e. one billionth of ameter), which is smaller than “micro” (one millionth of a meter) and larger than“pico”(one trillionth of a meter). Nanoparticles 1— 100 nm. In comparison,representative structures and materials found in nature are typically referenced to havethe following dimensions:Atom 0.1 nmDNA (width) 2 nmProtein 5—50 nmVirus 75—100 nmMaterials internalized by cells 100 nmBacteria 1,000—10,000 nmWhite Blood Cell 10,000 nmThe size domains of components involved with nanotechnology are similar to that ofbiological structures. For example, a quantum dot is about the same size as a smallprotein (<="" molecules).="" wound-healing="" and="" cells="" white-blood="" (e.g.=""nanostructures="" biological="" as="" just="" damages="" lesions="" repair="" sense=""can="" that="" hybrid="" synthetic="" such="" research="" health-related="" of=""areas="" many="" progression="" natural="" a="" is="" nanotechnology=""properties,="" functional="" certain="" scale="" in="" similarity="" this="" because=""nm).="" (<100="" viruses="" some="" size="" same="" the="" are="" drug-carrying=""
NANOMEDICINEThe emerging teld of medical nanorohorics is aimed at overcoming this shortcomings.The medicine and nanorohorics polls within the purview of nanotechnologies. Our bodiesare filled with intricate, active molecular structures. Where those structures are managed,health suffers. Modern medicine can affect the works of the body in many ways, but froma molecular viewpoint it remains crude incurred. Molecular manufacturing can constructa range of medical instruments and devices with fat greater abilities. The body is anenormously coming in world of molecules.To understand what nanotechnology can do for medicine, we need a picture of the bodyfrom a molecular perspective. The human body can be seen as a workyard, constructionsite, and battleground form molecular machines. It works remarkably well, using systemsso complex that medical science still doesn’t understand many of them. Failures, though,are all too common.Many of the cells are very tiny, but they are very active; they manufacture varioussubstances; they walk around; they wiggle; they fight infection; pump blood and they doall kings of marvelous things- all on a very small scale. They also store information•Nanorobotswould constitute any “smart”structure capable of actuation, sensing,signaling, information processing, intelligence, manipulation and swarm behaviorat nanoscale (10-9m).•Bio nanorobots–Nanorobots designed (and inspired) by harnessing properties ofbiological materials (peptides, DNAs), their designs and functionalities. These areinspired not only by nature but machines too.•Nanorobots could propose solutions at most of theBIOMEDICAL APPILICATIONS OF NANOROBOTICSThe enormous potential in the biomedical capabilities of nanorobots and the imprecisionand side effects of medical treatments today make nanorobots very desirable. Medicaltreatment today involves the use of surgery and drug therapy. Surgery is a direct, manualapproach to fixing the body. However, no matter how highly trained the specialists maybe, surgery can still be dangerous since anesthetics, infections, organ rejection, andmissed cancer cells can all cause failure. Surgeons lack fine-scale control. From theperspective of a cell, a fine surgical scalpel is as crude as a blunt tool. Invasive surgerywounds peripheral tissue and causes unnecessary harm to the patientDrug therapy affects the body at the molecular level. Drug molecules are dumped into thebody where they are transported by the circulatory system. They may come into contactwith un-targeted 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 totrack them down and destroy them wherever they ma~ be growing. This is why themedical profession is looking towards the use of biomedical, nanotechnologicalengineering to refine the treatment of diseases.PROPERTIES OF NANOMEDICAL ROBOTSNanorobots will typically be .5 to 3 microns large with 1-100 nm parts. Three microns isthe upper limit of any nanorobot because nanorobots of larger size will block capillaryflow. The nanorobot’s structure will have two spaces that will consist of an interior and
exterior. The exterior of the nanorobot will be subjected to the various chemical liquids inour bodies but the interior of the nanorobot will be a closed, vacuum environment intowhich liquids from the outside cannot normally enter unless it is needed for chemicalanalysis. A nanorobot will prevent itself, from being attacked by the immune system byhaving a passive, diamond exterior. The diamond exterior will have to be smooth andflawless because past experiments have shown that this prevents Ieukocytes activitiessince the exterior is chemically inert and have low bioactivity. Nanorobots willcommunicate with the doctor by encoding messages to acoustic signals at carrier wavefrequencies of 1-100 MHz. When the doctor gives a command to the nanorobots, thenanorobots can receive the message from the acoustic sensors on the nanorobots andimplement the doctor’s orders. Replication is a crucial basic capability for molecularmanufacturing. However, in the case of nanorobots, we should restrict manufacturing toin vitro (in laboratory) replication. Replication in the body (in vivo) is dangerous becauseit might go out of control. If even replicating bacteria can give humans so many diseases,the thought of replicating nanorobots can present unimaginable dangers to the humanbody. When the nanorobots are finished with their jobs, they will be disposed from thebody to prevent them from breaking down and malfunctioning.PRINCIPAL NANOROBOTIC APPLICATIONSThe availability of advanced nanomedical instrumentalities should not significantly alterthe classical medical treatment methodology, although the patient experiences andoutcomes will be greatly improved. Treatment in the nanomedical era will become fasterand more accurate, efficient and effective.A. DRUG DELIVERYNanotechnology provides a wide range of new technologies for developing customizedsolutions that optimize the delivery of pharmaceutical products.To be therapeutically effective, drugs need to be protected during their transit to the targetaction site in the body while maintaining their biological and chemicals properties. Somedrugs are highly toxic and can cause harsh side effects and reduced therapeutic effect ifthey decompose during their delivery. Depending on where the drugs will be absorbed(i.e. colon, small intestine, etc), and whether certain natural defense mechanisms need tobe passed through such as the blood-brain barrier, the transit time and delivery challengescan be greatly different. Once a drug an-ives at its destination, it needs to be released atan appropriate rate for it to be effective. If the drug is released too rapidly it might not becompletely absorbed, or it might cause gastro-intestinal 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, thedrug delivery system must allow the drug to bind to its target receptor and influence thatreceptor’s signalling and action, as well as other drugs, which might also be active in thebody.Drug delivery systems also have severe restrictions on the materials and productionprocesses that can be used. The drug delivery material must be compatible and bindeasily with the drug, and be bioresorbable (i.e. degrade intofragments after use which areeither metabolized or eliminated via normal excretory routes). The production processmust respect stringent conditions on processing and chemistry that won’t degrade the
drug, and still provide a cost effective product.Nanotechnology can offer new drug delivery solutions in the following areas.1. Drug EncapsulationOne major class of drug delivery systems is materials that encapsulate drugs to protectthem during transit in the body. Drug encapsulation materials include liposomes andpolymers (i.e. Polylactide (PLA) and Lactide-co-Glycolide (PLGA)) which are used asmicroscale particles. The materials form capsules around the drugs and permit timed drugrelease to occur as the drug diffuses through the encapsulation material. The drugs canalso be released as the encapsulation material degrades or erodes in the body.Nanoparticle encapsulation is also being investigated for the treatment of neurologicaldisorders to deliver therapeutic molecules directly to the central nervous system beyondthe blood-brain barrier, and to the eye beyond the blood-retina barrier. Applications couldinclude Parkinson’s, Huntington’s, Alzheimer’s, ALS and diseases of the eye.2. Functional Drug CarriersAnother class of drug delivery systems where nanotechnology offers interesting solutionsis in the area of nanomaterjals that carry drugs to their destination sites and also havefunctional properties. Certain nanostrucfures can be controlled to link with a drug, atargeting molecule, and an imaging agent, then attract specific cells and release theirpayload when required.B. DRUG DISCOVERYNano and micro technologies are part of the latest advanced solutions and new paradigmsfor decreasing the discovery and development times for new drugs, and potentiallyreducing the development costs. Traditional trial-anderror methods have contributed to adiscovery process lasting 10 years or more for new drugs to reach the market. In recentyears, a number of new and complementary technologies have been developed whichconsiderably impact the drug discovery process.High-throughput arrays and ultra-sensitive labeling and detection technologies are beingused to increase the speed and accuracy of identifying genes and genetic materials fordrug discovery and development. These micro and nano technologies along withinformation technology solutions such as combinatorial chemistry, computationalbiology, computer-aided drug design, data mining, and data processing tools areaddressing the challenges related to eliminating critical bottlenecks in drug discoveryreplacement. While most types of tissues repair the interaction of stem cells withchemical modulators, there are differences in the ways that various tissues heal.“Hard” tissues such as bone and teeth heal by reproducing tissues indistinguishable fromthe original. However in cases where a dental or artificial bone implant is required, thestructural material used in the implant may trigger immune rejection, corrode in the bodyfluids, or no longer bond to the host bone. This can require additional surgery or result inthe loss of the implant’s function. In many cases, the failure occurs at the tissue-implantinterface, which may be due to the implant material weakening its bond with the naturalmaterial.
To overcome this, implants are often coated with a biocompatible material to increasetheir adherence properties and produce a greater surface area to volume ratio for thehighest possible contact area between the implant and natural tissue. “Soft” tissues suchas skin, muscle, nerves, blood vessels and ligaments repair damaged areas with fibroustissue. Damaged tissue from various sources such as burns and ulcers can be self-repairedby the body, but can also result in scar formation. Graft material using artificial sheetscan replace skin and other tissue with reasonable graft stability and cosmetic outcome.Nanotechnology can new offer new solutions for tissue repair and replacement in thefollowing’ areas.. IMPLANTABLE DEVICSNanotechnology offers sensing technologies that provide more accurate and timelymedical information for diagnosing disease, and miniature devices that can administertreatment 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. Somemedical information is extremely time sensitive such as finding out if there is sufficientblood flow to an organ or tissue after transplant or reconstructive surgery, beforeirreversible damage occurs.Certain medical tests such as biopsies are subjective and can provide inconclusive orincorrect results. In a false negative result where a needle misses the tumor and thensamples a normal tissue, the cancer nay go untreated and can impact a patient’s chancesfor long-term survival.Some tests such as diabetes blood sugar levels require patients to administer the testthemselves to avoid the risk of their blood glucose falling to dangerous levels. Certainusers such as children and the elderly may not be able to perform the test properly, timelyor without considerable pain.People who are exposed to radiation or hazardous chemicals in their work environmentare at a higher risk of illness. Occasional testing is typically done but may not detect adisease in its early stage. Early detection could initiate timely treatment with a higherchance of success, and have a worker removed from the hazardous environment toprevent further damage.Nanotechnology can new offer new implantable and/or wearable sensing technologiesthat provide continuous and extremely accurate medical information. Complementarymicroprocessors and miniature devices can be incorporated with sensors to diagnosedisease, transmit information and administer treatment automatically if required.Example applications are as follows.I Retina ImplantsRetinal implants are in development to restore vision by electrically stimulatingfunctional neurons in the retina One approach being developed by various groupsincluding a project at Argonne National Laboratory is an artificial retina implanted in theback 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 bemore precise and offer greater sound quality.D. SURGICAL AIDS1 Operating ToolsMedical devices that contain nano and micro technologies will allow surgeons to performfamiliar tasks with greater precision and safety, monitor physiological and biomechanicalparameters more accurately, and perform new tasks that are not currently done.2 Surgical RoboticsRobotic surgical systems are being developed to provide surgeons with unprecedentedcontrol over precision instruments. This is particularly useful for minimally invasivesurgery. Instead of manipulating surgical instruments, surgeons use their thumbs andfingers to move joystick handles on a control console to maneuver two robot armscontaining miniature instruments that are inserted into ports in the patient. The surgeon’smovements transform large motions on the remote controls into micro-movements on therobot arms to greatly improve mechanical precision and safety.E DIAGNOSTIC TOOLS1 Genetic TestingNano and micro technologies provide new solutions for increasing the speed andaccuracy of identifying genes and genetic materials for drug discovery and development,and for treatment-lnked disease diagnostics products.dyes are not always precise or sufficiently sensitive3Ultra-sensitive Labeling and Detection TechnologiesSeveral new technologies are being developed to improve the ability to label and detectunknown target genes. At Genicon, gold nanoparticle probes are being treated withchemicals that cling to target genetic materials and illuminate when the sample is exposedto light.Killing cancer cells.The device would circulate freely throughout the body, and would periodically sample itsenvironment by determining whether the binding sites were or were not occupied.Occupancy statistics would allow determination of concentration. Today’s monoclonalantibodies are able to bind to only a single type of protein or other antigen, and have notproven effective against most cancers. The cancer killing device suggested here couldincorporate a dozen different binding sites and so could monitor the concentrations of adozen different types of molecules. The computer could determine if the profile ofconcentrations fit a pre-programmed “cancerous” profile and would, when a cancerousprofile was encountered, release the poison.Beyond being able to determine the concentrations of different compounds, the cancerkiller could also determine local pressure.By using several macroscopic acoustic signal sources, the cancer killer could determineits location within the body much as a radio receiver on earth can use the transmissionsfrom several satellites to determine its position (as in the widely used GPS system). .
The cancer killer could thus determine that it was located in (say) the big toe. If theobjective was to kill a colon cancer, the cancer killer in the big toe would not release itspoison. Very precise control over location of the cancer killer’s activities could thus beachieved. The cancer killer could readily be reprogrammed to attack different targets (andcould, in fact, be reprogrammed via acoustic signals transmitted while it was in thebody). This general architecture could provide a flexible method of destroying unwantedstructures (bacterial infestations, etc).Providing oxygenA second application would be to provide metabolic support in the event of impairedcirculation. Poor blood flow, caused by a variety of conditions, can result in serious tissuedamage. A major cause of tissue damage is inadequate oxygen. A simple method ofimproving the levels of available oxygen despite reduced blood flow would be to providean “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 timethat carbon dioxide is being released, and oxygen is being released in the tissues whencarbon dioxide is being absorbed, the energy needed to compress one gas can be providedby decompressing the other. The power system need only make up for losses caused byinefficiencies in this process. These losses could presumably be made small, thus albwingour artificial red blood cells to operate with little energy consumption conditions oftemperature and pressure. Thus, our spheres are over 2,000 times more efficient per unitvolume than blood; taking into account that blood is only about half occupied by redblood cells, our spheres are over 1,000 times more efficient than red blood cells.Artificial mitochondriaWhile providing oxygen to healthy tissue should maintain metabolism, tissues alreadysuffering from ischemic injury (tissue injury caused by loss of blood flow) might nolonger be able to properly metabolize oxygen. In particular, the mitochondria will, atsome point, fail.15Increased oxygen levels in the presence of nonfunctional or partially functionalmitochondria will be ineffective in restoring the tissue. However, more direct metabolicsupport could be provided. The direct release of ATP, coupled with selective release orabsorption of critical metabolifes (using the kind of selective transport system mentionedearlier), should be effective in restoring cellular function even when mitochondrialfunction had been compromised. The devices restoring metabolite levels, injected into thebody, should be able to operate autonomously for many hours ~depending on powerrequirements, the storage capacity of the device and the release and uptake rates requiredto maintain metabolite levels).8. Further possibilitiesWhile levels of critical metabolites could be restored, other damage caused during theischemic event would also have to be dealt with. In particular, there might have beensignificant free radical. damage to various molecular structures within the cell, includingits DNA. If damage was significant restoring metabolite levels would be insufficient, byitself, to restore the cell to a healthy state. Various options could be pursued at this point.
If the cellular condition was deteriorating (unchecked by the normal homeostaticmechanisms, which presumably would cease to function when cellular energy levels fellbelow a critical value), some general method of slowing further deterioration would bedesirable.Cooling of the tissue, or the injection of compounds that would slow or blockdeteriorative reactions would be desirable. As autonomous molecular machines withexternally provided power could be used to restore function, maintaining function in thetissue itself would no longer be critical. Deliberately turning off the metabolism of thecell to prevent further damage would become a feasible option. Following some intervalof reduced (or even absent) metabolic activity during which damage was repaired, tissuemetabolism could be restarted again in a controlled fashion.It is clear that this approach should be able to reverse substantially greater damage thancan be dealt with today. A primary reason for this is that autonomous molecular machinesusing externally provided power would be able to continue operating even when thetissue itself was no longer functional. We would finally have an ability to heal injuredcells, instead of simply helping injured cells to heal themselves.CONCLUSIONAll of these current developments in technology directs humans a step closer tonanorobots and simple, operating nanorobots is the near future. Nanorobots cantheoretically destroy all common diseases of the 2lstcenturythereby ending much of thepain and suffering. It can also have (alternative, practical uses such as improvedmouthwash and cosmetic creams that can expand the commercial market in biomedicalengineering. People can envision a future where people can self-diagnose their ‘ownailments with the help of nanorobot monitors in their bloodstream. Simple everydayillnesses can be cured without ever visiting the physician. lnvasivesurgery will bereplaced by an operation carried out by nano-surgical robots. Although research intonanorobots is in its preliminary stages, the promise of such technology is endless.