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This article discusses one of the applications of cutting edge nanotechnology, medicinal nanorobotics, as tools that could be used for detection and treatment for many medical conditions. This paper outlines the history of medicinal nanorobots and state of the art technologies that could be used to diagnose and cure medical conditions. Three main types of nanorobots are studied, respirocytes, microvibores and chromallocytes, and their wide application in the 21st century of advanced medicine. Concepts of respirocytes nanorobots and microvibores nanorobots are based on identical performance to natural human cells. On the contrary, chromallocytes are based on nanomachines which are not part of human nature, but can perform chromosome replacement operations within the living cell. Finally, significant focus of the article is on various approaches adopted to target cancer, using pharmacytes. Pharmacytes are agent delivery devices that would directly address particular human cell. With advanced digital precision they can penetrate human cells, initiate self- destruction process in cancer cells and leave no trace of existence when their operation is accomplished.
The term nanotechnology was coined by the Nobel Prize winning physicist Richard Feynman in his famous speech 'There is Plenty of Room at the Bottom'; dated 1959.He anticipated the move towards nanoscale world in technology. His suggestion was to involve available machines to produce small scale devices, from which even smaller could be made. This process would eventually allow manufacturing nanoscale machines.
However, the term nanorobotics started to appear in literature in late 1990s, as a result of joining two disciplines, robotics and nanotechnology. The two main leading pathfinders in this area of study are, Eric K. Drexler and Robert A.Freitas. Drexler mainly focused on studying molecule sized machines and their manufacturing process while Freitas's goal was to introduce medicinal nanorobotics . Both authors explained possible challenges that can arise while building and using these medicinal machines. They discussed wide ranges of issues related to managing molecules, sensor designs, and nanorobotics surface design, their source of power, communication and navigation systems, as well as manipulation and mobility aspects. Freitas also explained in great detail nanorobotics compatibility with an environment where they are going to be located .
The Idea of nanomedicine emerged from the concept of designing small nanorobots and other nano devices in order to enter them into a human body to target defect cells at their molecular level . Currently nanomedicine has expanded into many branches including molecular structures, such as nonbiological nano-materials, nonbiological devices, biotechnology materials and engineered organisms. Advancements in nanotechnology have been developing rapidly with the enormous financial support from many global governments and other institutions. This future technology could be used for the diagnosis, treatment and even prevention many diseases with the use of modern molecular size tools. The fundamental device used in nanomedicine is nanorobots. A nanorobot is a nanodevice or molecular device in the scale of a nanometre that can traverse the human body. Its main role is to perform various tasks at nanoscale . It is expected that in approximately ten years from now, nanorobots will be one of the integral part of medical equipment, targeting many aspects of human health.
Based on existing molecular level knowledge of human body, it will be possible to inject nanorobots into the cells and control their behaviour. Progress in constructing and developing nano tools within recent years, contributes to nanorobotics' performance and locomotion enhancement . It takes many disciplines, where experts in computer science collaborate with specialists in natural science to design and build comprehensive nanorobotics .
2. Anticipated design of Nanorobotics
The aim of today's medicine is to construct nanorobots with affordable resources and make them widely available in medicine to address many health conditions. In order to build reliable and efficient nanoscale robots, a vast part of the machine will have diamondoid structure and composition. It involves brand new manufacturing approaches so that the complex components of nanoscale elements can be assembled. It requires repetitive process of selecting molecular units and deploying them along controlled trajectories up to the point where nanorobot is engineered completely .
Medical nanorobots are designed to work in human body so they need to fulfil certain construction criteria in order to meet their various functionality requirements. Nanodevice motion is crucial to perform their tasks; therefore, they have number of driving parts. There are two mechanisms used for nanorobots motion namely active and passive driving. The passive drive allows the nanomachines to enter the patient's body and is also used while monitoring its actions. It adopts external power from magnetic and electric fields and also from blood circulation. Moreover, the nanoparts can obtain and transfer the energy if required. On the other hand, active drive uses its on board components to operate the device. These can be electric motors or pumps and membranes or molecular, which is most commonly used at present .
Another important aspect of nanorobotics construction is sensors. They provide guidance on surroundings, localization and nanomachine actions. There are long distance sensors that pilot the nanorobotics to a destination tissue. Along with them, there are short distance sensors, which can find undesirable cell. In order to navigate the device in patient's circulation system, there is range of ultrasonic and light sensors used in combination with manoeuvring action. Other biochemical sensors can detect values such as temperature, PH and radiation. There have been numerous researches conducted to build the DNA biosensor showing dependence of changes in PH and heat shock factors protein with DNA. Any variations in above mentioned values will reflect the sensor colour. This important feature will allow precisely allocating nanomachines and giving accurate diagnosis .
Moreover, medical nanorobots will be able to remove affected tissues, deliver drugs to cells and also repair genes. A tool built into the nanorobot will perform various motions in order to resect an unhealthy cell. The morbid tissue may also be damaged with microwave energy or laser evaporation and remaining material will be discharged by metabolism. The Chemical methods used by nanorobotics would interrupt development of unwanted cells and prevent their further progress. On the other hand, biological means would replace faulty gene strands with new ones .
Energy supply plays an essential role in nanorobotics operations .Nanomachines needs sufficient power for delivering its actions. Nanoscale robots will have internal energy supply coming from their microcells, charged condenser or through patient's natural energy transformation process. The external energy supply could be received from electric current physically connected with nanomachine by lead or by conversion of external energy by means of installed convertor in the nanorobotics body .
Imperative aspect of nanodevices' components is robustness of their integration. One way to combine the parts of nanorobotics is self-assembly, where biological and chemical features of particular objects are combined. Another method uses power or electromagnetic field to maneuver the component. In recent years there is an emphasis on linking organic and inorganic objects .
Finally, in order to introduce nanorobotics to human body, their biocompatibility with patient's organs must be achieved . This problem covers wide spectrum of immunity related issues, as well as physiological and biochemical reactions of human body to the foreign objects. Nanodevices will have to have biocompatible design to be recognised by human immune system and to avoid causing inflammation. Moreover, nanorobotics situated in patients' body will come across phagocytic cells that will try to absorb the devices. This arises another problem of adopting by nanorobotics certain physical functions and operations in order to avoid internalisation. Therefore, there must be many researches undertaken to prove reliability, safe use and effectiveness of these nanomachines .
3. Respirocytes, Microvibores and Chromallocytes as examples of medical nanorobotics
Respirocyte is a round shape molecular device with 1µm diamondoid and 1000 atmosphere pressure. It represents red blood cells that could provide tissues with significantly more oxygen than the natural cell. This tiny machine would also be able to handle carbonic acidity, resulting in maintaining appropriate PH levels of humans' body fluids. Respirocyte consists of 18 billion of atoms that fit into diamonoid pressure reservoir. According to designer of this machine,R. Freitas, it could pump even 3 billion gases particles, such as oxygen and carbon dioxide. The emission process can follow after the transportation of gases through the pumps and the sensors placed on the surface of the nanorobot can be used to monitor the gas accumulation. . The device will recognise the need to fill up oxygen and release carbon dioxide from lungs or another way round in case of tissues. Furthermore, internal chemical and pressure indicators along with miniature computer can be externally programmed by doctors, in order to perform various procedures .
These nanomachines are much more effective in storing and transporting gas in human red blood cells. In case of heart failure and lack of respiration, around one litre of respirocyte saline suspension injected into blood vessels could provide oxygen to patient's tissues for up to four hours. In effect, medical use of these nanorobotics will mainly support blood transfusion operations, anemia treatment, improve cardiovascular and neurovascular conditions, reduce the muscular fatigue and detect and target tumour cells .
Another kind of nanorobot that could potentially treat various medical conditions is microbivore. This type of nanorobot has an oblate, ellipsoid shape and contains 610 billion accurately positioned atoms within its microscopic body. The size of microbivore (2,0 microns width and 3,4 microns length) allows it to get through as narrow as approximately 4,0 microns in diameter human blood vessels . Its entire volume of 12.1 micron³ has two water chambers that normally remain empty and may up to 4,0 micron³ capacity. Moreover, dry mass constitutes 12.2 picograms. The machine has ability to digest captured pathogens with up to 2,0 micron³ throughput in 30 seconds cycle, using up to 200pWof constant power in this process . It is anticipated that microbivores will have much longer lifespan than leukocytes and can be even eighty times as productive as white blood cells. Their main advantage is the speed they can treat blood infections with. It will be matter of minutes to few hours when the nanorobotics remove the bacteria from the bloodstream. In comparison, leukocytes, sometimes with a support of antibiotics, take many weeks in order to eradicate particular bacteria from the blood. It proves that these nanomachines can be even a thousand times quicker acting than human natural white blood cells, whether they are assisted by antibiotics or not . Additionally, microbivores may broaden the treatment spectrum of many types of bacterial infections such as respiratory illnesses; as well as clearing the blood system from viruses and fungus molecules without causing sepsis threat . The bacteria annihilation process will involve selecting pathogens in a blood, consuming them and eventually discharging back to bloodstream in a form of harmless simple molecules. In effect, the microbivore aims the bacteria and attaches to its specially designed adhesive surface. The nanorobot then extends its microscopic manipulators in order to securely bind the pathogen and carries it to its entrance. Then the bacteria is engulfed into one of the 2 micron³ chambers where is going to be blended. The remainings of that infectious agent will then be transported to second 2 micron³ chamber, to undergo digestion process, where they will be exposed to appropriately fourty selected enzymes, turning them into inoffensive compounds. The last stage of that 30 seconds long cycle is discharging inactive molecules to bloodstream via the exhaust, placed at the back of microbivore. The whole process is known as 'digest and discharge' operation and is based on the identical concept to white blood cells in human body .
Another variance of nanorobotics is called chromallocyte, which is used in a process known as chromosome replacement therapy. It is expected that those machines will be able to enter human body cells and perform 'surgery' that is beyond the doctor's hand. Nanorobotics would be controlled to some extent by the surgeon. The root of majority of illnesses lies in the cell molecules. It is due to faulty chromosomes and gene expressions that people develop various medical conditions. In this case nanorobotics will be able to pull out faulty chromosomes from the cell and replace them with new ones. The fresh chromosomes will be prepared in external environment with use of sophisticated equipments. During the process of assembling molecules, patient's particular genome will be reproduced. This procedure will allow removing human's inherited or acquired diseases from their cells . Following the chromosomes replacement protocol, chromallocytes would leave the cell, join the bloodstream and eventually use kidneys or same mechanism used while entering, to exit the body .
4. Diagnosis and treatment of cancer with use of nanorobotics
Nowadays, there is much focus on detecting diseases in as early stages as possible, in order to deliver effective treatment and eradicate the problem completely. Modern, nanoscale technology is expected to provide faster and more precise diagnosis along with extremely responsive and reliable operations with fewer side effects. Nanorobotics will not only diagnose but also cure many general illnesses, even those presenting highest death rates. One of the medical conditions that could be a target of medical device is cancer. The cancer is a result of a change in a cell growth, showing unregulated expansion. Cancerous cells may be formed from any regular cell in the human body. With time they mount up and the mass of affected tissue violates neighbouring, healthy cells. Eventually, cancer may spread on many sides of the body .
The nanodevices are bringing promising results in spotting and curing cancer. Currently, patients undergoing radiation or chemotherapy treatments experience many adverse side effects like hair loss, fatigue, nausea and vomiting etc. This long term treatment tends to damage more normal cells than those cancer affected. The phenomenon of nanorobotics will emerge in ability to recognise the healthy cells from the malignant ones. On the other hand, there is a new process in obtaining control for dispersed collective activity in the cancer battle. With help of chemical sensors, nanorobots will be set to distinguish various amounts of E-cadherin and beta catenin proteins in both early and advanced cancer stages. Nanoscale devices will be capable to damage these particular cells .
Specific example of nanorobot that could aim cancer is pharmacyte. This medical nanodevice will be monitored by the computer and will use its own energy. It will be able to provide patient with medical agents with high precision, time efficacy and target oriented solutions .
With the current treatments , in order to aim cancerous cells, patient have to receive significant dose of chemotherapy, which destroys normal human cells at the same time. An option of pharmacytes carrying cytocidal molecules, would guarantee that only abnormal cells were addressed. Given simple instance of pharmacyte drug delivery, it will take approximately 2µg of cytocidal molecules to destroy even 1 billion malignant cells. These nanorobots would transport and distribute the agent to the aimed cells, starting their destruction . When reaching the tumour the nanomachine can directly inject the cytocidal payload to affected cells that are contiguous to blood vessels. Another way to target the malignant cell is by gradual cytopenetration of adherent cells as long as it takes to hit the tumour. Medicine has discovered that all human cells have death receptors which play role of self-destructors when certain triggers occur. The process is called apoptosis and takes place when particular cells are not needed or become dangerous to human body. In this case, the pharmacytes would be capable of activating these receptors only on cancerous cells. Featured with chemosensors, nanorobotics push appropriate ligand tool on the outer side of the malfunctioning cell, thus triggering a death receptor and consequently starting the cytocidal cascade. These types of display tools will save plenty of limited space within the nanoscale device. Other way to regulate the apoptotic operation is to use special pumps situated on nanorobot's surface. They will select threatening molecules from the affected cell . Another characteristic of pharmacytes is ability to tag their aimed cells with biochemical immune systems, in the process of 'phagocyting flagging'. Cancer cells show apoptotic behaviour, therefore, tagging procedures will target them successfully. In effect, newly recognised molecules are present on the surface of apoptotic cells. However, some molecules normally are located inside the membrane and only appear on the surface when apoptosis starts. Only cells with specific molecules are engulfed and damaged in phagocytic process. The role of pharmacytes will be to deliver and cover target cell with sufficient amount of the particular molecules. This would allow initiation of phagocytic behaviour towards cancerous cells . Any spare agent molecules would be taken back on the nanorobot board and next, pharmacytes will exit the human body, using excretory pathways. This measure can prevent from experiencing additional damage to patient's organs and will not cause inflamation after the procedure. Pharmacyte is an example of nanorobot that delivers cytocidal molecules to tumour cells, shows biocompatibility, performance and reliability and also causes minimum undesired side effects. It is also important to have control over nanodevices while they travel in human body, in order to modify their operations .
5. Nanorobotics - the other side of the coin.
Nanorobots are long awaited machines that could travel in human body and diagnose and treat many medical conditions. These smart devices would act at nanoscale, and could become the most powerful tools in a doctor's hands. Nanotechnology will allow us to distribute smallest particles such as atoms and molecules in various environments. Perspective of building and using these powerful nanorobots has raised security related concerns. Rapidly developing nanotechnology brings numerous benefits to improve human health standards. Contrary, a risk of misuse of these machines appears which could potentially harm millions of people at once. The misuse may be accidental or deliberate. Intentional abuse of nanotechnology by individuals could be avoided by in depth knowledge of that discipline. It is in scientists and engineers interest to provide reliable and safe technological solutions in order to protect whole society. The accidental misuse may occur when the molecular machines will self- replicate. There have been certain guidelines proposed, regarding manufacturing nanomachines to minimise the possibility of their misuse. Since nanotechnology is constantly evolving, outlines on its safe development are being updated along with the progress .
The aim of nanorobotics is to provide revolutionary alternative to conventional medicine. Their use is expected to bring brand new approaches in curing, examining and regenerating patient's body. Nanorobotics will be irreplaceable in situations where human's medical condition is particularly selective, sensitive and time restricted. The article has discussed some anticipated design of various nanodevices and their role in human body. More research is needed to successfully and efficiently manufacture, assemble nano scale components and testing them in the real environment. This article has presented particular example of pharmacytes and its detailed operations when targeting cancer cells. Accordingly, nanorobotics would be particularly useful when distinguishing exact position of cancerous cells and providing treatment to the specific area and finally, potential safety issues addressing the need to regulate policies on adopting and deploying nanotechnology in the real world.