This article describes and analyzes the state-of-the-art technology that could lead to novel medical applications and how they can improve outcomes for patients with medical conditions. Some of the issues to consider include the diagnostic and therapeutic applications and a possible model used in controlling medical conditions, such as diabetes. Just as biotechnology extends the range and efficacy of treatment options available from nanomaterials, the advent of molecular nanotechnology will again expand enormously the effectiveness, comfort and speed of future medical treatments while at the same time significantly reducing their risk, cost and invasiveness. This will help the ability to design, construct and deploy large numbers of microscopic medical nanorobots.
1 Introduction
Nanotechnology is the study of the control of matter on an atomic and molecular scale [3]. According to Bhushan, B., (2006, pg 1). nanotechnology "encompasses the production and application of physical, chemical, and biological systems at scales ranging from individual atoms or molecules to submicron dimensions, as well as the integration of the resulting nanostructures into larger systems" [1]. Nanotechnology generally deals with structures of the size 100 nanometers or smaller in at least one dimension, and involves developing materials or devices within that size.
Molecular nanotechnology (MNT) otherwise known as nanorobotics is the "technology of creating machines or robots at or close to the microscopic scale of a nanometer (10^9 meters) [12]. Medical nanorobotics refers to the still largely theoretical nanotechnology engineering discipline of designing and building nanorobots. This article presents an innovative nanorobot architecture based on nanobioelectronics for medical conditions, such as diabetes. "The progressive development towards the therapeutic use of nanorobots must be observed as the natural results from some on-going and future achievements in biomedical instrumentation, wireless communication, power transmission, new materials engineering, nanoelectronics, chemistry, proteomics, and photonics"[2].
Illustration about the nanorobots integral circuit architecture and layout described here with a computational approach with the application of medical nanorobotics for diabetes is simulated using clinical data. Integrated simulation can provide interactive tools for addressing nanorobot choices on sensing hardware design specification, manufacturing analysis and methodology for control investigation. A physician can help a patient to avoid hyperglycemia by means of a hand-held device, like cell phone, enclosed with cloth which is used as a smart portable device to communicate with nanorobots. Therefore, this type of technology provides a suitable choice to establish a practical medical nanorobotics platform for in vivo health monitoring.
2 Nanotechnology and Nanomedicine
According to Vogel (1999, p.3), "the offset of a gold rush into the 'nano' by which the world of the very small is currently discovered, will surely also lead to splendid new entrepreneurial opportunities" [11].
With the advancement of nanotechnology applications, such as nanorobotics, progress impacting on human health has come much faster than expected. People now associate nanomedicine with engineered nanoparticles in the context of drug delivery devices or advanced medical applications. Therefore, it is now important to integrate multiple tasks into drug delivery device, from targeting specific tissues to releasing drugs in contrast with their environment.
"Nanomedicine is the application of nanotechnology to medicine. It is the preservation and improvement of human health, using molecular tools and molecular knowledge of the human body" [4]. The third major development of nanomedicine is molecular nanotechnology (MNT), or simply nanorobotics. Just as biotechnology extends the range and efficacy of treatment options available from nanomaterials, the advent of molecular nanotechnology will again expand enormously the effectiveness, comfort and speed of future medical treatments while at the same time significantly reducing their risks, cost and invasiveness. This will help the ability to design, construct and deploy large numbers of microscopic medical nanorobots.
2.1 Medical Microrobotics
There are now series of attempts by researchers to build microrobots for in vivo medical use. In 2002, some researchers, Ishimaya et al. developed tiny magnetically driven spinning screws at Tohoku University. These screws were intended to swim along veins and carry drugs to infected tissues or even to burrow into tumors and kill them with heat [4]. Also in 2003, the "MR-Sub" project of Martel's group at the NanoRobotics Laboratory of Ecole Politechnique in Montreal tested using variable MRI magnetic fields to generate forces on an untethered microrobot containing ferromagnetic particles, developing sufficient propulsive power to direct the small device through the human body.
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Figure 1. A Nanobot created at Carnegie Mellon University [7]
2.2 Manufacturing Medical Nanorobots
According to Freitas (2005) "the greatest power of nanomedicine will emerge, perhaps in the 2020s, when we can design and construct complete artificial nanorobots using rigid diamondoid nanometer-scale parts like molecular gears and bearings" (see Figure 2) [4]. These nanorobots will have complete autonomous subsystems which include onboard sensors, motors, manipulators, power supplies, and molecular computers. Getting all these components together in the right sequence will prove increasingly difficult as machine structures become more and more complex. Building complex nanorobotic systems requires manufacturing techniques that can build a molecular structure by what is called "positional assembly". This process will involve picking and placing molecular parts one by one, moving them along controlled paths like the robot arms that manufacture cars on automobile assembly lines. The process is repeated over and over with all the different parts until the final product, such as nanorobot is fully assembled.
Figure 2. A molecular planetary gear [4]
2.2.1 Molecular Planetary Gear
A molecular planetary gear is a mechanical component that might be found inside a medical nanorobot [4]. The gear converts shaft power from one angular frequency to another. The case round it is made up of strained silicon shell with sulfur termination, with each of the nine planet gears attached to the planet carrier by a carbon to carbon single bond. The planetary gear shown in figure 2 has not been built as a result of an experiment, but has been modeled computationally. [Copyright 1995. Institute for Molecular Manufacturing (IMM).
2.2.2 Microbivores and Respirocytes
The ability to assemble complex diamondoid medical nanorobots to molecular precision, and then to build them cheaply enough in large numbers for them to be useful therapeutically, will involve the practice of medicine and surgery. Nanorobotic artificial phagocytes called "microbivores" [see figure 3] could go round the bloodstream, looking for and digesting unwanted pathogens including bacteria, viruses, or fungi [4]. Microbivores would achieve complete clearance of even the most severe infections in hours or less. This is much better than the weeks or months of antibiotic-assisted natural phagocytic defenses.
Figure 3. "Microbivores" Copyright 2001 Zyvex Corp.[4]
It is stated in an article written by Martinac, K and Metelko, Z that Freitas, R. A. has designed an artificial red blood cell called 'respirocyte', a spherical nanorobot of about the bacterium size. The respirocyte would be made up of 18 billion atoms, precisely arranged in a crystalline structure to form a miniature pressure tank [8]. According to research, the tank would hold as many as nine billion oxygen and carbon dioxide molecules. When respirocytes are injected to a patient's bloodstream, sensors on the surface would detect oxygen and carbon dioxide levels in the individual's blood.
When it is time to load oxygen and unload carbon dioxide, or vice versa, the sensors would signal. Respirocytes could store and transfer transport 200 times more gas than red blood cells [8].
Figure 4. Respirocyte [8]
2.2.3 Surgical Nanorobotics
Surgical nanorobots could be introduced to the body through the vascular system or at the ends of catheters into various vessels and other cavities in human body [4]. A surgical nanorobot could perform several functions, such as searching for pathology and then diagnosing and correcting any abnormal tissues or cells by nanomanipulation on a computer while maintaining contact with the supervising surgeon via coded ultrasound signals.
Nanorobots equipped with operating instruments and mobility will in future be able to perform precise and refined intracellular surgeries which will be beyond the capabilities of direct manipulation by human hand. Microsurgery was a considerable refinement over crude macrosurgery, and it opened up the possibility of using procedures that were not carried out previously or were associated with high mortality and morbidity [5]. By opening up the world beyond microscale, nanotechnologies will have a similar impact on medicine and surgery.
3 Medical Nanorobotics
Like a regular robot, a nanorobot may be made of many parts, such as gears and bearings [see Figure 2] composed of strong diamond-like material [5]. A nanorobot will have motors to make things move and probably arms and legs for movement. It will have a power supply for energy, sensors to guide its actions, and an on-board computer to control its behavior. Nanorobot is said to be very small in comparison to a regular robot. A nanorobot that would travel through the bloodstream must be tiny enough to squeeze through the human body.
Researchers working on medical nanorobotics are creating technologies that could lead to novel health-care applications, such as new ways of accessing areas of the human body that would otherwise be unreachable without invasive surgery (Kroeker, 2009). In a play in 1920, Karel Capek was the first person to use the word 'robot' [7]. Since then, different types of electromechanical systems have emerged from research laboratories. These systems are now making their way onto production lines for industrial tasks, being delivered into many toy stores for entertainment, and even into different homes to be used in performing household jobs.
3.1 Early Thoughts in Medical Nanorobotics
One of the first early thinkers of medical nanorobotics is the famous scientist, late physicist Richard P. Feynman. Feynman worked on the Manhattan project at Los Alamos during the second world war, he later taught at Caltech for most of his careers. Feynman wanted a medical application for his new technology; he then discussed his idea with a colleague and offered the first known proposal for a nanomedical procedure to cure heart disease.
In his prescient '1959' talk "There is plenty of room at the Bottom", Feynman proposed employing machine tools to make smaller machine tools, these smaller machines can be used in turn to make smaller machine tools and so on all the way to the atomic level. Feynman was clearly aware of the potential medical applications of the new technology he was proposing. He said in his proposal "although it is a very wild idea, it would be interesting in surgery if you could swallow the surgeon" [3]. He also said "you will have to put the mechanical surgeon inside the blood vessel and it goes into the heart and looks around. It will then find out which valve is the faulty one and take a little knife and slices it out. Other small machines might be permanently incorporated in the body to assist some inadequately functioning organ" [3].
During his historic lecture in 1959, Feynman urged people to consider the possibility, in connection with biological cells, "that we can manufacture an object that maneuvers at that level!" [3]. Two decades later, the vision of Feynman's remarks became a serious area of inquiry when K. Eric Drexler, while still a graduate student at the Massachusetts Institute of Technology, published a technical paper suggesting that it might be impossible to construct, from biological parts, nanodevices that could inspect the cells of a living human being and carry on repairs within them. This was followed a decade later by Drexler's seminar technical book laying the foundations for molecular machine systems and nanorobotics and subsequently by Freitas's technical books (6, 8) on medical nanorobotics.
3.2 Role of Nanotechnology in Medicine
As we can see in this article, the main objective of nano-scientists is to virtually imitate nature. Scientists are trying to construct objects out of their most basic components, atom by atom, the way that nature does it. This process offers an unprecedented degree of precision and control over the final product. With this in mind, we can consider nanotechnology as enabling technology; it will allow us to do radical new things in virtually every technological and scientific arena.
Nanoscale structured materials are parts of nanomedicine with a rapid evolution, because of the impact of pharmaceutical industry [8]. Pharmaceutical companies are now trying to develop targeted drug delivery using nanotechnology and drugs that already exist. The truth of the matter is that we do have useful drugs, but the problem we are experiencing is how to deliver drugs right where we need it. As a form of resolution, scientists are contemplating the possibility of using magnetic nanoparticles containing drugs to be delivered to specific parts of the body by means of magnetic field.
Drugs can also be attached to nano-ligand, the role of which would be to deliver the drug only to target tissue while at the same time reducing its side effects [8].
4 Medical Conditions and Nanomedicine
Many scientists have lately focused their research on nanomedicine and nanodiagnostics for many diseases, like diabetes, cancer, spinal cord injury, kidney, heart problems etc. For the scientists, to produce refined and complex nanomedicine (hypoglycemic drugs) for all types of diseases, especially diabetes is on the priority to reduce the cost and pain of the patients. It has been discovered that people with diabetes mellitus are more at risk having heart disease than people without diabetes. More than 60% of people with end-stage renal disease are people with diabetes [9]. Nanomedicine has potential impact on the prevention, early and reliable diagnosis and treatment of disease. The World Health Organization (WHO) recognizes three main types of diabetes: type 1, type 2 and type 3 which is also known as "gestational diabetes" which occurs during pregnancy [9].
Apart from acute glucose abnormalities, the main risks to health are the long-term complications involved, like cardiovascular disease, chronic renal failure, retinal damage (which can lead to blindness), nerve damage, and poor healing which can lead to gangrene and even amputation. Nanotechnology has now achieved the status as one of the critical research endeavors of the early 21st century, as scientists continue in their research to build the unique properties of atomic and molecular structure known as "positional assembly" built at the nanometer scale.
4.1 Role of Nanomaterials in Diabetes
According to research carried out by Mishra et al (2008) "about 150 million people suffer from diabetes in the world and it has been predicted that this number will be doubled within the next 15 years. Researchers state that type 2 diabetes accounts for about 85% of all cases with diabetes.
Type 2 diabetes is considered a paradigm for a multifactorial polygenic disease where common variations in several genes interact to cause the disease when exposed to an enriched environment of too much food and very little exercise [9].
4.2 Diagnostic and Therapeutic Applications (Diabetes Control)
Although the science of nanomedicine is still in its infancy, it has major potential applications in controlling medical conditions such as diabetes. These include solving non-invasive glucose monitoring using implanted nanosensors, with key techniques being fluorescence resonance energy transfer (FRET) and fluorescence lifetime sensing, as well as new nanoencapsulation technologies for sensors, such as layer-by-layer (LBL) films [10]. Other applications of nanomedicine include targeted molecular imaging in vivo (e.g. tissue complications) using quantum dots (QDs) or gold nanoparticles, and single-molecule detection for the study of molecular diversity in diabetes pathology.
Nanomedicine, which is the application of nanotechnology to medicine, has already offered some new solutions, and many pharmaceutical companies are trying to develop targeted drug delivery using nanotechnology and existing drugs. Scientists have offered some solutions in treating diabetes; these solutions include boxes with nanopores that protect transplanted beta cells from the immune system attack, artificial pancreas and artificial beta cell instead of pancreas transplantation, nanospheres as biodegradable polymeric carriers for oral delivery of insulin. The abilities of nanomedicine are huge, and nanotechnology could give medicine an entirely new outlook [8]
4.2.1 Pancreatic Beta Cells
Mauro Ferrari from Ohio State University and Tejal Desai from Boston have created what could be considered one of the earliest therapeutically useful nanomedical devices [8]. The scientists have created a tiny silicon box that contains pancreatic beta cells taken from animals. The box is surrounded by a material with a very specific nanopore size (about 20 nanometers in diameter) [8]. These boxes can be implanted under the skin of diabetes patients and could temporarily restore the body's delicate glucose without the need of powerful immunosuppressant that can leave the patient with a risk of serious infection.
4.2.2 Artificial Pancreas
Another possible permanent solution for diabetic patients is artificial pancreas. The idea of this solution is to create a sensor electrode that would repeatedly measure the level of blood glucose; this information feeds into a small computer that energizes an infusion pump, and the needed units of insulin enter the blood stream from a small reservoir.
4.2.3 Nanorobotic Delivery of Insulin
Researchers are also trying to create a nanorobot which would have insulin departed in inner chambers, and glucose-level sensors on the surface. When blood glucose levels increase, the sensors on the surface would record it and insulin would be released. This type of nano-artificial pancreas is still a theory, but scientists are working to develop them [8].
Conclusion
This article describes and analyzes the state-of-the-art technology that could lead to novel medical applications. It also discusses the diagnostic and therapeutic applications with a model to control medical conditions, such as diabetes. According to Freitas (2009), medical nanorobots are just theory at the moment. To actually build them, scientists will need to create a new technology called molecular manufacturing. Molecular manufacturing is the production of complex atomically precise structures [see Figure 2] using positional controlled fabrication and assembly of nanoparts inside a nanofactory.
There is also a critical analysis of different types of nanomaterials which could have impact on the prevention, early and reliable diagnosis and treatment of diseases, such as diabetes. Nanomedicine is defined as the application of nanotechnology to medicine. It takes advantage of the improved and novel physical, chemical and biological properties of materials at the nanometric scale.
The objective of developing nanomedicine is to target selected cells or receptors within the body. This technique is driven by the need to increase patient acceptability and reduce healthcare costs, and on the other hand to deliver new class of pharmaceuticals that cannot be delivered effectively by conventional methods.
