Nanotechnology is an evolving field of manufacturing micron-scale*4 devices in the scale of nano meters which is promising loads in term of medicine. Nanotechnology aims to construct objects at atomic level by binding molecule by molecule as nature does. Since the human body also functioning by the conjunction of molecules, scientists pay greater attention towards nanotechnology. The application of nanotechnology in the field of medicine is known as Nanomedicine. Though conventional medicine provides therapies, nanomedicine specifies clean, light weight and strong means.*7 Nanotechnolgy declare nanorobots to move in the blood stream, observe entire particles inside the body, perform nanosurgery and communicate with bio sensors, motors, power generators and observation systems. *6
Nanorobots are designed with nano particles, implanted into human body and react according to the pre programmed codes and provide clinical data to a receiver. Nanotechnology tends to provide diagnosis, therapeutic actions via targeted drug delivery through these microns. Nano robots are mostly made of carbon in the form of Diamond which doesn't get affected by the immune system of body. Though, other light molecules such as oxygen and nitrogen can be useful in some cases.
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Nanorobot fabrication process should achieve,
Precise assembling of molecules on formation
Able to fabricate any design in consistent adhere to physics laws
Less manufacturing cost *7
Manufacturing industry exercise two approaches to achieve above,
In positional assembly approach nanostructures assembled together manually by mini devices. For example, a mini robot could be employed to pick molecules one by one and build an artificial cell. This approach is more suitable to form complicate structures.
The other approach describes the way of just adding all the molecules together and let them assemble. Affinity between the molecules makes this possible which is a less painful approach. As an instance we could use DNA's for self assembling structures. DNA is made up of two complementary nucleotides. So a nucleotide chain formed with one kind binds automatically with the other one to form a DNA*6. However, in practical both of these methods applied together to deduct the cost of fabrication.
The power for nanorobots can be provided via metabolism or externally via acoustic energy. A navigational system can be installed with micro elements to keep track of the nano robots. The navigation system would collect and provide accurate information to the physician from nano robots which pass through. Then the physician can provide appropriate instructions on next level healing or flushing of nanorobots via acoustic signals. Nanorobots use surface antigens to distinguish between the cells.
When the tasks completed Nanorobotics can be expelled via natural excrete ways or they can be shattered into particles that could be useful for body such as iron.
The above technology remains as the basis for various diagnostic and therapeutic applications.
In medical terms, diagnosis is the process of determining the disease by its nature through various kinds of analyzing methods for prognosis and treatment. But with traditional sampling methods and imaging such as blood, saliva, urine, pulse and x-rays, false positive and false negative rates remain at consider rates.
Nevertheless nanotechnology promises to get rid of the word 'uncertainty' from medicine. For that there are plenty of ongoing R&D projects in vivo and in vitro to improve efficacy on sensitivity and reliability. *8 These envisioned nano devices will cover organs, tissues, vessels, hormones, and genetics. Even they can produce targeted three dimensional maps in vivo. This kind of data collection aids the physicians in situations where patient is depressed or unconscious or unaware of the disease or unable to clarify or dumb. Physicians do not need to remember each and every symptom and signs for disease. Practitioners should only remember what to look for in the diagnosis. In near future they will be aided with tools to provide details at molecular level in real-time.
With the application of nanotechnology diagnosis can be characterized into in vitro and in-vivo applications. Nano technology enables in-vitro applications such as bio agents, integrated devices and in-vivo applications such as imaging devices and implantable devices.
Traditional in-vitro methods as specified above are inaccurate, deteriorate, time consuming and hard to conclude. But with the combined effect of nanoelectronics field, contemporary devices provide more accurate, less complicate and cost effective nanoanalytical tools. Optical, electron and scanning probe microscopy is one of them. As an impact, the nanomedicine field has taken a step towards implementing the nanostructurers, which is still only a theory. The other major one is medical imaging field in which dramatic refinement of contrast agents is being applied. Consequently, diseases can be detected as early as possible at cellular level and effectiveness of therapy can be monitored.
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The biosensor is one of the other valuable in-vitro tool for analyzing and reporting. In terms of medicine biosensor is a detector which monitors the activity of a bimolecular and signals via biochemical reactions. Nano ink tattoo developed to monitor glucose levels is one of them. 10
The lab-on-a-chip (LOC) devices integrate many lab functions together and analyze for loads of signals from a single sample. As a superior technology "Cells on chips" analyze morphology and metabolism *11 at cell level.*8.1
In-vivo imaging aims to visualize real-time, realistic images at molecular level to improve diagnosis, therapy and continuous monitoring. Recently, nanomedcine R&Ds tend to focus on nanoparticles as contrast agents instead of Magnetic Resonance techniques and X-rays. Targeted molecular imaging leads to novel medical applications and become valuable in wide range as follows,
To scan the whole anatomy of human
Identify the exact impact of a disease (for instance cancer - cell)
Cure only the exact part of anatomy (targeted drug delivery R&D)
Researches on reducing toxicity with exact healing
Direct interaction with physician with sequential imaging *11 for therapy control and surgery
At present, contrast mediums such as Quantum dots and dye-doped silica nanoparticles are flourishing in the field of nanoimaging. *12
Quantum dots are semi conductor crystals which offers high luminous and photo stability. Compared to other conventional fluorescent techniques Quantum Dots in-vivo imaging is stable and tunable. *13 QDot implanted into a protein can monitor, which in-vivo molecules attracted to the protein, the parts attracted in the molecule, and signaling of receptors. This would be an ideal application for monitoring cancer cells of a patient by comparing the output with the expected results. *14
Dye-doped silica NPs
Dye-doped silica nano particle is a silica particle filled with dye molecules either organic or inorganic to provide fluorescence nanoimaging. As these NPs packed with large amount of dye they are reliable for long-lasting and highly tuned signals. Since, dye is separated from the environment by silica these NPs remains suitable for high intensity environments. *13
Nanomedicine proposes restoration and reconstruction at molecular level from cells and tissues. Therapeutic methods will reverse the pathological effects and transform the genes for healing. These methods will ascertain efficient and effective of curing in less time, less painful and no side effects. Further, nanotechnology could provide tools to alter the genes from birth to cure some diseases. For instance a drug fabricated with nanorobots can destroy the pathogens, repair the effects and defused in less time.
Targeted drug delivery
During the last decade pharmacology has achieved major milestones together with nanotechnology. Though most of the nanodevices remain only in theory and research, nanotechnology has succeeded in offering several pharmaceutics to the market.
Conventional drug delivery methods haven't been effective compared to targeted delivery. Targeted drug delivery achieves exact delivery of drug to the site of interest, no side effects and continuous supply of medicine. The nanotech based targeted drug delivery methods include liposomes, nanocapsules, antibodies, lipoproteins and much more, all which increase efficacy and non toxic. Targeting techniques can be categorized as active and passive. For instance in tumor drug delivery, chemotherapeutic agents apply Enhanced Permeability and Retention effect (EFR-effect) which is passive and nanorobots exercise antigen - binding sites effect which is active. The cascade molecule with linkers,*8 which attach to pathogens based on surface antigens and destroy them until they become resistless and let the immune system hold until it destroys them completely.*p The nanoparticle remains ignored from white cells by covering the devices with polyethylene glycol chains.*8
Respirocytes, is a preliminary design of artificial red cell by the theorist Robert Freitas. Respirocyte nanorobot is a 1 micron size repository of oxygen (O2) and carbon dioxide (CO2) in 1000atm pressure under diamond surface. This design imitates the function of Hemoglobin but promises 236 times more oxygen than a real red cell and deals with carbonic acid formation.
The same theorist Robert Freitas proposes a nanorobot to mimic white cells as well. The robot microbivore is a phagocyte for antimicrobial therapeutic pupose in micron size. Microbivore is an Oblate spheroid nanorobot, mimics exact interior atoms of a white cell with gas / water molecules. Pathogenes are bounded to the surface of the nanorobot via species-specific binding sites. Then the pathogen transferred into a chamber with piston in the nanorobot for destruction and digestion. Afterwards, the output of the destruction is discharged to environment via the port in the rear. The digest and discharge process is same as natural phagocyte process but, with less response time and side effects.
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Skin disease -
Skin creams can be produced mixed with nano robots. These nanorobots can get inside through the pores and remove dead skin, apply oils & vitamins in need and clearing the pores.
Mouth wash combined with nanorobots can reach anywhere inside the mouth, even the places tooth brush can't reach. They can be used to clear the food particles in between the teeth, destroy pathogens and flourish the good odor. These nanorobots can be designed to exist for certain time (2minutes) and to be demolished in to particles.
CRT repair *3
Chromallocyte is an imaginary nanorobot for nanosurgey of chromosomes within a living cell. In Chromosome replacement therapy (CRT), the nanorobot reaches the capillary bed of the defected organ or tissue and replaces the entire chromatin within the cell. Then it reaches the blood stream and defused. In the construction phase Chromallocyte is filled with defection free, original chromosomes in ex vivo environment.
Plasmonic nanobubbles (PNB) are hopefully capable of identifying and eliminating the cancer cells. This novel application has been designed by researchers by combining diagnosis and therapy which is named as 'theranostics'. *15 These PNBs holds multi-functionality, short treatment time and more efficient.*16
The way it works is: a probe, possibly a nanorobot is occupied with gold particles and antibodies. Based on antibody - antigen mechanism the probe in the blood stream binds to the cancer cell. When the gold particle hit by a laser pulse Plasmonic nanobubble will be formed. By varying the strength of the laser beam the bubble size can be tuned. *16 It can be a brighter, short-living small bubble, which can produce high sensitive image of the cancer cell *17 or larger bubble which can burst to destroy the cancer cell. Nanometer scale, small bubbles act as a diagnosis probe by scattering the laser beam to create high sensitive map which is visible via a microscope.*16 Further, micro bubble can used to track the destruction of cell, named as 'guidance' in terms of medicine.* 18 Micrometer, larger bubbles destroy the cancer cell by expanding by a mechanical impact and blasting in the nearby cell environment.
In future PNB could be used at cell, organ and tissue levels for various diseases. This will lead to novel applications in the field of theranostics. * 16
The body remains energetic by the blood stream carried via vessels. The energy for human body is produced by the process of metabolism and under usual circumstances, pancreas release the right amount of hormones to do so. But, glucose level becomes high or low when the produced insulin becomes insufficient or inefficient. In worst case diabetes could affect the eye, heart, kidney and lead to stroke. In the insulin release process hsGLT3 molecule plays the crucial role of sensing glucose level in blood.
Nano medicine takes concern of this molecule to provide a solution for diabetes. Scientists have simulated the functions of hsGLT3 with a nanorobot which is approximately 2 nano centimeters in size. The nanorobot is embedded with CMOS (Complementary Metal Oxide Semi-conductor) and due to its bio compatibility it remains intact by the immune system. In simple terms, the implanted nanorobot in the blood stream provides a series of clinical data for diagnosis and healing.
The interval between each test can be either pre-programmed or adjusted via Radio Frequency (RF) signals. When the blood glucose level reaches a critical stage, nanorobot transmits a signal to alert the patient via his phone. Then the patient would take his prescribed injection or drugs to bring back the level to average. The glucose level targeted by this model will be 130 mg/dl and it can vary up to 30 mg/dl as prescribed. Further, this alarm could be set to alert the patient's meal time and to remind injection of insulin during the day. In addition the implanted system provides the following benefits,
Nanorobots measure the glucose at various locations of the body as opposed to the conventional medicine where they take samples only in specific areas.
Proposed method covers the whole body including organs, tissues, vessels etc whichever passes the nanorobot. This will help physicians to conclude which parts of the body has been affected by diabetes and prescribe to heal them as well.
The same nanorobots could be used to identify and diagnose other diseases such as cancer and blood pressure.
Further, there are researches in vivo to implement artificial cells and pancreas with sensors in the surface. In theory, this artificial pancreas could be designed to release insulin in response to the changes of glucose level in the surface. This would be an absolute cure method for diabetes.
Possible model to control Heart attack
Heart attack is caused by plaque formed in coronary arteries to heart. A blockage formed on vessels by fatty acids, narrow the vessels and blocks blood supply, thus making the heart cells starve for oxygen and die. At present physicians exercise endarterectomy or coronary artery bypass graft (CABG) surgery method incase of a serious blockade.
To handle such situation a preliminary design has been proposed to employ nanorobots in surgery. The design proposes to implant a nanorobot into the blood stream to scratch and remove the fatty from the walls of vessels and let the blood flow uninterrupted. The out core of fancying nanorobot modeled with a propeller, fins and sensor.
The model utilize propeller to push the nanorobot to ride through the blood stream same as ship in sea. One or more nanomotors could be used to power up the propellers. An existing implementation of nano-sized motor by William McLellan perfectly fits into this nanorobot design. With the integration of the motor the blades of the propeller will be concealed as well, though the proposal minimizes the collisions with substances in blood and vessels while travelling.
Sensors will be integrated in nanorobots to identify the exact site of interest. Sensors can be either long or short range. Long range sensors used to reach the exact site of interest and short range sensors to reach further towards the exact lipid deposit in vessel. Further, sensors become essential in early stage of nanorobot implantation where, one robot can be tracked by the other. Infrared waves fit the purpose of long range sensor in the design. An infrared signal is generated from an out side source to reflect or pass through the body or combination of them to identify the exact coronary arteries blockage. The output image will be refined to eliminate natural body signals as, infrared is in the short wave length too. On the other hand, an infrared signal is rendered from nanorobot within the body to identify the location of it. Subsequently the small range sensor comes into play to make the final move towards the plaque, guide the nanorobot in surgery and analyze the results. Spectroscopic method could be used to do so. It would provide continuous sampling of the environment to do a surgery. Sampling could be done by generating laser pulse from a diode integrated to nanorobot which is constantly charged in by capacitors.
Afterwards, plaque is physically removed from coronary arteries by means of a probe, blade or edge of the fin/blade. Then the nanorobot let the fat particles to be mingled with blood stream and naturally excreted from body. The power source for nanorobot operation could be either internal or external. Internal sources include blood stream/ body heat /onboard energy and external sources involve physical connection or energy from waves (X-ray, micro wave) generated outside the body. Encapsulated Shielded nuclear power inside nanorobot (onboard) promises uninterrupted power supply and reduces the complexity in our scenario.
The fancying nanorobot can be injected into the body via a wide diameter artery such as femoral artery. After completing therapy it can navigate to a place where the nanorobot could be terminated and filtered out .Alternatively, it can anchor to a vessel which can be removed by a simple surgery. * 19
The proposed architecture could be used as backbone for several other, novel medical applications, to be used in with some alterations.
The nanotechnology holds the potential of utilizing nanorobots effectively and efficiently via various medical applications for both curable and incurable existing diseases on earth. To achieve those targets, more and more effort required towards research and development. Besides, governments and funding organizations also have the obligation to aid R&D since the technology could offer novel medical applications to mankind. Finally, with a clear road map from experts the fancying, academic driven novel applications would clear laissez-faire approach of industry and grasp attention towards the real world implementation. *20