Motivation

Well,Our motivation is to take you on a journey of a world which we cannot see with our naked
eyes and to explore the technology that has the potential to trigger the most significant revolution in
the history of medicine.

Background

The first scientist to mention the term “nanobots” was the physicist Richard Feyman in 1959; when
he gave his popular talk named “There’s Plenty of Room at the Bottom”. He commented about
nanodips and nanobots for curing heart diseases. Later, the scientist Eric Drexler, inspired by the
talk, published his book “Engines of Creation”, where genetically programmed molecular machines
were mentioned as upcoming technologies in cellular biology. The first study related to nanobots
was made by Robert Freitas. It was related to medical nanobots called respirocytes; resembling red
blood cells. Nanobots could be defined as a controllable nanoscale machine composed of a sensor
and a motor, capable by performing specific tasks. These are not comparable to a drone, instead are
more similar to a complex piece of fabric. Robert Wood defined them as devices that detect friends
or enemies; undergoing through a conformational change when they sense an enemy, catalyzing the
release of a substance that can act against it.

Introduction
Nanorobotics is an emerging technology field creating machines or robots whose components are
at or near the scale of a nanometre (10−9 meters).More specifically, nanorobotics (as opposed to
microrobotics) refers to the nanotechnology engineering discipline of designing and building
nanorobots, with devices ranging in size from 0.1–10 micrometres and constructed of nanoscale or
molecular components.The terms nanobot, nanoid, nanite, nanomachine, or nanomite have also
been used to describe such devices currently under research and development.

Figure 1:Nanobot
Figure 2: Animated view of Nanobot working inside
human body

Nanomachines are largely in the research and development phase,but some primitive molecular
machines and nanomotors have been tested. An example is a sensor having a switch approximately
1.5 nanometers across, able to count specific molecules in a chemical sample. The first useful
applications of nanomachines may be in nanomedicine. For example,biological machines could be
used to identify and destroy cancer cells.Another potential application is the detection of toxic
chemicals, and the measurement of their concentrations, in the environment. Rice University has
demonstrated a single-molecule car developed by a chemical process and including
Buckminsterfullerenes (buckyballs) for wheels. It is actuated by controlling the environmental
temperature and by positioning a scanning tunneling microscope tip.
Another definition is a robot that allows precise interactions with nanoscale objects, or can
manipulate with nanoscale resolution. Such devices are more related to microscopy or scanning
probe microscopy, instead of the description of nanorobots as molecular machine. Using the
microscopy definition, even a large apparatus such as an atomic force microscope can be considered
a nanorobotic instrument when configured to perform nanomanipulation.

Nanobots Development

In this section we will see the development of nanobots.

Nanobots properties

Nanobots can be produced using organic materials such as proteins and polynucleotides, or
inorganic materials such as metals or diamond. In the case of diamond, this stands out for its high
strength and high performance. Metals could have double purposes, for example silver. It can be the
base of a nanobot and to have an antibacterial effect.In some cases, they can act as a virus causing
irreversible cell damage. The surface properties of the nanobots are a key factor to define the
solubility and interactions with other macromolecules or cell surfaces. Size or shape of a nanobot
will affect directly their motion, permeabilization and reactivity.Different extracellular
nanostructures could be used as model. Ga et al used spiral water conduction vessels of plants
coated with thin Ti and Ni layers, achieving efficient propulsion in biological media. Depending on
the fuel used, the propulsion mechanism can be biocompatible or not.

Parts

One of the main interests for the research of nanobots in medicine has been to develop treatments
targeting the exact point where it is needed, with the idea of minimizing the impact on healthy parts
of the body that any regular treatment has. This idea suggests having nanobots designed to detect
and mobilize to a determined part of the body where the problem is located and, in the best
scenario, send feedback. Because of these determinant tasks (detect and mobilize), two devices can
be identified as essential: sensors and propulsion equipment; and from this information it can be
deduced some other devices will be needed as well, like power supplies and molecular computers,
without excluding devices to develop a specific task like storage compartments or manipulators.

Sensors

Sensors are one of the most important parts in nanobots. Mechanical, thermal, optical, magnetic,
chemical and biological sensors have been tested in nanobots applications. Any sensor that uses a
nanoscale phenomenon for its operation is classified as a nanosensor. On the organic part,
biosensors utilize biological reactions for detecting target analytes, and considering the need to
accomplish the target treatments goals of nanobots in medicine, this type of sensors are the most
evident devices to explore in the field of nanorobotics. A clear example of this type of sensors is the
utilization of nano cantilevers as a Nano Electro Mechanical System (NEMS). This system utilizes
biological material that will be attached by itself to a coated cantilever, causing fundamental
changes in mass or its surface tension.

However, in general terms, sensors provide two functions to the surface, detecting the presence of
the target molecules and indirectly know the amount of damage that exists from the change in the
functional properties of nanobot. Therefore, many types of sensors were developed in function of
the target molecules that are wanted to be detected, in addition, it has been demonstrated that they
possess a high and fast analysis of time. The cantilevers are characterized by their high sensitivity in
providing a good atomic resolution in the image of a certain surface, so they are commonly used in
atomic force microscopy (AFM). Currently, utilizing the AFM as an effector, nano-cantilevers are
being developed as sensors to be used in nanobots. The main advantage is real-time detection,
directly and quickly. In addition, they are able to measure cell mass, biomolecules, nucleic acids
and others, as well as detecting specific molecules or even manipulate and place nanoobjects in a
predefined arrangement. In general, it can be used to manipulate objects at a single-molecule level .
Cantilevers can operate in two different methods: dynamic mode and static mode. In the first case,
the cantilevers respond to the biochemical interactions of the surface through a change in the
resonance frequency, which is caused by the mass or rigidity of the target molecule. This way, the
frequency is used to analyze the topography of the surface, and detect the different molecular
bonds. On the other hand, working in static mode relies on the absorption of determined analytes
from a nonmoving cantilever, which causes differential surface stress (bending) and consequently,
deflection regarding the reference point.This differential surface stress defines the relationship
between the sensor and the analyte.These cantilever’s attributes can be utilized to detect the
presence of target biomolecules in a small volume of sample, which in medicine can imply an early
detection of diseases, such as cancer.
Another type of nanosensors are the carbon paste electrodes (CPE). They are made from graphite
and a pasting liquid, and are used for voltammetric measurements and even in coulometry, as a
renewable surface for electron transfer reactions.There are some advantages that make CPE
attractive for nanomedicine: they can be miniaturized, easy to fabricate, good electrical and
mechanical resistance, low cost, among others. Therefore, these nanosensors are being used to
detect nucleic acids since adenine and cytosine have been shown to provide redox signals, while
guanine gives an oxidative signal.Also, the thymine together with the other nitrogenous bases
already mentioned, has given good signals in carbon electrodes. This is supported by a calibration
curve obtained with very good linearity detecting concentrations from 1 ng/ml to 100 ng/ml.

Propulsion equipment

Propulsion is in charge of the movement of nanobots, and this is the reason why many different
motors and propulsion equipment in general have been designed. Nanomotors can be defined as
nanoscale devices with their own propulsion, obtaining the energy by chemical reactions of the
medium, electricity, magnetic or acoustic fields.Even so, nanotechnology presents great challenges
to control movement on this scale; the main ones are due to the viscosity and Brownian motion. It
should be noted that Brownian motion corresponds to the random motion of particles caused by the
thermal collisions between the molecules of the solvent and the colloidal particles. In other words,
the main problem is having a nanobot with sufficient energy to overcome the properties of a fluid in
nanoscale and achieve movement.
There are two approaches being utilized to facilitate the movement of the nanobots: external and
internal. In the external approach for propulsion, MRI devices became the leading option after some
predecessor studies in the eighties using magnets and super conducing-magnets. There are several
advantages of this system: the nanobots speed and direction are controlled from an external
computer, decreasing risk considerably, the MRI can be used to get real-time feedback of the
behavior of the nanobots, having all the power depending on the external machine, there is no need
to develop complicated and power consuming nanomotors, among others. However, with respect to
the internal approach, the best models, as is to be expected, are the biomotors that already exist in
nature; Therefore, it is a field in continuous development to find and to understand new mechanisms
of movement. Major examples include cell division, protein synthesis, DNA transcription, among
others; all of the above are cases in which chemical energy becomes movement.
A hybrid engine was obtained in the year 2000 by Bachand & Montemagno. This invention marked
the beginning of bionanomotors and had interesting results. They integrated nano-electro-
mechanical devices with adenosine triphosphate synthase (ATPase) like nanomotor. For this
purpose, individual F1-ATPase molecules, corresponding to a structural domain of the molecule,
were used and placed in nickel matrices by means of electron beam lithography. After conducting a
test, the performance of the motors was evaluated by these molecules, obtaining three stages of
rotation by part of the γ subunit during the hydrolysis of ATP. Further, during this hydrolysis, the γ
subunit of the ATPase was rotated at a rotation speed of about 3-4 rps. Experiments have shown that
the nanohybrid structure can be fed with a biological nanomotor.Several authors describe the
fabrication of nanospherical motors driven by catalytic reaction of H2O2.One of them is the Janus
motor, formed by Janus particles, that is, nanoparticles that on their surface have two or more sides
with different properties.The mechanism of this motor consists of a chemical reaction on only one
side of the Janus particles, which produces the force for the movement of these motors. There are
different types, one of these motors is characterized by having a catalytic Pt layer that catalyzes the
H2O2 decomposition reaction.For example, there is a solid silica based Janus spherical motor, which
has a catalytic layer of Pt for H2O2 decomposition. Another example of this propulsion is an Au/Pt
bimetallic nanomotor.However, other propulsion mechanisms were suggested, for example: a nano
sphere with a magnetic hemisphere or propulsion by osmosis.For the sphere based propulsion, nano
spheres are created with two different hemispheres. This allows one-half to be coated with a
catalyst that causes an asymmetrical distribution of a reaction product, which moves the spheres
along.Meanwhile, osmotic propulsion is based on the artificial version of the reaction generated
from the release of a semi permeable membrane after it separates a fluid containing colloidal
particles, because of a flow that was induced from the low to the high particle concentration side.
The pressure stopping the flow is the osmotic pressure. The osmotic pressure difference between the
two sides will cause it to move until equilibrium is established. In this way the microscopic kinetic
energy of the particles is transformed into macroscopic mechanical motion and work.
In addition, tubular nanomotors made by Pt and two other layers of InGaAs and GaAs, can also use
H2O2 as fuel. Initially the fuel contact with the catalytic material produces O 2 bubbles and when the
bubbles come out of inside they produce the propulsion.Nanowires motor has also been developed
in recent years, a flexible fuel-free nanowire motor is being manufactured with three segments: Ni-
Ag-Au. They are even able to achieve a speed similar to microorganism and this make them
promising for future biomedical application. Gold-nano wired ultrasounddriven motors are being
developed for their utilization as drug delivery devices in cancer cells. These motors are based on
the nanoporous gold segment for increasing superficial area and hence the loading capacity of the
drug. Improved versions of this devices combine ultrasound propulsion with magnetic guidance and
an infrared light as a trigger to release the load.
Although the sensor and motor are principal parts, nanobots may have other important components.
Nanocomputers can be electronic, biochemical, organic or quantum and have the function of
controlling or directing nanobots inside the body. For example, the development of a computer at
molecular level made up of DNA, which can regulate gene expression. It has a software coded with
the four letters of the DNA nitrogenous bases. In addition, it was programmed to detect the type of
mRNA associated with specific genes that in case of being over expressed or its opposite, induce
the cancer. This allows to diagnose different types of cancer and counter act the disease with the
indicated drug.On the other hand, nanotweezers and nanochips also have important roles in
nanobots, such as nanomachines movement within the body or its control.

Uses in medicine
In near future, nanobots will play an important role in medicine, like a “nanodoctor” inside the
body. The cancer treatment has a special interest because is one of the leading causes of death in the
world. The nanobot will move independently around the body and detect a cancer cell, Figure 3.
Therefore, when are inside or interacting with the cancer cells they will release the drug. In this
way, the side effects of anti-cancer drugs on other parts of the body will be reduced.In addition to
the cancer drug attack, some nanoscale robots can destroy cancer cells through thermal necrosis
when a non-invasive external source of heating or stimulus will be applied. As example, super
magnetic beads that can penetrate and destroy cancerous tissues with a magnetic field.
For atherosclerosis and other cardiovascular diseases such as ischemic or arrhythmias, nanobots
will be injected into the circulatory system by intravenous infusion techniques, for acting against
fatty deposits. In addition, nanobots are also a proposal for diagnosis and treatment of
demyelination, since they can reach the layer of myelin in the nerves. Also, specific nanobots that
detect Alzheimer’s disease based on the amyloid protein β deposits. Dentifrobots are especial
nanobots suggested for use in odontology. They could be a complement of the mouthwash or
toothpaste and basically, their functions will consist in the metabolization of the trapped material
and in the identification and destruction of pathogenic bacteria inside of the mouth. Nanobots can
also be used to travel through the patient’s gingiva, and thus they will deliver the analgesic to the
target site.It is expected surgeries at nano level in the retina and surrounding membranes and
pregnant women. Also, in gene therapy comparing two DNA chains; sensing proteins inside the cell
and replacing chromosomes.The applications of nanobots in medicine are many and diverse.

Figure 3:Application for cancer targeting treatment.

Biomimetics
An example of biomimetic derivated nanobots are the microbivores; similar to white blood cells in
the bloodstream. They are thought to bind to a specific target surface site, and next to destroy the
pathogen. As a result, amino acid residues, fatty acids, simple sugars are released, among others. A
second example of biomimetic nanobots are the respirocytes. They are a kind of artificial red blood
cell. They will have the capacity of pumping 3 million molecules of O 2 and CO2, which represents a
delivery of oxygen to tissues per unit volume 200 times higher than natural red blood cell. The
respirocytes are planned to treat anemia and lung problems.Other example are the biobots, they are
genetically modified bacteria. Its genetic material will be removed and replaced by an artificially
synthesized DNA. The function of these biological robots is to supply or collaborate in the patient’s
metabolic needs, i.e. in the production of hormones, vitamins, enzymes, and also in the absorption
of toxins. It is important to mention that for this case, in 2003 the first patent related to chemical
synthesis of gene and gene networks was published.

Patents and other applications in medicine

A patent related to nanowire motors fuel free was available since 2013.There are two designs of
fuel-free nanomotors: magnetically and electrically-propelled.Another patent corresponds to a
spherical nanomotor of 50 to 90 nm in size formed by mesoporous silica and a layer of platinum on
the partial surface. The preparation method consists of five steps: synthesizing mesoporous silica
nanoparticles, performing hydrophilic treatment to silicon chips, dripping silicon dioxide
nanoparticle dispersion liquid onto the hydrophilic silicon chips, drying and sputtering platinum
onto the silicon chips, and finally drying after ultrasonic vibration for shaking off.
Actually, the application of nanobots in medicine is on the first steps. In 2012 a patent “Diagnostic-
nanosensor and its use in medicine” was published”. Basically, the objective of the invention was to
obtain a new nanosensor for diagnosis in medicine and others applications, based on metallic
semiconductors and magnetic nanoislands. The surface of these nanoparticles can be modified to
achieve interaction with the molecule of interest or recognize specific substrate surface as a cell
membrane. In that way, the invention can be used for the detection of pathogens or toxins inside the
body.There are available patents about nanosensors that could be used for nanobots based on AFM
cantilevers and magnetic relaxation nanosensors.
Specifically in nanobots, several recent patents were found. Fritsch et al. proposed the robo-lens.
They will have the task of moving across the corneal surface lens and remove microorganisms and
impurities, improving the vision of the person, hygiene and durability of the lens.The second patent
is “Sensor molecular machine and controller added to programmable nano-robot” published in
2016. This invention has three parts: the sensor, the rotor and the controller. According to the patent
“this is the first time sensing in a single nano-robot created by organic synthesis”. These nanobots
are not only able to sense the environment, they can move, be effective even under high noise and
establish communication with external devices. With a controller installed they can also make
logical decisions, Figure 4.
Drugs used in cancer treatments like a bleomycin or mitomycin cause seriously side effects, for
example: anemia, vomiting and others. So, in order to create more efficient cancer markers and
achieve a better process, a new nanobot was developed and patented in 2016 by Zhang Yi Fei &
Yuan Zuo. This invention is composed of three different parts: a loading component, a power
component and a connecting component. The objective of this invention is using the nanobot as a
car to release a labeling reagent at the specific point where there is a tumor. The motor of the
invention is propelled by ATP, the payload (labeling reagent) could be alpha-fetoprotein (AFP),
carcinoembryonic antigen (CEA) or other tumor-specific markers. It has an inorganic nanomaterial
connecting component. When the nanobots arrive at the target point the connecting component will
be broken, and then the tagging reagent flows out and mark the sick cells. In that way, the doctor
can determine the distribution of cancer cells and recognize the disease status. In addition, the most
effective treatment of the disease.

Nanobots will have sensors for detecting levels of glucose and, if it is necessary, secrete insulin into
the blood.This may be done through hSGLT3 for detecting glucose concentration on diabetic
patients, this protein has into its functions regulating glucose levels.On the other hand, nanobots
that destroy brain cancer cells were recently simulated by Loscrí et al who called them
NanoBee.Nano Bees are able to detect cancer cells, destroy them, emit an acoustic signal when
detected the tumor and detect the acoustic waves.Also, the nanodevices can be used in nerve
system, specifically myelinated disorders. Many diseases can be generated as a result of the loss of
myelin sheath; multiple sclerosis, transverse myelitis and chronic demyelinating polyneuropathy are
some of them. So nanobots were considered being able to detect this demyelinating and eventually
to improve treatment procedure.

Figure 4: Components of nanobots

Applications of Nanobots
The following are some of the potential applications of the nanobots

Nanorobotics Applications for Cancer Detection

As cancer survival rates improve with early detection, nanorobots designed with enhanced detection
abilities will be able to increase the speed of a cancer diagnosis and therefore enhance the prognosis
of the disease. Nanobots with embedded chemical sensors can be designed to detect tumor cells in
the body. Proposed designs currently include the employment of integrated communication
technology, where two-way signaling is produced. This means that nanobots will respond to
acoustic signals and receive programming instructions via external sound waves along with
transmitting data they have accumulated.
The mechanism
These minute molecules have components that enable them to identify and attach themselves to a
cancer cell.
When activated by light, the nanobots’ rota-like chain of atoms begin to spin at an incredible rate –
around two to three million times per second. This causes the nanobot to drill into the cancer cell,
blasting it open.
The study is still in its early stages, but researchers are optimistic it has the potential to lead to new
types of cancer treatment.

Figure 5: The spinning nanobots burrow into cancer cells to

destroy them
Figure 6: Nanobots fighting cancer

Figure 7:Image of cancer cell that has been punctured and ripped by nano machine
Current Research/Future Scope

Nanobots in our veins

The destructive properties of the nanobots make them perfect for killing cancer cells. But the
technology can also be used to repair damaged or diseased tissues at a molecular level.

In the future, these nanomachines could essentially patrol the circulatory system of the human body.
They could be used to detect specific chemicals or toxins and give early warnings of organ failure
or tissue rejection.

Another potential function may involve taking biometric measurements to monitor a person’s
general health.

Searching for oil

The medicinal advantages of nanobots are clear to see, but industry might also benefit from the
technology.

Oil and gas is one example. The idea is that nanobots could be injected into geologic formations
thousands of feet into the earth. Changes to the chemical make-up of the machines would point to
the location of reservoirs.

Meanwhile, it’s also been suggested that nanotechnology could become a valuable tool in cleaning
up oil spills.

Nanorobotic Applications in the Field of Hematology

Current research is developing nanorobotic applications for the field of hematology. This ranges
from developing artificial methods of transporting oxygen in the body after major trauma to
forming improved clotting capabilities in the event of a dangerous hemorrhage.

Respirocytes are hypothetical nanobots engineered to function as artificial red blood cells. In
emergencies where a patient stops breathing and blood circulation ceases, respirocytes could be
injected into the blood stream to transport respiratory gases until the patient is stabilized.

Current proposals suggest respirocytes would be able to supply 200 times more respiratory gas
molecules than natural red blood cells of the same volume. Clottocytes are another type of nanobot
which function as artificial platelets for halting bleeds.

Clottocytes would mimic the natural platelet ability to accumulate at the bleed, in order to form a
barrier, by unfurling a fiber mesh which would trap blood cells when the nanobot arrives at the site
of the injury. The clotting ability of one injection of clottocytes would be 10,000 times more
effective that an equal volume of natural platelets.

Nanorobotics Applications for Biohazard Defense

Nanorobots will also have useful applications for biohazard defense, including improving the
response to epidemic disease. Nanobots with protein based biosensors will be able to transmit real-
time information in areas where public infrastructure is limited and laboratory analysis is
unavailable. This is particularly applicable for biomedical monitoring of areas devastated by
epidemic disease as well as in remote or war torn countries during humanitarian missions.

Nanorobotics may also reduce contamination and provide successful screening for quarantine. In
the event of an influenza epidemic for example, increased concentrations of alpha-NAGA enzyme
in the blood stream could be used as a biomarker for the influenza infection. The increased
concentration would trigger the nanorobot prognostic protocol which sends electromagnetic back
propagated signals to portable technology such as a mobile phone. The information would then be
retransmitted via the telecommunication system providing information on the location of the
infected person, increasing the speed of contamination quarantine.

Cure Stomach Ulcers

Nanobots in future may also be able to treat stomach ulcers.

Challenge

Since the early 2000s, the dream that tiny robots could clean cholesterol from arteries has grown.

Ingested or injected, nanoscale robots could effortlessly make their way through the body to
accomplish various missions, such as delivering drugs to cells in need, targeting cancerous cells,
unclogging arteries, destroying enemy invaders like viruses and bacteria, and etc.

With extreme miniaturization, which is no longer a technical obstacle, a challenging problem arises:
navigation.

Once injected into an organism, nanobots must be guided to spread medical treatment precisely
where it is needed, which means wading through the entire circulatory system.

One of the most promising paths is to use an external magnetic field to steer drug-delivering
nanobots while they swim inside circulatory pathways

Risks

As expected, the nanoparticles involved in certain medical devices interact with both the
environment and the human body. Currently, the number of innovations in the field of
nanomedicine increases and it is necessary to develop protocols for evaluating the risks.The main
risks to humans are in the adsorption of biomolecules or materials and oxidative stress, causing
DNA damage. Furthermore, the inability to control the movement of these nanoparticles throughout
the body creates a risk that can reach undesirable locations and thus lead to side effects. Moreover,
as already mentioned, one of the main characteristics of nanoparticles is that they can cross
biological barriers.This can be a disadvantage, the unnecessary cross of barriers may be a trigger for
inflammatory reactions At the same time, it is necessary to consider the whole manufacturing
process, because for some nanodevices toxic reagents are used during this stage, which limit the
applications that they can have in the diagnosis or the administration of drugs. The most common
fuel H2O2 produces oxygen bubbles that activate a propulsion mechanism. However, the body
tolerates only very low concentrations. In other words, even in concentrations less than 1% is highly
toxic for cells, while at high concentrations can lead to protein denaturation. For this reason, the use
of non-toxic fuels such as water or glucose is also suggested. Likewise, the ethical aspects involved
in the diagnosis of diseases should be evaluated. For example, in a case where patients are known to
be prone to disease, through gene analysis, one should consider: who will possess such information,
how fundamental rights can be protected, how can responsible use of nanomedicine be promoted,
etc .
In addition, the environmental impact of nanoparticles must also be considered, since they remain
dispersed in the environment from the moment they are discarded from the body, even from the
laboratory stages. Unlike the risk to human level, the risk they represent for the environment is
much more complex by the large number of interactions that are involved.On the other hand, the
nanotechnology has risks and benefits; a balance should be done before using a technology.

Conclusion
The nanobots are not an idea written on paper anymore, they are currently under development. The
components are sensors, propulsion and navigation systems. Nowadays, the research is mainly
focus on nanomotors; a key part of the propulsion component. Chemically, magnetic and acoustic
driven nanomotors have been produced and applied; mostly in the field of nanomedicine. However,
for medicine, a major effort should be done in technologies based on fuel free and biocompatible
approaches. There is a lot of research, but it is going to be needed a lot more in order to create a
functional nanobot, able to accomplish tasks beneficial for the human being; surface modifications,
structures, components and body response has to be well understood. However, the quick
development in nanotechnology, biotechnology and computing science will influence the prompt
creation of a nanobot. In this moment, we are still in the design and experimentation stage, even
some patents are in the market.