University of Thi Qar

College of Engineering
Department of Biomedical Engineering

Nanotube Innovations in
Biomedical Engineering

Supervised by:
Ahmed Ghazi Al-Zaidi

prepared by:
Kerrar Hayder

2024
 Abstract

With the advances in the field of nanotechnology many applications are

developing greatly, the appealing characteristic properties of carbon nanotubes
makes them one of the most studied and used part of the field in medical and
biomedical sectors. The greater surface area they have in addition to their
electrical and mechanical properties makes them exploited for a wide number of
applications in the biomedical field ranging from diagnostic to therapeutic
applications, they are able to form carrier systems which are also capable of site-
specific delivery of agents and have biosensing potential.
 {1} Introduction

The advancements of nanomaterials and biomaterials had a significant

bearing on the evolution of carbon nanotubes, carbon is one of the most
versatile elements in nature and humans are carbon-based life forms making
carbon structures one of the most used and safest biomaterials in most of its
structures (with limited exceptions)

In 1991 the Japanese scientist Sumio Iijima [5] created a new field of studies by
making the first ever nanomaterial being the carbon nanotube, this caused it to
be one of the most studied nanomaterials as it was the oldest and it also possess
some of the most useful

Carbon nanotubes have great thermal and electrical conductivity in addition to

outstanding mechanical properties while being light in weight, with multi walled
carbon nanotube being flexible having strength measured to around 14.3 ± 0.9
Gpa[1] it covers high surface area while being hollow inside and it shows
hydrophobic properties and extreme biocompatibility, due to the hollow
cylindrical shape of carbon nanotubes they are able to be used as drug delivery
systems and can act as superconductors.

Figure 1.1 (single layer carbon nanotube) figure 1.2 (mul� layer carbon nanotube)
{2} Properties of carbon nanotubes (CNT)

Carbon nanotubes consists of a layer of graphite rolled up into a cylinder with

a centre to centre distance of around 1.43 Å with an interlayer distance of
around 3.45 Å with each carbon having sp2 electron hybridization [1] . Carbon
nanotubes are either single walled consisting of a single lattice rolled into a
perfect cylinder with diameters ranging from 0.4-2 nm or multi walled made up
of several concentric cylindrical graphite shells [3] with diameters ranging from
2-100nm They were seen to be extremely biocompatible as it has been found
that human cells can be grown on carbon nanotubes and that they are nontoxic
in nature and they possess quite distinct properties which makes them a great
candidate in biomedical applications such as their great electrical properties
and they also possess penetrating capabilities on cell membrane[1]. They also
are susceptible to changes in different pH, temperature, and humidity, which
allows them to be manipulated depending on the needed application[4]. All of this
with addition to their extreme light weight makes them the perfect candidate for
numerous applications.

Both types of carbon nanotubes can be internalised by a variety of cell types

thus allowing for them to be used in delivery of therapeutic and diagnostic
molecules, and grants them he ability to be used for new vaccine production[2].

It has been reported that some diseases covalently link to carbon nanotubes
inducing specific anti body responses without any cross reactivity that could
potentially be harmful or toxic.
The resistivity of carbon nanotubes has been found to be as low as 10-6 Ω cm

With longitudinal thermal conductivity of around 3000-6000 W/m•K for a single

nanotube at room temperature, alongside an elastic modulus of 0.45 TPa at the
lowest and around 4.17 TPa at the highest with a specific surface area being
theoretically calculated at around 1316 m2g with tensile strength of around 100-
200Gpa making it one of the most tensile strong materials in existence despite
its extreme lightweight.[1]

All these in addition to other properties that are environment dependant which
can be manipulated has made it so researchers and scientists believe that even
life-threatening diseases such as cancer, tuberculosis, nervous tissue
regeneration, neural scaffolds, and myocardial conduction could easily be
treated using carbon nanotube-based drug delivery systems which target very
specific parts of the body with extreme accuracy [1]. And it has great nano-
compatibility and relative chemical inactivity as the constituent atoms are not
replaced with ease.

Electrical properties of carbon nanotubes is dependant on their exact structure

especially their n – m chirality

A B

Figure 2.1: 2 types of carbon nanotubes

A show a zigzag configura�on

B shows an armchair configura�on

An n – m that is equal then the carbon nanotube is metallic while if the n – m is a
multiple of 3 (armchair type) where n≠ m then the carbon nanotube is quasi-
metallic with a sharp band gap otherwise the nanotube is a moderate
semiconductor [6]

Figure 2.2: different carbon nanotube n-m configura�ons and their resul�ng electrical conduc�vity and
bandgaps.

The different types of n – m configurations are due to the different types of

impurities found in the carbon nanotube structure and the types of impurities
are as stated in figure 2.2.
They also have been shown to have fluorescent and absorption abilities that
offer the possibility of non-destructive characterization of large quantities of
carbon nanotubes and their fluorescence has been a topic of investigation in
terms of imaging and sensing purposes in biomedical applications.

{3} Carbon nanotube (CNT) synthesis methodology

Many techniques have been developed for CNT synthesis the first known
method was chemical vapor deposition where the first carbon nanotube was
formed and since then many other types of synthesis have been found and used
and experimented on such as arc discharge, laser ablation, plasma torch, liquid
electrolysis, and neutral controlled flame environments

[3.1] chemical vapour disposition (CVD)

During CVD a substrate is prepared with a later of metal catalyst particles

usually being nickel, cobalt, iron, or a combination[7] the metallic nanoparticles
could also be produced by other methods such as the reduction of oxides, the
size of the metal particle determines the diameter of the CNT that will be grown ,
this could be controlled by carefully patterned deposition of metals the
substrate is heated to 700 °C in order to initiate the growth of the CNT two
gasses need to be bled into the reactor tube. The first gas is a process gas like
ammonia, hydrogen or nitrogen, while the second gas needs to be a carbon
containing gas such as ethylene, ethanol or methane. CNT grows on the metal
catalysts with a slight impurity of the metal (depending on the metal type the
electrical properties of the CNT could differ) carbon gas is degraded at the
surface of the metal catalyst particles and so the carbon is transported to the
edges of these particles where it forms the CNT.[8] catalyst particles can remain
on the tips of CNT during its growth or remain at its base depending on the
adhesion between the catalyst and the substrate in which the reaction takes
place.

Figure 3.1: CVD method of CNT synthesis

Metal nanoparticles can be mixed with a catalyst support such as MgO or Al2O3
to increase the surface area for a higher yield of the catalytic reaction, an issue
with this is the need to remove the catalyst support using an acidic treatment
which could potentially destroy the original CNT structure a method to
overcome this is to use catalyst supports that are water soluble this method is
called super growth CVD .[9]

During the creation of the CNT if plasma is generated due to the strength of the
electrical field then the CNT will follow the direction of the electric field and by
adjusting the volume and geometry of the reactor then it becomes possible to
create vertically aligned carbon nanotubes being perpendicular to the
substrate, while if plasma is not present then the resulting CNT will often be
randomly oriented but under specific conditions even in the absence of plasma
the CNT can still maintain a vertical growth direction resulting in a dense array
of tubes .[10]

[3.2] Arc discharge

Arc discharge is a method of synthesizing CNT that involves having 2 graphite

electrodes being put into an open vessel containing deionised water then
running an electric current between the two electrodes the process usually uses
direct current in the range of 5-200A and voltage wavering between 20-30V.

Figure3.2: arc discharge method of CNT synthesis

When the arc between the two graphite electrodes is created one of the
electrodes sublimates while the other gets carbon deposits to reside on it in the
form of CNT and some other materials the CNT is in the form of a soot collected
on the cathode, this method produces single and multi-walled CNT with lengths
of up to 50 μm with very few structural defects as it uses high temperatures that
can go above 1700 °C which causes expansion hence fewer defects in
comparison with other methods of synthesis, and it is more cost effective than
other methods with relatively shorter time needed for synthesis and it doesn’t
require sophisticated equipment.[11]

[3.3] Laser ablation

A graphite target is placed into a chamber then an inert gas is led into the
chamber, afterwards a pulsed laser vaporizes the graphite in a high
temperature reactor, nanotubes form on the colder parts of the reactor when
the carbon vapour condenses. A water-cooled surface may be used to collect
the resultant nanotubes. This method primarily produces single walled CNT with
a controllable diameter which can be determined by the temperature.[12]

This method is more expensive than arc discharge or CVD

Figure3.3: Laser abla�on method of CNT synthesis

[3.4] Plasma torch

Single walled CNT can be synthesised by using a thermal plasma on a

carbon containing gas allowing for more efficient growth of CNT as
decomposing the gas can be up to ten times more energy efficient than graphite
vaporization.

A gas mixture is exposed to the thermal plasma which can reach several
thousand degrees Celsius then the carbon containing gas is also introduced to
the plasma torch and it acts as the foundation of the CNT, once this happens the
high temperature of the plasma will cause the carbon-carbon bonds to break
through a process called dissociation the atoms then undergo nucleation
growth as they cool down and recombine on the surface of a substrate

Figure3.4: Plasma torch method of CNT synthesis

[4] Biomedical applications of CNT

There are many applications to the CNT which help in the biomedical sector
as new advances in technology and CNT continues to find new things each day,
new applications and method of using CNT appear and evolve to number some
of the most important CNT applications they are:

[4.1] Biomedical imaging and diagnostic applications

CNT can be used in the case of imaging with two specialised methods being
photoacoustic imaging and magnetic resonance imaging and CNT are provoked
by applying an external magnetic field and the capacity of imaging can be
improved by adding external nanoparticles, those need to be checked for
toxicity levels.

Athe fluorescence emission in near infrared region by semiconducting single

walled CNT allows them to be excellent bio imaging probes due to their
properties of near infrared absorbance it makes them very suitable for
photoacoustic imaging which can be utilized in the diagnostics of tumour cells.[3]
the CNT electrode can result in low distortion images during MRI tests in
comparison with other electrodes.

[4.2] Biosensing applications

CNT can be used in biosensors as the basic principle of them is to use a

specific biochemical reaction that is mandated by a specific isolated enzyme or
tissue or even cell or cell organelles. Since biosensors detect biological signals
from the human body, they can be used in a broad number of applications
ranging from diets and food, healthcare and medicine monitoring to
environmental monitoring and industrial testing.
Biosensors are required to be sensitive selective rapid and portable, making the
carbon nanotube the perfect candidate as it has the properties to suit all these
needs in a biosensor.

Figure4.2.1: Components of biosensor

Typically, biosensors consist of a bioreceptor a transducer and a signal
processing unit. Bioreceptors are materials that interact with biological analytes
sensitively such as glucose, neurotransmitters, toxins, etc. the interaction
between a bioreceptor and an analyte produces various forms of signals such
while transducers convert these signals from analogue bio signals to digital
electrical signals, and finally the electrical signal is then processed by a signal
processing unit so that we are able to interpret information of the analyte and
filter out external noise caused by environmental factors or unwanted signals.[4]

Carbon materials have broad potential window and relatively low cost and have
good chemical stability making them widely used as electrodes in various
applications in addition to offering rich electrochemical reaction sites due to
their relatively large surface area, among those carbon nano ube fibres have
been investigated as micro electrode materials as they have a small diameter
and superb temporal resolution and cause negligible tissue damage while being
electroconductive and biocompatible with high sensitivity for neurotransmitter
detection. CNT based electrodes are superior to traditional electrodes as they
have shorter response time and higher selectivity and sensitivity while having a
low detection limit unlike other options such as glassy carbon or Pt or Au
electrodes all these are attributed to the nanotubes electrical properties and
their high electron transfer rate and low overvoltage.[4]

Taking advantage of that coating the surface of carbon fibres with CNT giving us
CNT-modified carbon fibre microelectrode (CFME) which gives more effective
results and improved electrochemical performance, however the CNT modified
CFME has seen some concerns about being toxic to cells with cytotoxicity in
alveolar macrophages and inhalation of it causes immunotoxicity because they
interact directly with immune cells due to their nanoscale dimensions and size [4]

This toxicity can be overcome or limited by using a macroscopic assembly of

CNT while preserving anisotropic properties of individual CNTs for example CNT
films which shoed no cytotoxicity or any immune system response
CNT are used in implantable glucose biosensors which are mostly enzymatic
biosensors as they sense a class of enzymes called glucose dehydrogenases
(GDH) which are enzymes that catalyse the oxidation of glucose

Figure4.2.2: CNT based glucose sensor

Dopamine can also be detected using CNT biosensors, dopamine is one of the
most important neurotransmitters and abnormal levels can cause neurological
diseases such as schizophrenia and depression, since dopamine is an
electrochemical compound then it can be sensitively and selectively detected by
the CNT sensor however it is difficult to detect it due to oxidation potential of
dopamine CNTFs have been used to overcome such limitations several reports
have shown that they improve electrochemical properties and have long term
resistance to dopamine fouling.
 Figure4.2.3: this shows how CNT fibers detect analytes with bioreceptors

[4.3] Nervous tissue regeneration

CNT can theoretically be used to regenerate nervous tissue damage as it is

the most suitable candidate for that and for repairing sonal cord injuries.

CNT is usually used alongside phosphate used glass microfiber (PGF) scaffold
with CNT running through the spun nanofibers as they are wrapped around the
CNT which when tested on rats it was able to grow up to 10mm of sciatic nerve
after about 5 weeks of regeneration[1] scaffolds could also be 3D printed which
help with variation and progress of neural cell CNT is neurotoxic by nature
which is a big roadblock for neural applications and we are unable to bypass the
toxicity issues while attaching CNT with substrate so numerous studies are
required before it is possible to integrate CNT into devices that deal with the
nervous system
 Figure4.3: CNT PGF scaffold used as a nerve conduit

[4.4] Tissue engineering

All cells should have adhesion properties for making scaffolding materials
these scaffolding materials should help in replacing dead tissue and treatment
processes and they should have good mechanical resistant properties and be
biocompatible, hydrogel prepared from biopolymers which merge with
nanofillers such as CNT to augment the needed mechanical properties and
electrical conductivity. Several cases where regenerative performance of
cardiac or nervous regeneration improved by adding 1wt% of single walled CNT
in an alginate scaffold and showed improvement in physical properties such as
in cardiac applications such as cardiomyocytes fitting or cardiac patches

Figure4.4: modified CNT being used as a scaffold to support bones

[5] Limitations of Carbon nanotubes

Carbon Nanotubes have unique properties which makes them a prime

candidate in most biomedical applications but their toxicity remains a big issue
as they are cytotoxic and neurotoxic.

The toxicity is caused by various routes of exposure such as oral inhalation, skin
injection or direct ingestion. Once the CNT is exposed to the body organs it
causes several problems such as asthma and bronchitis at initial exposure,
while prolonged exposure to it could potentially lead to even lung cancer, and it
affects other parts of the body such as the digestive system casing colon cancer
and circulatory system causing heart disease and blood clotting and it would
also mount up on the liver and spleen.[1]

The toxicity of CNT could be reduced by shape, size, and composition and it also
depends on the number of walls.

CNT is usually eliminated from the body through excretory system by exciting
via urine and smaller CNTs are engulfed by macrophage and drained by lymph
vessels. If the solubility of the CNT is not enough then the CNT would
accumulate in bundles causing discomfort and leading to inflammation of the
immune system and development of cancer.[1]
 Figure5: factors affec�ng toxicity of CNT

[6] Conclusion

in conclusion CNTs are a revolutionary class of nanomaterials with

remarkable properties that has made them one of the most studied and explored
materials in the biomedical sector, originating in 1991 from the work of Sumio
Iijima they have gathered significant attention due to their mechanical and
electrical characteristics and their unique structures.

Studying has shown their properties to be exceptional in biocompatibility and

electrical conductivity and paired along their high surface area, that makes
them an ideal candidate for most biomedical applications from drug delivery
systems, to biosensing technologies, allowing versatile solutions in nervous cell
regeneration and tissue engineering.
With numerous synthesis methods each providing a different structure of CNT
each with unique electrical and mechanical properties due to their structure and
impurities held within allows them to be one of the most versatile materials
known to man.

Despite all that potential their spread in biomedical applications is hindered by

concerns of toxicity, studying these concerns and attempting to address these
challenges could be the key to propelling biomedical technology forward as they
show limitless potential in terms of use and functionality.

In summary, the exploration of carbon nanotubes represents a frontier in

nanotechnology with high implications of biomedical research and healthcare
innovation, and through continued investigation CNTs hold the promise of
transforming the medical landscape to a new era for precision of diagnostics
and regenerative medicine.
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