This document discusses molecular nanomachines and nanobiosensors, detailing their types, structures, and applications in fields such as biotechnology, medicine, and agriculture. It includes information on molecular motors, switches, shuttles, tweezers, and various biosensors that utilize nanoscale interactions for detection and analysis. The document emphasizes the advantages of nanobiosensors, including their sensitivity and specific interaction capabilities, while also noting their current limitations and developmental challenges.

1. MOLECULAR NANOMACHINES,
NANOBIOSENSOR - TYPES AND
APPLICATIONS
Dr. P. SAMUEL
Asst. Professor of Biotechnology

2. Introduction
• A machine is any device that transmits or modifies energy, and in general speech
the word "machine" generally implies that the energy is transformed into some kind
of mechanical work.
• Nature has been doing it forever - muscle contractions are driven by the ATPase
activity of the protein myosin interacting with another protein called actin.
• The challenge for organic chemists is in actually designing and building a
molecular machine that can perform a specified task.
• In fact, nanostructures are just molecules or noncovalent clusters of molecules.
They have properties determined by their structures just like every other molecule.
Some are likely to be harmful while others may be helpful.

3. Nanocars
• In 2005 Tour's laboratory published the synthesis of the first nanocar - a molecular
machine that moved over a gold metal surface by rolling on wheels.
• The synthesis of this molecule took Tour and his students 8 years, but since then his
laboratory has produced several other nanovehicles of various sorts.
• It has the molecular formula C430H275O12 and a molecular weight of 5633.78.
• The "wheelbase" (length) of the nanocar is about 2.1 nm, and the "track" (width) is
3.3 nm.
• The nanocars use roughly spherical molecules called "buckminsterfullerenes" as
wheels.
• Each "buckyball" is a 60-carbon truncated icosahedron made up of aromatic rings.
• The axles and chassis consist of phenyl rings and alkyne units.
• It was necessary to include several C10H21chains on the axle/chassis units to give
the nanocars solubility in typical organic solvents for handling and processing.

4. • When the synthesis was complete, the nanocars were dissolved in toluene and the solution
was applied to a freshly-prepared and crystallographically defined layer of gold atoms under
high vacuum.
• The nanocars did not move until the surface was heated above 170 °C.
• At that temperature they began to roll forwards and backwards and to pivot.
• The STM images shown were taken at 200 °C.
• When the temperature reached 225 °C the motions became so fast and erratic that STM could
not longer observe the nanocars.

5. MOLECULAR MOTOR
Molecular motors are biological molecular machines that are the essential agents of
movement in living organisms.
In general terms, a motor is a device that consumes energy in one form and converts it
into motion or mechanical work; for example, many protein-based molecular motors
harness the chemical free energy released by the hydrolysis of ATP in order to
perform mechanical work.

6. Molecular propeller
• Molecular propeller is a molecule that can propel fluids when rotated, due to its special
shape that is designed in analogy to macroscopic propellers.
• Molecular propellers can be rotated by molecular motors that can be driven by chemical,
biological, optical and electrical means, or various ratchet-like mechanisms.
• Future applications of these nanosystems range from novel analytical tools in physics and
chemistry, drug deliveryand gene therapy in biology and medicine, advanced nanofluidic lab-
on-a-chip techniques, to tiny robots performing various activities at the nanoscale or
microscale.

7. MOLECULAR SWITCH
• A molecular switch is a molecule that can be reversibly shifted between two or
more stable states.
• The molecules may be shifted between the states in response to environmental
stimuli, such as changes in pH, light, temperature, an electric current,
microenvironment, or in the presence of ions and other ligands.

8. Molecular shuttle
• A molecular shuttle in supramolecular chemistry is a special type of molecular
machine capable of shuttling molecules or ions from one location to another.
• This device is based on a molecular thread composed of an ethyleneglycol chain interrupted
by two arenegroups acting as so-called stations.
• The terminal units (or stoppers) on this wire are bulky triisopropylsilylgroups.
• The bead is a tetracationic cyclophane based on two bipyridine groups and two para-
phenylenegroups.
• The bead is locked to one of the stations by pi-pi interactions but since the activation
energy for migration from one station to the other station is only 13 kcal/mol (54 kJ/mol) the
bead shuttles between them.
• The stoppers prevent the bead from slipping from the thread. Chemical synthesis of this
device is based on molecular self-assembly from a preformed thread and two bead fragments
(32% chemical yield).

9. Molecular tweezers
• The term "molecular tweezers" was first used by Whitlock.
• Molecular tweezers, and molecular clips, are host molecules with open cavities capable of
binding guest molecules.
• The open cavity of the molecular tweezers may bind guests using non-covalent bonding
which includes hydrogen bonding, metal coordination, hydrophobic forces, van der Waals
forces, π-π interactions, and/or electrostatic effects.
• These complexes are a subset of macrocyclic molecular receptors and their structure is that
the two "arms" that bind the guest molecule between them are only connected at one end
leading to a certain flexibility of these receptor molecules (induced fit model).

10. Nanobiosensor
• Nanobiosensor is a modified
version of a biosensor which
may be defined as a
compact analytical device/
unit incorporating a
biological or biologically
derived sensitized element
linked to a physico-chemical
transducer.
• In the year 1967, the first
biosensor was invented
which led to the
development of several
modified biosensors.
• Overall, there are three so-
called “generations” of
biosensors;
• First generation biosensors
operates on electrical response,
• Second generation biosensors
functions involving specific
“mediators” between the
reaction and the transducer for
generating improved response,
• Third generation biosensors
the reaction itself causes the
response and no product or
mediator diffusion is directly
involved.

12. • Highly specific for the purpose of the analyses i.e. a sensor must be
able to distinguish between analyte and any “other” material.
• Stable under normal storage conditions.
• Specific interaction between analytes should be independent of any
physical parameters such as stirring, pH and temperature.
• Reaction time should be minimal.
• The responses obtained should be accurate, precise, reproducible and
linear over the useful analytical range and also be free from
electrical noise.
• The nanobiosensor must be tiny, biocompatible, nontoxic and non-
antigenic.
• Should be cheap, portable and capable of being used by semi-skilled
operators.
Characteristics for an Ideal
Nanobiosensors

13. Constituents of Nanobiosensors
• A typical nanobiosensor comprises of 3 components; biologically sensitized
elements (probe), transducer and detector.
• 1) The biologically sensitized elements (probe) including receptors,
enzymes, antibodies, nucleic acids, molecular imprints, lectins, tissue,
microorganisms, organelles etc., which are either a biologically derived
material or bio-mimic component that receives signals from the analytes
(sample) of interest and transmits it to transducer. And such nano-receptor
may play a vital role in the development of future nanobiosensors.
• 2) The transducer acts as an interface, measuring the physical change that
occurs with the reaction at the bioreceptor/sensitive biological element then
transforming that energy into measurable electrical output.

14. 3) The detector element traps the signals from the transducer, which are then
passed to a microprocessor where they are amplified and analyzed; the data is
then transferred to user friendly output and displayed/stored.

15. Advantages of Nanobiosensors over
Conventional Biosensors
• These sensors are ultra sensitive and can detect single virus
particles or even ultra-low concentrations of a substance that
could be potentially harmful.
• Nanobiosensors works at atomic scale with highest efficiency.
• Nanobiosensors also have increased surface to volume ratio.
• Disadvantages of nanobiosensors.
• Nanobiosensors are very sensitive and error prone.
• Nanobiosensors are still under infancy stage.

16. Mechanical Nanobiosensors
• Nanoscale mechanical forces between biomolecules provide an exciting
ground to measure the biomolecular interaction.
• This helps in the development of minute, sensitive and label free
biosensors.
• Microscale cantilever beams can be used to identify biomolecules by
deflecting upon interaction with a specific biomolecule.
• The advantage of nano-mechanical devices is that they are highly mass
sensitive. More the size decreases, more the mass reduces and hence the
addition of bound analyte molecules results in an increased relative change
to the main mass.

17. Optical Nanobiosensors
• Optical biosensors are based on the arrangement of optics
where beam of light is circulated in a closed path and the
change is recorded in resonant frequency when the analyte
binds to the resonator.
• The resonator can be basically divided into linear resonator
(light bounces between two end mirrors) and ring resonators
(light is circulated in two different directions as end mirrors
are absent).
• Unlike mechanical resonators optical ones are based on the
oscillating light within a cavity.
• Most of the commercially available optical biosensors rely on
the use of lasers to monitor and quantify interactions of
biomolecules that occur on specially derived surfaces or
biochips

18. Nanowire Biosensors
• Nanowire biosensor is a hybrid of two molecules that are extremely
sensitive to outside signals: single stranded DNA, (serving as the
“detector”) and a carbon nanotube, (serving as the transmitter).
• The surface properties of nanowires can be easily modified using chemical
or biological molecular ligands, which make them analyte independent.
• This transduces the chemical binding event on their surface into a change in
conductance of the nanowire with extreme sensitivity, real time and
quantitative fashion.
• Boron-doped silicon nanowires (SiNWs) have been used to create highly
sensitive, real-time electrically based sensors for biological and chemical
species.

19. Electronic Nanobiosensors
• Electronic nanobiosensors work by electronically detecting the binding of a
target DNA that actually forms a bridge between two electrically separated
wires on a microchip.
• Each chip contains multiple sensors, which can be independently addressed
with capture probes for different target DNA molecules from the same or
different organisms.

20. Viral Nanobiosensors
• Virus particles are essentially biological nanoparticles.
• Herpes simplex virus (HSV) and adenovirus have been used to trigger the
assembly of magnetic nanobeads as a nanosensor for clinically relevant
viruses.

21. Applications of Nanobiosensor
• Nano sensors may be used to diagnose soil disease (caused by infecting soil
micro-organisms, such as viruses, bacteria, and fungi) via the quantitative
measurement of differential oxygen consumption in the respiration (relative
activity) of “good microbes” and “bad microbes” in the soil.
• A nanofertilizer refers to a product that delivers nutrients to crops
encapsulated within a nanoparticle.
• Pesticides inside nanoparticles are being developed that can be timed-
release or have release linked to an environmental trigger. Also, combined
with a smart delivery system, herbicide could be applied only when
necessary, resulting in greater production of crops and less injury to
agricultural workers.
• Several nanobiosensors are designed to detect contaminants, pests, nutrient
content, and plant stress due to drought, temperature, or pressure. They
may also potentially helpful for farmers to enhance competence by
applying inputs only when necessary.

22. Applications of Nanobiosensor
• Several nanosensors like ssDNA-CNTs probes/ optical biosensors to detect
specific kinds of DNA oligonucleotides.
• Vitamins analysis: The SPR biosensor monitors interactions of a specific
binding protein with the vitamin immobilized on a CM5 sensor chip.
• Antibiotics detection: Recently the presence of prohibited antibiotics was
detected in honey. Biosensors analyze the presence of antibiotics reliably,
effecttively and in a short time.
• Detection of food spoilage: Amperometric biosensor using immobilized
enzyme diamine oxidase (DAO) has been developed for the rapid
monitoring of the histamine levels in tiger prawn (Penaeus monodon),
similarly a potentiometric biosensor could analyse isocitrate using a -
selective electrode and enzyme immobilization in flow injection analysis
(FIA)

23. Single molecule device
 Otherwise called as Single-molecule electronics
 It is a branch of nanotechnology that uses single molecules, or nanoscale
collections of single molecules, as electronic components. Because single
molecules constitute the smallest stable structures imaginable, this
miniaturization is the ultimate goal for shrinking electrical circuits.
 Conventional electronics have traditionally been made from bulk materials.
Ever since their invention in 1958, the performance and complexity
of integrated circuits has undergone exponential growth, a trend
named Moore’s law, as feature sizes of the embedded components have shrunk
accordingly.
 In single-molecule electronics, the bulk material is replaced by single
molecules.
 Instead of forming structures by removing or applying material after a pattern
scaffold, the atoms are put together in a chemistry lab.
 In this way, billions of billions of copies are made simultaneously (typically
more than 1020 molecules are made at once) while the composition of
molecules are controlled down to the last atom.
 The molecules used have properties that resemble traditional electronic
components such as a wire, transistor or rectifier.

24. Wires• The sole purpose of molecular
wires is to electrically connect
different parts of a molecular
electrical circuit.
• As the assembly of these and their
connection to a macroscopic circuit is
still not mastered, the focus of
research in single-molecule
electronics is primarily on the
functionalized molecules: molecular
wires are characterized by containing
no functional groups and are hence
composed of plain repetitions of a
conjugated building block.
• Among these are the carbon
nanotubes that are quite large
compared to the other suggestions but
have shown very promising electrical
properties.
• The main problem with the molecular
wires is to obtain good electrical
contact with the electrodes so that
electrons can move freely in and out
of the wire.

25. Transistor
• Single-molecule transistors are fundamentally different from the ones known from
bulk electronics.
• The gate in a conventional (field-effect) transistor determines the conductance
between the source and drain electrode by controlling the density of charge carriers
between them, whereas the gate in a single-molecule transistor controls the
possibility of a single electron to jump on and off the molecule by modifying the
energy of the molecular orbitals.
• A popular group of molecules, that can work as the semiconducting channel
material in a molecular transistor, is the oligopolyphenylenevinylenes (OPVs) that
works when placed between the source and drain electrode in an appropriate
way. Fullerenes work by the same mechanism and have also been commonly used.
• Semiconducting carbon nanotubes have also been demonstrated to work as channel
material but although molecular, these molecules are sufficiently large to behave
almost as bulk semiconductors.
• Physicists at the University of Arizona, in collaboration with chemists from
the University of Madrid, have designed a single-molecule transistor using a ring-
shaped molecule similar to benzene. Physicists at Canada's National Institute for
Nanotechnology have designed a single-molecule transistor using styrene. Both
groups expect their respective devices to function at room temperature, and to be
controlled by a single electron.

26. Rectifier
• Molecular rectifiers are mimics of their bulk counterparts and have an
asymmetric construction so that the molecule can accept electrons in one
end but not the other.
• The molecules have an electron donor (D) in one end and an electron
acceptor (A) in the other.
• This way, the unstable state D+ – A− will be more readily made than D− –
A+.
• The result is that an electric current can be drawn through the molecule if
the electrons are added through the acceptor end, but less easily if the
reverse is attempted.

27. Methods
• Molecular gaps
• One way to produce electrodes with a molecular sized gap
between them is break junctions, in which a thin electrode is
stretched until it breaks. Another is electromigration.
• Here a current is led through a thin wire until it melts and the
atoms migrate to produce the gap. Further, the reach of
conventional photolithography can be enhanced by chemically
etching or depositing metal on the electrodes.
• Probably the easiest way to conduct measurements on several
molecules is to use the tip of a scanning tunneling
microscope (STM) to contact molecules adhered at the other
end to a metal substrate.

28. Anchoring
• A popular way to anchor molecules to the electrodes is to make use
of sulfur's high chemical affinity to gold.
• In these setups, the molecules are synthesized so that sulfur atoms
are placed strategically to function as crocodile clips connecting the
molecules to the gold electrodes.
• Though useful, the anchoring is non-specific and thus anchors the
molecules randomly to all gold surfaces.
• Further, the contact resistance is highly dependent on the precise
atomic geometry around the site of anchoring and thereby inherently
compromises the reproducibility of the connection.
• Fullerenes could be a good candidate for use instead of sulfur
because that can electrically contact many more atoms at once than
one atom of sulfur.