BIOELECTRONIC MEDICINES

CONCEPT-
The nervous system is the most complex system in our body because of
its neurons and their interactions with one another. The interactions or
the way of communications between these neurons are able to
generate very complex patterns of dynamic activity. It is the centre for
control and coordination. Every movement in our body either the
stimulation of hormones or movement of muscles by voluntary or
involuntary is controlled by the brain and its nerves. Brain nearly
consists of 36 billion neurons and each and every neuron of it is in use.
Every neuron communicates with other neurons to share information.
The information is shared in the form of electrical impulses with the
help of neurotransmitters.

Some of the involuntary functions are carried out by spinal cord and
smooth muscles i.e., in cardiac muscle. Heart consists of its own
conduction system in which electrical impulses are employed as action
potential. Hence, we can they say that either voluntary or involuntary,
electrical impulses which are generated by neurons helps in proper
functioning of the body. All the functions of human body are carried
well until occurrence of any damage to the neuron, if a neuron gets
damaged its specific function gets effected, which ultimately results in
the improper function of that specific area or hormone and leads to
disorders.

Generally, drugs are used to treat these disorders. But long-term usage
of these drugs can cause severe side effects. So, some of the scientists
and researchers are looking after an alternative which would replace
this drug therapy perfectly without any side effects. Hence, by
modifying the neural signals, we can cure or treat a disfunction or a
disorder in our body.
The technology is changing convergently all around us. Almost
everything is possible with the technology we have. Most of the
technical advancements have happened the convergence which means
the movement towards one point of time to other point of time.
In healthcare system, bioelectronic medicines is a new therapeutic
field-
 increases the understanding of immunology and neuroscience
 involves the implantation of active medical devices
 creates the awareness of side effects in pharmaceuticals
It is field that shows a promising therapy that gained more than $1
billion investment in the last 3 years

DEFINITION-
Bioelectronic medicine is a tiny implantable device to treat a disease by
changing the electric impulses which are produced in the nerves of a
specified organs.
(Or)
BEM is one of the miniatures (i.e., small), implantable device which can
be attached to the individual peripheral nerves in the viscera for
treating a specific disease.
(Or)
The integration of biomaterials with electronic elements such as
electrons, chips, and transistors give a hybrid system which is known as
BEM.

INTRODUCTION-
By using bio electronical medical technologies, we can record, stimulate
or block a neural signal which can change the way we treat diseases,
injuries, or some of the conditions such as Rheumatoid Arthritis,
Diabetes, Paralysis, Bleeding disorders and also Cancer. BEMs are the
convergent fields of Neuroscience, Molecular medicine and
bioengineering to develop devices that are used to diagnose and treat
diseases.

National Institute of Standards and Technology (NIST), an agency of US

Department of Commerce defined BEM in 2009 as, “The discipline
resulting from the convergence of biology and electronics. BEMs are
also known as ‘Electroceuticals’ as it is a complimentary drug-based
system which uses electrical impulses to treat diseases. BEMs diagnose
diseases by using some of the biomarkers and these types of BEMs are
known as ‘Smart Bioelectronics’. For example, saliva-based detection
and blood-based detection.

BIOMARKERS- A biomarker is a substance that is present in an

organism which indicates the phenomenon of disease or infection or
environmental exposure.
Generally, some of the doctors and researchers use biomarkers for
measuring the normal, biological or pathological process or the
responses of the body to a particular therapy.

BIOSENSORS- These are the analytical devices that are able to convert
biological response into an electrical signal. These biosensors are
defined as analytical devices which incorporates a biological material
such as tissues, microorganisms, organelles, cells, receptors, enzymes,
antibodies, nucleic acids, natural products, etc., a biologically derived
material such as recombinant antibodies, engineered proteins, etc. and
biomimic (synthetic receptors combined with ligands, etc.) which are
intimately associated with or integrated within physicochemical
transducer or transducing microsystem that may be optical, electro
chemical, magnetic, etc., . These biosensors are used in the following
areas-
 General healthcare monitoring
 Disease screening
 Clinical analysis and diagnosis of disease
  In veterinary and agricultural applications
 Industrial processing and monitoring
 Environmental pollution control

HISTORY:

 The first reference to bioelectronics, published in 1912, focused

on measurement of electrical signals generated by the body,
which is the basis of electrocardiogram.

 In the 18th century “LUIGI GALVANI “ was the scientist who

study the first bioelectronic, he applied voltage to pair of
detached frog legs. The movement of leg through sparking
genesis of bioelectronics.

 In 1960’s a trend in bioelectronics began to appear by the

invention of transistor. This enabled the development of an
implantable electronic device to be placed in the body for
stimulating organs. Eg: pacemaker.

AT PRESENT:

 Researchers at north western university and washington

university school of medicines have developed the first
example of BEM and defined it as “ an implantable,
biodegradable, wireless device that spreads nerve regeneration
and improves the healing of a damaged nerve”.
 When we are discussing about BEM, we should surely discuss
about a person who enormously developed this field and he is
“Dr. KEVIN J. TRACEY”.
  He is a neurosurgeon and an inventor. He is a professor at
institute of bioelectronics medicines at feinstein institute for
medical research.
 He is also an exceutive vice president of research at north well
health.
And top all he is the present president and CEO of
feinstein institute for medical research.
 The major focus on Dr. KEVIN laboratory is the molecular
basis of inflammation and identification of the
mechanisms by which neurons control the immune
system.
 His laboratory discovered the inflammatory reflex.
This discovery led to the first clinical trails of
neuromodulating devices to replace anti inflammatory drugs termed as
“ BIO ELECTRONICS”

ADVANTAGES:

 Painless approach to cure diseases.

Bioelectronics is consider as a painless cure because bioelectric
therapy relieves pain signals before they reach the brain. Bioelectric
therapy also prompts the body to produce endorphins which helps to
relieves pain.
 Targeted treatment
bioelectronics medicines are considered as targeted treatment
because bioelectronic medicines are implantable at a specific site to
treat the disease of a particular organ or system.
 Bioelectronics would minimal or zero side effects.
By using this bioelectronics medicines we can overcome the problems
faced by conventional dosage forms.
 Increased selectivity and cellular control.
 Better patient compliance.
DISADVANTAGES:

 Costly process, if a single chip is damaged the total technique will

be meaningless.
eg. Bionic eye
 High compact state of nerve and cardiac systems, indiscriminate
stimulator can lead to undesirable effects.
 Chances to get electric shock.
 Installation of an implant may cause harm to our body.
 Bioelectronic therapy is not suitable for all people.
for example: the pregnant ladies, and the persons who are
suffering from thrombosis (blood clots) and the persons having
bacterial infection. They are not suitable for bioelectric therapy

MECHANISM:
Peripheral nerves are responsible for sending the signals on electrical
impulses from brain to the body parts or organs. A small device, as
small or as tiny as a rice grain is implanted to a nerve bundle . This
device either blocks or alters the signalling patterns in the nerve
bundle. The signals which are modified i.e., modified signals travels to
the targeted organs through the nerve fibres for treating or curing
diseases.

NEXT GENERATION NEUROMODULATION:

Next generation neuromodulation devices are expected to improve

these key areas:
 Sensitivity:Capability of sending signals from neurons in the
cortex and nerve fascicles and fibres in the periphery, in a highly
sensitive manner against other background interference.
  Selectivity: Which can precisely target nerves near the visceral
organs central in chronic diseases with clear end points.
 Responsiveness: Which form closed loop around recording of
neural signals and detections of biomarkers (several
communicating devices may be needed for the close-loop
biomarkers detection and stimulation.
 Acceptance: A miniaturised low power devices that can be
delivered with minimal invasive implantation thereby reducing
patient burden and improving access.

CURABLE DISEASES:
Some examples of diseases that are the potential targets of BEMs are:
 Acid reflux
 Bleeding and haemophilia
 Cancer
 Chronic pain
 COPD (Chronic Obstructive Pulmonary Disease)
 Congestive heart failure
 Chron’s disease
 Diabetes Epilepsy
 Heard disease
 Sepsis
 Shock
 High blood pressure
 Irritable bowel disease
 Lupus
 Mental illness
 Depression and schizophrenia
 Migraine
 Multiple diseases
 Paralysis
  Parkinson’s disease
 Pulmonary hypertension
 Rheumatoid arthritis
 Spinal cord injury
 Traumatic brain injury

VAGUS NERVE STIMULATION:

Vagus nerve is the X cranial nerve and main parasympathetic nerve in
the body and travels from brain stem to colon. It carries sensory
information about pain, touch and temperature from throat, inner and
outer ear and meninges near the back of the head and receives sensory
information from internal organs in neck, chest and abdomen. It also
carries information from baroreceptors (to detect change in blood
pressure) and chemoreceptors (to sense oxygen levels).

The vagus nerve stimulation is used in treatment of individuals with

epilepsy and inflammation. It has been in use since 1997 for epilepsy .
Recently, it gained approval by FDA for its use in depression.

Position of fixation: It is entailed in a little incision in the chest where

the electrodes of this device are put in contact with the nerve and
other incision in collarbone where stimulator itself stimulates these
electrodes.

Working:It works by sending electric messages to brainstem, which

includes nucleus of tractus tereus and locus coeruleus areas, that
project to the surface of the brain with specific neurotransmitters
including norepinephrine and this transmission end up by inhibiting the
seizures. When stimulated electrically, it modulates seizures threshold
and decreases seizures frequencies. Generally, it is started with low
parameters like low stimulus intensity and low frequency, low duty
cycle, then escalated gradually to titrate to the therapeutic response.
Initial seizure reduction may not be impressive but for a long period like
1year later 50% of the individuals with this device implanted will
experience 50% decrease in their seizure frequency.

In case of depression, when it gets stimulated it increases vagal tone

and slows heart rate and breathing and calms down nervous system,
making us feel better. It could easily overcome the stress and are less
likely to show symptoms of depression.

Now-a-days VNS is developed in responsive function i.e., it will detect

heart rate and in majority of seizures there are increased levels of heart
rate at the time of seizures and when VNS detects this increase in the
heart rate it will deliver electric stimulation to the nerve in an attempt
to abort the seizures.

Device:This VNS device contains a magnet (which orders to fire

immediately), that can be swiped near the collarbone in an attempt to
decrease the seizures. A London based manufacturer LIVANOVA, is one
of the companies that manufactures this VNS device.

VARIOUS BIOELECTRONIC MEDICINES AVAILABLE:

REFLUX STOP OR LINNX:
 It is BEM which is used to treat acid reflux.
 Generally the entrance of our stomach has a ring of
muscle valve called as lower oesophageal
sphincter(LES).
Normally, this LES closes as soon as the food passes through it.
If this LES doesn’t close all the way or it opens too often, acid produced
in our stomach can move up into oesophagus.
This condition can cause some of the symptoms such as burning ,
chest discomfort which is commonly called as heart burn. It this
conditions persists and happens more than 2 times a weeks, we can say
that the particular person is suffering from acid reflux disease which is
also known as gastro oesophageal reflux disease( GERD).
To treat this disease, one of the most recent approved,
procedure is by placing LINX around the outside of the lower end of
oesophagus.
LINX is a bioelectronic device which consists of the magnetic
titianum beads that are held together by titianum wires. This device
helps by preventing the reflux of the stomach contents from backing up
into oesophagus.
BIONIC EYE:
Bionic eye is an electrical prosthesis[ prosthesis means artificial
replacement] of human eye. It is surgically implanted into the eye
inorder to allow the transduction of light. Here, transduction of light
means changing of light means changing of light from the environment
into such impulses that the brain can process and understand. Bionic
eye is placed or implanted into people who have a sustained and severe
damage to the retina.
Retina is the light sensitive tissue layer that transfers images obtained
from the outer world into neural impulses which are then passed along
the optic nerve to the thalamus and finally to the visual cortex ( that
means the visual processing centre) which is located in the optical lobe
of the brain.

Bionic eye is beneficial for the people who are suffering from the
macular degeneration or retina pigmentosa. Macular degeneration is a
condition in which the cells found at the centre of retina degenerated.
&
Retintis pigmentosa is a hereditary disease in which photo
sensitive rods and cones of retina are destroyed.
Bionic eye consists of an external camera, transmitter and internal
microchip.
 Camera is mounted on a pair of eyeglasses where it serves to
organize the visual stimuli of the environment.
The stimulator microchip consists of an electrode array that is
surgically implanted into the retina. This function as an electric relay in
the place of degenerated retinal cells.
The radio waves that are emitted by external camera and
transmitter are received by the stimulator, which then tiggers the
electrical impulses.
The impulses are relayed by the fear remaining retinal cells and
are transduced as normal to the optical nerve pathway which results in
vision.
PACEMAKER:
The artificial cardiac pacemaker is a medical device that generates
electrical impulses delivered by electrodes which help in regulating the
electrical conduction system, of heart.
Pacemaker is suggested in the patients who are suffering from
arrhythmia.
Generally, the electrical activity within the heart is used to
determine the heart rate. If this electrical activity is delayed, a slow
heart rhythm may occurs.
And the people who have slow heart rhythm may feel tired, dizzy,
light headed and also loss their consciousness sometimes.
Arrhythmia is a condition of irregular rhythm rate or heart rate. It
happens when the electrical impulses that direct and regulate heart
beats don’t function properly. This causes the heart to beat too fast
( which is nothing but tachycardia) or the heart beat is too slow ( which
is known as bradycardia) or to beat early ( which means premature
contraction ) and too (Which means fibrillation).

The modern pacemaker have 2 parts. One part is pulse generator

which contains a battery and electronics that are used to control the
heart beat.
 And the other part is the lead. Lead is nothing but wires that runs
from pulse generator to heart. The leads are used to send electrical
signals to the heart.
Generally the pacemakers are used to treat 2 types of arrhythmias.
i.e, the tachycardia & bradycardia.
But some people need a special type of pacemaker known as
biventricular pacemaker or also called bivent. This bivent is only used
when there is a severe heart failure.
The bivent makes the 2 sides of the heart to beat in a synchronized
manner. This is known as cardiac resynchronization therapy (CRT).
We need a pacemaker only if our heart pumps the blood too quick
ot too slow. In both these cases, the body does not get enough blood
for normal functioning. This can causes fatigue, light headaches,
shortness of breath, damage to vital organs or eventual death.

COCHELAR IMPLANTS:
 A cochlear implants is an bioelectronic device that partially
restores hearing.
 Cochlear implants mainly useful for deaf people.
 It can be an option for people who have severe hearing loss
from inner ear damage who longer helped by using hearing
aids.
 Cochlear implants may be placed in one ear (unilateral) or
both ears (bilateral).
 Cochlear implants in both ears have started to be used more
often to treat bilateral severe hearing loss.
HOW IT WORKS :
Cochlear implants to use a sound processor that fits behind the
ear. The processor captures sound signals and sends them to receiver
implanted under the skin behind the ear.
The receiver sends the signals to the electrodes implanted in the
snail shaped inner ear ( cochlea).
 The signal stimulate the auditory nerve, which then directs them
to the brain. The brain interprets those signals as sounds.
GN Resound, Sonova, Starkey, Widex. These are the companies
which markets the cochlear implants.

ARTIFICAL LIMBS:
 The people who have lost their legs or hands in an accident
or any other natural cause and they are treated by
bioelectronics devices.
 An artificial limb is a type of prosthesis ( it is an artificial
extension of replacing a missing body part ) that replaces a
missing part such as arms or legs.
 These artificial limbs perform daily activites such as walking,
eating or dressing.
 These artificial limbs let you function nearly as well as
before.
 Bioelectronics are used to power them, control them,
modify them and capable of independent thought ans
manipulate their structure as per needs.
ALIMCO ( Artifical limbs manufacturing corporation of
india) which markets the artificial limbs.
ASTHMA:
 Asthma is a condition in which a person’s airways
become inflamed, narrow and swell and produce extra
mucus which makes it difficult to breathe.
 The device is attached to a pulmonary nerve to
potentially block the signals that causes that lungs to
constrict.
HYPER TENSION:
 A condition in which the force of the blood against
the artery walls is too high.
 And the blood pressure is above 120/80.
  Left vagus nerve is major key role in regulating the
blood pressure.
 In this, regard it is well known that fibers conducting
BP signals from the arotic baro receptors (ABR) to
brainstem centres are running through the left vagus
nerve and stimulation of such fibres elicits BP
decrease.
 As such, a bioelectronic system performing closed
loop stimulation of the LVN for BP decrease could use
this nerve for delivering the stimulation pulses to ABR
fibers.

BIOLUNG:

It is implanted in the chest.

ECMO- refered to the Extra Corporeal Membrane Oxygenation.
It uses a pump to circulates the blood through an artificial
lung back into the blood stream.
It provides heart lung by pass.
It does the job of the lungs and heart allowing the organs to
rest and recover when the patients are incredibly.
This is used when all other forms of heart and lung support
have failed for critically ill patients.
WORKING:
 It works temporary drawing blood from the body to allow artificial
oxygenation to RBC’s and removal of CO2 with machine.
 The machine is connected to a patient through cannula
(plastictubes).
 The tubes are placed in large veins and arteries in the leg, neck or
chest.
 ECMO machine pumps blood from the patient’s body to an
artificial lung ( oxygenation) that adds O2 to it and removes CO2.
 Thus, it replaces the function of the persons own lungs.
  The ECMO machine then sends the blood back to the patient via.
Pump with same force as that of heart.

HEART CONDITION WHEN ECMO INCLUDED:

 Acute MI (Myocardial infraction)
 Heart muscle diseases ( decompensated cardiac myopathy)
 Inflammation of heart muscles ( myocardial)
 Life threatening to the life ( sepsis)
 Post transplant complications.
DISADVANTAGES:
 Can’t be used long term.
 To keep blood moving through machine without clotting blood
thinning drugs are used which in turn may cause bleeding.
 Mechanical pumps may damage RBC’s.
IT IS TWO TYPES:
1. V-V ECMO ( veno venous):
It is dual site cannulation. Drainage cannula inserted into
the right femoral vein and return in theright internal jugular
vein.
2. V-A ECMO ( veno artereous):
It is dual site cannulation. Drainage cannula inserted into
the right femoral vein return cannula to the left femoral
artery.
HOW TO REMOVE:
Same as ventilator by slowly reducing amount of support.
Now, in the present situation this treatment is being used to
support critically ill patients with COVID-19 pneumonia for whom
ventilation is insufficient to sustain blood O2 levels.

RECENT INVENTIONS:

 Spinal cord stimulator

  Deep brain stimulator
 Googles recently announced contact lenses that mointor glucose
levels.

FUTURE OF BIOELECTRONICS:

 The therapeutic approaches currently available for metabolic

diseases don’t provide long term control of the disease,
combined with significant side effects.
 A bioelectronic medicine approach could bring significant
improvement in the standard care for type-II diabetes by
targeting nodal metabolic pathways and avoiding systemic
effects.
 Implanted devices which can be attached to peripheral nerves
anywhere in the viscera, are used to treat hypertension and
sleep apnea.
 Neuromodulation- recent approach
 Restore movement in a paralysed human by
1. Neural decoding: Control of temporarily paralysed
muscles.
2. neural bypass : Serve the function of damaged network.
 Many devices are wearable devices

MARKETING:

 The field potential to provide new treatment approaches uses

electric pulses to activate mechanisms in the body has attracted
investments from compaines including “ GLAXO SMITH KLINE”,
“GOOGLE “& “GENERAL ELECTRONICS”.
 This three pharmaceutical compaines is developing an
implantable device that will adjust the electrical signals in
nervous systems to treat chronic diseases.
  Europe is currently leading the global bioelectronics, asia pacific
and north america following it closely.

APPLICATIONS:

 The integration of biomaterials with electronics, such as

electrodes, chips and hybrid system that may function as biofuel
cells, biosensors and biocomputing devices.
 Bioelectronic devices have huge scientific and practical
importance for the basics sciences as well as for possible
applications in medicine, high tech industry, the military etc..
 For people with diabetes, sensor could detect in real time, if
glucose levels were too high or too low, the device could modify
the nerve impluse that stimulate insulin production in pancreas.
 It is also used to treat cancers.

CONCLUSION:

BEM’s are the future of general medicine. The application of

electronics technology to biology is not new research that enabled
those applications grow out of many disciplines of science and
engineering.
Science and technology experts ressembling representing the
nano electronics and biotechnology communities provided inputs for
this report.
The strategic drivers that were most frequently cited wire:
disease detection, disease prevention and prosthetics.
The technologies and devices that will enable applications in
these areas will impact other vital areas such as home land and national
security, forensics and the environment.
 Progress in all of these sectors requires innovation in cross
cutting areas, including measurement and characterization, fabrication
and power sources.
As a next step, stakeholders from government, academic and
industry should jointly develop effective planning and resources
management for increasing the productivity and commercialization of
bioelectronics research and development.