Abstract— through the digestive system to achieve certain diagnostic

 

Abstract—
Electronic medical implants have been emerging in the field of biomedical
engineering in the past few decades. Along with the great inventions came a few
challenges, including infection and inflammation risks, and the costs for the
surgical implant procedure. The idea of edible electronics, or electronic
devices consumed through the digestive system to achieve certain diagnostic or
therapeutic goals was proposed as a solution to these problems. Reliability is
all the more critical because it often turns out to be a case of life or death!

Keywords—component;
formatting; style; styling; insert

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I.      Introduction

Despite so many risks and challenges, it is awesome to
see how implants have developed since the days of the first pacemaker in 1958.
From cardiac pacemakers to cochlear implants, from brain interfaces to retinal
implants, there are numerous implantable medical electronic devices available
today. Even more exciting is the emerging field of edibles—tiny, capsule-sized
electronic devices that are consumed orally for diagnosis and treatment of
diseases. Some edibles are designed to remain inside the body for some time, while
others do their job and get disposed of within minutes.

Today, we have reached a state where inventions like
these no longer surprise us because our minds have become tuned to a sci-fi
future, and we have started expecting such developments. So let us put aside
the wow-factor, and instead look at the current and future state of implants
and edibles.

II.    Painless diabetes
testing, drug delivery and more

  With
improvements in quality and reliability, there is now a reasonably good demand
for cochlear, retinal and cardiovascular implants. Cardiovascular implants have
evolved much in recent years, and have overcome past constraints regarding
compatibility with imaging systems such as magnetic resonance imaging (MRI).
Interestingly, the rise in lifestyle diseases like diabetes has also led to an
increased demand for implantable devices like implantable continuous glucose
monitoring and implantable infusion pumps. There are also implantable devices
for phrenic nerve stimulation to restore breathing function in patients, and
sacral nerve stimulation for patients with bladder disorders. Implantable
neuro-stimulators, on the other hand, help those with neurological disorders
like Parkinson’s disease.

  With the availability of better biocompatible
materials that minimize the possibility of infections, there is greater faith
in implants. Researchers at the Graeme Clark Institute have developed an
implant that is fitted under the scalp to diagnose and treat epilepsy and even
forecast a likely seizure. They are also developing an implantable drug pump
for patients with drug-resistant epilepsy.

  Cochlear
implants are used when hearing aids don’t work well—that is, when the patient
has severe sensorineural hearing loss due to absent or reduced cochlear hair
cell function. The implant basically carries out the function of the cochlea or
inner ear, stimulating the auditory nerve directly.

   Retinal
implants are giving vision to the impaired around the world. Going one step
further, the Monash Vision Group is developing Gennaris—a bionic vision system
that bypasses damage to the eye and optic nerve to restore functional vision
for people who have injured both these or lost sight due to glaucoma and
acquired the retinal disease. This system interfaces directly with the brain,
bypassing the retina and optic nerve.

  Elsewhere,
researchers are also exploring biocompatible, implantable photonic devices that
can improve health monitoring, diagnostics and light-activated therapies.
Consider the possibility of biocompatible and wirelessly powered light-emitting
diodes (LEDs) and miniature lasers implanted inside the body. Advances in
biotechnology, such as optogenetics, will enable these photonic implants to be
integrated tightly with neurological or physiological circuits.

  A good interface
between implanted devices and the brain can help in great ways—for example, it
can return motor function to amputees and people paralysed due to stroke or
spinal cord injury. A minimally invasive electrode called the Stentrode
developed at the University of Melbourne might be a step in this direction.
Implanted into a blood vessel adjoining the area of the brain that controls
movement, it may help control an exoskeleton, enabling crippled or paralysed
people to move. The implant can apparently be installed without opening the
skull, which is what makes it attractive!

  Neuralink, a
company funded by Elon Musk, is also working on implantable brain-computer
interfaces. They are developing syringe-injectable, flexible, sub-micron-thickness
substrates that can be used in implantable electronics. The substrate is soft
enough to sit harmlessly in the brain, and has electrical properties that
enable only the targeted part of the brain to receive the electrical stimulus.

  Brain-computer
interface is the future of implantable systems. It can help people with
degenerative brain diseases and neurological disorders. However, it must be
handled with care because an electrode implanted in the brain can be used both
for good and bad purposes!

III.   Rise of edibles for diagnostics and drug delivery

 

 When
the electronic device needs to stay inside the body forever or for a reasonably
long time, it is worth operating on a patient to implant the device. However,
if you just want it to stay inside for a few minutes, hours or even days, for
the purpose of monitoring a health condition or temporarily dispensing some
medicines, operating on the patient doesn’t make sense. This requirement led to
the development of ingestible or edible electronics, which industry-watchers expect to create
huge waves like wearable did.

 The electronics
that you swallow, encapsulated in a pill, will sit in your gastrointestinal
tract for a short time, before being ejected from your body like regular food
waste. During this time it can capture videos, release drugs, monitor heart
rate and respiration, and perform other such tasks.

 Proteus Digital
Health was one of the pioneers in ingestible tech, and their technology is now
used commercially by close to ten health systems. Their solution comprises a
pill, a patch that is attached outside to the side of the stomach, and a mobile
app/desktop portal. The pill is made of whatever drugs are required, and fitted
with a sensor made of natural, ingestible materials like copper, magnesium and
silicon. When a patient swallows the pill, it dissolves like a normal pill in
the stomach but leaves behind a sensor, which is activated by fluids in the
body. This sensor sends a signal to the patch, which also measures heart rate,
body position and time of medication detection. This information is sent to the
patient’s or doctor’s mobile phone.

  Regular drug
intake is very important for those undergoing complex medical treatments such
as organ transplants. This pill could be very useful for such patients. Proteus
has teamed up with Tokyo-based firm Otsuka to embed Proteus’ sensors into
Abilify—a drug used for serious mental illnesses.

  Another
forerunner in the space is Israel-based Given Imaging. Their PillCam series
comprises pills with ingestible cameras, which can help doctors to view
different parts of the patient’s digestive system like the oesophagus or colon.
It is a painless alternative to tests like endoscopy and colonoscopy. The PillCam
Colon, for instance, uses a battery-powered camera to take high-speed photos as
it slowly goes down the intestinal tract over a time period of eight hours. The
images are transmitted to a recording device worn around the patient’s waist
and later reviewed by a doctor. Although the images are not as sharp as those
obtained through normal colonoscopy, it is a viable alternative for those who
cannot bear the pain or feel embarrassed by the procedure.

  Other versions
of PillCam help doctors to see the small intestine and oesophagus. The company
has also developed SmartPill— an ingestible capsule that measures pressure, pH
and temperature as it travels through the gastrointestinal tract. This helps
doctors to assess GI motility.

  Bravo pH is
another capsule-based test that helps to test for acid reflux. The miniature pH
capsule attaches to the oesophagus and sends pH data wirelessly to a small
recorder worn on a shoulder strap or waistband. Information is collected
over multiple days, enabling doctors to study the frequency and duration of
acid flowing back up into the oesophagus. This helps to confirm the presence of
gastroesophageal reflux disease (GERD). This is a totally catheter-free
solution, so the patients can go about normal activities and have a normal diet
while the pill unobtrusively monitors their acid reflux. They can remove the
receiver to take a shower. This type of monitoring under a normal routine gives
better results than keeping the patient under observation.

IV.   Unique engineering challenges

  The
most obvious challenge to edible electronics is, obviously, miniaturisation. It
is impossible to implant or consume something that is bulky. With the
electronics industry in general moving towards miniaturisation in everything,
this goal has become more achievable in implantable devices, too. Unlike the
traditional pacemaker, the newer leadless pacemakers are about the size of a
large capsule, and can be placed directly in the heart. These can be implanted
through a femoral vein puncture in about half an hour. No more bulges or scars,
these pacemakers are very unobtrusive and apparently also less prone to
infections. The National Heart Centre Singapore (NHCS) began implanting such
pacemakers last year.

  Thermal
management is another huge challenge in implantable devices. Like any other
electronic device, implantable devices too vent out waste heat. However, this
heat should not harm the surrounding tissues. So while designing an implantable
device, engineers have to consider thermal properties of biomaterials, the
effect of blood flow on temperature distribution, interfacial contact
resistance, effect of temperature change on various types of tissues and
communication duty cycles of embedded electronic components.

  Further, the
in-vivo electronic device must be biocompatible—it must not cause any adverse
reaction inside the body. It must be stable over time, despite the temperature
and pH variations in the human body. The biocompatible materials must not
contain cancer causing toxins, and must mostly be made of materials naturally
suitable to the human body. The insulation materials must match the texture and
smoothness of the surface they interface with, be it tissue, bone or skin.

  Currently, we
have biocompatible polymers for use in drug delivery devices, skin or cartilage
and ocular implants; metals for dental and orthopaedic work; semiconductor
materials for bio-sensors and implantable microelectrodes; and ceramics for
bone replacements, heart valves and dental implants. But, ingestible electronics
adds to the constraints, requiring the device and its power source to be made
of materials that are part of our diet and can be disintegrated and disposed of
easily by the body. The search is on There is a lot of ongoing research on
bio-inspired, biocompatible materials and power sources, which can improve the
performance and reliability of implantable and ingestible devices. A recent
paper by MIT researchers, published in Nature, describes a biocompatible power
source that lasts much longer than current options that can power the edible
device only for a few minutes or at the most a few hours. This
energy-harvesting galvanic cell for continuous in-vivo temperature sensing and wireless
communication could deliver an average power of 0.23pWper square-mm of electrode
area for an average of 6.1 days, when used for temperature measurements in the
gastrointestinal tract of pigs.

  In yet another
development, Dr Christopher Bettinger of Carnegie- Mellon University proposed
biodegradable elastomers as structural polymers, and melanin- based pigments as
materials for on-board energy storage in implantable and ingestible
electronics. His lab focuses on the development of biomaterials-based
microelectromechanical systems (MEMS) for use in regenerative medicine, neural
interfaces, drug delivery, etc. They have developed edible, biocompatible
batteries that use non-toxic materials already present in the body, with
available liquids such as stomach acid as the electrolyte. Their cathodes use
melanin, while anodes are made of manganese oxide. These electrodes dissolve
harmlessly after use.

  A team of
researchers, including Zhaowei Guo and others from Fudan University in China,
have developed a family of flexible and biocompatible aqueous sodium-ion
batteries for implants. Instead of toxic electrolytes, these batteries use
sodium-containing aqueous electrolytes such as normal saline and cell-culture
medium. The cell culture medium comprises amino acids, sugars and vitamins,
which is quite similar to the fluid that surrounds cells in the human body.

  The team made
two kinds of batteries. One was a two-dimensional belt-shaped battery made of
thin films of electrode material stuck on a mesh made of steel strands. The
other used a woven carbon nanotube fibre backbone with embedded nano-particle
electrode materials.

  This
fibre-shaped electrode with normal saline or cell-culture medium electrolyte
surprised the researchers by accelerating the conversion of dissolved oxygen
into hydroxide ions, and changing the pH. While this could be detrimental to
the effectiveness of the battery, it could be very useful in biological and
medical investigations like cancer starvation therapy.

  In Stanford, a
team led by Zhenan Bao has developed a flexible electronic device that can
easily be degraded into non-toxic compounds just by adding a weak acid like
vinegar to it. Apart from the polymer and thede gradable electronic circuit,
the team has also developed a new cellulose-based biodegradable substrate
material for mounting the electrical components. According to them, this
substrate supports electrical components, flexing and moulding to rough and
smooth surfaces alike.

  Bao is not new
to this field. Human skin has always fascinated her, and she previously
developed a skin-inspired stretchable electrode, which was so flexible that it
could easily interface with the skin or brain. However, the electrode’s
non-degradability made it unsuitable for implantable devices.

  Bao says in a
media report that they came up with an idea of making these molecules using a
special type of chemical linkage that can retain the ability for the electron
to smoothly transport along the molecule. But this chemical bond is sensitive
to weak acid— even weaker than pure vinegar. So the result was a polymer
material that could not only carry an electronic signal but also break down
easily to product concentrations much lower than the published acceptable
levels found in drinking water.

  How do sensors
made of biocompatible materials compare with those made of food itself? Well,
obviously you would prefer the latter. So thought a team of researchers from
the University of Wollongong in Australia! In a paper, they reveal that the
development of highly swollen, strong, conductive hydrogel materials is
necessary for the advancement of edible devices. So they analysed the
electrical properties of everyday food products like jelly, Vegemite and
Marmite (two popular brands of yeast extract) and harnessed them to make edible
hydrogel electrodes. These gels were used to demonstrate a capacitive pressure
sensor that can help detect digestive pressure abnormalities such as intestinal
motility disorders.

                                                                                                    
V.    eat your robot

  We have
biocompatible materials as well as transistors, sensors, batteries, electrodes
and capacitors made using such materials. So you might think, why not a robot,
too? But, what sets a robot apart from other computing systems is its ability
to move—a robot needs an actuator, and attempts at making an edible one have
been unpalatable all along! Switzerland-based research organisation EPFL
has made some headway recently. At a conference held this year, researchers led
by Dario Floreano presented the prototype of a completely edible, soft,
pneumatic actuator made of gelatin, glycerin and water. The design and performance
of this new gelatin actuator is comparable to standard pneumatic actuators. Its
structure causes it to bend when inflated and straighten out again when
pressure is reduced. The main benefits are that it is edible, biodegradable,
biocompatible and environmentally sustainable. Since gelatin is melty, the
actuator also turns out to be
self-healing!

  The researchers
explain several exciting applications for this actuator. The components of such
edible robots could be mixed with nutrients or pharmaceutical components to
improve healing, digestion and metabolism. These can be used as disposable
robots to explore, study the behaviour of wild animals, cure sick animals or
train protected animals to hunt. These can also be used in relief measures. In
search-and-rescue operations, the robot can be sent without a payload to
stranded people as the robot itself is food!

                                                                                       
VI.   but can we pay the bills?

 

  A recent Frost
& Sullivan report noted that the fastest growing segment amongst the many
types of implants is implantable neuro stimuIators, which help treat
neurological disorders such as epilepsy, dementia, Alzheimer’s disease,
Parkinson’s disease and dystonia. It is also likely that in the future, these
implantable electronics will be digitally connected to improve the scope of
remote drug delivery, testing and diagnostics.

  The cost of
researching and developing implants continues to be high due to the criticality
and complications involved—and often this cost reflects in the end price
points. In the report, Frost & Sullivan industry analyst Bhargav Rajan
noted that the constant stream of innovations has attracted substantial private
funding to the implantable electronics market, while public funding is
expected to improve in the future. He also suggested that technology developers
can lower development costs by collaborating with early-stage start-ups and
small- and medium-sized enterprises. This will allow them access to cross-
industry expertise and cutting-edge innovations, which, in turn, will help
lower the price points.

  A majority of
the population seeking implants belongs to low- and middle-income groups.
Taking note of this factor, the report also stressed that the growth of this
sector depends not entirely on technological development but also the
availability of insurance coverage and reimbursements for such devices.

 

A.    Figures and Tables

1)  Positioning Figures and Tables: Place figures and tables at the top
and bottom of columns. Avoid placing them in the middle of columns. Large
figures and tables may span across both columns. Figure captions should be
below the figures; table heads should appear above the tables. Insert figures
and tables after they are cited in the text. Use the abbreviation “Fig. 1,”
even at the beginning of a sentence.

TABLE I.            
Table Styles

Table Head

Table Column Head

Table column subhead

Subhead

Subhead

copy

More table copya

 

 

                                                                                                                                                                                                                                                                                       
a. Sample of a Table footnote. (Table footnote)

                                                                                                                                                                                                                                                                                                                                                                                 
b.  

Fig. 1.   
Example of a figure caption. (figure caption)

Figure Labels: Use 8 point Times New
Roman for Figure labels. Use words rather than symbols or abbreviations when
writing Figure axis labels to avoid confusing the reader. As an example, write
the quantity “Magnetization,” or “Magnetization, M,” not just “M.” If including
units in the label, present them within parentheses. Do not label axes only
with units. In the example, write “Magnetization (A/m)” or “Magnetization (A (
m(1),” not just “A/m.” Do not label axes with a ratio of quantities and units.
For example, write “Temperature (K),” not “Temperature/K.”

Acknowledgment
(Heading 5)

The preferred spelling of the word “acknowledgment”
in America is without an “e” after the “g.” Avoid the stilted expression “one
of us (R. B. G.) thanks …”.  Instead,
try “R. B. G. thanks…”. Put sponsor acknowledgments in the unnumbered
footnote on the first page.

 

References

 

1    
G. Eason, B. Noble, and I.N. Sneddon, “On certain integrals of
Lipschitz-Hankel type involving products of Bessel functions,” Phil. Trans.
Roy. Soc. London, vol. A247, pp. 529-551, April 1955. (references)

2    
J. Clerk Maxwell, A Treatise on Electricity and Magnetism, 3rd
ed., vol. 2. Oxford: Clarendon, 1892, pp.68-73.

3    
I.S. Jacobs and C.P. Bean, “Fine particles, thin films and
exchange anisotropy,” in Magnetism, vol. III, G.T. Rado and H. Suhl, Eds. New
York: Academic, 1963, pp. 271-350.

4    
K. Elissa, “Title of paper if known,” unpublished.

5    
R. Nicole, “Title of paper with only first word capitalized,” J.
Name Stand. Abbrev., in press.

6    
Y. Yorozu, M. Hirano, K. Oka, and Y. Tagawa, “Electron
spectroscopy studies on magneto-optical media and plastic substrate interface,”
IEEE Transl. J. Magn. Japan, vol. 2, pp. 740-741, August 1987 Digests 9th
Annual Conf. Magnetics Japan, p. 301, 1982.

7    
M. Young, The Technical Writer’s Handbook. Mill Valley, CA:
University Science, 1989.