1. Endeavors of Chemical Engineering: Artificial
Organ
Pranshu sharma, Rishabh chaudhary
USCT DELHI, USCT DELH, GGSIPU INDIA, GGSIPU INDIA
Pranshu22@gmail.com
rishabh_chaudhary@hotmail.com
Abstract—One of the most significant frontiers of Chemical
engineering is Biomedicine and chemical engineers have made
some of their greatest achievements in this field. This paper states
and elucidates the contribution of chemical engineers in
development of artificial organs and engineering challenges faced
by them in this endeavor. More specifically the paper deals with the
role of chemical engineering in development of Heart and Lung
Machine, Artificial Kidney.
Keywords—artificial organs, heart-lung machine, artificial kidney.
INTRODUCTION
It is very logical to think of human body as a complex and
sensitive chemical factory with a number of heat and mass
transfer processes going on, sometimes accompanied with
chemical reactions. Muscles shiver to warm the body when the
temperature falls. The pancreas produces insulin to control
blood sugar levels. The kidneys remove urea, minerals, and
water from the blood. White blood cells organize themselves to
defend the body against infection. These need to be controlled to
ensure the working of body.
Efforts to understand and view humans as a collection of
interrelated “chemical” systems began in the mid-1800s, when
Claude Bernard, a French physician and physiologist, helped
introduce the rigors of the scientific method to medicine such as
• establishing the role of the pancreas in controlling digestion,
• determining the glycogenic function of the liver (which later
helped understand the critical roles played by glucose and
insulin in regulating vital bodily processes), and
• demonstrating that nerves could either expand or constrict
blood vessels, a breakthrough that helped understand the
vasomotor system (vaso refers to blood vessels).
Over the last half century, chemical engineers have contributed
to various biomedical endeavors. They have helped modernize
disease diagnosis and treatment options, improve the safety and
efficacy of drug delivery mechanisms, and achieve better
therapeutic outcomes, resulting in longer, healthier, more
productive lives for patients.
It was in 1970s when chemical engineers first started to analyze
mass transfer phenomenon and rheological issues related to
artificial organs for example, diffusion rates through
biomembranes.
A growing number of chemical engineers were engaged in
solving complex flow problems—related to, among other things,
heart valves—by using Newtonian fluid-mechanics analysis.
(Newtonian fluids flow like water, while non-Newtonian fluids
are those whose viscosity, or ability to flow, changes as the
applied rate of strain changes.)
HEART and LUNG MACHINE
Coronary bypass surgery, widely used to treat cardiovascular
disease, involves redirecting a patient’s bloodflow around the
heart in order to allow surgeons to operate. Heart-lung machines
synthetically oxygenate and pump blood during such surgeries
in order to keep the patient alive. The first heart-lung machine
dates back to the 1930s and consisted of many of the same
components as the machines of today. The design of each of
these components is inspired by different principles of physics
and engineering, including fluid dynamics and pressure
gradients. Engineers are now applying these same concepts to
create new heart-lung machine models such as miniaturized or
portable versions. With its foundations in biology, physics, and
engineering, the heart-lung machine has proven to revolutionize
the treatment of heart disease.
Historical Background

2. The first machine of this type was developed by surgeon John
Heysham Gibbon in the 1930s [2]. During this time, physicians
were looking into the possibility of extracorporeal circulation, or
blood flow outside of the body [3]. They wondered if there was
a way to extend this extracorporeal circulation to bypass not just
minor organs, as was often done in surgery at the time, but to
bypass the heart completely. Saddened at a patient’s death mid-
surgery, Gibbon made it his mission to come up with an
artificial heart-lung machine that would keep a patient alive
during heart surgery.
Fig 1 a) John Gibbon, Jr. b) Heart-Lung Machine
Between 1934 and 1935, Gibbon built a prototype of his heart-
lung machine and tested its function on cats in order to assess
what problems needed to be addressed before using it with
humans [4]. For example, in one model Gibbon observed that an
inadequate amount of bloodflow was exiting the machine, so he
decided to make the flow continuous, instead of in short pulses
[4]. By introducing bloodflow that would remain at the same
rate continuously, instead of increasing and decreasing with a
set rhythm, he increased the total blood volume capacity that
could flow throughout the machine.
In the 1940s, Dr. Gibbon met Thomas Watson, an engineer and
chairman of International Business Machines (IBM). Gibbon
and Watson, along with other engineers from IBM, collaborated
on the quest for an effective cardiopulmonary bypass machine,
and together they created another new model [2]. When this
model was testing by performing surgeries on dogs, they noticed
that many of their test subjects died after surgery due to
embolisms (An embolism occurs when a small particle or tissue
migrates to another part of body and causes the blockage of a
blood vessel, which prevents vital tissues from receiving
oxygen) [5]. From these experiments, they saw the need to add a
filter to their apparatus. Gibbon and the IBM engineers decided
to use a 300-micron by 300-micron mesh filter, which proved
successful in trapping these harmful tissue particles [4].
In 1953, Gibbon himself completed the first successful surgery
on a human patient with the help of the cardiopulmonary bypass
machine [6]. Since then, open heart surgeries have been
performed for over 55 years, with almost 700,000 performed
annually in recent years [1]. Much has changed since Gibbon’s
first model, but the main engineering concepts behind his
machine have remained the same. Today’s heart-lung-machine
contains the same basic components: a reservoir for oxygen-
poor venous blood, an oxygenator, a temperature regulator, a
pump to drive the blood flow back to the body, a filter to
prevent embolisms, and connective tubing to tie all the other
elements together [4].
Fig 1 Representation of Heart Lung Machine
Working of Heart Lung
To function, the heart lung machine must be connected to the
patient in a way that allows the blood to be removed, processed
and returned to the body. Therefore, it requires two hook-ups.
One is to a large artery where fresh blood can be pumped back
into the body. The other is to a major vein where “used” blood
can be removed from the body and passed through the machine.

3. In fact, connections are made on the right side of the heart to the
inferior and superior vena cavae (singular: vena cava). These
vessels collect blood drained from the body and head and empty
into the right atrium. They carry blood that has been circulated
through the body and is in need of oxygenation. Another
connection is made by shunting into aorta, the main artery
leading from heart to the body, or the femoral artery, a large
artery in the upper leg. Blood is removed from the vena cavae,
passed into the heart lung machine where it is cooled to lower
the patient’s body temperature, which reduces tissues’ need for
blood. The blood receives oxygen which forces out carbon
dioxide and it is filtered to remove any detritus that should not
be in circulation such as small clots. The processed blood then
goes back into the patient in the aorta or femoral artery.
During surgery the technician monitoring the heart lung
machine carefully watches the temperature of the blood, the
pressure at which it is being pumped, its oxygen content, and
other measurements. When the surgeon nears the end of the
procedure the technician will increase the temperature of the
heat exchanger in the machine to allow the blood to warn. This
will restore the normal body heat to the patient before he is
taken off the machine.
Major Challenges in Design
 The machine made by Dr. Gibbon required many pints
of blood to prime the machine and it was bulky and
took up much of the room in the operating room.
 Clotting in oxygenator films due to inadequate
heparinization.
 Maintaining adequate bloodflow.
Today’s Machines
In an open-heart surgery, the surgeon first connects the bypass
machine to the patient by inserting tubes called the venous
cannulas into the vena cavae, the large blood vessels leading to
the heart [7]. This redirects the flow of blood into the heart-lung
machine, bypassing the heart completely. Engineers must design
the venous cannulas such that a precise and controlled amount
of blood will flow through them into the machine. They do so
by creating the tubes in varying sizes and resistances [8].
According to fluid dynamic principles, the larger a tube is, the
more liquid can flow through it at a given point in time. On the
other hand, if a tube has a greater resistance, which is controlled
by surface roughness and fluid viscosity, then less fluid may
pass through. By adjusting these two properties, an engineer can
create venous cannulas that allow specific rates of blood to flow
from the body and into the machine.
From the cannulas, the blood flows into the venous reservoir, a
chamber made of plastic or polyvinyl chloride (PVC) that
collects and stores the blood from the patient’s body [9]. The
reservoir must have a large volume capacity to accommodate a
large volume of blood. According to Boyle’s Law, pressure and
volume are inversely related under constant temperature; as one
increases, the other decreases. Thus, the venous reservoir’s large
volume gives it a low pressure. All solvents naturally move
from regions of higher pressure to regions of lower pressure.
Therefore, since the reservoir has a low pressure, blood flows
from the high-pressure vessels in the body into the bypass
machine’s venous reservoir.
Upon leaving the venous reservoir, blood next travels into the
heart-lung machine’s pump, which utilizes compression force or
centrifugal force to drive blood flow. A pump may come in
either one of two types: roller pumps or centrifugal pumps. In a
roller pump, the blood enters a curved track of tubing made of a
flexible material, often PVC, latex, or silicone [8]. As the blood
enters, two cylindrical rollers rotate and slide forward,
constricting the tubing. This compression reduces the volume in
the tube, giving the blood no room to go but forward. Just as
squeezing a tube of toothpaste pushes the paste forward and out
of the tube, compressing the roller pump forces the blood to
flow forward, through the rest of the bypass machine. While
roller pumps may be used as the primary pump in a heart-lung
machine, centrifugal pumps are often used as an alternative. The
centrifugal pump is comprised of a plastic wheel that rotates
rapidly, propelling the liquid away from the center of rotation
[8]. Imagine spinning a bucket of water overhead fast enough so
that water is pressed outward against the bucket and does not
fall out. The same force is utilized in the heart-lung machine as
the rotation of the centrifugal pump forces the blood to flow past
the spinning wheel and out towards the next section of tubing.
While some heart-lung machine manufacturers prefer this type
of pump because they believe it reduces the formation of
harmful clotting elements in the blood, at this point in time, both
types of pumps are widely used [10].

4. Blood flows from the pump into the heat exchanger, which uses
the concept of heat transfer to cool the blood down to the
optimal temperature for surgery. The human body normally
maintains an internal temperature of 37 degrees Celsius but
during cardiac surgery, physicians lower the patient’s core
temperature to a state of moderate hypothermia or 5 to 10
degrees lower than usual [8]. Oxygen gas is more soluble in cold
blood than in warm blood [11]. Thus, lowering the temperature
maximizes the amount of oxygen the patient’s blood cells can
carry.
Following the basic principle of heat transfer, a warmer object
will always transfer heat to any colder object with which it is in
contact. Similarly, if a cold object touches a warmer object, the
warmer object will be cooled. That is precisely what occurs in
the heart-lung machine’s heat exchanger. It consists of a
thermally adjustable compartment of cold water with plastic
rubes submerged in it. As blood flows through the tubes,
thermal energy is transferred between the water and the tubing,
and then between the tubing and the blood. The warmer object,
the blood, becomes colder, while the cooler object, the water,
becomes warmer. Thus, the heat exchanger cools the blood to
the desired temperature.
From the heat exchanger, the cooled blood enters the
oxygenator, where it is imbued with oxygen. Today’s heart-lung
machines use an oxygenator that attempts to mimic the lung
itself. This oxygenator, aptly called a membrane oxygenator,
consists of a thin membrane designed like the thin membranes
of the alveoli, the air-filled sacs that comprise the lungs. Venous
blood from the heat exchanger flows past one side of the
membrane, while oxygen gas is stored on the other. Micropores
in the membrane allow oxygen gas to flow into the blood and
into the blood cells themselves. Just as blood spontaneously
flows along a pressure gradient, gases also move from regions
of high pressure to regions of low partial pressure. The
oxygenator is designed such that the oxygen pressure on the gas
side of the membrane is much higher than the pressure in the
blood [12]. Thus, oxygen passes through the membrane into the
blood, following the natural high-to-low pressure gradient.
At this point in the journey through the heart-lung machine, the
blood has been collected, cooled and oxygenated, so it is nearly
ready to return to the patient’s body. Before this can happen,
however, it must pass through a filter to eliminate the potential
for embolisms. Anything that could lead to blockage of a blood
vessel, whether it is an air bubble, a piece of synthetic material,
or a clotting protein, poses a great risk to the patient and must be
filtered out of the returning blood. The filters used in the heart-
lung machine are comprised of nylon or polyester thread woven
into a screen with small pores [8]. The small pores trap the
harmful bubbles or particles, allowing purer blood, free from
dangerous embolism-causing particles, to flow through. After
being filtered, the blood travels through plastic tubes called
arterial cannulas. Arteries, the blood vessels that deliver oxygen-
rich blood from the heart to the rest of the body, have the
highest speed of any vessel. In order to imitate this, engineers
designed the arterial cannulas to be very narrow [8]. In fluid
dynamics, the flow rate of a liquid through a vessel is equal to
the cross-sectional area times the speed of flow. Thus, tubes like
the arterial cannulas that have a smaller diameter allow for a
higher blood velocity. During surgery, the physician inserts the
cannulas into one of the major arteries of the patient, such as the
aorta or the femoral artery [7]. Blood then leaves the last
component of the cardiopulmonary bypass machine, enters the
patient’s own vessels, and again makes its natural journey
through the circulatory system.
Heart Machines of Future
Recent breakthroughs of biomedical engineers give a glimpse
of the cardiopulmonary bypass machines of the future. In 2007,
the world’s first portable heart-lung machine received the CE
mark, which officially allowed it to be sold across Europe.
Weighing only 17.5 kilograms and powered by a rechargeable
battery, the Lifebridge B2T can be transported to different parts
of a hospital, giving paramedics or emergency room physicians
the chance to start extracorporeal circulation in critical patients
before even reaching the operating room [13] (Fig. 2).

5. European Hospital/European Hospital
Figure 2: The compact 17.5 kg heart-lung machine Lifebridge B2T.
Another new development of the heart-lung machine is the
MiniHLM, a miniaturized heart-lung machine developed for
infants. Instead of having all the components spaced separately,
as with normal-sized machines, the MiniHLM integrates the
functions so the machine is much smaller and more compact
[13]. This allows cardiac bypass surgery to be performed on
neonates, something that will surely expand the capacity with
which heart conditions in newborns can be treated.
Current implementations of the cardiopulmonary bypass
machine have advanced far past John Gibbon’s original idea
almost 80 years ago. Yet no step in the process has been
insignificant, as every improvement has improved the safety and
usability of the machine. Engineers continue to consider both
the biological needs of the human body and the basic principles
of physics in order to create a functional biocompatible device
that performs what was once unthinkable, sustaining human life
without the use of one’s heart or lungs. Hundreds of thousands
of patients undergo open-heart bypass surgeries every year,
intense procedures which require extracorporeal circulation
[14]. That’s hundreds of thousands of lives saved with the help
of one essential biomedical device: the heart-lung machine.
ARTIFICIAL KIDNEY MACHINE
Kidneys
Kidneys are paired vital organs located behind the abdominal
cavity, at about the level of the bottom of the ribcage. They
perform about a dozen physiologic functions, and are fairly
easily damaged.
Fig.3 1. Renal pyramid • 2. Interlobular artery • 3. Renal artery • 4. Renal vein
5. Renal hilum • 6. Renal pelvis • 7. Ureter • 8. Minor calyx • 9. Renal capsule •
10. Inferior renal capsule • 11. Superior renal capsule • 12. Interlobular vein •
13. Nephron • 14. Minor calyx • 15. Major calyx • 16. Renal papilla 17. Renal
column
Function of Kidneys
1. Excretion of wastes
The kidneys excrete a variety of waste products produced by
metabolism. These include the nitrogenous wastes called "urea",
from protein catabolism, as well as uric acid, from nucleic acid
metabolism. Formation of urine is also the function of the
kidney. The concentration of nitrogenous wastes, in the urine of
mammals and some birds, is dependent on an elaborate
countercurrent multiplication system. This requires several
independent nephron characteristics to operate: a tight hair pin
configuration of the tubules, water and ion permeability in the
descending limb of the loop, water impermeability in the
ascending loop and active ion transport out of most of the
ascending loop. In addition, countercurrent exchange by the
vessels carrying the blood supply to the nephron is essential for
enabling this function.
2. Acid-base homeostasis
Two organ systems, the kidneys and lungs, maintain acid-base
homeostasis, which is the maintenance of pH around a relatively
stable value. The lungs contribute to acid-base homeostasis by
regulating carbon dioxide (CO2) concentration. The kidneys
have two very important roles in maintaining the acid-base
balance: to reabsorb bicarbonate from urine, and to excrete
hydrogen ions into urine
3. Osmolality regulation
Any significant rise in plasma osmolality is detected by the
hypothalamus, which communicates directly with the posterior

6. pituitary gland. An increase in osmolality causes the gland to
secrete antidiuretic hormone (ADH), resulting in water
reabsorption by the kidney and an increase in urine
concentration. The two factors work together to return the
plasma osmolality to its normal levels.
ADH binds to principal cells in the collecting duct that
translocate aquaporins to the membrane, allowing water to leave
the normally impermeable membrane and be reabsorbed into the
body by the vasa recta, thus increasing the plasma volume of the
body.
There are two systems that create a hyperosmotic medulla and
thus increase the body plasma volume: Urea recycling and the
'single effect.'
Urea is usually excreted as a waste product from the kidneys.
However, when plasma blood volume is low and ADH is
released the aquaporins that are opened are also permeable to
urea. This allows urea to leave the collecting duct into the
medulla creating a hyperosmotic solution that 'attracts' water.
Urea can then re-enter the nephron and be excreted or recycled
again depending on whether ADH is still present or not.
The 'Single effect' describes the fact that the ascending thick
limb of the loop of Henle is not permeable to water but is
permeable to NaCl. This allows for a countercurrent exchange
system whereby the medulla becomes increasingly concentrated,
but at the same time setting up an osmotic gradient for water to
follow should the aquaporins of the collecting duct be opened by
ADH.
4. Blood pressure regulation
Although the kidney cannot directly sense blood, long-term
regulation of blood pressure predominantly depends upon the
kidney. This primarily occurs through maintenance of the
extracellular fluid compartment, the size of which depends on
the plasma sodium concentration. Renin is the first in a series of
important chemical messengers that make up the renin-
angiotensin system. Changes in renin ultimately alter the output
of this system, principally the hormones angiotensin II and
aldosterone. Each hormone acts via multiple mechanisms, but
both increase the kidney's absorption of sodium chloride,
thereby expanding the extracellular fluid compartment and
raising blood pressure. When renin levels are elevated, the
concentrations of angiotensin II and aldosterone increase,
leading to increased sodium chloride reabsorption, expansion of
the extracellular fluid compartment, and an increase in blood
pressure. Conversely, when renin levels are low, angiotensin II
and aldosterone levels decrease, contracting the extracellular
fluid compartment, and decreasing blood pressure.
5. Hormone secretion
The kidneys secrete a variety of hormones, including
erythropoietin, and the enzyme renin. Erythropoietin is released
in response to hypoxia (low levels of oxygen at tissue level) in
the renal circulation. It stimulates erythropoiesis (production of
red blood cells) in the bone marrow. Calcitriol, the activated
form of vitamin D, promotes intestinal absorption of calcium
and the renal reabsorption of phosphate. Part of the renin-
angiotensin-aldosterone system, renin is an enzyme involved in
the regulation of aldosterone levels
Renal Failure
Kidney failure results in the slow accumulation of nitrogenous
wastes, salts, water, and disruption of the body's normal pH
balance. Until the Second World War, kidney failure generally
meant death for the patient. Several insights into renal function
and acute renal failure were made during the war, not least of
which would be Bywaters and Beall's descriptions of pigment-
induced nephropathy drawn from their clinical experiences
during the London Blitz.[17]
Hemodialysis
Hemodialysis is a method for removing waste products such as
creatinine and urea, as well as free water from the blood when
the kidneys are in renal failure. The mechanical device used to
clean the patient’s blood is called a dialyser, also known as an
artificial kidney.
One of the ten wonders
In 1964 Les Babb, a chemical-biochemical engineer, along with
his colleagues at the University of Washington, designed a
portable, fail-safe, single-patient dialysis machine. Within five
years this stand-alone machine would become the dialysis
system of choice throughout the world. In 1990 the Biomedical
Engineering Society named this machine one of the “Ten
Wonders of Biomedical Engineering.” [18]
Artificial Kidney
Artificial kidney is often a synonym for hemodialysis, but may
also, more generally, refer to renal replacement therapies (with
exclusion of renal transplantation) that are in use and/or in
development. This article deals with bioengineered
kidneys/bioartificial kidneys that are grown from renal cell
lines/renal tissue.

7. Modern dialysers typically consist of a cylindrical rigid casing
enclosing hollow fibers cast or extruded from a polymer or
copolymer, which is usually a proprietary formulation. The
combined area of the hollow fibers is typically between 1-2
square meters. Intensive research has been conducted by many
groups to optimize blood and dialysate flows within the dialyser,
in order to achieve efficient transfer of wastes from blood to
dialysate.
Fig.4 Dialyser used in hemodialysis
Gordon Murray and the artificial kidney
Introduction :
Few people even amongst nephrologists are aware that Canadian
surgeon Gordon Murray (1894–1976) built the first North
American artificial kidney, independently of work by Willem
Kolff in the Netherlands and Nils Alwall in Sweden at about the
same time. Perhaps this is because Kolff is generally recognized
as the `inventor' of the artificial kidney in a clinically useful
form, whereas Murray's fame, publicly and professionally, came
from his work in cardiovascular surgery.
Murray became interested in renal therapy during the 1940s
after seeing several patients die of uraemia [19]. Frustrated by
the profession's ignorance of this disease, he began investigating
the kidney with the prospect of mechanically replicating its
functions and in the end he built two different artificial kidney
machines. His first successful artificial kidney was a coil design
built in 1945–46, with the assistance of Edmund Delorme, a
young surgeon from the University of Edinburgh, and Newell
Thomas, an undergraduate chemistry student at the University
of Toronto. In 1952–53, a second-generation flat-plate model
was designed and constructed by Murray and scientist Dr Walter
Roschlau, originally from Heidelberg. Unfortunately, these
artificial kidneys remained relatively crude prototypes, and were
never refined or commercially produced for wider distribution.
Fig.5 Gordon Murray
Murray's first artificial kidney machine (1945–46)
As no one had yet designed and used an `artificial kidney' when
he began his experiments, Murray encountered several technical
difficulties in the building of his first machine: discovering a
suitable dialysing membrane, finding the proper dialysing
solution or dialysate, and selecting a viable mechanism for
circulating blood through the machine. The dialysing membrane
that led the blood through the dialysate had to be a semi-
permeable membrane to allow the molecules of harmful wastes
to pass into the dialysate. After experimenting with various
natural and synthetic products and following the work of
William Thalhimer in New York [20], Murray found (like
Kolff) that the best semi-permeable membrane was a type of
Cellophane used for sausage casing in the form of long tubes.
He experimented with the size and length of tubing before
settling for the satisfactory size of ¼ in (6.5 mm) diameter,
varying in length from 35 to 150 feet (10–50 m). The tubing was
coiled vertically around a wire-mesh cylinder and contained in a
large bath jar or drum filled with the dialysate. Next, Murray
sought a dialysate consistent with the normal substances of the
blood. Finally, after a number of false starts, he settled on using
Ringer's solution. To circulate the blood through the machine,
Murray decided to work exclusively within the venous system,
taking blood from and returning it to a vein, using a novel
atraumatic pump system (in contrast to arteriovenous circuiting
chosen by other pioneering researchers, notably Kolff and Nils
Alwall). A rubber tambour was inflated and deflated by the
action of the piston-syringe, acting as the pump, attached to an
electric motor. Intake and outlet valves controlled the blood
flow. Tinkering away with relative simple materials at hand,
Murray completed the building of his prototype machine [21]

8. Fig.6. Murray's first dialyser, a coil design wound on a steel frame (left). Note
the narrow calibre of the blood tubing, which was only 6 mm wide, but up to 50
m long. Also shown is Murray's atraumatic blood pump (centre), which allowed
venovenous dialysis.
History of Murray’s Experiment
To test his artificial kidney, Murray first ran trials with uraemic
animals, treating them for hours, even overnight, with relative
success. The real test, however, came with Murray's first clinical
case in December 1946. A 26-year-old female patient lay in a
uraemic coma at the Toronto General Hospital as a result of an
abortion attempt. Her doctors declared her case hopeless, and
they called Murray. They were not terribly convinced that the
artificial kidney would actually work, but were at a loss as to
what else to do for the patient. They agreed to the experimental
therapy because the alternative seemed to be certain death.
Murray quickly arrived on the ward with his odd-looking
machine. It was massive and cumbersome, and took three men
to carry it to the bedside. Murray cut into the large femoral vein
on the inside of the patient's left thigh. A long, plastic catheter
was inserted into it and connected to the dialyser coils. Then
Murray cut into the femoral vein in the right thigh, pushing
another catheter up into the vessel until it reached the inferior
vena cava. Heparin solution (the other vital component for
successful dialysis that Murray had himself helped to develop)
was then injected into the patient's bloodstream and into the
machine. When the machine was switched on and its pump
started moving, dark red venous blood was carried into the
Cellophane tubing and slowly flowed through the narrow coils
in a 15-quart (14 litre) glass jar containing the dialysate, perched
on the bedside table. The blood then passed through an air trap
that removed any bubbles, and returned to the patient's
circulatory system. A thermostat control had been built into the
machine to maintain the patient's blood temperature outside the
body [22].
It was a case of trial and error. Murray was experimenting with
the number and length of treatments. The first treatment was
discontinued after only 1 h when the patient developed a severe
chill. Nevertheless, the patient had been revived from the coma.
A second treatment was administered 2 days later when the
patient slipped back into unconsciousness. After 8 h of treatment
from the artificial kidney, the patient was again revived. A third
treatment was necessary 3 days later when the patient relapsed.
After 6 h of treatment, she was revived once more. This final
session on the artificial kidney constituted the breakthrough.
The following day, the patient's kidneys began to function and
residual uraemic toxins and excess liquid were soon washed out
of her body. She made a steady recovery and was released from
hospital 33 days after being admitted [23].
Despite its initial success, the artificial kidney machine was used
in few cases thereafter—over the next several years up to 1949
no more than 11 patients received treatment. There were several
reasons for this. Toronto Hospital medical men viewed the
artificial kidney machine—rightly—as still experimental,
offering only short-term, intermittent treatment to patients
suffering from acute renal failure, and they were reluctant to use
the machine as anything but a last-ditch therapy. Also there
were no full-time laboratory services or technicians available to
support dialysis treatments. The treatments therefore
monopolized Murray's and his assistants' time, and for Murray,
the artificial kidney was only a secondary line of investigation.
He was a surgeon, and he devoted more and more of his time to
the new, exciting field of cardiac surgery. Therefore poor
promotion and acceptance of this first artificial kidney was due
to a lack of support and interest in renal therapy at the Toronto
Hospital, and perhaps Murray's own restless nature. The
artificial kidney was eventually moved to the hospital basement
and seldom used after 1949.
Murray's second artificial kidney machine (1952–53)
By the early 1950s, Murray was director of a privately funded
laboratory with full-time research staff. Also by this time, a
greater number of commercial and home-made artificial kidney
machines were being circulated and used in North American and
European hospitals. But these machines remained large and
clumsy, and reported clinical series continued to deliver mixed
results. The initial success of Murray's first artificial kidney and
his new research setting stimulated him to build a second,
improved machine. In 1952, Murray initiated work on a second-
generation artificial kidney with Dr Walter Roschlau. They
intended to offer a more compact and efficient machine to the
medical marketplace.
The Murray–Roschlau artificial kidney was an improved model
from the original machine with substantial differences . The
significant feature of this second-generation machine was its
parallel plate design instead of the original vertical coil dialyser,

9. making it much more compact. Roschlau (who appears to have
been unaware of similar designs by Skeggs and Leonards [24]
and McNeil [25]) had designed a plate-type dialyser with an
enlarged surface area and reduced blood-volume requirements.
He experimented with flow patterns, volume requirements,
dialysing membrane surfaces, and the production of multiples of
blood and dialysate chambers, cannibalizing the original
artificial kidney machine for its electric motor, mounting boards,
glassware, etc. The fluid storage container was designed to be
tucked out of sight under the table, showing `less' machine at the
bedside. Its operation was simplified and its efficiency
improved; it was easier to handle, clean, and less `frightening'.
In 1954, 27 experiments, involving 10 dogs, were conducted to
test the performance and reliability of their new machine.
Shortly thereafter, this second-generation artificial kidney was
used in two clinical cases. Roschlau assembled, sterilized, and
transported the machine to the Toronto General Hospital and
administered the dialysis treatment. The experimental therapy
once again brought successful results. No flaws in the design or
function of the machine were noted; however these clinical
cases were never reported [26].
Fig.7 The Murray–Roschlau `second-generation' flat-plate dialyser. This was an
advanced flat-plate parallel-flow dialyser with 30 layers of dialysis units each
with two membranes and two dialysis compartments, forming a dialyser of 0.6
m2
surface area and with a priming volume of only 225 ml.
Conclusion
Murray built and used successfully the first artificial kidney
machine in North America. Few medical men outside Toronto
were aware of its existence, and Murray himself regarded it as
only a secondary line of investigation, losing all interest in the
artificial kidney when he lost control over the designs of his
machine. Moreover, his machine benefited very few patients.
Inventor of Artificial Kidney
Willem Johan "Pim" Kolff (February 14, 1911 – February 11,
2009) is credited for developing first clinically used artificial
kidney machine.
Fig 8. Willem Johan
Kidney dialysis
Kidney dialysis machines represent an excellent example of the
life-enhancing synergies that result when chemical engineers
join forces with physicians and biomedical researchers. These
“artificial kidneys” are essentially mass-transfer devices. They
cleanse the blood, removing elevated levels of salts, excess
fluids, and metabolic waste products.
The first practical dialysis machine was developed during World
War II. Since then many major developments have taken place.
One of the major obstacles that had to be overcome, however,
was size. To be truly practical a single-patient portable machine
was needed.
Fig.9 The first machine used for home hemodialysis, the Milton-Roy Model A,
was designed by chemical engineering professor Les Bab in order to help the
daughter of a friend. Photo by Jim Curtis. Courtesy Home Dialysis Central.

10. Bioengineered kidneys
Currently, no viable bioengineered kidneys exist. Although a
great deal of research is underway, numerous barriers exist to
their creation [27][28][29]
However, manufacturing a membrane that mimics the kidney's
ability to filter blood and subsequently excrete toxins while
reabsorbing water and salt would allow for a wearable and/or
implantable artificial kidney. Developing a membrane using
microelectromechanical systems (MEMS) technology is a
limiting step in creating an implantable, bioartificial kidney.
The BioMEMS and Renal Nanotechnology Laboratories at the
Cleveland Clinic's Lerner Research Institute have focused on
advancing membrane technology to develop an implantable or
wearable therapy for end-stage renal disease (ESRD). Current
dialysis cartridges are too large and require superphysiologic
pressures for blood circulation, and pores in current polymer
membranes have too broad of a size distribution and irregular
features. Manufacturing a silicon, nanoporous membrane with
narrow pore size distributions improves the membrane's ability
to discriminate between filtered and retained molecules. It also
increases hydraulic permeability by allowing the mean pore size
to approach the desired cutoff of the membrane. Using a batch-
fabrication process allows for strict control over pore size
distribution and geometry.[8]
In recent studies, human kidney cells were harvested from
donated organs unsuitable for transplantation, and grown on
these membranes. The cultured cells covered the membranes
and appear to retain features of adult kidney cells. The
differentiated growth of renal epithelial cells on MEMS
materials suggests that a miniaturized device suitable for
implantation may be feasible.
How artificial Kidney works
Artificial kidney works the same manner as the real kidney, in
that unwanted substances are removed from blood across a
differentially permeable membrane, which allows small
molecules(molecular weight up to 300 or 400) to be separated
from larger ones. This is known as dialysis.
The principle on which the artificial kidney works is therefore
simple: the patient's blood must flow on one side of the
membrane, or through a tube made of the membrane, with a
dialyzing fluid (or dialysate) on the other.
Some substances (with small molecules) will diffuse out of the
patient's blood into the dialysate and be carried away as waste.
The blood cells, protein, and amino acid molecules which are
too large to escape will remain in the blood. The differentially
permeable membrane is made of viscose-cellulose (Visking
tubing) 0-025 mm thick, and its surface area is 0-9 m2 , about
half that of the total filtering area of both kidneys.
The artificial kidney simulates the various functions of the
kidney in the following ways.
1 Salts and waste products of metabolism will diffuse out of the
blood into the dialysate and be carried away. The problem here
is not just to remove substances but to prevent the removal of
too much. The dialysate is therefore made up from sodium
chloride, sodium acetate, potassium chloride, magnesium
chloride, and calcium chloride, in aqueous solution, in the same
concentra-
tion of salts as is present in the plasma of a normal person at a
pH of 7-4. Unwanted substances will thus be removed but
needed ones kept. In addition, the dialysate contains 1-2 per cent
of dextrose to maintain a high osmotic pressure on the outside of
the membrane.Ionic exchange between blood and dialysate takes
place until equilibrium is reached. Perfect equilibrium may
never be achieved, but enough urea, potassium, and sodium are
removed to keep the patient well. Unlike the real kidney, the
artificial one has no problem of having to reabsorb valuable sub-
stances back into the blood. They are retained owing to the
composition of the dialysate and the small pores of the Visking
tubing. The process of achieving equilibrium is slow and
chronic patients have to spend all night, twice a week, connected
to the machine. Acute cases are put on to the machine once
every few days. Blood which has abnormal salt concentrations
at the start of the process of dialysis is normal at the end, the
waste products having been removed.
2 The removal of water presents a different problem. It cannot
diffuse out of the blood because there is more water in the
dialysate than in the blood itself. The problem is solved by
partially closing the venous tube with a clip to increase the
blood pressure to 200 mmHg (the normal pressure is about 90
mmHg). This causes ultra-filtration in the same way as in the
real kidney and some 100-200 cm3 of water are removed per
hour.
3 The pH of the blood falls only from 7-4 to about 7-3 between
two treatments. This is because the body's store of bicarbonate is
utilized to buffer the blood, the bicarbonate being reduced to
about 75 per cent of its normal value. The machine therefore
maintains pH by replacing the lost bicarbonate.
Earlier treatments used to incorporate bicarbonate (as sodium
bicarbonate) into the dialysate, but sodium acetate is now used.
This diffuses into the blood, and is then metabolized to
bicarbonate.

11. Fig.10 working of artificial kidney
The artificial process thus differs from the natural one in two
ways:
a. reabsorption of some of the materials which pass through the
membrane does not take place, and
b. there is a continuous flow of water on the outside of the
membrane carrying away those materials which have passed
through. These, then, are the general principles on which all
types of artificial dialysers work. To see how the principles have
been translated into workable reality, one must look more
closely at one type of machine.
Need for a bioartificial kidney
Over 300,000 Americans are dependent on hemodialysis as
treatment for renal failure, but according to data from the 2005
USRDS 452,000 Americans have end-stage renal disease
(ESRD).[2]
Intriguing investigations from groups in London,
Ontario and Toronto, Ontario have suggested that dialysis
treatments lasting two to three times as long as, and delivered
more frequently than, conventional thrice weekly treatments
may be associated with improved clinical outcomes[30]
Implementing six-times weekly, all-night dialysis would
overwhelm existing resources in most countries. This, as well as
scarcity of donor organs for kidney transplantation has prompted
research in developing alternative therapies, including the
development of a wearable or implantable device.[31]
USES OF ARTIFICIAL KIDNEY
An Artificial Kidney to take Patients off the Transplant Waiting
List
Real organs are in short supply, so maybe this mechanical one
(made with real human cells!) can help instead.
As anyone who has watched a medical drama knows, organs are
in short supply and must be rushed everywhere in coolers, only
to be delivered at the last possible moment. This is actually kind
of true. In the U.S., 570,000 people suffer from chronic kidney
failure, but last year there were only 16,812 kidneys available to
be transplanted. A staggering 92,000 patients were left on the
waiting list, which can be a death sentence.
There is no substitute for a real kidney, but researchers at UCSF
and nine other labs have for years been working on an artificial
version that can allow patients to live without dialysis, and
without having to take immune suppressing drugs that normally
prevent transplanted kidneys from being rejected by the body.
This month, the FDA announced that it has selected the artificial
kidney project for its Innovation Pathway, a program designed
to help breakthrough technologies reach market faster than they
might otherwise.
The implantable artificial kidney performs the water-balancing
and metabolic functions of the real thing using lab-grown cells
and nanofilters that remove blood toxins. No pumps or outside
power supplies are needed; the body’s blood pressure pushes
along filtration. "It’s a mechanical device combined with cells,"
explains Dr. Shuvo Roy, the leader of the artificial kidney
project.
The device isn’t a perfect replica of a real kidney, but it provides
enough functionality that patients can ditch dialysis and have
complete freedom of mobility. The device can’t, for example,
produce an important kidney chemical, called erythropoietin,
which stimulates red blood cell production. Patients using the
artificial kidney will have to take a drug for this, just like
dialysis patients.
But unlike real transplanted kidneys, which have an average
lifespan of 10 to 12 years, the artificial kidney can last
indefinitely (new cells may have to be implanted through an
injection or small port every two years.)
It’s a mechanical device combined with cells.
The kidney transplant waiting list won’t disappear anytime
soon, even with the emergence of the artificial kidney. But the
people who get kidneys from the waiting list are often close to
death; healthier patients are left waiting. The artificial version

12. could be an option for patients who are unlikely to get a real
transplant.
Roy hopes that a clinical trial can begin in 2016. The device
could be on the market by the end of the decade, with a price tag
that’s comparable to what it currently costs to maintain a
transplant (about $30,000 a year).
"One of the encouraging things for us is that the fundamental
scientific basis for the artificial kidney has already been
established. We know the concept works. The challenges ahead
are mostly engineering challenges," says Roy.[32]
Fig.11 Dr Shuvo Roy at work in lab
New Artificial Kidney a Viable Alternative to Dialysis
Dialysis is only an imperfect solution to kidney failure, as it
replicates the kidneys’ waste functions, but cannot carry out any
of the kidneys’ endocrine functions. Dialysis also limits
mobility and carries with it an infection risk at the dialysis site.
Researchers at UCSF and nine other labs are in the process of
creating an artificial kidney that could be used in case a donor
organ is not available and as a better alternative to dialysis. The
artificial kidney is a combination of real cells and nanofilters, a
“mechanical device combined with cells,” describes project lead
Dr. Shuvo Roy.
The artificial kidney can last indefinitely, as long as new cells
are injected into the kidney every two years or so. Although the
artificial kidney can’t produce any of the compounds that a real
kidney can, the artificial kidney gets the job of waste filtering
done without any hassle to the patient.
Fig.6 A research team at led by UCSF professor Dr. Shuvo Roy may have found
an alternative to kidney dialysis and a solution to kidney shortages in the U.S
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