From the 6th International Micromachine Symposium Special Lecture

Artificial Heart Research by the Use of
Micromachines
Sinichi Nitta
Vice President of Tohoku University andProfessor of the Inst. of Develop. Aging and Cancer
Good morning, everybody. My name is Nitta. I havelong been vice-chairman of the Medical Application
Working Group of the Micromachine Center. Naturally
I have been closely related to micromachines. I specialize in cardiosurgery, and am working in a boundary area
now popular, specifically in the area of biomedical engineering.
Today I have been requested to talk about micromachines and artificial organs, so will talk about whatcomes to mind. However, I am not confident about how
to relate micromachines to this lecture.
[Kinds of Artificial Organs and the Current Situation]
The artificial organs are now applied systemically.
For example, blood is pumped from the heart in the circulatory system to circulate through the whole body.
Every organ related to it falls under this category.
The use of heart pacemakers is now a well-established practice for the circulatory system. It was formerly
as big as 10 cm in diameter and 3 cm in thickness, but is
now miniaturized to a weight of only 20 g. Its battery
lasts as long as 10 years. It drives the heart by emitting
electricity periodically. As a cardiac surgeon, I often havea look at the heart by inching an optical instrument
through the chest. When I touch the heart lightly, itreadily reacts to this mechanical stimulus. It also reacts to a flow of electricity. The heart shrinks when electricity passes through it. The heart pacemaker is basedon this principle. If this device is rendered much smaller,
it will sooner or later be incorporated into the heart andenergized wirelessly from a device in or near the heart.
This will also depend on how micromachine systems
advances in the future.
Next comes an artificial valve. The heart is driven
by a pulsation. Naturally, valves are required at every
inlet. This valve is also manufactured artificially. It lasts
20 to 30 years in the human body.
Next, let me explain about an artificial heart in which
I specialize. An artificial heart is to be embedded after
the original heart has been removed from the humanbody. How long do you think it will last? May I ask thisgentleman sitting in the front. Two years? Great! You
are worthy of being at the top. The artificial heart we
made works for about two to two and a half years. However, there are several problems to be solved. One is theformation of a thrombus. When blood touches an artificial material, it judges whether the material is friend or
foe. On finding it is a foe, blood coagulates to concentrate on attacking it. This is what we call the formationof a thrombus. This should be prevented. The humanheart works by a pulsation. It is known now that a man
can live with a steady-flow pump, such as a centrifugal

pump. However, what God gave us is a pulse pump. Thispulse pump is subjected to a fatigue test, a pulsation of
100,000 times a day. No material on the earth can withstand a fatigue test of 100,000 operations a day for over
five years. This means that no artificial heart is available that can last over five years. This is a task imposed
upon us to find an answer to this problem. We are now
getting various kinds of materials of a living bodythrough gene manipulation, including cell engineeringand tissue engineering. So eventually, we will be able tomanufacture an artificial heart that will last over five
years or over ten years if cell engineering, tissue engineering, and organ engineering work to cover an artificially-made one, moving parts, and the parts to withstand a fatigue test. The current heart transplantation
has attained a five-year survival rate of 70 to 80%. If an
artificial heart surpasses the transplanted heart, whichlasts five years, we will be able to manage without relying on the human heart. The general ethical view prevailing in Japan is hindering the progress of heart transplantation. We researchers who are now developing artificial organs think it is ideal that God forgives us if we
succeed in managing without relying on the organs ofothers by manufacturing a heart more excellent thanthe one God gave us with God-blessed wisdom.
This circulatory system is directly connected to life.
For example, a man dies if his heart stops. This system
is very important, because a man dies if oxygen is not
supplied to the brain for three minutes. Another factor
to be considered is the contact with blood. This is very
specific, because artificial hearts will not work well unless a more advanced form is devised than other artificial organs.
Next, the respiratory system, where gases are exchanged. An artificial lung dominates this area. An example of lung transplantation survival was reported forthe first time in Japan by Tohoku University the other7From the 6th International Micromachine Symposium Special Lectureday. We make this artificial lung. We are researching
into an artificial lung even now. At present, a heart-lungmachine is used clinically, which can be used as long as
seven hours for heart operation with almost total safety.
However, an artificial lung poses a problem if the operation lasts longer. It is very difficult to make this unit
last longer. Our research into a built-in artificial lungare already under way. However, another factor weshould consider after the removal of the lung is that thelung is used for speaking. The lung is used for utteringwords. This mechanism of speaking should also be manufactured separately. The lung itself is very important,because it functions in various ways, such as the production of hormones. It is utterly impossible for us tocopy the lung. What we can do well is only to exchanges
gases. The current situation governing an artificial lungis that no artificial lung has been made available thatcan be used for a prolonged period of time because of its
contact with blood.
Then, the digestive system and artificial intestinescome next. Organs for the urological area should also
be considered. We are working to make artificial valves
for patients who are finding it difficult to urinate. Sincean artificial valve should open and close, we are using
shape memory alloys for the manufacture of artificial
valves for patients suffering from dysuria, and confirming whether they serve the purpose by using laboratory
animals. The test of laboratory animals is going on successfully.
Next, motor-related organs.
And the sensory system, which should desirably be
studied in preference to other areas. We have sensory
organs with which we can see, hear, and touch. We aretrying to replace this sensory system with a sensor system, which, for example, resembles the eyes of a robo
cop such as we see in the movies. However, the information those eyes are actually collecting is different fromwhat our eyes collect. We may copy a human system
when we think of a sensor system. It is desirable, however, that, if a microsensor system, for example, is capable of collecting the volume of information beyond thereach of a human system, this function should be utilized to the full. This should be a well-developed area.
For example, our brain thinks various things, issues
commands, and controls in various ways. The brain issues various commands through the neural system, suchas moving hands, raising blood pressure, and secreting
hormones. If we can intercept the commands midway toobtain the information and convert it to electric signals,
we will be able to do what the brain intends to do next
while thinking to do something. We are now doing thisby varying the quantity of electricity. The subject of thisinterface will come up later. I think this will be a mainarea in which micromachines take part in the future.
Then, the ear, the nose, the intestines, the esophagus, the windpipe, the lung, the liver, the ovaries, joints,
and artificial blood vessels. The artificial blood vessel isnearly perfected among the artificial organs in the circulatory system. The aorta and a blood vessel with a8large diameter are in the stage of nearly ideal perfection. What is left unsolved is that an artificial blood vessel does not expand as desired when it should expand
because of the difference between the properties of thehuman blood vessel and those of an artificial one. We
refer to this as the mismatching of a living body. Such athing has not yet been solved, but an artificial bloodvessel that lasts for a considerably long time has been
made available. However, an obstacle has not yet been
removed in the case of a slender blood vessel, say, with adiameter of 1 mm, an obstacle in which, when blood takes
a slender blood vessel as a foe, it coagulates there. I think
this may be a situation in which micromachines willplay an active part.
In addition, an eye, a tooth, an artificial heart, a valve,a pacemaker, an artificial kidney, the bladder, the urethra, the skin, and an artificial leg are the subjects ofstudy.
[The Artificial Heart]
Please allow me to dwell on the artificial heart inwhich I specialize. The artificial heart beats 100,000
times a day with a discharge volume of about 70 cc eachtime. A displacement of about 70 cc is therefore required
if we are to make a pulse pump. Its size is determinedin this way. A steady-flow pump and a centrifugal pumphave come to be used for men as well. When I started
studying artificial hearts, it was believed that a man
would not survive with a steady-flow pump. However, aman was found to survive. What makes the difference isthat, if a man is required to have 100 cc of blood per kg
of his weight for living, a steady-flow pump should havea capacity of 100 cc plus 20 cc. Conditioned as such, however, it is quite intriguing for us in that it can be miniaturized. A man has two pumps for the right and left
ventricles. God combined the two together, but the twolook like one. Actually, however, there are two pumps.
One is a low-pressure pump for sending blood to thelung, a low pressure equivalent to about 20 mm/Hg. The
other, the left pump, sends blood systemically with apressure equal to blood pressure. It therefore follows
that the pump should have a power as great as four tofive times. Since the right heart sends blood to the lung,it pulsates by breathing. When air is inhaled, the pressure in the lung becomes negative to allow blood to return with a rush. When the heart is checked, it stops
sometimes, for example, when struck with a catheter.
The patient is conscious, so he keeps breathing. Then,the breathing pressure only comes out in arterial pressure. When the patient is conscious, I tell him, “Cough alittle”, while his heart isn’t beating. He coughs, then hisheart begins beating again in some case in response tothis mechanical stimulus of coughing. Just coughing
raises the pressure to about 120. Such a thing occurs at
a place just outside the right heart. Therefore, I think asteady-flow pump will do for the right heart in the future, because it makes such pulses, though slow. As forthe left heart, a pulsating flow is better than a steadyone for making men and laboratory animals vivid. I dare

From the 6th International Micromachine Symposium Special Lecture

say vivid. If I am allowed to say so, a steady-flow pumpis very small, easy to make, and inexpensive. In the future, I believe, a steady-flow pump will be used for theright and a pulsating-flow pump for the left.
This is an artificial heart developed for the first timein the U.S. by Dr. Akutsu, now honorary chairman of
TERMO CORPORATION if I remember right. Since it
was made in 1957, its history is very short. Generally,
an artificial heart has only a short history usually lessthan half a century. At that time, a laboratory animal
could survive only 1.5 hours.
This was also made by Dr. Akutsu in 1975. In thismanner, we now have two artificial pumps. This pumpserved to help a calf survive experimentally 268 days.
However, when an artificial pump is embedded in a calf
for 268 days, the calf grows two times heavier. This
makes it impossible for this heart to answer the purpose.
[Current Problems Related to Artificial Organs]
The artificial organs we are now confronted with are
under study by researchers including myself who are
currently researching into an artificial heart nearly as
long as its history. The points at issue are how deftly we
can make very small artificial organs and how we canmake them serviceable for a long time without problems. I am thinking of having as many researchers as
possible participate in studying the extent to whichmicromachines can answer the needs so that ideal artificial organs can be made.
Therefore, we have summarized the defects andpoints at issue with the artificial organs now available.
They are too heavy and too big. These problems are indisputably the ones micromachines can answer. The sensors do not work as desired, either. Micromachines arealso good at this point. Moreover, they are not well controlled automatically. There are two kinds of controls:
one type of control is to have the unit fit the body itself
when embedded, and the other, to have the unit last
longer such as with an artificial heart, the durability ofwhich poses a problem. However, micromachines enable
the processing and control of information, thus dominating this sphere of activity.
They are not energy-effective, either. For example, I
am now developing an engine for medical treatmentusing a shape memory alloy. The shape memory alloy I
am now using is a commercially available large-diameter unit. I believe that if the alloy can be divided intovery small elements and then re-assembled, it will beeasier to control and be energy-effective. I am proposing this concept to the industry, but to no avail.
The engine has been completed in my head, but theindustry is quite reluctant in complying with my request.
Further, it does not last long. To make matterÇì worse,
unpleasant things occur one after another, such as noiseand vibration, accompanied by thrombus as a by-product. Since an artificial heart is a foreign body, it can also
become a source of infection. The human body reacts toforeign bodies in various ways. Bleeding also poses a

problem.
[Characteristics Desired for Upcoming Artificial
Organs]Desirable characteristics for newly developed artificial organs are, first, miniaturization, second, to interface with nerves for automatic control, third, to have acontrol system that is acceptable for both the living bodyand the embedded artificial organs, and fourth, to harmonize with the living body in various ways. Many issues have come up in the past, such as noise. Anotherdesirable characteristic for artificial organs is to last
several years. The artificial hearts now available last alittle over two years, but should desirably last longer.
Now, we have two large national projects in Japan,
led by the Ministry of Health and Welfare and NEDO.
We are setting about dealing with an artificial heart.
The project by the Ministry of Health and Welfare haslasted five years and will come to an end this year. We
hope it continues longer. As one of the members participating in the NEDO project, I am glad to know of thedecision to continue this project one more time.
Recent Research of Artificial Organs
This is an artificial heart we developed. It is stilllarge, but it has two pumps, right and left, in this form.
This shows how it was embedded in the thoracic cavity.
And this is an artificial heart equipped with amicrosensor, undoubtedly related to micromachines. I
think it is the first product in the world into which achip was inserted directly. It is a result of the work I did
about fifteen years ago together with Professor Esashi
at Tohoku University. Frankly, I was also a student ofProfessor Matsuo for one and half years, who was Professor Esashi’s teacher. So I started this work.
This is an auxiliary artificial heart. Pressure sensors are attached to the outlet and inlet, where they areconnected to the living body. This is an artificial bloodvessel leading to the aorta, and this is a duct. This is acannula with which to draw blood from the heart. Attached at the top in this manner is a microsensor. Hereis another. It is made in this manner, and its surface iscovered with an antithrombotic material so that blood
can hardly perceive it as a foreign body. It is about 20
microns thick, covering the sensor surface.
This is a diagram of the sensor itself. I am not a specialist in this field, but, according to Professor Esashi, it
is very difficult to connect a lead wire to a sensor. I think
the solution to this can be found by integrated molding.
Actually, it is being perfected. This is the surface of apressure sensor to be pressured. This is the rear side.
This is a connecting part. This is an experiment using agoat. This is a system to assist the left ventricle. This isa sensor. This is a trace of the micro-sensor after two
weeks.
We also have to measure the flow. This is a bloodflow meter using ultrasonic waves, developed jointly with
Cornell University. This is its trace, which is almost thesame as that of the conventional electromagnetic flowmeter.

9

From the 6th International Micromachine Symposium Special LectureThen, we use an artificial heart to assist the heart.
To ensure that the heart can set up for itself, we draw
two hysteresis curves of the left ventricle in this manner to connect them with a straight line. The more upright the inclination of the straight line, the more active is the heart. The more it declines, the worse is theheart. We therefore measure using a hysteresis curve to
see how active is the left ventricle. This necessitates
measuring pressure and the quantity of the discharge
from the left ventricle. By measuring the two, we canmeasure how active the heart is.
[Neural Interface]
Let me explain about the neural interface we justtalked about.
This shows the findings of the experiment using agoat. Above is aortic pressure. This is a neurogram, ameasurement of the integrated action potential of anerve. This is aortic flow.
Here, “stand up” is written. When a goat tries to standup, we can obtain neural information in advance. Thismeans that we can obtain neural information in advancewhen a goat stands up. With this method, we can manage well by accelerating the beat rate if we can judge
whether various kinds of artificial hearts are in a state
acceptable to the body and what should be done fromthat point. This means that we can get signals earlier
than God. In the case of God, it sends signals in likemanner to have an organ that raises blood pressure andsecretes hormones, which in turn raises blood pressure.
This takes dozen or so seconds. In the case of an artificial heart, however, we can control the above process ina few seconds instead of dozen or so seconds. This is
welcome for us. This kind of work is carried out infrequently, and we are the first in the world to take theinitiative.
This is a neural device for that purpose. It is madeinto a cuff containing a nerve so that the nerve is protected from damage when pierced directly. The cuff isalso a kind of interface used, for instance, for applying
electricity or stimulation. This is exactly the process bywhich the nerve is electrically converted to a control
system or for use as information. A new trial like thishas appeared. As I mentioned just before, this may explain the reason why a new trial like this to what wecall a sensor system will be applied more and more frequently.
[Microsensors]
With microsensors, we can obtain a variety of information on vital signs, including blood pressure, blood
flow, pulse rate, breathing condition, temperature, andchemical substances for artificial heart, such as glucose,
insulin, CRP and ammonia. The microsensors also enable us to obtain information from a living body, such as
the concentrations of oxygen and carbon dioxide in the
blood, pH level, and electrocardiogram. Those microsensors are embedded in the body, and driven elec-

10

tromagnetically. Our system also has them. In short, amicrosensor can send electricity into the body, a device
with primary and secondary coils wound around it.
Therefore, a microsensor can transmit power and information wirelessly without a cord piercing the skin evenwhen embedded in the body. Its efficiency is such that it
can send electricity with an efficiency of about 90% byincreasing flux density with an amorphous material in
our case. In the future, therefore, various devices will
be embedded in, for instance, the body of a sick patientor a postoperative patient, to be controlled intensively
at a given place. It is not necessary for those devices topierce the body for communication. We therefore assume
that, as with the artificial heart, we will eventually beable to go to an electric station after several decades
when we are short of electric supply in our daily life as
we now go to a gas station for gasoline.
At present, most of the microsensors are used for acatheter. It is desirable, however, that microsensors beembedded in artificial organs. If so, we can obtain a variety of information and use it for controlling.
This is a sensor that Esashi Laboratory is researching. This is a self-mobile active catheter, for insertion
into a blood vessel in the brain, which is one of our
projects we are doing our utmost to promote as members of the committee in the Micromachine Center. Since
artificial blood vessels are considered a hard nut to crack,
we are in the process of developing this, accompaniedby the development of various element technologies.
As I am a cardiac surgeon, we are thinking of embedding sensors in various parts of the heart. By so doing, we can understand well how a pump works. And
this is an artificial valve which stands for 20 to 30 years.
Since its movement is actuated by a difference in pressure, it moves only passively. If a micromachine can beused skillfully, a valve will come to open spontaneously
by controlling it with greater skill.
[Review of the Study of Artificial Organs in the 21stCentury ]In 2018 such as, for instance, an artificial kidney,
now used in vitro, will be made available for embeddingin the body. Here is what we call a hybrid. It will become possible to make what an artificial thing cannot
do by using various cells and tissues of the living body.
We are also expecting the emergence of a bio-cell byaround 2014 as researchers of artificial organs.
In this presentation today, we are looking forward to
the realization of artificial organs that are durable, reliable, stable, miniaturized, and biocompatible alongwith energy transportation or a battery system by utilizing micromachine technology.
Thank you very much.

(This paper is a summary of Prof. Nitta’s lecture, prepared by MMC.)