Background to the development of the pulse oximeterthat has been in demand around the world since thestart of the COVID-19 pandemic
Susumu Nakajima
Director of Moriyama Memorial Hospital,Social Medical Corporation Genseikai

Alumni Journal of Department of Surgery II, Hokkaido University, 46th edition

Background to the development of the pulse oximeter that has been in demand around the world since thestart of the COVID-19 pandemic(Alumni Journal of Department of Surgery II, Hokkaido University, 46th edition)
Susumu Nakajima, Director of Moriyama Memorial Hospital, Social Medical Corporation Genseikai

Introduction
This fall, I received a letter from Dr. Eiji Shimozawa, who is the editorial
chairperson of the Alumni Journal of Department of Surgery II, Hokkaido
University, as well as an old acquaintance of mine. In the letter, he suggested
that I write an article about the background to the development of the pulse
oximeter, which has been the focus for monitoring the respiration of patientswith COVID-19, and my relationship with Mr. Takuo Aoyagi, who was a coresearcher and died on July 18, and then post in the Alumni Journal. Somereaders may think posting an article about a device for measuring oxygen
concentration in the Alumni Journal of a surgical department is irrelevant;however, I am one of the readers who finds the Alumni Journal of Departmentof Surgery II interesting with its wide variety of topics covered. So, I hope
you accept my article as one of the various topics.
In 1960, when I joined the Department of Surgery II, Hokkaido University,
I was engaged in medical examinations as a surgical intern. However, after
suffering from hepatic disorder, I stayed in Misumai Sanatorium near
Sapporo as recommended by the medical office. Since I had time to spare
after my surgical internship in the morning, I decided to attend a class led byProfessor Seiji Mochizuki of the Research Institute for Applied Electricity,
Hokkaido University. As soon as I acquired my driver’s license, I started
going to Hokkaido University. The Research Institute for Applied Electricity,
Hokkaido University was a unique place where specialists in a wide range offields gathered, from basic science to medical science. I remember that seniordoctors at the Department of Surgery II, such as Dr. Ryozo Sawaguchi andDr. Keisuke Sakai, were co-researching the detection of intracardiac shunts
using platinum electrodes, the development of a domestic cardiac pacemaker,
the development and application of an electrode blood flow meter, etc. I
chose the class of Professor Mochizuki because he was a world-classresearcher of oxygen diffusion theory of the lungs, as well as the strictest
professor. At that time, the development of a glow discharge expired gas
analyzer, demonstration experiments of Mochizuki’s theory on oxygen
diffusion, and such like were being conducted. Back then, I never imaginedthat I would be involved in the development of an oxygen saturation
measuring device in the future, nor was I aware I was learning from someone
who was in charge of oxygen-related subjects in the respiratory physiologyof the Japanese physiology system.

One day, I was suddenly summoned by Dr. Akihiko Kuze who was theDirector at that time. According to him, the Ministry of Health and Welfare
was planning to establish an Intensive Respiratory Care Unit (IRCU) at major
sanatoriums nationwide, and since Misumai Sanatorium was selected, heappointed me as a person in charge of selecting required medical equipment.
I believe the budget was over 12 million yen at that time. Bennett-type
ventilators and blood gas analyzers were quickly decided upon. When I waslooking for a respiratory monitor that was not available at other facilities, Mr.
Sugiyama, who was the sales manager of Nihon Kohden, told me that a groupresearching the measurement of cardiac output with the dye injection method
using ICG in the company laboratory had found something interesting. The
group led by Mr. Aoyagi successfully observed a new pulse wave on thecurve with cardiac output measurement, and there was possibility of creatinga new oximeter by utilizing the new pulse wave. So, I allocated a budget of
2.5 million yen and had them create a custom-made device. Eventually, an
oxygen saturation measurement device based on a new principle wasdelivered to Misumai, and both Mr. Aoyagi and Mr. Yamaguchi also
participated in the first animal experiments and helped me adjust the device.
Nihon Kohden also made another prototype of the same device andconducted clinical tests at Sapporo Medical University. However, they put apause on the pulse oximeter research project after this device. The company
restarted the project after clinical applications really took off in the UnitedStates. I brought the prototype device to the Physiology Department of theResearch Institute for Applied Electricity, Hokkaido University, which had
world-class facilities for oxygen research, and continued conducting
performance tests and clinical application for patients I was in charge of at
the sanatorium. At that time, there were people like Mr. Arai who hadexcellent crafting skills, Mr. Miura who had excellent glass skills, and Mr.
Shindo who was knowledgeable in electricity and computers at the ResearchInstitute. There were many occasions I helped them compose a thesis on
applied electricity written in English. On the other hand, they helped me withmy experiments and kept me in the best condition. I must say they were mygood friends and daily drinking buddies.

Figure 1. Performance tests of the pulse oximeter conducted at the Physiology

Photo (2) Report of the world's first clinical application of a finger-tip type pulse

Department of the Research Institute for Applied Electricity, Hokkaido University

oximeter developed by Minolta Camera

The top reading indicates continuous recording of expiratory oxygen concentration

The patient developed hypoxemia after receiving postoperative radiation

using a glow discharge oxygen concentration recorder

treatment for an esophageal tumor

The middle reading indicates a pulse oximeter recording
The bottom reading indicates the output of oxygen concentration in the femoral

The dog suffered from lower inspired oxygen partial pressure, which wasarterial blood using a Pt oxygen electrodetriggered by increasing nitrogen gas that the dog inhaled, slightly raising the(Directly inserted an electrode into the femoral artery)oxygen concentration in the inspired oxygen. At this moment, the pulse
oximeter captured the change faster than the platinum electrode. At a time
when there were no medical mass spectrometers, I think the level of theperformance tests was considered high on a worldwide scale. The world’s
first clinical application of a pulse oximeter was conducted in the patientroom at Misumai Sanatorium (Photo (1)). The patient underwent
thoracoplasty for tuberculosis treatment. Oxygen concentration wascontinuously measured with a pulse oximeter, and the partial pressure ofcarbon dioxide was also continuously measured with a capnometer using
infrared rays. After we examined the increasing tendency of carbon dioxide
concentration during oxygen inhalation, the effect of light exercise and thePhoto (1) The world’s first clinical application of a pulse oximeter conducted in theeffect of Diamox administration, we published a research paper inpatient room at Misumai Sanatorium"Respiration and Circulation," Vol. 23, No. 8 in 1975. Later, Professor

The patient had respiratory failure after he underwent thoracoplasty for

Severinghaus of the University of California mentioned our paper when hetuberculosis treatment

was searching for the roots of pulse oximeter development.

dog. The top reading indicates continuous recording of expiratory oxygen

Clinical tests of the world’s first finger-tip type pulse
oximeter and publication of research paper in the Journalof Japan Surgical Society

concentration using a glow discharge oxygen concentration recorder, theIn 1977, an employee from Mochida Pharmaceutical and a technician frommiddle reading indicates a pulse oximeter recording, and the bottom reading

Minolta Camera visited the medical office of the Department of Surgery, andindicates continuous recording of the partial pressure of oxygen in the arterythey asked the medical stuff to clinically evaluate a device they hadobserved by inserting a platinum electrode into the femoral artery.

developed that could measure oxygen concentration through a fingertip. The

Figure 1 shows the results of a performance test on the new device used on adevice and a patient are shown in Photo (2). The patient received radiation

treatment before surgery and suffered from hypoxemia post-surgery. The

earpiece-type and fingertip-type pulse oximeters and published a researchdevice was simpler and easier to use, and the output of pulse was stablepaper.

compared to an earpiece-type one. This clinical result was presented at the12th Congress of European Society for Surgical Research held in Warsaw in1977 under the joint names of Dr. Yoshihiko Kubo, Dr. Natsuki Samejima,and me, Nakajima. It was the first clinical application result of a finger-tip
pulse oximeter ever reported in the world. I remember when I presented it toa medical conference in Japan, a young anesthesiologist questioned thenecessity of the device since there was a blood gas analyzer, and thisdisappointed me. Whereas in Warsaw, a professor of the Anesthesiology
Department in France stood up and praised it as very interesting research.
Since then, as the number of clinical application cases had increased, I
published "Experience of using a new pulse-wave type oximeter: for dynamic

Photo (3) Photo taken when Professor Severinghaus visited Japan

monitoring of postoperative respiratory failure" with other co-researchers in

From the left, Mr. Aoyagi, Professor Severinghaus, Professor Honda and me,

the Journal of Japan Surgical Society, Vol. 41, No. 1. This research paper

Nakajima

was later translated into English by Mochida Pharmaceutical and distributed

Taken in front of the Hilton Tokyo on January 27, 1987

as reference when OXIMET was sold in the United States. I believe thisEnglish version of research paper contributed to the massive spread of pulse

During the research, Professor Severinghaus found a handwritten abstract byoximeters in the United States later on.

Mr. Aoyagi in the abstract collection of the fourth Japanese Society for
Medical Engineering, which I referenced for my research paper. Since then,A letter from Professor Yoshiyuki Honda of RespiratoryPhysiology, Chiba University
At the end of 1986, I received a letter from Professor Yoshiyuki Honda ofRespiratory Physiology, School of Medicine, Chiba University, who wasfamous for respiratory physiology. In the letter, he wrote that when he wasattending the International Congress of Physiological Sciences held inVancouver, Canada in July of the same year, he spoke with his old
acquaintance, Professor Severinghaus of the Department of Anesthesiology,University of California. Apparently, Professor Severinghaus wasresearching the origin of the pulse oximeter and asked Professor Honda forcooperation.

Mr. Aoyagi has been recognized as the originator of the pulse oximeter
principle, and I have been recognized as the first person to ever conduct a
clinical application of the earpiece-type and fingertip-type pulse oximetersand published a research paper.
In 1987, Professor Severinghaus visited Japan to verify the facts. A rare
photo of the four of us was taken in front of the Hilton Tokyo (Photo (3)).
In the same year, Professor Severinghaus and Professor Honda publishedthe following paper and concluded:
Severinghaus JW, Honda Y. History of blood gas analysis VII.
Pulse oximetry. J Clin Monit 1987; 3:135-138

During the conversation, Professor Severinghaus mentioned someone
named Nakajima who discovered a pulse oximeter and worked at Minolta

ABSTRACT. Pulse oximetry is based on a relatively new concept, using theCamera, and his research paper could be found in anesthesia-related

pulsatile variation in optical density of tissues in the red and infrared

magazines, which led Professor Honda to me after he went through thewavelengths to compute arterial oxygen saturation without the need for

medical magazine Respiration and Circulation. During the research,calibration. The method was invented in 1972 by Takuo Aoyagi, a bio-Professor Severinghaus found a handwritten abstract by Mr. Aoyagi in theengineer, while he was working on an ear densitometer for recording dye

abstract collection of the first Japanese Society for Medical Engineering,

dilution curves. Susumu Nakajima, a surgeon, and his associates first tested

which I referenced for my research paper. Since then, Mr. Aoyagi has been

the device in patients, reporting in 1975.

recognized as the originator of the pulse oximeter principle, and I have been

A competing device was introduced and also tested and described in Japan.

recognized as the first person to ever conduct a clinical application of theWilliam New and Jack Lloyd recognized the potential importance of pulse

oximetry and developed interest among anesthesiologists and others

between the Wood-type oximeter and a pulse oximeter. The results showed

concerned with critical care in the United States. Success brought patentthat ischemic operation was complicated and the baseline deviated, making

litigation and much competition.

it difficult to measure a stable oxygen saturation with the Wood-type oximeter.

REFFRENCES

Initially, Mr. Aoyagi worked on improving the Wood-type oximeter; however,

1.

Severinghaus J.Astrup P. History of blood analysis. VI. Oximetry. J

he came to the same conclusion as ours. After he could not find a way toClin Monit 1986; 2:270-288

improve it, he started the development of a cardiac output meter using dye

2.

Peterson J. The development of pulse oximetry.

Science 1986;

method, he immediately found that light transmitted through tissue pulsated.

232:G135-136
3.

Aoyagi T, Kishi M, Yamaguchi K, Watanabe S. Improvement of theFigure 2 shows experiments. A dye (ICG) was injected into a vein, andearpiece oximeter. Abstract of the 13 annual meeting of the Japanese

the change in the amount of transmitted light through an earlobe wassociety of Medical Electronics and Biological Engineering, 1974:90-91

measured and the dilution curve observed. At a wavelength of 805 nm, the(Jap)

pulse wave was superimposed on the dye curve as noise. On the other hand,Nakajima S, Ikeda K, Nishioka H, et al. Clinical application of a newat a wavelength of 930 nm, only a pulse wave was recorded, and no effect of(fingertip type) Pulse wave oximeter. Translated from the Japanese. Jap

the injected dye was observed. It was experimentally shown that the pulsation

J Sur 1979, 41:57-61 (Jap)

portion could be conveniently offset by using signals of both wavelengths,th4.

(indocyanine green or ICG). After experimenting with the dye dilutionthat was, by dividing the absorbance obtained at 805 nm by the absorbance

How was the principle of the pulse oximeter born?
Mr. Aoyagi died on April 18 of this year in Tokyo just when COVID-19
was beginning to spread. He was born in Niigata in 1936, and joined
Shimadzu Corporation after graduating from the Faculty of Engineering,
Niigata University. Later, he joined Nihon Kohden where he was involved in
the development of circulatory and respiratory ME devices. He was about
five years older than me. We used to exchange letters about twice a year.
When he and Seisyu Hanaoka were chosen from Asia and named as one of
100 people who have contributed to the development of anesthesiology in thelast 100 years in a book "Notable Names in Anesthesia" (edited by J. Roger
Maltby, published by Sogo Igaku Sha, Co., Ltd), he was extremely excited.
If Mr. Aoyagi had not collaborated with our research group, he would neverobtained at 930 nm. In addition, as shown in Figure 2 (2), the dye curve was
successfully observed without the influence of the pulse wave. From theexperiment results, we discovered that the baseline (zero point) could becontinuously obtained from the fluctuation of the pulsation wave without theavascularization of the whole earlobe. Shortly after this discovery, from theexamination of eliminating the pulse wave component as noise, we realized
there was a possibility of measuring continuous oxygen saturation byutilizing the dye information of the pulse wave component, that is, the arterial
blood pulsation component. It was December 1972. Professor Severinghaus
later showed great interest in the fact that the pulsatile wave, which wasconsidered a noise component when calculating cardiac output, played amajor role when calculating oxygen saturation.

have met Professor Severinghaus and the pulse oximeter research at Nihon
Kohden would be buried in history especially with that company’s attitude atthe time. Rest in peace Mr. Aoyagi.
Traditionally, the Wood-type oximeter was used for medical practices. The
Wood-type oximeter was convenient for measuring oxygen saturation since
the light absorption of hemoglobin changes significantly when oxygen
saturation changes at around 660 nm. Also, a method of calculating oxygen
saturation at dual wavelengths using another wavelength of 890 nm wasseparately used. In order to calculate the absolute value of oxygen saturation
at these dual wavelengths based on the Beer-Lambert law, an accurate valueof blood volume was required. Thus, Wood tried to calculate oxygen
saturation by squeezing the earlobe (ischemia method) in order to obtain anabsolute oxygen saturation value. We conducted a comparative experiment

Expanding the use of pulse oximeters especially for athome treatment
I am currently working as the Director of Moriyama Memorial Hospital,
which has a convalescent ward for rehabilitation and nine types of at-homesupport organizations. In recent years, I have investigated the increased useof pulse oximeters at Moriyama Hospital and Moriyama Memorial Hospital(Table (1)). As shown in the table, such use increased 2.3 times in the fiveyears from 2013 to 2018. The use in home care facilities has increased inparticular, and it has become common for individuals to have their own pulse
oximeter in the home-visit nursing and home-visit rehabilitation sectors.
Photo (4) shows the home-visit nurses presenting their own pulse oximeter
during their work.

Figure 2 (a) Record of received transmitted light at 805 nm and 904 nm(b) Chart of calculated dye concentration

Table (1) The number of pulse oximeters used at Moriyama Hospital andPhoto (4) Pulse oximeters carried by nurses when they visit at-home care patients

Moriyama Memorial Hospital

blood samples from. Professor Shibata has also published several books on

Acknowledgement of doctors who supported me with thepulse oximeter research
Professor Yoshinobu Osaki of Respiratory Center, Asahikawa Medical
University (Present: Assistant Director of Yoshida Hospital, Keiyukai Group)
has consistently supported me throughout my pulse oximeter research. He
has given me advice and introduced me at various lectures. Professor Osakihas the fingertip-type pulse oximeter made by Minolta Camera mentioned in
the research paper. The other day, the Japanese Museum of Anesthesiology
in Yokohama requested that this device as a donation, but I politely declined.
Pediatric Professor Mutsuo Shibata of Hokkaido Medical University
developed an interest in my work after he attended Professor Osaki’s lecture.
Professor Shibata, who has a rebellious spirit, searched through documents
and pointed out how our clinical application report on respiration andcirculation, which was the first publication ever made in the world, wasundervalued. So, he invited me to speak at the 51st Annual Conference of theJapanese Society of Pediatric Pulmonology held in Sapporo on September 18,
2018. Once again, I reaffirmed how much pulse oximeters are being used formonitoring the respiration of children who it is usually difficult to collect

Senryu (short poetry similar to Haiku), and he sent me one. One of his Senryu
called "Cannot find a good reason to give up my dreams" is my favorite.

Epilogue
Pulse oximeters are now gaining in popularity around the world and being
deployed in almost every anesthesia care system, intensive care unit,
emergency outpatient department, hospitalized patient care, ambulance, as
well as at-home care sector. It is an essential device for adjusting oxygen
concentration and observing respiratory status, and yet so compact that you
can store it in a pocket. Coronavirus, which caused the pandemic, is known
to damage capillaries in the lungs and cause early hypoxemia. Thus, use of apulse oximeter in the early stage of patients with COVID-19 is being urgently
called for around the world. I feel fortunate to have been part of thedevelopment of such an oxygen monitoring device. Before the pandemic, I
used to attend the Alumni of Department of Surgery II, Hokkaido Universityand studied the leading science of surgery once a year, and I joined the GoClub of Department of Surgery II and played Go with senior doctors a few
times a year. Those days are truly missed. I would like to thank Dr.

Shimozawa for giving me the opportunity to share my story, and wish theAlumni of Department of Surgery II, Hokkaido University the best and muchsuccess.