Between Issues

The Ratio of Ratios and the Nobel Prize

June 10, 2021

Kirk Shelley MD, PhD
Adapted from Special Feature on Pulse Oximeters: The invention that changed the paradigm of patient safety around the world. (LiSA (1340-8836) vol28 No3 Page237-308, 2021.03 (in Japanese)

View more articles from this special collection hosted by the APSF on Pulse Oximetry and the Legacy of Dr. Takuo Aoyagi.

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Pulse Oximeter on PatientI was truly heartbroken to hear of Dr. Aoyagi’s passing. His remarkable genius created the device I have spent most of my life devoted to studying. He was a warm and gentle man who was profoundly humble. Shortly after the Yale symposium of the Innovations and Applications of Monitoring Perfusion Oxygenation and Ventilation conference (IAMPOV) in 2012 the Noble Prize Committee approached me for a nomination for the 2013 Noble prize in Physiology or Medicine. This was done under an air of great secrecy. I wrote up Dr. Aoyagi’s nomination with care and thoughtfulness. I am disappointed to say he was not given the award. To this day, I see this as my failure and not his.

When we met again face to face in 2015 in Tokyo at their IAMPOV. I took Dr. Aoyagi aside (with his translator) and broke the strict confidentiality rule. I explained to him that he had been formally nominated and considered for the Noble Prize in Medicine in 2013. I apologized for the ineptness of my writing in being unable to convey the importance of the lifesaving nature of his work. He smiled warmly, thanking me most graciously.

Now that he has passed away, I am content that I violated my confidentiality agreement. He deserved to know how he came to be considered for the award and in what high regard people held him in.

Below contains the essence and update of what I wrote in 2012. I have been subsequently invited to submit additional nominations over the years for other potential candidates. I find that I am unable to because of the sadness I feel at the passing of Dr. Aoyagi.

It was my pleasure and honor to nominate Dr. Takuo Aoyagi for the Nobel Prize in Medicine for 2013. My nomination was based upon his discovery of the “Ratio of Ratios”. That discovery is the core technology behind the modern day pulse oximeter. In 1972, Dr. Aoyagi was interested in measuring cardiac output noninvasively by the dye dilution method using a commercially available ear densitometer. He concluded it would require calibration because arterial pulsatile “noise” prevented accurate recording of the dye clearance, he invented a method to eliminate this noise, which led to his great contribution1.

To quote Dr. Aoyagi2, “These [pulsations] prevented accurate extrapolation of the down-slope of the dye curve after recirculation begins. I investigated this problem mathematically using the Lambert-Beer law. Then I conceived the idea of eliminating the pulsation by computing the ratio of optical densities of the two wavelengths. This supposition was proved workable by experiments.”

Dr. Aoyagi goes on to say, “For this prototype, components of the dye densitometer were used. The light source was a small tungsten lamp. The transmitted light was divided into two beams, and each beam was received by a combination of an interference filter and a phototransistor. I used wavelengths of 630nm and 900nm. The wavelength of 630nm was selected to maximize the hemoglobin extinction change caused by the oxygen saturation change, and the 900nm wavelength was selected to avoid interference by the ICG dye. From the transmitted light intensity data, the pulsation amplitude AC and the total intensity DC were obtained, and the ratio, AC/DC, was calculated. This AC/DC ratio was obtained at both wavelengths, and their ratio, phi (Φ), was calculated. This is the so-called ratio of ratios. This phi (Φ) was supposed to correspond to SaO2.”

Dr. Aoyagi was correct; the ratio of ratios did correspond to the arterial saturation. The pulse oximeter has gone on to become a critical piece of medical equipment that is used all around the world on a daily basis. Its use is now considered to be a standard of care during surgical procedures and is part of a routine set of vital signs3. Its importance is further emphasized by the initiative, by the World Health Organization (WHO), called the “Global Pulse Oximetry Project”. This project was committed to the introduction of pulse oximetry technology throughout the world with an emphasis on developing countries4.

The Nobel Prize committee has a tradition of awarding significant technical innovation in medicine. Willem Einthoven, in 1924 for his discovery of the electrocardiogram, Allan Cormack with Sir Godfrey Hounsfield, in 1979 for the development of computer assisted tomography and Sir Peter Mansfield, in 2003 for his discoveries concerning magnetic resonance imaging are such examples. I believe Dr. Aoyagi discoveries concerning pulse oximetry had achieved that degree of significance.

☆ Comment: One of the main contributors to this project, the Lifebox Foundation with Professor Atul Gawande, has also submitted an article to this special memorial issue.


Kirk Shelley MD, PhD
Professor Emeritus of Anesthesiology
Yale University, New Haven, CT USA


  1. Severinghaus, J.W., Takuo Aoyagi: discovery of pulse oximetry. Anesth Analg, 2007. 105(6 Suppl): p. S1-4.
  2. Aoyagi, T., Pulse oximetry: its invention, theory, and future. J Anesth, 2003. 17(4): p. 259-66.
  3. Eichhorn, J.H., Pulse oximetry as a standard of practice in anesthesia. Anesthesiology, 1993. 78(3): p. 423-6.
  4. Thoms, G.M., G.A. McHugh, and E. O’Sullivan, The Global Oximetry initiative. Anaesthesia, 2007. 62 Suppl 1: p. 75-7.


Short bibliography of the most important publications of Takuo Aoyagi:

Aoyagi T, Kishi M, Yamaguchi K, Watanabe S (1974) Improvement of an earpiece oximeter. Abstracts, 13th Annual Meeting of the Japan Society of Medical Electronics and Biological Engineering, Osaka, Japan, April 26–27, pp 90–91 (in Japanese)

Yamaguchi K, Aoyagi T (1975) Study of earpiece method in cardiac output measurement. Jpn J Med Elec Biol Eng 13[Suppl]:203–204 (in Japanese)

Aoyagi T, Miyasaka K (1990) Pulse oximetry and its simulation. IEEE Tokyo Section Denshi Tokyo 29:184–186

Aoyagi T (1992) Theoretical and experimental study of optical attenuation of blood. Jpn J Med Elec Biol Eng 30:1–7 (in Japanese)

Aoyagi T (1993) Study of noninvasive measurement of light absorbing substances in the blood based on pulsation of vital tissue transmitting light. Ph.D. Thesis, Tokyo University, Tokyo, Japan (in Japanese)

Aoyagi T (1992) Theoretical and experimental study of optical attenuation of blood. Jpn J Med Elec Biol Eng 30:1–7 (in Japanese)

Aoyagi T (1996) Theory and improvement of pulse oximetry. Jpn J Med Instrum 66:440–445 (in Japanese)

Aoyagi T (2000) Pulse spectro-photometry. In: Abstracts, Symposium of Autumn 2000, Spectroscopical Society of Japan, pp 65–74 (In Japanese)

Aoyagi, T. and K. Miyasaka (2002). “The theory and applications of pulse spectrophotometry.” Anesth Analg 94(1 Suppl): S93-95.

Aoyagi, T. and K. Miyasaka (2002). “Pulse oximetry: its invention, contribution to medicine, and future tasks.” Anesth Analg 94(1 Suppl): S1-3.

Aoyagi T, Fuse M, Kobayashi N, Ukawa T, Miyasaka K, Nakagawa S (2003) Analysis of motion artifact of pulse oximetry. Trans Jpn Soc Med Biol Eng 41[Suppl]:421 (in Japanese)

Aoyagi, T., M. Fuse, N. Kobayashi, K. Machida and K. Miyasaka (2007). “Multiwavelength pulse oximetry: theory for the future.” Anesth Analg 105(6 Suppl): S53-58.


Short curriculum vitae of Takuo Aoyagi:

1958 Graduated electric engineering course of Faculty of Engineering, Niigata University.
1958 Entered Shimadzu Corporation, Kyoto City as a researcher in the Central Research Laboratory.
1966 Joined the Electronic Division, Faculty of Engineering, Tokyo University, where he studied cardiac output measurement using the dye dilution method.
1971 Entered in Nihon Kohden Corporation, Tokyo City, where he engaged in the study of:
<1> cardiac output measurement using dye dilution method.
<2> pulse oximetry: invention, making pilot model, and first announcement.
<3> pulse oximetry: constructing theory for improvement of pulse oximetry.
<4> pulse dye densitometry: for measurement of circulating blood volume
<5> biomedical impedance method for lung monitoring.
1993 Received a Ph.D. of Engineering at the Tokyo University, with a thesis topic of:
“Study of Noninvasive Measurement of Light Absorbing Materials in the Blood using the Arterial Pulse.”
1995 Achievement Prize by the Medical Instrument Society of Japan.
2007 The Medal with Purple Ribbon (given by Japanese Emperor).
2007 Social Prize by Japanese Society of Anesthesiologists.
2012 The Harvey W. Wiley Lifetime Achievement Award
2013 J.S. Gravenstein Award Lifetime Achievement by Society for Technology in Anesthesia
2015 IEEE Medal for Innovations in Healthcare Technology


Read more articles from this special collection hosted by the APSF on Pulse Oximetry and the Legacy of Dr. Takuo Aoyagi.