Dr. Nils Kaiser: the originator of non-invasive glucose measurement
Authors: Dr. Katrin Kraatz, Matthias Heinz
Non-invasive glucose measurement is a pipe dream for many diabetics. Researchers all over the world are working on the development of such a method. Many of the present day developments are based on the principles which the originator, Dr. Nils Kaiser, already began to develop back in 1957. He was able to register patents at that time for some procedures and apparatus.
Dr. Nils Kaiser answered our questions.
Non-invasive glucose measurement – which diabetic would not yearn to have this new method when seeing his finger tip completely pricked all over? And you would no doubt also find it much easier to recommend multiple blood glucose measurements per day, knowing that the patient would not be obliged to constantly injure himself. The suppressed cry of pain before meals taken together during training would no longer cause you pain as well. For a long time now, headlines have regularly appeared in the media announcing the breakthrough of the new method. Taking a closer look at these and inquiring, it turns out they are mostly early research results; there is still a long long way to go till we have the final device for the general public. As the following interview shows, the first promising approaches in research date from the 50s. Almost 50 years have passed since then - 50 years in which advances have been made in the right direction.
How did you get the idea anyway to measure blood glucose without taking blood?
Dr. Nils Kaiser:
Based on the physiological-chemical theme of my PhD, Professor Forst, Ordinarius for Pharmacology at Ludwig-Maximilian-University, Munich, requested me to study the effect of Calcium-ions on isolated guinea pig hearts. The envisaged method of study appeared to me to be so unphysiological, that I began to search for a physiologically better method of measurement. This method of measurement still to be developed should make it possible to observe the continuous sequence of metabolic processes in the observed organisms with the least disturbance and be ultimately applicable for humans and also be cheap. As a doctor I had in mind a screening method which would warn patients of metabolic disorders way before he or she even felt ill or noticed any symptoms. Special emphasis should be on non-invasive in-vivo blood glucose measurement in connection with early recognition of diabetes and the control of its development
DP: Which were the key points of your original procedure?
The infrared-(IR-) spectroscopy was a possible procedure to study biological objects under physiological conditions. However, I had to soon accept the fact that this route at first appeared impassable, since at that time water was classified as the ‘deadly enemy of IR-spectroscopy’. For this reason, practically in the complete infrared field there was no viable spectrendocumentation of watery solutions.
Hence, we tried at first to advance into the field of IR-wavelengths using powerful microwave generators from the field of microwaves. This technique did not need any water sensitive optical parts and besides had further advantages. Due to this the measurement-sensitivity towards the IR-technology of that time was improved considerably. Together with Dr. O’Brien I built an interferometer with a wavelength of 3 cm (10 GHz) with which we were able to measure the highly sensitive phase and quantum. However, it soon became apparent, that an advance into the really interesting field of infrared wavelengths with microwave technology was not possible for biology and medicine.
In 1965 I came in contact with the latest development in laser technology. This technology made it possible to overcome both the high intensity loss with watery solutions and biological issues. We did expect to be able to measure the CO2 level in the blood of an experimental animal in an extra corporal circulation with a CO2-laser. This procedure demonstrated both in animal experiments and in technical- industrial issues an exceptionally high measurement sensitivity.
In the meantime conventional spectrometer technology had also made considerable advances (FTIR-technology). Using the principle of ATR (attenuated total reflection) for the coupling of the IR-radiation source to the object to be measured, it was possible to gain the information needed on the composition of the probe to be measured e.g. tissue or blood, and their potential changes, without damaging the object to be measured. In addition, the thermal load is distributed over several areas whereby the absolute measurement intensity can be increased.
DP: How long ago was this? which steps were patented?
It all began in 1957 when I was employed by Professor Forst. I registered the first patent in November 1958 under: “Procedures and device for registering chemical reactions”. In 1962 the patent “Procedures to study the chemical and physical nature of materials followed, “1965 Device to study the chemical and/or physical nature of materials”. “Device to determine the CO2 content of a biological substance” and the patent “Apparatus for determining a substance by an optical radiation” was registered in 1970. My last patent “Apparatus to determine the content of metabolic substances in blood” followed in 1976. All the patents listed relate to measurement procedures with electromagnetic waves. In 1979 the company Hoechst took out an option on my patents but – as far as I could ascertain – made little or no use of them. Unfortunately all my patents have expired in the meantime. However, it can be ascertained that my patents are quoted as references in 35 US patents of current developments.
DP: Are there parallel developments?
According to my extensive research there were no parallel developments before 1979. Worldwide interest in my procedure only started after the publication of the second Max-Planck-Institute press release in 1978. My first contact with Professor Shichiri of Kumamoto in Japan, who developed a very interesting version of fiber optics with ATR crystals on the lip using my suggestions, stems from this time. I have heard from reliable sources that the companies Johnson & Johnson, Abbot and Roche Diagnostics have invested quite considerable sums into the development of corresponding devices.
DP: What results were really achieved with the procedure?
At a conference on Infrared spectroscopy in California in 1998 researchers from all over the world presented highly diverse applications of this technology as a new tools in medicine: in cancer detection, in microbiological diagnostic but also in the analysis of blood components – as e.g. glucose.
DP: In your opinion is there already a device which, based on your original idea, that comes close to the aim of "non-invasive glucose measurement"?
Without any doubt the Diasensor (UltraPharm) and the device from Professor Shichiri come very close to my original idea. However, the measurement values of both developments are not yet exact enough to allow them to be used by patients.
DP: How do you evaluate the Diasensor 1000?
The problem of the press pressure on the measuring device has been solved very well by Diasensor. However, the more or less good circulation in the underarm, e.g. after sport activity poses a much too high source of error. The amount of blood, which supplies the measurement reading, must be as exact as possible when supplied to the software for the calculation.
DP: Why was this at first rejected by the American Food and Drug Administration?
I suspect it was due to the problem stated above but I do not know for sure.
DP: What do you think, how will it progress? When will there be really marketable developments?
My original idea was to develop a large device e.g. for clinics. For them this would have been a cheap and quick to carry out screening method, with which multiple metabolic parameters could have been measured in one measuring process. But my opinion is that, above all for commercial reasons, the attempt was to first of all produce a small and relatively inexpensive device for a wide range of users, such as diabetics. If that were possible I would be very happy.
DP: Many thanks Dr. Kaiser for answering our questions.
This article was taken in a modified form from “Diabetesprofi” 04/2000, Verlag (Publishers) Kirchheim + Co GmbH, Darmstadt, Germany.
© Merck Pharma GmbH, Darmstadt, Deutschland