Infrared Spectroscopy and its potential possibilities in clinical chemistry
With reference to the review lecture by H.M. Heise from the Institute for Spectrochemistry and applied Spectroscopy Dortmund (Lab. med 15.470- 476, 1991).
The review lecture by H. M. Heise gives a very informative view of the current status of the research in this field. The device cited in the closing reflection of this article that could possibly be considered for bloodless glucose determination for the diabetic at home, which was my vision of the future even at the beginning of my work (1958), looks as if it will be reality much quicker than anticipated (1), since the Firm Futrex in Gaithersburg MD/USA have already begun to address the question of clinically testing an apparatus that they have developed themselves. In addition to considerable ease for the diabetic it also implies the potential possibility of developing a sensor for an artificial pancreas.
This breakthrough now approaching of a non-invasive measuring concept free from biologically damaging side effects, can be applied not only to register glucose levels but in principle also for the measurement of a number of other blood and tissue parameters. As a laboratory Dr. of medicine, who has been active in this research field for over 30 years, it gives me great pleasure to now see the successful technical realisation of my original concept. However, since I have been incompletely and incorrectly quoted both here and elsewhere, I would like to make a few comments for the historical record.
Since 1958 I have been investigating the possibility of bloodless registration of metabolic processes using electromagnetic waves, which lead to the registration of the first patents 1958 (2) and 1962 (3). For many years I pressed ahead with this research project alone. From 1960 onwards I enjoyed the guest rights of hospitality firstly at the Institute for Physics and Astrophysics in Munich and later at the Institute for Plasma physics in Garching – Max Planck Institute – whereby advisors and colleagues (degree and Ph.D. students) were intermittently at my disposal.
At the commencement of the project there was practically no experience in the area of research on aqueous solutions in the field of Infrared technology. W. Brü̈gel had classified water as the “arch enemy” of IR-spectroscopy (4). At that time there were neither powerful generators nor sufficiently sensitive detectors in the IR field to study watery solutions. Since most of the optical components consisted of NaCl they were only of limited or no use at all for such projects; hence, in the early years I tried to advance into the IR field with the, at that time, mature microwave technology (5, 6, 7, 8, 9), until the feasibility proved to be technically too difficult.
However, we succeeded in qualitatively registering clotting experiments (recalcification of citrate blood) with a microwave measuring bridge after intensity and phase in-vitro. (6, 1965; 10)
A completely new perspective presented itself in the then stormy development of laser technology, with which by now powerful generators were available in the IR field. With the help of colleagues in the IPP of MPG I succeeded in constructing a CO2 laser measuring station. It was expected that with this the CO2 content of the blood in the resonance frequency could be significantly measured. Together with Professor Meßmer, experimental surgery at the LMU, Munich, we carried out an animal experiment laying an extra-corporal circulation with a measuring cuvette and registered the CO2 content of the blood by altering the breathing of the intubated dog. Blood samples taken parallel indirectly confirmed the significant measured data due to the relatively simple determination of the HbO concentration.
In addition, with this experiment we were able to prove that the extra corporal circulation could be kept stable using a measuring cuvette with a measurable layer thickness without the flowing blood coagulating due to the high laser power; likewise, we were able to show that the cell structure of the blood which, at least in the case of the erythrocytes, lies in the scale of the measured wavelength, did not disturb the measuring procedure (11, 12, 13,). These experiments proved that my fundamental considerations were correct.
Further experiments demonstrated the possibility of applying this measuring concept also to technical-industrial questions (15).
The quantitative determination of substances using spectroscopy requires a preferably wide frequency band on the side of the generator. With lasers as the source of light at that time this target could not be achieved in near and far IR. This disadvantage stood clearly in opposition to the benefits of the lasers as an intensive source of radiation. In the meantime conventional spectrometer technology had made considerable advances (FTIR-Technic). In order to avoid a direct irradiation of the tissue due to the high absorption rate and the consequent thermal load on the probe, I started early on to use the ATR (attenuated total reflection) principle to couple the IR source to the probe. This technique, alone by irradiation of the surface of the probe, enables the extraction of the required information on the composition (13, 16, 17, 18, ). This principle was tested in practice in several experiments, among others by pressing a previously dried lip or tongue on to an ATR-plate in the radiation path. The results measured were encouraging (17).
Nevertheless, at that time it was unfortunately not possible to convince even experts in the respective committees of the possibilities and the importance of continuing the research in this field and to ensure the continuance of the project. Professor J. Kruse-Jarres approached me in 1979 with the proposition of a collaboration; but even a combined application for funding, in which we cited my, as yet unpublished, results was of no avail.
In 1987 Mr. R. Marbach informed me of his intention to follow up and continue with this research project. Since at this time, due to my advanced years, I had already resigned from active research, I put all the records acquired up to then and the knowledge, as well as prospective work and evaluation suggestions (Application together with Prof. J. Kruse-Jarres), that were essential for the continuation of the project at his disposal. Herr R. Marbach then made contact with Dr. H. Heise in ISAS in Dortmund which led to the successful collaboration described in the existing review lecture to which I was able to sporadically give some advice.
Thus, a funding application submitted by me to the BMFT on 6th June 1984 contained the suggestion to further process the existing results achieved using computer aided evaluation algorithms. In the near future we can expect technology to make great strides in both the IR-radiation sources, for example with tunable lasers for the technique of coupling onto the measurement probe (ATR-principle), and also in the area of the detectors. Together with the new computer aided evaluation algorithms mentioned by Heise, these developments make the introduction of IR-spectroscopy into the routine of medical and biological laboratory analysis to be almost within our grasp.
A large number of people and institutions took part in the promotion of my work, above all the Foundation Association of German Industry, Max Planck Institute, the German Research Group (Deutsche Forschungsgemeinschaft), the German ministry for research and technology, and the Fraunhofer Institute. I owe my thanks especially to the managers of these institutions who helped me personally. I gladly take this opportunity to thank all those who stood by me with advice and help. The number is so large that it is unfortunately not possible to mention each one personally here.
1. Rosenthal Robert, D. & Paynter Lynn, N. (1991) A Portable Noninvasive Blood Glucose Meter. 14th Internat. Diabetes Federation Congress 23.-28. Juni 1991 Washington DC, May 1991 Volume 40, Supplement 1, Poster Nr. 1244. Private communication 3. Februar 1992.
2. Kaiser, N. (1958) Procedure and apparatus for registering chemical reactions. DBP-Anmeldung Nr. K 36308 IX/42 1.
3. Kaiser, N. (1961) Procedure to study the chemical and physical properties of materials. DBP-Anmeldung Nr. 1 698 234.
4. Brügel W. (1962) Introduction to ultrared-spectroscopy. Steinkopf Verlag, 3. Auflage, 255.
5. Kaiser, N. (1962) Examination of the usability of electromagnetic waves to register metabolic procedures in biological tissues. O’Brien, B.B. Calculation of the minimum measurable phase and performance variance. Preuß, H. Discussion of possibilities which arise when using high frequency microwave- and ultrared-spectroscopy on reaction procedures under special consideration of biological issues. Tutter, M. Measurement of dielectric material constants with microwaves. Combined lab report. MPI for physics and astrophysics, Munich.
6. Kaiser, N. Laborberichte: Juli 1963, Januar 1964, Juni 1964, Dezember 1964, Juni 1965 Lab reports: Study of the usability of electromagnetic waves for registering metabolic procedures in biological tissues. Lab reports from MPI for physics and astrophysics, Munich.
7. Kaiser, N. (1965) Apparatus to study the chemical and/or physical properties of materials. DBP Nr- 1 291 541 as well as 8 related overseas copyright and related rights
8. Von Casimir, W., Kaiser, N., Keilmann, F., Mayer, A., Vogel, H. (1968) Dielectric Properties of Oxyhemoglobin and Deoxyhemoglobin in Aqueous Solution at Microwave Frequencies. Biopolymer, Vol. 6, PP 1705-1705.
9. Kaiser, N. (1968) Measurement of the dielectric constants of changes in haemoglobin structures in aqueous solutions using a microwave interferometer with a highly sensitive detector and using a flowcuvette. 16th Colloquium of the Biological Fluids. Brügge Vol. 16, S. 8.81-86, Pergamon Press.
10. Kaiser, N. (1969) lnvestigations of the Metabolism in Biological Systems Using Microwave and Infrared Spectroscopy. The Third International Biophysics Congress of the International Union for Pure and Applied Biophysics. 29th Aug.- 3rd. Sept. 1969, Cambridge, Massachusetts Abstracts IZ, 4 p. 159.
11. Institute for Plasmaphysics, Garching, Munich. IPP-No. 14/15. 12.1969 Medical diagnostics of the future with Laser light
12. Schenker, N. D. (1970) Medical Potential of Lasers, Educational film for the medical profession by the Upjohn company; approx. 100 copies
13. Kaiser, N. (1970) DBP Nr. P 20 39 382, P 20 45 386, P 20 58 064, P 26 06 991. As well as 18 related overseas copyright and related rights
14. Kaiser, N. (1973) Access to Metabolic Processes in Living Matter Made Possible by the Laser. Modern Techniques in Physiological Sciences. Gross, J. F., et al. Academic Press. London, p. 237-243
15. Kraus, G., Maler, M., Kaiser, N. (1974) Detection of Water Pollution by a CO2-Laser Optics Communications Vol. 11, Nr. 2, p. 175,-177
16. Kaiser, N. (1977) Laser absorptions spectroscopy with ATR-plate. Laser 77 Opto-Electronics, Conference Proceedings ipc science and technology press, S. 543-551.
17. Max-Planck-Ges. München MPG-Press information PRI 19/78 14. Sept. 1978 Non-invasive test blood test.
18. Kaiser, N. (1979) Laser Absorption Spectroscopy with ATR- Prism, IEEE Transactions on Miomedical Eng. BME 26, p. 597-600
Dr. Nils Kaiser, Laboratory Physician, Germeringer Straße 36, 8035 Gauting