Continuous glucose monitoring: "Our method is based on the principles of infrared photometry"

Interview with Prof. Herbert Michael Heise, South Westphalia University of Applied Sciences

Patients in intensive care units do not just have to struggle with the consequences of a severe injury or disease – they are also subject to acute glucose fluctuations that compromise the healing success. These sometimes happen so quickly that they cannot be caught in time with existing discrete measurement methods.


Photo: Herbert Michael Heise

Prof. Herbert Michael Heise; © private

In this interview with, Professor Herbert-Michael Heise explains how a continuous measurement method based on infrared spectroscopy can help in this case. It is not just meant to measure blood glucose levels but also other values in critical care patients, and could also benefit diabetics in the future.

Professor Heise, patients in intensive care units are sometimes subject to acute blood glucose fluctuations. What is the reason for this?

Herbert-Michael Heise: This patient group faces a large amount of elevated stress, because of surgeries, loss of blood, sepsis or other diseases for example. These are extreme situations. The body produces hormones that cause the release of glucose from reservoirs in the liver. However, not enough glucose is able to enter cells with the insulin hormone as the enabling key, causing glucose concentration in the blood and in tissue fluids to increase. This is a similar phenomenon to what occurs in diabetic patients, but the cause is different. These fluctuations have a very adverse effect on the healing outcome, mortality and morbidity.

What does blood glucose monitoring look like in this case?

Heise: For the most part, this is presently a manual process performed by nursing staff in the wards: there are corresponding systems in which the measured glucose concentration values are being entered and that subsequently recommend insulin administration and operated as a decision support system or regulate an insulin pump controlled by the staff. The values are then only available from many intermittent measurements. Stress however can lead to acute changes in a short time interval, which cannot be monitored in time with several single measurements. We want to change this with a continuous measurement method.
Photo: Blue box on optical bench

Laboratory optical bench with blue box, containing four broadly tunable external-cavity quantum cascade lasers; © private

What does this method look like?

Heise: It is based on the principles of infrared photometry. The substance we want to measure – glucose – exhibits a specific absorption spectrum in the infrared spectral region, which becomes measurable when the substance is penetrated with specific wavelengths beyond the visible light. Each substance has its own absorption pattern that is as distinctive as a fingerprint. You can identify and quantify substances with it.

In the previous CLINICIP project, we extracted small molecules like glucose, urea and lactate from abdominal subcutaneous adipose tissue with a microdialysis catheter. The fluid in the catheter, the so-called dialysate contained information on the concentration of these small molecules in the body fluid. The continuously harvested dialysate was analyzed outside of the body in a measuring cell with a small bedside spectrometer next to the patient. The infrared absorption spectrum is very well suited for this. The advantage is that we are not just able to analyze one fluid compound such as blood glucose, but several components, which are also of interest to intensive care physicians. Aside from the aforementioned, these include dissolved CO2 and bicarbonate, which offer clues about the pH-value of the examined body fluid and deliver insights into the electrolyte status of the body.

You use a quantum cascade laser as a source of radiation. How can we imagine this?

Heise: The smallest conventional IR spectrometers have approximately a footprint of a DIN A4 paper sheet. During the CLINICIP project, we developed a bedside system for critically ill patients using this format. However, further miniaturization is desirable in this case, since physicians are not very pleased of accepting another device by the hospital bed. Yet miniaturization is difficult, since spectrometers on the one hand have a thermal radiation source so that the device also needs to be designed for heat transfer; on the other hand, the measurement technology is also quite intricate. Further miniaturization of these devices is not expected in the near future.

Quantum cascade lasers represent a cold source for infrared radiation where less heat needs to be removed. At this point, we are using a system the size of half a DIN A4 paper sheet, which we would like to reduce to the size of a pack of cigarettes or a matchbox. Aside from the radiation source, we would then have a cuvette for measuring or a fiber optic probe and corresponding photodetector on this chip. Miniaturization is definitely feasible. You can also see this in modern mobile cell phones for example.

Photo: Prof. Heise with team mates

Left: Prof. Michael Heise, center: Dr.-Ing. Konstantinos Nalpantidis, right: Dipl.-Ing Markus Grafen (both researchers at the GLUQCL Project, Chair of Applied Laser Technology, Ruhr-Universität Bochum); © private

Do you already have something like a basic concept for an “artificial pancreas“?

Heise: Right now, we are still working on a reliable sensor system. Then we would have to cooperate with insulin pump manufacturers and furnish the devices with appropriate software. These would be algorithms that independently deliver insulin doses based on the previous blood glucose concentrations and caloric intake of the patient. We are trying to close the gap between basic research and application in a current project. Within this framework, we are not just working on the miniaturization aspect, but are also comparing conventional measurement techniques with our technology. In doing so, we will find out whether our technology can be more reliable, smaller and more cost effective.

How reliable do you actually rate your technology?

Heise: Current continuous measurement systems utilize needle-type sensors and operate on an electrochemical basis. These sensors do not possess the reliability they should have however, and require frequent recalibration. This necessitates recalibration several times a day, which is performed by a simultaneous comparative measurement directly in the blood drawn from the patient’s fingertip using a lancet device. This is why diabetics also need to continue using test strip systems where errors can be limited at this point, and they must not determine their insulin dose based on continuously measuring, commercially available sensor systems. Our photonic-based measurement method is expected to be more reliable, since the glucose absorption spectrum we measure is a physical constant. This is why our system should operate without the need for calibration in further use after the initial setup.

Our goal at the moment is still the bedside measurement system for critical care patients. If it can be further miniaturized, it could definitely also become a system for everyday use for diabetics that could be directly adhered to the skin with some adhesive tape in the future.
Photo: Timo Roth; Copyright: B. Frommann

© B. Frommann

The interview was conducted by Timo Roth and translated from German by Elena O'Meara.