Research and Life

The right nose for precise diagnostics

Precision spectroscopy uses Rydberg excitation to measure minute traces of nitrogen oxide
[Photo: Stock/synto]

Dogs’ noses are a hundred times more sensitive than our own. With the appropriate training, “man's best friend” can even detect certain human diseases by smell alone. Physicists at the University of Stuttgart have thrown down the gauntlet to our four-legged friends and are constructing an artifi cial nose that is even more sensitive that its natural prototype.

By contrast with a dog's nose, the new measuring process will not only detect specifi c substances, but also their precise concentrations over time. The process that Professor Tilman Pfau and his team from the University of Stuttgart's Institute of Theoretical Physics V will be using, in collaboration with the Interdisciplinary Center for Integrated Quantum Science and Technology (IQST), for their analyses is known as optogalvanic Rydberg spectroscopy. The physicists are initially concentrating on measuring nitrogen monoxide (NO). “We use our lasers to put certain molecules – nitrogen monoxide molecules in this project – in a highly excited state”, Harald Kübler, one of the project staff, explains.“

In this so-called Rydberg state, electrons are only loosely attached to the atomic nucleus. As soon as the molecules within the gas cloud collide with one another they become ionized”. The resulting electrical charges are counted allowing inferences to be drawn about the number of nitrogen monoxide molecules in the sample. “Our gas sensor is able to detect NO concentrations of less than 10 ppm, i.e., ten molecules in every one million molecules. It works at normal atmospheric pressure and is currently only limited in terms of precision by the method we use to rarefy the gas”, Pfau says, summarizing the current research status. Another benefi t, apart from the precision of the measurements, is that the gas fl ow can be analyzed relatively quickly, which makes it possible to measure more rapid changes in the NO concentrations.

Professor Tilman Pfau and his team from the University of Stuttgart's Institute of Theoretical Physics V have developed the so-called optogalvanic Rydberg spectroscopy process in collaboration with IQST Ulm. The process components still cover an area about the size of an outsized ping-pong table. As soon as it starts delivering flawless results, the plan is to shrink the cumbersome spectroscopic laboratory onto a chip the size of a fingernail and to fit it into a gas cell. (c) University of Stuttgart/ Max Kovalenko
Professor Tilman Pfau and his team from the University of Stuttgart's Institute of Theoretical Physics V have developed the so-called optogalvanic Rydberg spectroscopy process in collaboration with IQST Ulm. The process components still cover an area about the size of an outsized ping-pong table. As soon as it starts delivering flawless results, the plan is to shrink the cumbersome spectroscopic laboratory onto a chip the size of a fingernail and to fit it into a gas cell.

Collaboration with the University of Ulm

For some time now, the importance of Rydberg atoms, named after the Swede Johannes Rydberg, for quantum technology has been increasing. Possible longer-term industrial uses of Rydberg states based on novel processes are being investigated at the IQST. The IQST’s current project is about ascertaining the extent to which optogalvanic gas sensors based on Rydberg gases could be useful in the fi eld of precise medical diagnostics and may produce new medical findings.

To this end, the process is being theoretically assessed and further optimized at Pfau's institute and, in collaboration with the University of Ulm's Institute of Analytical and Bioanalytical Chemistry, headed up by Professor Boris Mizaikoff, compared with existing measuring processes. “Initially, we were motivated by something else entirely”, experimental physicist Pfau explains: “We wanted to improve our spectroscopic technology and install electronic components into a gas cell of this type. In the course of this, we realized that a novel sensor principle would be possible using this combination of highly miniaturized electronics and Rydberg atoms with which it would be possible to detect minute quantities of certain atomic or molecular gases”. In a subsequent step, the scientists want to use and test this sensor principle for analyzing relevant molecules, such as the aforementioned nitrogen oxide, a biomarker for inflammation and other nitrogen oxides (NOx) in exhaled respiratory gas. This is where the expertise of biochemist Boris Mizaikoff becomes relevant. In addition to increased precision, it will then mainly be all about parameters such as increasing ease of use, and lowering costs both in the manufacturing process and in everyday practice.

Relevance for environmental analysis

The gas sensor technology is not only suitable for the analysis of respiratory gasses but also for measuring nitrogen oxide concentrations in the environment. To put it in only slightly exaggerated terms, if this process had already been marketable and rolled out across the board, the Diesel scandal may never have happened. A small metering device of this level of precision and size could easily have been installed in vehicles and would have immediately indicated the discrepancy between the target and actual concentrations of nitrogen oxide emissions. Of course the requirements for car exhaust sensors are highly demanding, particularly due to the high operating temperatures of around 1000 degree Celsius. Nevertheless, even if there are still a few technical hurdles to overcome before Rydberg gas sensor technology can be deployed in cars, the benefits outweigh the drawbacks by far: it can be used selectively for any specific molecule and can determine its concentration in a gas mix with an extremely high degree of precision. In the case of car exhausts, for example, hundreds of different molecules are emitted. Despite this complex mix, it is possible to excite specific molecules – just like the nitrogen monoxide in the respiratory gas mix – and to precisely measure their concentration.

Diagnostic terra incognita

Another unique selling proposition of the new process is its ability to monitor NO concentrations along a timeline, i.e., the concentrations present in the first and then subsequent milliliters of exhaled respiratory gas. Of course, it has long been known that is possible to excite specific molecules extremely selectively via Rydberg states, but, in terms of its practical application, this form of gas analysis is still in its infancy. “In the next few years”, says Pfau, “we will need to get more clarity on exactly what new information we can obtain with this sensor as well as its significance”. For example, it is not yet known what new medical evidence could be revealed by continuous real-time measurements, for instance if it were found that the exhaled gas contained a lot of NO at the start of the exhalation and less towards the end; this is another research question that Pfau and Mizaikoff are working together to clarify. “If this measuring principle turns out to be as sensitive as we expect it to be, there will certainly be other potential applications”, say the scientists, feeding the desire for new diagnostic processes.

From industrial laboratory to chip size

The “artificial nose” is currently still about the size of an outsized ping-pong table. It is covered with a labyrinth of optical components, that focus the laser beam to enable precise measurements. This makes it easy to monitor the applied processes and adjust them as required. As soon as it starts delivering flawless results, the plan is to shrink the cumbersome spectroscopic laboratory with all its functions onto a chip the size of a fingernail and to fit it into a gas cell similar to a pipette. The actual sensor head can become extremely small, but lasers we use as a light source of the measuring process are still relatively big and it probably won’t be possible in the next few years to shrink them dramatically”, says Pfau. To facilitate progress on the miniaturization of this cell, the physicists have been working closely with electronics engineers under the auspices of Professors Norbert Frühauf and Jens Anders in Stuttgart.

Early on, Frühauf, Head of the Institute of Large Area Microelectronics (IGM) and experts in high-resolution screen technology came up with the idea of integrating the electronics needed to process the gas stream directly into the Rydberg gas cell to produce a compact sensor. Anders, who heads up the Institute of Smart Sensors (IIS), has been working on the design of highly sensitive and, above all, rapid gas stream processing circuits for a long time. Anders and his team use so-called CMOS semiconductor technologies for their electronic designs, i.e., the same technologies used in computer CPUs. This means that the electronic components only need a tiny fraction of the area currently used by the cumbersome electronics at the Institute of Theoretical Physics V, and are, therefore, extremely suitable for the desired miniaturization of the cells. The engineers are currently working on reducing the noise level of the electronic components. This could result in sensitivity levels in the parts per billion range, the relevant range for precise respiratory gas measurements. At that point, the electronic system could hold its own against, or even outdo the dog's nose. Because the microchips can be produced extremely cost effectively – especially in large batches – the approach adopted by Pfau, Frühauf and Anders is very promising in terms of long-term commercialization. As it stands, the three scientists have succeeded in producing the first prototype of an already significantly smaller Rydberg gas cell.

Susanne Roeder

Dieses Bild zeigt Mayer-Grenu
 

Andrea Mayer-Grenu

Scientific Consultant, Research Publications

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