A mini breath sensor can detect ulcer-causing bacteria

Most of the bacteria residing in the human upper gastrointestinal tract is the friendly sort. But Helicobacter pylori, if it gets a foothold, can cause pain, bloating, ulcers, and even stomach cancer. One of doctors’ best diagnostic tools for this infection is a breath test. But feasibility depends on having access to an expensive spectrometer, which can cost a clinic thousands of dollars, says Boris Mizaikoff of Ulm University and Hahn-Schickard, an institute for applied research.

Mizaikoff, an analytical chemist, plans to bring that cost way down. He and his team have harnessed mid-infrared (MIR) light to create a breath sensor for H. pylori that is small enough to eventually attach to a cell phone (ACS Sens. 2025, DOI:10.1021/acssensors.4c02785).

H. pylori is one of few bacteria that make urease, which breaks down urea into carbon dioxide and ammonia. If a person swallows a pill of ¹³C-labeled urea, after 20–30 min they will breathe out ¹³CO₂. In current breath tests for H. pylori, the samples are sent to a lab-based IR spectrometer, which checks for a wavelength shift from ¹²CO₂ to ¹³CO₂. In Mizaikoff’s design, the breaths will be directly analyzed in a miniaturized gas cell with an IR spectrometer attached—allowing for portable, on-site testing.

MIR miniaturization has been brewing for decades and is made possible by two shifts. One is swapping the IR light source from a broadband emitter, such as a heated ceramic element, for a pointed, narrow-band source such as a laser or light-emitting diode; the other is creating a tiny space for the gas and photons to interact.

In this work, Mizaikoff’s lab created the tiny space. It’s a hollow aluminum channel about the width and length of a thick mechanical pencil lead, bookended by BaF₂ windows that retain the gas but allow in MIR light. On top is a breath inlet and outlet. The volume is so small that gas molecules constantly bump into photons, Mizaikoff says. “We ensure intimate and extensive interaction of photons with molecules. That’s the trick.”

Mizaikoff and colleagues found that they could reduce the channel length to 3 cm and still accurately identify a ¹²CO₂ to ¹³CO₂ wavelength shift of 2349 to 2280 cm^-1, thus proving that miniaturization will work in the diagnosis of H. pylori. The researchers used an IR spectrometer light source and tested with calibrated ¹³CO₂ concentrations. Their next steps are to swap in a narrow-band light source like a laser or LED and test the device on the breath of real patients.

Hossam Haick at Technion-Israel Institute of Technology says that while the test needs to be validated with real patient samples, it is a compelling proof of concept “with a clear trajectory toward future miniaturization using laser technology” and that its potential extends beyond H. pylori.

“This research represents a step forward in making breath-based diagnostics more accessible,” Haick says. Accurate miniaturization technology “could catalyze a new era of personalized and point-of-care diagnostics, minimizing the dependence on invasive procedures and large centralized laboratories.”

Mizaikoff expects that once the tech is optimized and further miniaturized with the laser light, his team can make a cell-phone accessory for about $25. He is also working with a coalition of European labs to miniaturize the device even more so that it will fit on a chip. The moves are part of a broad effort to shrink MIR spectroscopy for all types of chemical and biological sensing. Mizaikoff is developing similar breath sensors for breast cancer, long COVID, and renal dysfunction. “We are reaching a level in mid-infrared breath diagnostics that we have been hoping for in the last 20 years.”