Children with cystic fibrosis (CF) often get airway infections, which can be difficult to diagnose. The methods are invasive and highly unpleasant for the child, and the microbiological culturing methods lack sensitivity. Researchers at DTU Nanotech are developing a chip which is able to detect specific gases produced by the bacteria in the lungs. When the patient breathes onto the chip, the gases are detected, and airway infections can be diagnosed.
Chronic lung infections caused by the bacterium Pseudomonas aeruginosa are responsible for the majority of illnesses and deaths among CF patients. Therefore, it is important to detect the infection and give antibiotics before the infection becomes chronic.
Children below the age of 8-9 years do not produce sufficient amounts of sputum in the airways to cough up a sample. Therefore, a tube is inserted through the nose and into the larynx to induce a cough reflex, and a sample for microbiological investigation is obtained through the tube. Especially for young children, this is a very unpleasant experience. In Denmark, CF patients are tested for the presence of P. aeruginosa on a monthly basis. A quick, sensitive and non-invasive test for P. aeruginosa would facilitate more frequent sampling and thereby an earlier diagnosis of airway infections.
PhD Student Rikke Kragh Lauridsen says: “We hope that our chip can be developed into a point-of-care device for home diagnostics of P. aeruginosa lung infections. This would mean less suffering and a possible longer life expectancy for the patients”.
Bacteria emits gases
P. aeruginosa emits the poisonous gas hydrogen cyanide (HCN), which is specific to this bacterium and can be used as a biomarker. This means that patients with early P. aeruginosa infections have HCN in their breath. HCN can be detected on the chip down to part-per-billion levels, which corresponds to the level found in the breath of a child with an early P. aeruginosa infection.
Rikke Kragh Lauridsen explains that “the chip is equipped with nanopillars and thanks to these, breath detection based on the so-called surface-enhanced Raman scattering (SERS) is possible”. The technology is described in the article “Nanopillars – a state-of-the-art optical sensor”.
The original nanopillar chip was developed by Senior Researcher Michael Stenbæk Schmidt, to detect explosives in the air. However, modifications of the chip make it useful for other applications and in Rikke Kragh Lauridsen’s PhD project the chip has been optimised to detect cyanide in the gas phase. This was done by changing the metal layer on top of the nanopillars from silver to gold; by including extra cleaning steps in the preparation of the chip and by changing the metal layer thickness and the rate for deposition of the metal.
Figure 2: The device containing the SERS substrate being exposed to breath from a patient
From lab tests to clinical studies
”We started to work with HCN in the gas phase”, Rikke explains, “and after this had been demonstrated, we made serial dilutions of potassium cyanide (KCN). The serial dilution experiments were made to establish the limit of detection for cyanide on the chip”.
Microbiological investigations were then made, detecting HCN above cultures of P. aeruginosa isolated from the airways of children with CF. In the spring of 2016 the chip was taken to the first clinical pilot study at Rigshospitalet in Copenhagen, which included 50 CF children and 19 control patients, and the results are encouraging.
Rikke Kragh Lauridsen’s research is part of the ‘NAPLAS – NAnoPLAsmonic Sensors’ project funded by The Danish Council for Independent Research. The research was done in collaboration with DTU Systems Biology, the Novo Nordisk Center for Biosustainability, University of Copenhagen (KU), and University Hospital of Copenhagen (Rigshospitalet). Rikke Kragh Lauridsen handed in her PhD thesis in November 2016.
Read more about the Nanoprobes research group.