Defining the problem

Chronic inflammatory diseases (CIDs), such as arthritis, asthma and inflammatory bowel disease, are life-long, debilitating illnesses, where patients suffer from chronic pain, fatigue, swelling and fever. Due to the complicated disease profiles, treatments of CIDs do not always work and there is usually a long search process for the right treatment [1-3].

Generally, people who suffer from CID’s need to monitor their conditions closely. This may include regular hospital visits to measure levels of inflammation and monitor disease progression. These visits are not only time consuming but also mentally exhausting to the patients. Not only do the visits remind patients of their illness, but the time spent on transport and testing is a life-long burden to the individual. Current methods for disease tracking are almost exclusively invasive and include blood sampling and, occasionally, more comprehensive procedures such as endoscopies. Invasive methods of testing are not only expensive and unpleasant, but also require well-trained personnel and can lead to complications. In addition, they do not allow the patient to self-monitor, requiring regular hospital visits.

Conclusively, suffering from a chronic inflammatory disease can be extremely exhausting both physically and mentally. Although wide research is being conducted in regards to the treatment of all types of inflammatory diseases, not many monitoring devices exist to make it easier for the individual living with a CID. In order to improve the quality of life for patients worldwide, we have created CIDosis.

Scientific approach

Our project is founded on previous research showing the presence of interleukins IL-1β, IL-6 or IL-10 (ILs) in sweat [4,5,6], and the correlation with their respective levels in blood [5]. The CIDosis patch implementation is based on an engineered S. cerevisiae (baker’s yeast) biosensor capable of detecting the inflammation markers IL1, 6 and 10. The activation of the biosensor leads to the expression of a pigment biosynthesis gene and further to the accumulation of a colored compound. The biosensor will be located inside a patch specifically designed to sit on the skin and continuously collect sweat from the wearer. Once interleukins from the sweat reach our patch, our yeast receptors will sense these, and produce the aforementioned colored pigment corresponding to the level of the IL in question.

The biosensor design (Fig. 1) relies on the dimerization of modified human IL receptors on the yeast plasma membrane upon activation by their respective ligands. The modified receptors contain a synthetic transcription factor bound on their intracellular side that can be released upon dimerization of the receptors. Specifically, dimerization of the receptors leads to the co-localization of two halves of a split-actuator protein, which, when re- united, leads to cleavage of the protein resulting in the release of the transcription factor. The synthetic transcription factor, in turn, binds a specific synthetic promoter and finally activates the expression of the colorimetric reporter gene.

Our vision is a modular design, allowing for easy swap of the interleukin receptor in the yeast, so the patch can be tailored to the need of the individual patient group. The yeast is powered by designed receptors that boast very high sensitivity and selectivity, coupled with an efficient pheromone pathway for signal amplification. The SPY can be photographed with a specialized app to analyze the exact level of coloration regardless of light conditions.