Fungal infections are a serious problem in modern health care. A critical factorin their successful treatment is time: the faster they are detected, the moreeffectively dangerous infections can be prevented. At the Institute of PhysicalChemistry of the Polish Academy of Sciences in Warsaw a chemical sensorhas been devised enabling the detection time of fungi to be shortened fromthe current couple of days to just a few minutes.
When it comes down to it, nearly every one of us is a walking time bomb for ourselves. Almost halfthe population – and practically all medical personnel – are carriers of Candida fungus. Theseyeasts live in a delicate balance with our organisms, on the mucous membranes of the digestivetract and the urogenital system as well as the skin. But when this balance is disturbed, fungi beginexpansive uncontrolled colonization. In extreme cases, rapidly developing infection can lead to apatient’s death in just a few days. Meanwhile, at present, standard tests for the presence of fungi ina patient’s body fluids take at least a dozen or so hours, and the results may be false positive orfalse negative. In the near future, physicians will have the chance to react much more rapidly andcertainly with the appropriate antifungal therapy – thanks to the sensor devised at the Institute ofPhysical Chemistry of the Polish Academy of Sciences (IPC PAS) in Warsaw.
“The most important element of our sensor is a film of polymer selectively recognizing D-arabitol. Itcaptures molecules of D-arabitol, a compound indicating the presence of fungi. The measurementtakes only a few minutes, and the D-arabitol is detected with a high degree of certainty even in thepresence of interfering substances with a similar molecular structure,” says Prof. WlodzimierzKutner (IPC PAS).
The number of fungal infections is expected to steadily increase over the coming decades. Theseinfections develop particularly frequently in people with impaired immunity, that is, in patients(especially those receiving immunosuppressive therapy or chemotherapy), and the elderly, whosepercentage share in the community continues to grow. Appropriately early diagnosis takes on a keyrole here, the less troublesome it is for the patient, the more frequently and more quickly carriedout – the better. Yeasts, unlike bacteria that can be combated by antibiotics, are eukaryotes, andso just like human cells they have cell nuclei and from a molecular (biochemical) point of view, theyare very similar. Substances that are harmful to fungi therefore create havoc not only amongstfungi but also in the human cells. For this reason, drugs must be administered early, when thefungus is just beginning its conquest of the body. Unfortunately, at the initial stage of developmentof fungal disease, it is currently rarely possible to establish its true cause.
One of the markers of fungal disease is arabitol, a simple sugar alcohol. This compound occursnaturally in mammalian cells, where it is produced in two forms which are mirror images(enantiomers). In healthy humans these forms, known as D-arabitol and L-arabitol, are formed inroughly the same amounts. However, cells of Candida species produce only D-arabitol. Therelative increase in the concentration of this enantiomer in body fluids can therefore heraldinfection.
D-arabitol can be detected in cerebrospinal fluid (CSF), plasma, and urine. From the diagnosticpoint of view, the best solution is the measurement of its concentration in urine. The test is thencompletely non-invasive and can be performed without any risk to even a newborn baby or a veryill person.
“The key – and I mean this almost literally! – stage of devising of the sensor was to construct apolymer with molecular cavities of the appropriate shape and locations selectively recognizing Darabitol.In other words, we had to invent and build a molecular lock, which would only fit one key:the D-arabitol molecule. The task was not easy, because L-arabitol, xylitol, and ribitol are moleculesthat are very, very similar to each other,” explains PhD student Marcin Dabrowski (IPC PAS).The polymer film with molecular cavities binding D-arabitol was prepared using the molecularimprinting technique. The process began by dissolving D-arabitol in acetonitrile. Then boric acidlabeled with bithiophene, whose molecules bound to the D-arabitol in particular positions, wasadded to the solution. The bithiophene substituent permitted the electrochemical polymerization ofthe solution. A polymer film having a rigid structure was thus created, from which all that wasneeded was to rinse out the D-arabitol molecules to obtain a film with molecular cavities of thedesired shape and properties.
The detection polymer films produced at the IPC PAS have a thickness of ca. 200 nanometers.They are deposited either on gold electrodes, or on quartz resonators. After immersing a sampletaken from a patient in the solution, D-arabitol particles get stuck in the molecular cavities of thefilms and depending on the method of detection, either change the flow of current through a fieldeffecttransistor having a gate connected to an electrode or the oscillation resonance frequency ofa piezoelectric resonator.
“What is especially important here is the fact that the molecular cavities of our polymer do notcapture molecules of other compounds that could generate false positive signals misleadinglyindicating the presence of D-arabitol. The film is almost completely ‘deaf’ even to other isomers ofarabitol, including those that differ from D-arabitol only by their optical properties,” stressesDabrowski.
The chemical sensors constructed at the IPC PAS using the technique of molecular imprintinghave simple construction suitable for repeated use, and their production is trouble-free andinexpensive. In the future, they can be used not only in hospitals or physicians’ offices, but even bypatients themselves at home. Perhaps one day such sensors will be able to be installed in typicalsanitary equipment. Analyses could then be carried out repeatedly during the day and in acompletely non-invasive manner. One of the basic problems of modern medicine would thendisappear: that of delayed diagnosis, carried out at the stage where, concerned about hissymptoms, the patient himself sets out to consult a physician.
