Quantitatively detecting disease biomarkers, especially those non-invasive in plasma, urine and faeces, is of great importance for early diagnosis, which facilitates effective treatments and improves the survival rate of patients. Among several routines of detecting the level of biomarkers, optical methods (via fluorescence or colorimetric changes) represent powerful sensing modalities due to their low cost, ease of use and high sensitivity, which have gained considerable attention and demonstrated various applications in the fields of diagnosis and bioimaging. For a few years, we have focused our research interest on developing novel reporter pairs. We achieved ultrasensitive and specific detection of disease biomarkers by executing indicator displacement assay (IDA) and supramolecular tandem assay (STA).

Lysophosphatidic acid (LPA) is an ideal biomarker for the early detection of ovarian and other gynecologic cancers. Quantitatively detecting the concentration of LPA in plasma is still challenging considering its low physiological concentration (0.1-63.2 µM), coexistence of interfering substances and complicated physiological milieu. According to the structure of LPA, we designed a water-soluble guanidinium-modified calix[5]arene, which affords the desired strong binding and ultrasensitive fluorescence detection of LPA by means of IDA and differential sensing in aqueous media. Moreover, we showed that, using a calibration line, the LPA concentration in untreated serum can be quantified in the biologically relevant low µM range with a detection limit of 1.7 µM. Furthermore, we applied the sensing systems to analyze cancerous and non-cancerous blood samples. Significant difference was observed that the cancerous group gave rise to more fluorescence response than the non-cancerous group. These results form the chemistry basis for new protocols and devices to diagnose ovarian cancer and other gynecologic cancers, especially during their early stages (Chem. Sci., 2018, 9, 2087–2091).