Currently, several biosensors are reported to confirm the absence/presence of an abnormal level of specific human biomarkers in research laboratories. Unfortunately, public marketing and/or pharmacy accessibility are not yet possible for many bodily fluid biomarkers. The questions are numerous, starting from the preparation of the substrates, the wet/dry form of recognizing the (bio)ligands, the exposure time, and the choice of the running buffers. In this context, for the first time, the present overview summarizes the pre-functionalization of standard and nanostructured solid/flexible supports with cysteamine (Cys) and glutaraldehyde (GA) chemicals for robust protein immobilization and detection of biomarkers in body fluids (serum, saliva, and urine) using three transductions: piezoelectrical, electrochemical, and optical, respectively. Thus, the reader can easily access and compare step-by-step conjugate protocols published over the past 10 years. In conclusion, Cys/GA chemistry seems widely used for electrochemical sensing applications with different types of recorded signals, either current, potential, or impedance. On the other hand, piezoelectric detection via quartz crystal microbalance (QCM) and optical detection by surface plasmon resonance (LSPR)/surface-enhanced Raman spectroscopy (SERS) are ultrasensitive platforms and very good candidates for the miniaturization of medical devices in the near future.
Keywords: biofunctionalization of substrates; biomarkers; biosensors; cysteamine (Cys); electrochemistry; glutaraldehyde (GA); optics; quartz crystal microbalance (QCM).