Abstract

Many diseases and disorders of the endocrine system are characterized by a shift in the concentrations of certain biomolecules from their normal physiological levels. Notable examples include diabetes, which results in elevated glucose levels in the blood and urine, prostate cancer, which is characterized by an increase of sarcosine in the urinary sediments of patients, and sepsis, which is associated with high levels of lactate in the blood. Efficient and reliable monitoring of these analyte concentrations is therefore of significant clinical relevance. First generation biosensors represent a unique approach to this issue and offer a promising future for the diagnosis of many endocrine diseases. Through the use of enzyme catalyzed reactions, these biosensors can indirectly measure an analyte by testing for the presence of the products resulting from the reactions. They also provide continuous signaling in real time, effectively decreasing the time between onset and diagnosis of a particular disease. This technology can be adapted to test for a variety of substrates, but there are modifications that must be made to optimize the biosensor’s performance for any given analyte. These modifications include custom-tailoring enzyme-immobilization platforms and selectivity filters that are systematically deposited onto the sensor surface in a layered fashion. To bypass this process, we have developed an adaptable sensor design built to accommodate a wide variety of biomarkers. This scheme incorporates: 1) a silane-derived xerogel layer meant to immobilize the enzyme; 2) an electropolymer layer and a polyurethane layer meant to block interference. Rather than designing a sensor from scratch for any chosen substrate, we simply screen for the silane-precursor, electropolymer, and polyurethane blend that will best accommodate our new analyte. This scheme was developed using a glucose model system, but has since been applied to a uric acid sensor, a galactose sensor, and most recently, a lactate sensor that has the potential to improve the diagnosis of sepsis, given that suppressed lactate clearance and increased blood lactate levels are associated with the progression of the infection. Given the endocrine system’s heavy reliance upon signaling molecules such as hormones, developing biosensors that can detect the concentrations of these molecules with high sensitivity and specificity represents an especially attractive direction for improving the diagnosis of diseases associated with that system. In this pursuit, the method presented represents an efficient means of quickly adapting a universal template to a wide range of target molecules.

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