Potentiometric Sensors Based on Molecularly Imprinted Polymers for the Detection of Sarcosine
Authors: López Miguel Alberto , Fernández Soane , Chávez Abraham Ulíses , Valdés Arístides Camilo , Lazo Ana Rosa 
Published: February 2020

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. Prostate cancer (PCa) is the second most diagnosed cancer and the sixth leading cause of death in men worldwide. PCa incidence is 2 to 5 times higher in developed countries as a result of variations in risk factors and diagnostic practices. PCa new cases represent between 6-14% of all global cancer deaths in 2008.

In 2013, malignant tumors were ranked in third place as the cause of death in men (10.5%) in Mexico and the most frequent was PCa (16.3%). PCa mortality increased steadily by 2% per year from 1980 to 2011. The incidence varies due to the practice of prostate-specific antigen (PSA) screening and prostate biopsy. In Latin America, the early detection of PCa is very low and it gets frequently detected in advanced stages. Since the introduction of PSA test in 1986, detection and prevention had been improved, but it is still common to found false positive and false negative results.

For PCa detection, it is commonly used ELISA test for PSA screening, digital rectal exam for physical inspection of the prostate and the biopsy to confirm or discard the presence of cancer cells. ELISA test is highly sensitive and specific but also its cost is expensive due to the need for natural specific antibodies, their handling and storage and their low chemical stability. Digital rectal exam (DRE) and biopsy are invasive methods and their main disadvantages are several health risks after the biopsy and the incapacity of PCa detection in areas out of the tumor. Hence, there is a need to develop new technologies with high sensibility and lower response time for the detection of prostate cancer biomarkers during the early stage of the disease.

Chemical sensors and biosensors have emerged in recent years as particular interest inside the field of analytical chemistry due to their versatility in clinical assays, drugs detection, food and environmental analysis. An essential part of every sensor is the recognition element, which it gives selectivity towards the analyte in a complex matrix. Biosensors used biological components for recognition such as enzymes, receptors, and antibodies. These allowed a high selectivity but due to their low physical and chemical stability, they cannot be used in rough environments.

As an alternative, it can be used biomimetics components, which mimic and selectively bind to a natural molecule. Molecularly imprinted technology is based on the “key-lock” principle, which used a template molecule to create a specific recognition site for it through a polymeric matrix. This molecularly imprinted polymer can be used as a recognition element in chemical sensors for detecting cancer biomarkers.

For processing signal, a transducer must be used. Epoxy resins constitute a versatile class characterized by excellent chemical and corrosion resistance, good adhesion to various materials, electrically insulating and easy to fabricate. The addition of powdered fillers like carbonaceous material increases the electrical and heat conductivities of epoxies, providing composite materials that combine a high conductivity. These materials can be used as an all solid-contact electrode and can be used in sensors as a transducer.

The present work proposes the construction of selective potentiometric electrodes for the detection of biomarkers related to prostate cancer in early stages of the disease. For that, the use of molecularly imprinted polymers as an element of recognition in a liquid membrane, coupled with a conductive support was investigated. All of this will provide a better response time, limits of detection below concentrations from blood and urine, high selectivity, sensitivity, and reproducibility.

Transducers were constructed by using 3 types of carbonaceous materials (graphite, graphene and carbon nanotubes) and epoxy resin. They were characterized by cyclic voltammetry, electrochemical impedance spectroscopy, and four-point probe technique to obtain electrical properties of the materials. A molecularly imprinted polymer was synthesized non-covalent via and analytically characterized. The constructed potentiometric sensor employed an all solid-state electrode for sensing and the effect of pH, selectivity, response time and its potentiometric features were evaluated.