Biomarkers for Serum Diagnosis of Infectious Diseases and Their Potential Application in Novel Sensor Platforms

Abstract

Nanotechnological tools and biomarkers for diagnosis and prognosis, as well as strategies for disease control and monitoring populations at higher risk, are continuous worldwide challenges for infectious diseases. Phage display and monoclonal antibody combinatorial libraries are important sources for biomarker discovery and for improved diagnostic strategies. Mimetic peptides were selected against polyclonal antibodies from patients with dengue fever, leprosy, and leishmaniasis as model diseases, and from immunized chickens with total antigens from all three pathogens. Selected single or combined multi-epitope peptide biomarkers were further associated with four different sensor platforms, classified as affinity biosensors, that may be suitable as general protocols for field diagnosis. We have also developed two methods for nanoparticle agglutination assays (a particle gel agglutination test and a magnetic microparticle [MMP]-enzyme-linked immunosorbent assay [ELISA]) and two electrochemical biosensors (impedimetric and amperometric) for DNA and antibody detection. For the agglutination tests, micro- and nanoparticles were coupled with filamentous bacteriophages displaying the selected mimotopes on their surfaces, which has favored the formation of the antigen-antibody or peptide-protein complexes, amplifying the optical detection in ELISA assays or after the chromatographic separation of the microagglutinates. We have also demonstrated a proof-of-concept for the electrochemical biosensors by using electrodes modified with novel functionalized polymers. These electrochemical biosensors have proven to be fast, very sensitive, and specific for the detection of pathogen DNA and circulating antibodies of patients, which may become important in a wide range of diagnostic devices for many infectious agents.

Detection of a Specific Biomarker for Epstein-Barr Virus Using a Polymer-Based Genosensor

“…These techniques have a high cost, demanding skilled labor and time-consuming analysis [9–12]. Other recent technologies, such as the development of biosensors, are emerging and may revolutionize the disease diagnosis [13]. Generally, electrochemical biosensors have high sensitivity and low-cost, having superior properties when compared to alternative analytical techniques [14–16].…”

Leishmania spp. Detection Using a Surface Plasmon Resonance Biosensor

“…A highly specific and sensitive-constrained synthetic peptide (LC2) derived from a mimotope of Leishmania chagasi antigen, selected by phage display (is a selection technique in which a library of peptide or protein variants is expressed as a genetic fusion to a bacteriophage coat protein), was used as probe for IgG detection [4] were synthesized and pre-validated by the enzyme-linked immunosorbent assay (ELISA) method. Phosphate buffer saline solution (pH 7.4) was used as the baseline.…”

“…The methods currently employed in visceral leishmaniasis clinical diagnoses are costly, requiring numerous steps to perform besides specialized labor, have also shown low sensitivity to detect the initial cases of the disease, generating false negatives for the disease. Therefore, it is clear the need to develop methodologies that allow a more sensitive and faster diagnosis, guaranteeing greater control of visceral leishmaniasis [3,4].…”

Sensing parasites: Proteomic and advanced bio-detection alternatives

“…As mentioned in previous points, micro-and nanotechnologies can offer new technological tools and potential applications for developing bio-sensing devices for infection´s biomarkers. Many of these biosensors have proven to be useful for the detection of pathogen signatures and circulating proteins in patients [118]. The access to timely and accurate diagnostic tests has a significant impact in the management of many parasitic diseases like malaria.…”