Integration Of Electrochemiluminescence And Nanotechnology For The Sensitive Detection Of Haptoglobin: One Biomarker For Multiple Diseases

Haptoglobin (Hp) plays an important part in the binding and transporting of hemoglobin. The plasma concentration of Hp increases several-fold in carcinoma, tissue necrosis, coronary artery, schizophrenia, and in the event of an inflammatory stimulus such as infection, injury, or malignancy, whether local (vascular) or systemic (extravascular).

Hp has been reported to be involved in modulating the immune response, autoimmune diseases, and major inflammatory disorders. Elevated Hp levels are sometimes found in diabetes mellitus, renal disease, and endocrine imbalance. Diseases such as intravascular hemolysis, anemia, malaria, liver disease, jaundice, cirrhosis, mononucleosis, and transfusion of incompatible blood can significantly lower the amount of Hp in plasma. Clearly, Hp has a great clinical importance as a biomarker in diagnostics and monitoring the response of multiple diseases.

Image by allinonemovie via Pixabay is licensed under CC0

Currently, electrochemiluminescence (ECL), an electrochemical phenomenon in which light is emitted without producing heat when high voltage is applied to a suitable electrochemical system, has become an important and powerful analytical technology. As a result, ECL-based biosensors have gained immense popularity. However, ECL behavior greatly depends on electrode materials, dimensions, surface area, electronic conductivity, and size.

However, nanotechnology is the branch of modern inter-and multidisciplinary science which deals with materials, substance, compounds, and biomolecules having all or at least one dimension in 100 nm. Such materials are collectively known as nanomaterials (NMs). Physicochemical properties of NMs include a large surface-to-volume ratio, high aspect-ratio, and high electronic conductivity, and examples include gold nanoparticles (AuNPs) and single-walled carbon nanotubes (SWCNTs).

Further, two or more NMs could be mixed in definite proportions to form composite materials using biopolymers such as chitosan (CS). Such developed composite materials synergistically interact to produce desirable properties such as high effective surface area, electronic conductivity, high ECL intensity, and biocompatibility as demonstrated by a nanocomposite of cadmium telluride quantum dots (CdTe-QDs), AuNPs, SWCNTs, and CS (CdTe-QDs/AuNPs/SWCNTs/CS).

Therefore, in this work, ECL and nanotechnology were integrated to fabricate an ECL biosensor on a carbon nanofiber, screen-printed electrode (CNFs-SPE) modified with the nanocomposite of CdTe-QDs/AuNPs/SWCNTs/CS. The aim was to produce highly sensitive, highly specific, resistant to non-target proteins, rapid, and reliable, with the ability to detect a wide range of Hp concentration in a serum, label-free, the potential to mass-production, economical, and eco-friendly biosensor for Hp detection that could be stored for a long period of time.

Using increased ECL intensity, increased electron conductivity, and increased effective surface area of CdTe-QDs/AuNPs/SWCNTs/CS-nanocomposite modified electrode, a label-free ECL biosensor was fabricated for the detection of Hp. This fabricated biosensor demonstrated a dynamic linear range of detection of Hp from 0.1 pg mL-1 to 10 ng mL-1 with an LOD 100 fg mL-1. In addition to high specificity, interference-resistant excellent reproducibility, and longer storage time, the proposed biosensor to detect Hp also demonstrated high potential to detect the Hp in biological samples. Therefore, the developed platform using nanotechnology could also be used to design economical and eco-friendly, highly selective and sensitive ECL biosensors to detect other clinically important biomarkers such as cardiac troponin I and ciprofloxacin.

Minhaz Uddin Ahmed, Ph.D. (Project PI: left) and Mohammed Rizwan (Graduate Student: right)

These findings are described in the article entitled Efficient double electrochemiluminescence quenching based label-free highly sensitive detection of haptoglobin on a novel nanocomposite modified carbon nanofibers interface, recently published in the journal Sensing and Bio-Sensing Research.

This work was conducted by Mohammad Rizwan, Natasha Ann Keasberry and Minhaz Uddin Ahmed at the Universiti Brunei Darussalam, Brunei Darussalam.

About The Author

Mohammad Rizwan

Dr. Mohammad Rizwan was awarded a Ph.D. in Biotechnology at Universiti Brunei Darussalam (UBD) under the supervision of Senior Assistant Professor Dr. Minhaz Uddin Ahmed, Faculty of Science, UBD in 2018. Subsequently in August 2018, Dr. Rizwan joined Dr. Christopher Gwenin, Senior Lecturer in Physical Chemistry (Biological Sensors & Medical Diagnostics) to work as a Research & Development Innovation Officer on CALIN project, funded by the European Regional Development Fund through the Welsh Govt., Welsh, UK, at School of Natural Sciences, Bangor University, United Kingdom. Earlier he obtained his M.Phil. M.Sc. and B.Sc. (Hons) degrees in Nano Sciences, Biochemistry, and Biotechnology with Chemistry and Botany respectively. He is a recipient of prestigious Graduate Research Scholarship offered by Govt. of Brunei Darussalam for the year 2015-18. His area of research interest includes Electroanalytical Chemistry, Biosensors and Bioelectronics, Nanotechnology, Nanobiotechnology and Bionanotechnology, Electrochemical and Electrochemiluminescence based Chips and Sensors, Targeted and Controlled Nanodrug Delivery Systems, Environmental Biotechnology, and Nanobioremediation.

Minhaz Uddin Ahmed

Dr. Minhaz Uddin Ahmed is a Senior Assistant ProfessorĀ of Analytical Chemistry and Biotechnology at the Universiti Brunei Darussalam (UBD). He obtained his Ph.D. in Chemical Materials Science from the Japan Advanced Institute of Science and Technology (JAIST) in 2008 under the supervision of Prof. Eiichi Tamiya and later worked as a JSPS post-doctoral fellow at Osaka University, Japan (2008-2009, with Prof. Eiichi Tamiya); DARPA post-doctoral research associate at Duke University, US (2009-2010, with Prof. April S. Brown); and NSERC post-doctoral fellow at INRS-EMT, Canada (2010-2012, with Prof. M. Zourob). His research interests are in the areas of biosensors and diagnostic technologies as well as applications to nanobiotechnology and clinical and environmental chemistry. Dr. Ahmed is an alumnus of JAIST and a prestigious young participant/fellow of the 57th Lindau Nobel Laureate Meeting for Physiology and Medicine in Germany in 2007. In 2008, he was awarded the prestigious Japanese Society for the Promotion of Science (JSPS) young scientist award to work in the Graduate School of Engineering of Osaka University. In 2009, he was awarded the United States Defence Advanced Research Project Agency (DARPA) post-doctoral fellowship to work at the Pratt School of Engineering at Duke University.Ā Currently, Dr. Ahmed is also serving as one of the Associate Editors of the journal ā€œRSC Advancesā€ published by the Royal Society of Chemistry (RSC), UK.

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