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9. Ultrasensitive Biosensors for Quantification of Multiple Immune Checkpoint Inhibitor Biomarkers from Blood, Plasma and Serum with Investigation of Protein Corona Formation and its Implications

Author

Moazzam, Parisa

Subjects
Immune checkpoint inhibitors, Ultrasesnitive biosensors, 3401 Analytical chemistry, Protein corona, Biosesnors fouling, Programmed death ligand-1 (PD-L1), 340108 Sensor technology (incl. chemical aspects), Liquid biopsies
Abstract

The expression levels of immune checkpoint inhibitor biomarkers including programmed death-ligand 1 (PD‐L1), cytokine lymphocyte antigen 4 (CTLA-4) and B7-homolog3 (B7-H3) can be used to identify the presence of diseases, and also show a good correlation with therapeutic outcomes. Invasive solid biopsies are used to achieve samples with immunohistochemistry assays being the detection method of choice to identify the expression levels of these biomarkers in clinical practice. These assays are qualitative or semi-quantitative due to biopsy heterogeneity. There is an unmet clinical need for quantitative detection methods that are less invasive, to improve the efficacy of treatments that are closely associated with PD-L1, CTLA-4 and B7-H3 expression levels. The detection of PD-L1, CTLA-4 and B7-H3 in whole blood is an attractive pathway for the early detection, prediction and evaluation of cancer treatment response because of its simplicity but remains almost completely unexplored. The challenge is that a limit of detection of less than picomolar must be achieved for a detection technology to satisfy the requirements of the unmet need. The purpose of this work is firstly to address the unmet need for improved conventional immune checkpoint inhibitor biomarkers detection techniques by designing an ultrasensitive quantitative biosensor based on gold-coated magnetic nanoparticles, referred to as dispersible electrodes. The research demonstrates the ultrasensitive, selective and rapid electrochemical detection of PD-L1, CTLA-4 and B7-H3 directly in whole blood. These dispersible electrodes selectively capture analytes within biofluids and upon application of a magnet, they are reassembled into a macroelectrode for electrochemical detection of the target antigen using a classic sandwich immunoassay with a detection range of nanomolar to attomolar and a response time of only 15 min. The research then focuses on how this system is capable of detecting these species in whole blood without being completely fouled by proteins. Investigations show that ‘soft protein corona’ layer forms around the antibody-modified particles, which can be resulted in lower signal intensity and greater uncertainties of dispersible electrodes but does not completely suppress electrochemistry.

Published
2021
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13. Investigating the BSA protein adsorption and bacterial adhesion of Al-alloy surfaces after creating a hierarchical (micro/nano) superhydrophobic structure

Author

Moazzam, Parisa, Razmjou, Amir, Golabi, Mohsen, Shokri, Dariush, Landarani-Isfahani, Amir, Moazzam, Parisa, Razmjou, Amir, Golabi, Mohsen, Shokri, Dariush, and Landarani-Isfahani, Amir

Abstract

Bacterial adhesion and subsequent biofilm formation on metals such as aluminum (Al) alloys lead to serious issues in biomedical and industrial fields from both an economical and health perspective. Here, we showed that a careful manipulation of Al surface characteristics via a facile two-steps superhydrophobic modification can provide not only biocompatibility and an ability to control protein adsorption and bacterial adhesion, but also address the issue of apparent long-term toxicity of Al-alloys. To find out the roles of surface characteristics, surface modification and protein adsorption on microbial adhesion and biofilm formation, the surfaces were systematically characterized by SEM, EDX, XPS, AFM, FTIR, water contact angle (WCA) goniometry, surface free energy (SFE) measurement, MTT, Bradford, Lowry and microtiter plate assays and also flow-cytometry and potentiostat analyses. Results showed that WCA and SFE changed from 70 degrees to 163 degrees and 36.3 to 0.13 mNm(-1), respectively. The stable and durable modification led to a substantial reduction in static/dynamic BSA adsorption. The effect of such a treatment on the biofilm formation was analyzed by using three different bacteria of Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus. The microtiter plate assay and flow cytometry analysis showed that the modification not only could substantially reduce the bacterial adhesion but this biofouling resistance is independent of bacterium type. An excellent cell viability after exposure of HeLa cells to waters incubated with the modified samples was observed. Finally, the corrosion rate reduced sharply from 856.6 to 0.119 MPY after superhydrophobic modifications, which is an excellent stable corrosion inhibition property. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2220-2233, 2016., Funding Agencies|University of Isfahan Research Council

Published
2016
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15. Ultrasensitive Biosensors for Quantification of Multiple Immune Checkpoint Inhibitor Biomarkers from Blood, Plasma and Serum with Investigation of Protein Corona Formation and its Implications

Author

Moazzam, Parisa ; https://orcid.org/0000-0001-6672-5053

Subjects
Ultrasesnitive biosensors, Immune checkpoint inhibitors, Liquid biopsies, Protein corona, Biosesnors fouling, Programmed death ligand-1 (PD-L1), anzsrc-for: 3401 Analytical chemistry, anzsrc-for: 340108 Sensor technology (incl. chemical aspects)
Abstract

The expression levels of immune checkpoint inhibitor biomarkers including programmed death-ligand 1 (PD‐L1), cytokine lymphocyte antigen 4 (CTLA-4) and B7-homolog3 (B7-H3) can be used to identify the presence of diseases, and also show a good correlation with therapeutic outcomes. Invasive solid biopsies are used to achieve samples with immunohistochemistry assays being the detection method of choice to identify the expression levels of these biomarkers in clinical practice. These assays are qualitative or semi-quantitative due to biopsy heterogeneity. There is an unmet clinical need for quantitative detection methods that are less invasive, to improve the efficacy of treatments that are closely associated with PD-L1, CTLA-4 and B7-H3 expression levels. The detection of PD-L1, CTLA-4 and B7-H3 in whole blood is an attractive pathway for the early detection, prediction and evaluation of cancer treatment response because of its simplicity but remains almost completely unexplored. The challenge is that a limit of detection of less than picomolar must be achieved for a detection technology to satisfy the requirements of the unmet need. The purpose of this work is firstly to address the unmet need for improved conventional immune checkpoint inhibitor biomarkers detection techniques by designing an ultrasensitive quantitative biosensor based on gold-coated magnetic nanoparticles, referred to as dispersible electrodes. The research demonstrates the ultrasensitive, selective and rapid electrochemical detection of PD-L1, CTLA-4 and B7-H3 directly in whole blood. These dispersible electrodes selectively capture analytes within biofluids and upon application of a magnet, they are reassembled into a macroelectrode for electrochemical detection of the target antigen using a classic sandwich immunoassay with a detection range of nanomolar to attomolar and a response time of only 15 min. The research then focuses on how this system is capable of detecting these species in whole blood without being completely fouled by proteins. Investigations show that ‘soft protein corona’ layer forms around the antibody-modified particles, which can be resulted in lower signal intensity and greater uncertainties of dispersible electrodes but does not completely suppress electrochemistry.

Published
2021

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