74 research outputs found

    A general process for the development of peptide-based immunoassays for monoclonal antibodies

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    Monoclonal antibodies (mAb) are an important and growing class of cancer therapeutics, but pharmacokinetic analyses have in many cases been constrained by the lack of standard and robust pharmacologic assays. The goal of this project was to develop a general method for the production of immunoassays that can measure the levels of therapeutic monoclonal antibodies in biologic samples at relevant concentrations. Alemtuzumab and rituximab are monoclonal approved for the treatment of B-cell malignancies and were used as a model system. Phage-displayed peptide libraries were screened for peptide sequences recognized by alemtuzumab (anti-CD52) or rituximab (anti-CD20). Synthetic biotinylated peptides were used in enzyme-linked immunosorbent assays (ELISA). Peptides directly synthesized on polymer resin beads were used in an immunofluorescent-based assay. Peptide mimetope sequences were recovered for both mAb and confirmed by competitive staining and kinetic measurements. A peptide-based ELISA method was developed for each. The assay for rituximab had a limit of detection of 4 μg/ml, and the assay for alemtuzumab had a limit of detection of 1 μg/ml. Antibody-specific staining of peptide conjugated beads could be seen in a dose-dependent manner. Phage-displayed peptide libraries can be a source of highly specific mimetopes for therapeutic mAb. The biotinylated forms of those peptides are compatible with conventional ELISA methods with sensitivities comparable to other assay methods and sufficient for pharmacological studies of those mAb given at high dose. The process outlined here can be applied to any mAb to enable improved pharmacokinetic analysis during the development and clinical use of this class of therapies

    Hafnium-zirconium oxide interface models with a semiconductor and metal for ferroelectric devices.

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    Density functional theory (DFT) is employed to investigate ferroelectric (FE) hafnium-zirconium oxide stack models for both metal-insulator-metal (MIM) and metal-insulator-semiconductor (MIS) structures. The role of dielectric (DE) interlayers at the ferroelectric interfaces with metals and semiconductors and the effects of thickness scaling of FE and DE layers were investigated using atomic stack models. A high internal field is induced in the FE and DE layers by the FE polarization field which can promote defect generation leading to limited endurance. It is also shown that device operation will be adversely affected by too thick DE interlayers due to high operating voltage. These DFT models elucidate the underlying mechanisms of the lower endurance in experimental MIS devices compared to MIM devices and provide insights into the fundamental mechanisms at the interfaces

    Synthesis and surface functionalization of silica nanoparticles for nanomedicine.

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    There are a wide variety of silica nanoformulations being investigated for biomedical applications. Silica nanoparticles can be produced using a wide variety of synthetic techniques with precise control over their physical and chemical characteristics. Inorganic nanoformulations are often criticized or neglected for their poor tolerance; however, extensive studies into silica nanoparticle biodistributions and toxicology have shown that silica nanoparticles may be well tolerated, and in some case are excreted or are biodegradable. Robust synthetic techniques have allowed silica nanoparticles to be developed for applications such as biomedical imaging contrast agents, ablative therapy sensitizers, and drug delivery vehicles. This review explores the synthetic techniques used to create and modify an assortment of silica nanoformulations, as well as several of the diagnostic and therapeutic applications

    Alkaline and ultrasonic dissolution of biological materials for trace silicon determination.

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    A simple method for trace elemental determination in biological tissue has been developed. Novel nanomaterials with biomedical applications necessitate the determination of the in vivo fate of the materials to understand their toxicological profile. Hollow iron-doped calcined silica nanoshells have been used as a model to demonstrate that potassium hydroxide and bath sonication at 50 °C can extract elements from alkaline-soluble nanomaterials. After alkali digestion, nitric acid is used to adjust the pH into a suitable range for analysis using techniques such as inductively coupled plasma optical emission spectrometry which require neutral or acidic analytes. In chicken liver phantoms injected with the nanoshells, 96% of the expected silicon concentration was detected. This value was in good agreement with the 94% detection efficiency of nanoshells dissolved in aqueous solution as a control for potential sample matrix interference. Nanoshell detection was further confirmed in a mouse 24 h after intravenous administration; the measured silica above baseline was 35 times greater or more than the standard deviations of the measurements. This method provides a simple and accurate means to quantify alkaline-soluble nanomaterials in biological tissue

    InGaAs (110) Surface Cleaning Using Atomic Hydrogen

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