This Small Business Innovation Research (SBIR) Phase II project is to build upon the feasibility of using MIMS technology to determine the presence and measure the concentration of multiple protein biomarkers (specifically autoantibodies) within a single sample. In order to achieve our primary objective in Phase II, PHB proposes to produce a new highly-sensitive and stable MIMS system prototype for clinical use. We will develop a prototype disposable, reliable, easy to use biochip cassette with limited potential for biohazard exposure. To reduce the need for off-chip processing, PHB will implement a cartridge- based fluidic channel to remove blood cells. We will develop specific attachment strategies for antibodies and/or F(ab)2 fragments of antibodies that enable the efficient capture of antigens to be used as targets for autoantibodies. This will eventually lead to the development of reverse capture arrays for identification of autoantigens against which autoAb expression may be used to differentiate between normal and disease states. We will optimize the protein printing methodology, and blocking protocols to enable the optical interference detection system to provide reproducible results in molecular binding reactions on a multiplicity of nanostructured protein chips. We will evaluate the performance of the optimized substrate and platform in real-time with a representative set of antibody targets. Our initial focus will be a panel consisting of Thyroperoxidase antibody, TSH receptor antibodies and thyroglobulin antibodies. These tests can potentially be used to diagnose an autoimmune thyroid disease and to separate it from other forms of thyroiditis.
The broader impacts of this research are to develop the Molecular Interaction Measurement System (MIMS) which has the potential to measure multiple analyte types (protein, RNA, DNA etc.) in real-time. MIMS uses optical interference to measure the changes in thickness, resulting from binding of a ligand to a macromolecule attached to the surface of a detector chip. The array format of the MIMS assay permits simultaneous detection of the binding of multiple analytes. One application of interest and immediate clinical value is in the detection of autoantibodies which target host tissue and mediate autoimmune diseases. MIMS can enable specific detection without having to tag (e.g. with radioisotope or fluorescence) a patients sample: resulting in more accurate and cost effective diagnoses In addition, the finding that patients with cancer produce autoantibodies against antigens in their tumors suggests that such autoantibodies could have both diagnostic and prognostic value. Commercially, MIMS can be a tool to easily, rapidly and cost effectively screen a large number of patients with different types and stages of cancer and other diseases providing value to clinicians, to patients and the clinical research community.
