Sensor arrays based on molecularly imprinted polymers for diagnosis of Sjogren's syndrome

基于分子印迹聚合物的传感器阵列用于诊断干燥综合征

• 批准号: 9357588
• 负责人: Eric V. Anslyn
• 金额: $ 33.96万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9357588
• 关键词: Acute; Affect; Affinity; Antibodies; Autoimmune Diseases; Behavior; Binding Sites; Biological Markers; Biopsy; Biosensor; Collection; Deglutition; Detection; Diagnosis; Diagnostic; Diffusion; Disease; Early Diagnosis; Electrostatics; Elements; Enzymes; Formulation; Gland; Goals; Gold; Inflammation; Ionic Strengths; Label; Lacrimal gland structure; Liquid substance; Lymphocyte; Metals; Methods; Molecular; Monitor; Nanotechnology; Optics; Oral cavity; Patients; Pattern; Phase; Polymers; Property; Protein Engineering; Proteins; Quality of life; Radioactive; Refractive Indices; Saliva; Salivary; Salivary Glands; Signal Transduction; Silicon Dioxide; Sjogren' s Syndrome; Solid; Surface; Surface Plasmon Resonance; Swelling; Testing; Work; associated symptom; base; biochemical tools; clinical diagnostics; cost; covalent bond; cross reactivity; crosslink; design; experimental study; imprint; improved; macromolecule; molecular recognition; monomer; multiplex detection; nanomaterials; nanoparticle; nanoshell; optical sensor; protein biomarkers; receptor; sensor

PROJECT SUMMARY Diagnosing Sjögren's syndrome (SS) in the early stages of the disease can help mitigate damage from systemic manifestations that occur later in the disease. Current tests for establishing an SS diagnosis include salivary gland biopsy to look for lymphocytic inflammation and using radioactive labeling to test salivary gland function. While these tests are effective in the diagnosis of SS, the multiplex biosensor developed in this proposal will provide a low-cost method for detecting molecular evidence of both salivary/lacrimal gland hypofunction and lymphocytic inflammation without the need for invasive testing. Molecularly imprinted polymers (MIPs) are synthetic materials capable of semi-selective molecular recognition and are lower cost and more environmentally robust than antibodies. In this proposal, MIPs will be synthesized on the surface of nanomaterials with unique optical properties for use in sensing applications. Specifically, collections of MIP- coated gold nanomaterials will be employed in “differential sensing,” routines to monitor biomarkers of lymphocytic inflammation and gland hypofunction simultaneously, providing a more comprehensive view of protein mixtures. Instead of identifying a single biomarker, the developed sensor arrays will generate a pattern based on numerous biomarkers, providing a more robust diagnostic tool for biochemical changes. The overall hypothesis of this proposal is that imprinted nanomaterials in optical sensor arrays may detect biomarkers that could be used to establish an SS diagnosis in symptomatic patients. The specific goals of this proposal are (Aim 1) to rationally choose strong-bonding monomers (non-covalent or reversible-covalent) to improve MIP affinity, (Aim 2) to synthesize MIPs on the surface of gold nanomateirals to generate receptors with built-in signal transduction and (Aim 3) to test these imprinted nanomaterials in sensor arrays to detect SS biomarkers.

项目摘要 在疾病的早期阶段诊断舍格伦综合征（SS）可以帮助减轻 在疾病后期出现的全身性表现。目前用于建立SS诊断的测试包括 唾液腺活检以寻找淋巴细胞性炎症，并使用放射性标记检测唾液腺 功能虽然这些测试在SS的诊断中是有效的，但是本发明中开发的多重生物传感器在诊断SS方面是有效的。 一项提案将提供一种低成本的方法来检测唾液腺/泪腺的分子证据， 功能减退和淋巴细胞炎症，而不需要侵入性测试。分子印迹 聚合物（MIPs）是具有半选择性分子识别能力的合成材料，并且成本较低 并且比抗体更环保。在这个提议中，将在表面上合成MIPs， 具有独特光学性质的纳米材料，用于传感应用。具体来说，MIP的集合- 涂金纳米材料将用于“差分传感”，例行监测生物标志物， 淋巴细胞炎症和腺体功能减退同时进行，提供了更全面的观点， 蛋白质混合物开发的传感器阵列将产生一种模式， 基于许多生物标志物，为生化变化提供了更强大的诊断工具。整体 该提议的假设是，光学传感器阵列中的印迹纳米材料可以检测 可用于在有症状的患者中建立SS诊断。该提案的具体目标是 (Aim 1）合理选择强键合单体（非共价或可逆共价）以提高MIP 目的2：在金纳米材料表面合成分子印迹聚合物，使其与金纳米材料表面的受体结合， 信号转导和（目的3）测试传感器阵列中的这些印迹纳米材料以检测SS生物标志物。