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 在疾病的早期诊断Sjögren综合征（SS）可以帮助减轻损害 疾病后期发生的全身表现。建立SS诊断的当前测试包括 唾液腺活检以寻找淋巴细胞炎症并使用放射性标记来测试唾液腺 功能。尽管这些测试可有效地诊断SS，但在此过程中发展了多重生物传感器 提案将提供一种低成本的方法来检测唾液/泪腺的分子证据 不需要侵入性测试的功能障碍和淋巴细胞炎症。分子印刷 聚合物（MIPS）是能够半选择性分子识别的合成材料，成本较低 比抗体更环保。在此提案中，MIP将在表面合成 具有独特光学特性的纳米材料用于灵敏度应用。具体而言，MIP的集合 涂层金纳米材料将用于“差异传感”，以监测生物标志物 淋巴细胞注射和腺体功能低下，提供更全面的视野 蛋白质混合物。开发的传感器阵列没有识别单个生物标志物，而是生成模式 基于众多生物标志物，为生化变化提供了更强大的诊断工具。总体 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到生物标志物 可用于在有症状的患者中建立SS诊断。该提议的具体目标是 （目标1）合理选择强键单体（非共价或可逆共价）以改善MIP 亲和力，（目标2）合成金纳米表面表面的MIP 信号传递和（目标3）在传感器阵列中测试这些印迹纳米材料以检测SS生物标志物。