Smart Polymer Reagents for Sensitivity and Speed-enhanced Clinical Diagnostics

智能聚合物试剂可提高临床诊断的灵敏度和速度

• 批准号: 8640196
• 负责人: Barrett J Nehilla
• 金额: $ 61.78万
• 依托单位: NEXGENIA, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8640196
• 关键词: Address; Agreement; Antibodies; Archives; Area; Automation; Binding; Biological Assay; Biological Markers; Biological Sciences; Blood Plasma Volume; Caliber; Cardiac; Categories; Cells; Chemicals; Chemistry; Clinical; Communicable Diseases; Complex; Cyanovirin-N; Data; Diagnostic; Diffuse; Diffusion; Dimensions; Endocrine System Diseases; Engineering; Enzyme-Linked Immunosorbent Assay; Evolution; Excision; Generations; Goals; HIV; HIV Core Protein p24; HIV-1; HIV-2; Healthcare; Heart Diseases; Human Chorionic Gonadotropin; Human immunodeficiency virus test; Immunoassay; Immunoglobulin G; In Vitro; Intellectual Property; Laboratories; Lead; Libraries; Licensing; Magnetism; Malignant Neoplasms; Manufacturer Name; Medical; Modeling; Nanotechnology; Nature; Nucleic Acid Amplification Tests; Nucleic Acids; Outcome; Patient Care; Patients; Performance; Phase; Plasma; Polymers; Preparation; Process; Production; Property; Proteins; Reaction; Reaction Time; Reagent; Recombinants; Relative (related person); Research Personnel; Sales; Sampling; Serum; Solid; Solutions; Specificity; Specimen; Specimen Handling; Speed; Stimulus; Sulfhydryl Compounds; Surface; System; Techniques; Technology; Temperature; Testing; Viral Load result; Virion; anti-IgG; antibody conjugate; antigen binding; improved; innovation; magnetic beads; magnetic field; nanomaterials; nanometer; nanoparticle; novel; particle; pathogen; polymerization; public health relevance; response; scale up

DESCRIPTION (provided by applicant): Magnetic beads have gained increasing use as a convenient separation technique for many forms of cell, nucleic acid and protein isolations and analyses. In particular, the manufacturers of clinical immunoassays utilize magnetic beads both as a solid support for antibodies specifically targeted to analytes of clinical importance, and as the separation means to isolate and detect those bound analytes. But use of magnetic beads imposes a paradox. The magnetic beads must have sufficient size - normally on the order of several microns in diameter - in order to be separated in an easily achievable magnetic field. But magnetic beads of this size diffuse only very slowly, and present limited surface area for antibody binding compared to their volume. Thus the size of the current magnetic beads limits the speed and sensitivity that can be achieved in clinical assays. Through advances in template-directed polymer synthesis and nanotechnology, a new class of magnetic nanoparticles can be made. These magnetic nanoparticles, bearing stimuli-responsive polymers, can change from a monodispersed small diameter particle of roughly 20 nanometers diameter to a macro- aggregate of microns diameter in response to an environmental stimulus like a temperature or pH change. By using these advanced nanomaterials, assays can be developed in which the high surface area to volume ratio and the small size / high diffusion of the magnetic nanoparticles provides for higher sensitivity and faster binding reactions compared to current magnetic bead reagents. And then a discrete pH or temperature stimulus can cause these nanoparticle reagents to rapidly co-aggregate into a macro-complex of micron dimensions which can be separated by a magnetic field as easily and quickly as currently used magnetic beads. This project will develop, optimize, and begin scale-up of these unique assay reagents, and will then demonstrate their value in a model p24 (HIV) protein immunoassay. Phase II of this project will also demonstrate the ability to multiplex various types of HIV tests using these reagents, and demonstrate the potential of removing serum interferences for certain important clinical analytes. The HIV target assay of this project is only a model. These materials present the promise of faster, more sensitive clinical immunoassays for important biomarkers of cardiac disease, cancer, endocrine disorders and other infectious diseases. The multiplex capabilities of these reagents and the potential for removal of serum interferences will be broadly applicable to other clinically important analytes.

描述（由申请人提供）：磁珠已越来越多地用作许多形式的细胞，核酸和蛋白质分离和分析的方便分离技术。特别是，临床免疫测定的制造商利用磁珠作为针对针对临床重要性分析物的抗体的坚实支持，并且由于分离意味着分离和检测这些结合的分析物。但是使用磁珠会施加悖论。磁珠必须具有足够的尺寸 - 通常按直径为几微米的顺序 - 才能在易于实现的磁场中分离。但是，这种尺寸的磁珠仅非常缓慢地扩散，并且与其体积相比，抗体结合的表面积有限。因此，电流磁珠的大小限制了临床测定中可以实现的速度和灵敏度。通过模板定向的聚合物合成和纳米技术的进步，可以做出新的磁性纳米颗粒。这些磁性纳米颗粒具有刺激响应性聚合物，可以从直径约20纳米直径的单直径颗粒变为微米直径的宏观聚集体，以响应温度或pH变化（例如温度）。通过使用这些高级纳米材料，可以开发出高表面积与体积比，而磁性纳米颗粒的尺寸小 /高扩散可提供更高的灵敏度和更快的结合反应，与当前的磁性磁珠试剂相比。然后，离散的pH或温度刺激会导致这些纳米颗粒试剂迅速将其共聚集成微米尺寸的宏观复合物，可以像当前使用的磁珠一样轻松，迅速地通过磁场分离。该项目将开发，优化并开始扩大这些独特的测定试剂，然后在模型P24（HIV）蛋白质免疫测定中证明其价值。该项目的第二阶段还将证明使用这些试剂多重多种类型的HIV检测的能力，并证明了去除某些重要临床分析物的血清干扰的潜力。该项目的艾滋病毒目标测定只是一个模型。这些材料呈现出对心脏病，癌症，内分泌疾病和其他传染病的重要生物标志物的更快，更敏感的临床免疫测定速度的希望。这些试剂的多重能力以及去除血清干扰的潜力将广泛适用于其他重要的临床上重要分析物。