Low cost electronic detection of molecular aggregation for rapid drug development

用于快速药物开发的分子聚集的低成本电子检测

• 批准号: 8832677
• 负责人: Franklin Monzon
• 金额: $ 21.35万
• 依托单位: SPECTRADYNE, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2015-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832677
• 关键词: Address; Automation; Caliber; Cosmetics; Detection; Development; Dimensions; Discrimination; Drug Delivery Systems; Drug Formulations; Drug Industry; Electric Conductivity; Electronics; Environment; Feedback; Food; Foundations; Future; Geometry; Goals; Health; Immune response; Indium; Individual; Industry; Letters; Liquid substance; Manuals; Manufacturer Name; Measurement; Measures; Methods; Metric System; Molds; Molecular; Nanotechnology; Particle Size; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Play; Polystyrenes; Process; Reagent; Resolution; Safety; Sampling; Signal Transduction; Small Business Innovation Research Grant; System; Technology; Testing; Time; Translating; United States National Institutes of Health; Variant; base; commercialization; constriction; cost; drug development; fluid flow; improved; industry partner; innovation; instrument; instrumentation; manufacturing process; meetings; member; nanofluidic; nanometer; nanoparticle; nanopattern; nanoscale; new technology; operation; particle; pressure; programs; prototype; public health relevance; response; sensor; submicron; success; tool; visual feedback

DESCRIPTION (provided by applicant): Nanoparticles are ubiquitous yet notoriously difficult to detect and measure-practical technologies for their characterization are effectively restricted to particles larger than about 500 nanometers in diameter. This limitation is acutely felt in the drug development industry: Because aggregate drug particles in parenteral formulations elicit a severe immune response in some recipients, their detection is a major safety concern for manufacturers and patients. Millions of these critical tests are performed each year across the pharmaceutical industry, and the lack of effective particle sizing technology significantly increases the time and cost of these tests: a 1000-fold reduction in both time and reagents required for each test would be realized if molecular aggregates could be reliably detected at diameters of 50 nanometers rather than 500 nanometers. Spectradyne will address this unmet need by commercializing an innovative particle sizing technology that completely changes the way submicron aggregates are detected and measured in the pharmaceutical industry. The Spectradyne instrument will be capable of 1) robust detection of individual particles as small as 20 nanometers in diameter, more than ten times smaller than existing commercially available methods, with 2) size discrimination better than 5%, enabling resolution of polydisperse samples and 3) detection rates higher than 100,000 particles per second, (1000-fold faster than other commercially available methods). The platform will comprise single-use consumable nanofluidic cartridges and a compact, benchtop instrument capable of controlling flow in the cartridge and performing electrical readout of particles as they flow through the sensor. To accomplish these goals three specific aims will be met. In Aim 1, reliable and repeatable manufacture of the consumable nanofluidic cartridges will be demonstrated-successful completion of this aim will define a viable path to mass manufacture of these components, a critical requirement for the success of the technology. In Aim 2, an instrument prototype will be developed that is capable of automated control of fluid flow in the cartridge and electrical readout. Success in Aims 1 and 2 will produce a reliable control system with which to systematically evaluate the performance of the technology. Lastly, in Aim 3 the key performance metrics of the system will be characterized: limit of detection, linear dynamic range, and measurement accuracy and precision. The fully characterized instrument prototype will then be validated for use in drug development applications by analyzing authentic formulations provided by our collaborators in the pharmaceutical industry. This technology will significantly reduce the time, money and materials required for the development of new drug formulations, in particular the detection of particle aggregation, and reduce the overall time and cost of drug development.

描述（由申请人提供）：纳米颗粒是普遍存在的，但众所周知难以检测和测量-用于其表征的实用技术有效地限于直径大于约500纳米的颗粒。这种限制在药物开发行业中感受强烈：由于胃肠外制剂中的聚集药物颗粒在一些接受者中引起严重的免疫反应，因此它们的检测是制造商和患者的主要安全问题。每年在制药行业进行数百万次这些关键测试，缺乏有效的粒度测量技术显着增加了这些测试的时间和成本：如果分子聚集体可以在50纳米而不是500纳米的直径下可靠地检测，则每个测试所需的时间和试剂将减少1000倍。Spectradyne将通过商业化一种创新的粒度测量技术来解决这一未满足的需求，该技术完全改变了制药行业中检测和测量亚微米聚集体的方式。Spectradyne仪器将能够1）稳健地检测直径小至20纳米的单个颗粒，比现有的市售方法小十倍以上，2）尺寸区分度优于5%，能够实现多分散样品的分辨率，以及3）检测速率高于每秒100，000个颗粒，（比其他商业方法快1000倍）。该平台将包括一次性消耗性纳米流体盒和一个紧凑的台式仪器，该仪器能够控制盒中的流量并在颗粒流过传感器时对颗粒进行电读出。为了实现这些目标，将实现三个具体目标。在目标1中，将证明可消耗纳米流体盒的可靠和可重复制造-成功完成该目标将定义这些组件的大规模制造的可行路径，这是该技术成功的关键要求。在目标2中，将开发一种仪器原型，能够自动控制盒中的流体流动和电子读数。目标1和目标2的成功将产生一个可靠的控制系统，利用该系统可以系统地评估该技术的性能。最后，在目标3中，将描述系统的关键性能指标：检测限、线性动态范围以及测量准确度和精密度。然后，通过分析我们在制药行业的合作者提供的真实配方，验证完全表征的仪器原型是否可用于药物开发应用。该技术将大大减少开发新药物制剂所需的时间、金钱和材料，特别是检测颗粒聚集，并减少药物开发的总体时间和成本。