Low cost electronic detection of molecular aggregation for rapid drug development

描述（由申请人提供）：纳米颗粒无处不在，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制在直径大于500纳米的颗粒上。这种限制在药物开发行业中得到了强烈的感受：由于肠外制剂中的药物颗粒聚集会引起一些接受者的严重免疫反应，因此对它们的检测是制造商和患者的主要安全问题。整个制药行业每年进行数百万次这样的关键测试，缺乏有效的粒度技术大大增加了这些测试的时间和成本：如果能够在50纳米而不是500纳米的直径上可靠地检测分子聚集体，则每次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检测和测量亚微米聚集体的方式。Spectradyne仪器将能够1)对直径小至20纳米的单个颗粒进行可靠的检测，比现有的商用方法小10倍以上；2)尺寸判别优于5%，能够对多分散样品进行分辨率；3)检测速率高于每秒100,000个颗粒，比其他商用方法快1000倍。该平台将包括一次性耗材纳米流体墨盒和一个紧凑的台式仪器，该仪器能够控制墨盒中的流量，并在颗粒流过传感器时执行电子读出。要实现这些目标，必须达到三个具体目标。在目标1中，将演示可靠和可重复的可消耗纳米流体墨盒制造-成功完成这一目标将为这些组件的大规模生产确定可行的途径，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，能够自动控制墨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，用于系统地评估该技术的性能。最后，在目标3中，系统的关键性能指标将被表征：检测极限，线性动态范围，测量精度和精度。然后，通过分析我们在制药行业的合作者提供的真实配方，对完全表征的仪器原型进行药物开发应用的验证。这项技术将大大减少开发新药物配方所需的时间、金钱和材料，特别是颗粒聚集检测，并减少药物开发的总体时间和成本。

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.