SBIR Phase I: Design of custom ultrasonic lens for uniform sonication of biological samples in microplates

小型企业创新研究(SBIR)第一阶段项目的更广泛影响/商业潜力是开发高通量、低成本的解决方案，以缓解基因组学和癌症研究中的一个主要瓶颈。特殊的下一代测序(NGS)工作流已成为个性化医学最重要的工具之一，帮助科学家发现诊断癌症和其他疾病的新方法，最终改善患者结果。虽然测序平台在技术上不断进步，但人们对改进必要而困难的步骤--裂解或剪切基因组DNA(GDNA)以准备NGS样本--的关注较少。据估计，现代分析实验室75%-80%的工作活动都花在了样品的处理和准备上。目前的gDNA剪切行业标准需要昂贵的仪器(15万美元)，连续处理96个样本可能需要超过2个小时。价格较低的替代解决方案性能不稳定，不适用于高吞吐量应用程序。迫切需要一种用于该工艺部分的高吞吐量、低成本的解决方案。拟议的项目专注于为高通量、低成本的超声设备开发一种定向透镜技术。该项目的最终目标是为NGS应用程序提供廉价、一致、快速和广泛的样品处理。该小型企业创新研究(SBIR)第一阶段项目旨在为NGS应用程序开发一种变革性的解决方案，以解决不一致、昂贵和繁琐的样品处理问题。靶向多焦点透镜(TML)技术将能够在标准的PCR微孔板中对96个样本进行一致、平行的gDNA剪切，从而将吞吐速度和降低的资本成本提高一个数量级。TML技术采用了Kinoform理论，只使用一个声源就可以对多个样品进行聚焦超声处理，从而消除了对机器人扫描系统的需求。在第一阶段，我们将设计并制作一款集成了TML技术的新型浴式声化器。我们将进行理论和实验建模和表征，以证明TML用于96孔微板的一致声学的可行性。我们最终将通过在15分钟内并行剪切96个gDNA样本来验证原型声化器的性能。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the development of a high-throughput, low-cost solution to alleviate a major bottleneck in genomics and cancer research. Special next-generation sequencing (NGS) workflows have become one of the most important tools for personalized medicine, helping scientists discover new ways to diagnose cancer and other diseases, ultimately improving patient outcomes. While sequencing platforms continue to advance technologically, less attention has been given to improving the necessary and difficult step of fragmenting or shearing genomic DNA (gDNA) to prepare samples for NGS. An estimated 75-80% of work activity in a modern-day analytical lab is spent on processing and preparing samples. The current industry standard for gDNA shearing requires expensive instrumentation ($150,000), and can require more than 2 hours to serially process 96-samples. Less expensive alternative solutions perform inconsistently, and are not amenable for high-throughput applications. A critical need exists for a high-throughput, low-cost solution for parts of this process. The proposed project is focused on developing a targeted lens technology for a high-throughput, low-cost sonication device. The ultimate goal of this project is to make sample processing for NGS applications inexpensive, consistent, fast, and widely available.This Small Business Innovation Research (SBIR) Phase I project aims to develop a transformative solution to inconsistent, costly, and cumbersome sample processing for NGS. The Targeted Multifocal Lens (TML) technology will enable consistent, parallel gDNA shearing of 96 samples in a standard PCR microplate, improving by an order of magnitude both throughput speed and reduced capital costs. The TML technology employs kinoform theory to enable focused sonication of multiple samples using just a single acoustic source, thus eliminating the need for robotic scanning systems. In Phase I, we will design and prototype a novel bath-type sonicator that integrates with the TML technology. We will perform theoretical and experimental modeling and characterization to demonstrate feasibility of TML for consistent sonication of a 96-well microplate. We will finally validate the performance of the prototype sonicator by shearing 96 samples of gDNA in parallel, in under 15 minutes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.