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

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是开发一种高通量、低成本的解决方案，以缓解基因组学和癌症研究的主要瓶颈。特殊的下一代测序（NGS）工作流程已经成为个性化医疗最重要的工具之一，帮助科学家发现诊断癌症和其他疾病的新方法，最终改善患者的治疗效果。虽然测序平台在技术上不断进步，但人们对改进基因组DNA （gDNA）片段或剪切以制备NGS样品的必要和困难步骤的关注较少。在现代分析实验室中，估计75-80%的工作活动都花在处理和制备样品上。目前的gDNA剪切工业标准需要昂贵的仪器（15万美元），并且连续处理96个样品可能需要2个多小时。较便宜的替代解决方案执行不一致，并且不适合高吞吐量的应用程序。对于该过程的某些部分，迫切需要一种高通量、低成本的解决方案。该项目的重点是开发一种高通量、低成本超声设备的目标透镜技术。该项目的最终目标是使NGS应用程序的样品处理便宜、一致、快速和广泛可用。这个小企业创新研究（SBIR）第一阶段项目旨在开发一种变革性的解决方案，以解决NGS中不一致、昂贵和繁琐的样品处理问题。靶向多焦点透镜（TML）技术将在标准PCR微孔板上对96个样品进行一致、平行的gDNA剪切，从而提高了吞吐量速度并降低了资本成本。TML技术采用kinoform理论，仅使用单个声源即可对多个样品进行聚焦超声，从而消除了对机器人扫描系统的需求。在第一阶段，我们将设计和制造一种集成了TML技术的新型浴式超声波探测仪。我们将进行理论和实验建模和表征，以证明TML对96孔微孔板一致超声的可行性。我们将在15分钟内通过平行剪切96个dna样本来验证原型声纳器的性能。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.