Accurate, High-Throughput, and Affordable Nucleic Acid Sequencing Technology

准确、高通量、经济实惠的核酸测序技术

• 批准号: 10258663
• 负责人: Farshid Ghasemi
• 金额: $ 35万
• 依托单位: WEDDELL TECHNOLOGIES LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258663
• 关键词: Address; Adult Respiratory Distress Syndrome; Affect; Architecture; Base Pairing; Biological Markers; Biological Sciences; Biosensor; Capital; Cell Communication; Cells; ChIP-seq; Chemistry; Clinic; Clinical; Clinical Laboratory Improvement Amendments; Clinical Trials; Communicable Diseases; Complex; Consensus; Cytomegalovirus; DNA; DNA sequencing; Data Analyses; Detection; Development; Diagnosis; Diagnostic; Disseminated Malignant Neoplasm; Dose; Engineering; Enzymes; FDA approved; Future; Genome; Genomics; Goals; Health; Immune; Immunologic Monitoring; Immunotherapy; Industry; Inflammation; Inflammatory; Infusion procedures; Investments; Label; Laboratories; Lasers; Lead; Length; Light; Liquid substance; Maintenance; Major Histocompatibility Complex; Malignant Neoplasms; Medical; Methods; Minor; Monitor; Noise; Non-Small-Cell Lung Carcinoma; Nucleic Acids; Nucleic acid sequencing; Nucleotides; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Personal Satisfaction; Phase; Play; Polymerase; Public Health; RNA; Reagent; Repetitive Sequence; Role; Running; Sampling; Selection for Treatments; Semiconductors; Ships; Signal Transduction; Silicon; Surface; Symptoms; T-cell receptor repertoire; Technology; Testing; Time; Transducers; Treatment Effectiveness; Tumor-infiltrating immune cells; Variant; base; cancer immunotherapy; cancer therapy; clinical application; commercialization; convalescent plasma; cost; design; diagnostic technologies; flexibility; genetic testing; genomic tools; health goals; imager; innovation; instrument; instrumentation; manufacturing scale-up; metal oxide; next generation sequencing; novel; nucleic acid detection; operation; optical imaging; personalized health care; photonics; point of care; precision medicine; prognostic; side effect; single molecule; technology validation

Project Summary / Abstract Remarkable progress in cancer immunotherapy, and decreasing cost of Next Generation Sequencing (NGS) diagnostics, have sparked clinical tests targeting tumor-immune cell interactions using genomic tools. Non-small cell lung cancer (NSCLC) exemplifies precision medicine with multiple FDA-approved biomarkers. Despite these advancements, the practical use of NGS remains limited. Instrument setup and operating costs are prohibitive for the majority of smaller labs. Patient samples thus need to be shipped to specific labs set up for conducting the test, which results in longer turnaround time and higher costs. Short turnaround time plays a vital role in clinical decisions. The availability of NGS at local CLIA (Clinical Laboratory Improvement Amendments) labs will take us one step closer to truly personalized healthcare. This project develops a first-of-its-kind biosensor chip for long-read nucleic acid sequencing. The proposed lab- on-chip technology allows the parallel detection of incorporated bases into a growing strand of DNA. The technology requires a relatively low capital investment to allow smaller laboratories to acquire the instrument and provide medical professionals with critical information, such as the ideal timing of future injected doses and any potential side effects. The critical innovations behind the proposed technology include its high-throughput biosensor architecture, the ability to scale-up manufacturing using existing silicon foundries, simple operation and product design, and real-time data analysis. Moreover, the commercialization of the proposed technology is facilitated by a mature semiconductor industry to achieve this high level of multiplexing in a small form factor. The proposed project focuses on engineering and optimization of the proposed biosensor platform and iterative development using a well-characterized cytomegalovirus CDR3β sequence. This Phase I project will use synthetic templates for technology validation and calculation of the consensus accuracy. Successful completion of the project will provide a proof-of-concept, informing the productization and commercialization of the technology. The global DNA sequencing market is expected to grow to $25B in 2025 at a CAGR of 19.0%, with a potential immune monitoring sector worth over $3B. If successful, the proposed technology will be a groundbreaking development in clinical NGS diagnostics, especially for early and accurate profiling of the T cell receptor repertoire in fast-developing infectious diseases. More affordable and available sequencing will advance the effectiveness of the treatment for cancer and infectious diseases for millions of people around the world.

项目总结/摘要 癌症免疫治疗取得显著进展，下一代测序（NGS）成本下降 诊断学，已经引发了使用基因组工具靶向肿瘤-免疫细胞相互作用的临床试验。非小 细胞肺癌（NSCLC）通过多种FDA批准的生物标志物验证了精准医学。尽管有这些 尽管取得了一些进展，但NGS的实际应用仍然有限。仪器设置和运行成本过高 对于大多数小型实验室来说。因此，患者样本需要被运送到特定的实验室， 测试，这导致更长的周转时间和更高的成本。短的周转时间在以下方面起着至关重要的作用： 临床决策当地CLIA（临床实验室改进修正案）实验室的NGS可用性 让我们离真正的个性化医疗更近一步。 该项目开发了首个用于长读核酸测序的生物传感器芯片。拟议中的实验室- 芯片上技术允许平行检测掺入到生长的DNA链中的碱基。的 技术需要相对较低的资本投资，以允许较小的实验室获得仪器， 为医疗专业人员提供关键信息，例如未来注射剂量的理想时间以及任何 潜在的副作用所提出的技术背后的关键创新包括其高通量 生物传感器架构，使用现有硅铸造厂扩大制造的能力，操作简单 产品设计和实时数据分析。此外，所提出的技术的商业化是 由成熟的半导体工业促进以小形状因数实现这种高水平的多路复用。 该项目的重点是工程和建议的生物传感器平台的优化和迭代 使用充分表征的巨细胞病毒CDR 3 β序列开发。第一期工程将采用 用于技术验证和计算共识准确性的合成模板。成功完成 该项目将提供一个概念验证，为产品化和商业化提供信息， 技术.全球DNA测序市场预计将在2025年以19.0%的复合年增长率增长至250亿美元， 一个潜在的免疫监测行业价值超过30亿美元。如果成功，这项技术将是一项 临床NGS诊断的突破性发展，特别是对于T细胞的早期和准确分析 快速发展的传染病中的受体库。更便宜和可用的测序将向前推进 为全世界数百万人提供癌症和传染病治疗的有效性。