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.

项目摘要 /摘要 癌症免疫疗法的显着进步，下一代测序的成本降低（NGS） 诊断已经引发了使用基因组工具针对肿瘤免疫细胞相互作用的临床测试。非小all 细胞肺癌（NSCLC）具有多种FDA批准的生物标志物的精密药物。尽管如此 进步，NGS的实际使用仍然有限。禁止仪器设置和运营成本 对于大多数较小的实验室。因此，需要将患者样品运送到设置用于进行的特定实验室 该测试导致周转时间更长和成本更高。短时间时间在 临床决策。在当地CLIA（临床实验室改进修订）实验室的NGS的可用性将 将我们带到真正个性化的医疗保健方面一步。 该项目开发了用于长阅读核酸测序的首个生物传感器芯片。拟议的实验室 片上技术可以并行检测到成长的DNA链中。这 技术需要相对较低的资本投资，以允许较小的实验室获取该工具，并 为医疗专业人员提供关键信息，例如未来注入剂量的理想时机和任何 潜在的副作用。拟议技术背后的关键创新包括其高通量 生物传感器建筑，使用现有硅铸造厂扩大制造的能力，简单操作 和产品设计以及实时数据分析。而且，提议的技术的商业化是 由成熟的半导体行业促进，以在小型形状中实现高水平的多路复用。 拟议的项目着重于拟议的生物传感器平台的工程和优化和迭代 使用良好的巨细胞病毒CDR3β序列开发。我项目将使用这个阶段 共识精度的技术验证和计算的合成模板。成功完成 该项目将提供概念验证，并告知 技术。预计全球DNA测序市场将在2025年以19.0％的复合年增长率增长到25B美元，其中 潜在的免疫监控部门价值超过$ 3B。如果成功，提议的技术将是 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 快速发育的传染病中的受体曲目。更实惠的可用测序将进步 全世界数百万人治疗癌症和传染病的有效性。