Micromolded Digital Nucleic Acid Test Consumable

微模数字核酸检测耗材

• 批准号: 9347291
• 负责人: Paul Ju-Sung Hung
• 金额: $ 21.5万
• 依托单位: COMBINATI, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347291
• 关键词: Antineoplastic Agents; Attention; Automation; Benchmarking; Biological Assay; Biological Markers; CCL3L1 gene; Capital; Clinical Research; Communities; Complement; Copy Number Polymorphism; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Event; Gene Dosage; Genes; Genomic DNA; Genomics; Gold; Image; Immunoassay; Injection of therapeutic agent; Intercept; Lead; Libraries; Literature; Medical; Microscope; Molds; Monitor; Mutation; Mutation Detection; Nature; Nucleic Acid Amplification Tests; Nucleic Acids; Nucleotides; Oils; Performance; Phase; Polymerase Chain Reaction; Process; Property; Protocols documentation; RNase P; Reaction; Reader; Reagent; Research; Research Personnel; Resolution; Running; Sampling; Scanning; Signal Transduction; Slide; Small Business Innovation Research Grant; Specificity; Technology; Testing; Therapeutic; Time; Validation; Variant; Viral Load result; Vitronectin; cost; data acquisition; deep sequencing; density; design; digital; experimental study; fluorescence imaging; improved; liquid biopsy; manufacturing process; next generation sequencing; operation; outcome forecast; personalized medicine; prototype; success

Abstract For the Phase 1 SBIR project, COMBiNATi will prove the feasibility of an array digital PCR (adPCR) consumable using copy number variation (CNV) analysis as the application. Digital PCR (dPCR) technology has drawn attentions in both genomic research and clinical research communities for its ability to detect rare events (high sensitivity), less prone to inhibition (high specificity), quantify without a standard curve (high precision), and access to well-developed qPCR reagents. Applications which could benefit from the high precision nature of dPCR include:  Quantification or validation of NGS (Next Gen Sequencing) library to maximize yield  Highly sensitive viral load test for early disease interception  Mutation guided prescription of cancer drugs for improved efficacy  Liquid biopsy with nucleic acids for continuous therapeutic monitoring However, current dPCR platforms are slow to overtake the current gold standard qPCR, mainly because the cost of consumables is high, the workflow is complicated, and the commercially available platforms are not amenable to automation. With the proposed adPCR consumable technology, we will deliver the first turnkey dPCR platform with efficient running cost for absolute nucleic acid quantification. The 9 month Phase 1 SBIR project will allow COMBiNATi to complete the following key value hypothesis of our consumable, which will serve as the new product design spec for platform development effort in Phase 2: 1. Efficient running cost: <$2 COGS/data point with the consumable technology which allows high density reagent digitization on a standard format using a scalable manufacturing process. 2. Open platform: Off-the-shelf PCR reagents are compatible with the consumable without purchasing of additional reagents such as oil for ddPCR. 3. Value in CNV analysis: Demonstrate a viable assay where digital analysis outperforms conventional qPCR technology.

抽象的 对于第一阶段 SBIR 项目，COMBiNATi 将证明阵列数字 PCR (adPCR) 的可行性 使用拷贝数变异 (CNV) 分析作为应用的消耗品。 该技术因其独特的优势而引起了基因组研究和临床研究界的关注 能够检测罕见事件（高灵敏度），不易受到抑制（高特异性），无需进行定量 标准曲线（高精度），并可使用成熟的 qPCR 试剂。 dPCR 的高精度特性带来的好处包括：  对 NGS（下一代测序）文库进行定量或验证，以最大限度地提高产量  用于早期疾病拦截的高灵敏度病毒载量测试  突变引导抗癌药物处方以提高疗效  核酸液体活检用于持续治疗监测 然而，当前的 dPCR 平台要超越当前的黄金标准 qPCR 的速度很慢，主要是 由于耗材成本高，工作流程复杂，市售的 平台不适合自动化。 提供第一个交钥匙 dPCR 平台，具有高效的绝对核酸运行成本 量化。 为期 9 个月的第一阶段 SBIR 项目将使 COMBiNATi 完成以下关键价值 我们的消耗品的假设，它将作为平台的新产品设计规范 第二阶段的开发工作： 1. 高效的运行成本：<2 美元 COGS/数据点，采用可实现高 使用可扩展的制造工艺以标准格式进行密度试剂数字化。 2.开放平台：现成的PCR试剂与耗材兼容，无需任何耗材 购买额外的试剂，例如用于 ddPCR 的油。 3. CNV 分析的价值：展示数字分析优于数字分析的可行检测方法 传统的 qPCR 技术。