Micromolded Digital Nucleic Acid Test Consumable

摘要 对于第1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，使用消耗品。数字PCR（dPCR） 技术已经引起了基因组研究和临床研究界的关注， 检测罕见事件的能力（高灵敏度），不易抑制（高特异性）， 标准曲线（高精度），以及获得成熟的qPCR试剂。应用程序可以 dPCR的高精度特性带来的好处包括： NGS（Next Gen Sequencing）文库的定量或验证以最大化产量 高度敏感的病毒载量检测，用于早期疾病拦截 ·癌症药物的突变指导处方，以提高疗效 ·使用核酸进行液体活检，用于连续治疗监测 然而，目前的dPCR平台在超越目前的黄金标准qPCR方面进展缓慢，主要是 因为消耗品的成本高，工作流程复杂， 平台不适合自动化。利用所提出的adPCR耗材技术，我们将 交付第一个具有高效运行成本的绝对核酸交钥匙dPCR平台 量化 为期9个月的第1阶段SBIR项目将使COMBiNATI完成以下关键价值 假设我们的消耗品，这将作为新的产品设计规范的平台 第二阶段的开发工作： 1.高效的运行成本：<$2 COGS/数据点，采用耗材技术， 使用可扩展的制造工艺在标准格式上实现密度试剂数字化。 2.开放平台：现成的PCR试剂与耗材兼容， 购买额外的试剂，如ddPCR用油。 3. CNV分析的价值：展示一种可行的检测方法，其中数字分析优于 常规qPCR技术。

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.