Development of a Point-of-Care Volumetric Bar-Chart Chip for Drug Quantitation

摘要 重新提交：开发用于药物定量的护理点容量条形图芯片 本建议书是R01(DA035868-01)三年期续期的重新提交。在.期间 在上一次授权期，我们发表了40篇同行评议论文，申请了4项专利，其中17项 出版物和2项专利直接来自于这一授予奖的支持。我们还有很多 来自这笔赠款的原始数据和4份待定出版物。授权书中提到了最初的专利， 体积条形图芯片(V-Chip)专利，于2015年正式颁发(US9097710 B2)和 授权给Etta Healthcare和Ovagen。我们的实验室芯片系统也是2015年研发100强的获胜者 获奖。 在重新提交中，我们专注于进一步发展量化能力和重点- OF-CARE药物定量V-Chip平台的用户友好性。关键创新和 我们为解决评审者的关切而进行的修改包括：1.改进设计 V型芯片，使设备在定量方面更强大，在护理点上用户友好 布景。这包括修改芯片上的表条，以消除单独的 通过集成芯片上的泵，消除了手动移液的需要； 将手工刻蚀玻璃的工艺改为计算机引导的激光生产。2.添加 更多关于PtNP共轭的数据，以证明技术上的可行性。3.将触点PI更改为 王平博士作为提案的重点转移到临床验证和最终用户中试测试上。 我们将评估临床敏感度、临床特异度、用户内部和用户间的可变性 环境(宾夕法尼亚大学医院)，目标终端用户。这些变化 应该证明我们的设备的临床价值和健壮性。 当前的非侵入性(或微侵入性)护理点(POC)平台可帮助 物质使用障碍(SUD)的治疗面临着非量化的挑战， 不准确，与各种生物样本不兼容，检测时间长，以及 对精密仪器和/或读数专业知识的要求。 在这里，我们提出了一种集成的竞争多路复用体积条形图芯片(ICV- 芯片)来检测尿液、全血和唾液中的药物靶点。ICV-Chip平台是 定量、灵敏、准确、快速、便携、方便、成本低。ICV-CHIP生物检测 是否是非侵入性/微创性的，能够评估患者对治疗的坚持程度 通过整合黏附标记乙酰唑胺。ICV芯片的发展也因此 克服了目前大多数技术限制，开启了免仪器的可能性 药物滥用的个性化评估。

Abstract Resubmission: Develop Point-of-Care Volumetric-Bar-Chart-Chip for Drug Quantitation This proposal is a resubmission of a three-year R01 (DA035868-01) renewal. During the last grant period, we published 40 peer-reviewed papers and applied for 4 patents, with 17 publications and 2 patents directly resulted from this grant award support. We still have numerous raw data and 4 pending publications from this grant. The original patent featured in the grant, Volumetric-Bar-Chart-Chip (V-Chip) patent, was officially issued in 2015 (US9097710 B2) and licensed to Etta Healthcare and Ovagen. Our lab chip system is also a winner of 2015 R&D 100 award. In the resubmission, we focus on further developing the quantitation capability and point- of-care user friendliness of the V-Chip platform for drug quantitation. Key innovations and changes we incorporated to address the reviewers' concerns include: 1. Improving the design of the V-chip so that the device is more robust for quantitation and user-friendly in a point of care setting. This includes modifying the on-chip meter bar to eliminate the need for separate calibration, eliminating the need for manual pipetting by the integration of on-chip pumps, and changing the manual glass etching process to computer-guided laser-based production. 2. Adding more data on PtNP conjugation to prove the technical feasibility. 3. Changing the contact PI to Dr. Ping Wang as the focus of the proposal shifts to clinical validation and end-user pilot testing. We will assess clinical sensitivity, clinical specificity, intra- and inter-user variability in a clinical environment (Hospital of University of Pennsylvania) with targeted end-users. These changes should demonstrate the clinical value and robustness of our device. Current non-invasive (or minimal-invasive) point-of-care (POC) platforms to assist the therapeutics for Substance Use Disorder (SUD) are facing challenges of non-quantitation, inaccuracy, non-compatible with diverse biological specimens, long assay time, and requirement for sophisticated instrument and/or expertise for readout. Here, we propose an Integrated Competitive Multiplexed Volumetric Bar Chart Chip (ICV- Chip) to assay drug targets in urine, whole blood, and saliva. The ICV-Chip platform is quantitative, sensitive, accurate, fast, portable, convenient and low cost. The ICV-Chip bioassay is non/minimally invasive and able to assess the patients' adherence to their medical treatment by the integration of an adherence marker Acetazolamide. The development of the ICV-Chip thus overcomes most of the current technology limits and opens up the possibility of instrument-free personalized assessment of drug abuse.