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

描述(由申请人提供)：目前非侵入性(或微创性)辅助物质使用障碍(SUD)疗法临床试验的方法通常受到以下问题的限制：1)无法准确和定量地监测受试者非法药物暴露的频率和水平，2)在评估受试者对试验用药方案的依从性方面存在不确定性。这些限制主要是由于以下技术挑战：(1)非定量测量，(2)不准确，(3)需要频繁的临床就诊，以及(4)对仪器和/或读数的专业知识的要求。几个可用的护理点(POC)ELISA平台能够对药物使用情况进行定性筛查。然而，POC定量测量在评估药物滥用方面仍然是一个尚未得到满足的关键需求。微流控技术因其在多路和定量测量方面的潜在能力、便携性、低成本、高通量和其他优点而成为POC药物测试和个性化诊断的潜在方法。然而，一个克服所有列出的挑战的平台的全面发展尚未实现。在这里，我们提出了一种多路容量条形图芯片(V-Chip)来检测不同临床样本中的药物靶点，它集成了定量、免仪器读数、便携性和可负担性等功能。体积读数基于过氧化氢酶和过氧化氢反应产生的氧的测量，允许即时和可视地定量目标药物和生物标志物，并生成可视化条形图，而不需要外部仪器、数据处理或图形绘制。因此，V-Chip的发展标志着POC的一个里程碑，并开启了免仪器个性化诊断和SUD管理的可能性。

DESCRIPTION (provided by applicant): Current non-invasive (or minimally invasive) methods to assist outpatient clinical trials of therapeutics for Substance Use Disorders (SUD) are usually limited by issues such as 1) the inability to accurately and quantitatively monitor the frequency and level of a subject's illicit drug exposure and 2) uncertainty in assessing the level of a subject's adherence to the trial medication regiment. These limitations are mainly due to the technological challenges of (1) non-quantitative measurements, (2) inaccuracy, (3) requirement for frequent clinical visits, and (4) requirement for instrument and/or expertise for readout. Several available Point-of-Care (POC) ELISA platforms are able to screen drug usage qualitatively. However, the POC quantitative measurement remains an unmet, yet critical need in the assessment of drug abuse. Microfluidics has emerged as a potential approach for POC drug tests and personalized diagnostics, because of its potential capabilities for multiplexed and quantitative measurements, portability, low cost, high throughput, and other advantages. However, the full development of a platform that overcomes all the listed challenges has not yet been realized. Here, we propose a Multiplexed Volumetric Bar-Chart Chip (V-Chip) to assay for drug targets in diverse clinical samples, which integrates functions including quantitation, instrument free readout, portability, and affordability. Volumetric readouts, based on measurements of oxygen generated by a reaction between catalase and hydrogen peroxide, allow instant and visual quantitation of target drugs and biomarkers and generate visual bar charts without the need for external instruments, data processing, or graphic plotting. The development of the V-Chip thus marks a POC milestone and opens up the possibility of instrument-free personalized diagnosis and SUD management.