A Paper-Based Synthetic Biology Platform for the On-Demand Testing of Water Quality

用于水质按需检测的纸质合成生物学平台

• 批准号: 10483253
• 负责人: Khalid Kamal Alam
• 金额: $ 77.68万
• 依托单位: STEMLOOP, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483253
• 关键词: Address; Adoption; Aging; Americas; Analytical Chemistry; Area; Awareness; Biochemical; Biochemical Reaction; Biosensing Techniques; Biosensor; Cell-Free System; Cells; Characteristics; Chronic; Collection; Communities; Companions; Consumption; Contractor; Dangerousness; Detection; Development; Developmental Disabilities; Devices; Diagnostic Reagent Kits; Diagnostic Sensitivity; Engineering; Ensure; Environment; Event; Exposure to; Eye; Filtration; Flushing; Funding; Genetic; Goals; Gold; Health; Heavy Metals; Homologous Gene; Household; Inequality; Infrastructure; Instruction; Interview; Investments; Laboratories; Lateral; Lead; Lead levels; Life; Ligands; Logistics; Methods; Microfluidic Microchips; Molecular; Monitor; Outcome; Paper; Performance; Phase; Plumbing; Poison; Positioning Attribute; Procedures; Process; Production; Proteins; Public Health; Quality Control; Reaction; Reporter Genes; Running; Safety; Sampling; Schools; Sensitivity and Specificity; Series; Shipping; Signal Transduction; Site; Source; System; Technical Expertise; Techniques; Technology; Testing; Time; Toxin; Transportation; United States; Validation; Visual; Visualization; Water; Water Pollutants; Water Supply; Work; Zinc; aged; anthropogenesis; base; chronic Pb exposure; contaminated drinking water; cost; cross reactivity; design; drinking water; field study; hazard; home test; human centered design; improved; innovation; interest; lead contamination; lead exposure; manufacturing scale-up; microorganism; mobile application; operation; physically handicapped; preservation; prototype; quality assurance; remediation; response; risk mitigation; scale up; screening; sensor technology; success; synthetic biology; technology validation; tool; transcription factor; usability; validation studies; water quality; water sampling; water testing

PROJECT SUMMARY/ABSTRACT Safe drinking water is essential for public health yet is increasingly threatened by anthropogenic activities and aging infrastructure that contaminate it with heavy metals and other toxins. Most notable in the United States is the contamination of drinking water with lead, a heavy metal that is pervasive in America’s water infrastructure and indoor plumbing. Chronic exposure to lead results in numerous adverse health and societal outcomes and is an environmental injustice that widens inequalities. Upon discovery, lead contamination can be mitigated by changing drinking water source, flushing, and existing filtration technologies. However, as recent events such as the crises in Flint, MI or Newark, NJ exemplify, improper management can lead to major public health threats by creating community-wide exposure to dangerously high levels of lead. Lead contamination of drinking water is widespread across the United States due to aged infrastructure and domestic plumbing that heavily relied on lead. Frequent monitoring for the presence of lead contamination in drinking water is part of the solution. It can identify where problems exist, alert consumers without delay, and inform risk mitigation and remediation strategies. However, reliable testing remains limited to analytical chemistry techniques that are costly, time consuming, and require substantial laboratory infrastructure and technical expertise. This complicates the large- scale of testing needed to address the lead in drinking water crisis and is a barrier to the routine testing of water supplies by consumers. Here, we propose to address these issues by pursuing the next stage of development of our technology platform that will allow for the reliable, inexpensive, on-site, and on-demand monitoring of lead in drinking water. Our technology is built from recent innovations in synthetic biology that allow us to repurpose biological sensor proteins that detect specific toxic ligands, such as heavy metals, into ‘cell-free’ reactions that produce detectable signals when lead is present. These biochemical reactions are safe and can be embedded on paper devices for long term storage and distribution. Adding water to these paper-based devices activates the biochemical reaction and produces a visual signal in the presence of a toxic compound. This Phase II proposal details a series of complementary aims for achieving improved specificity and sensitivity of this lead testing device, using a human-centered design process to improve test operation and results interpretation, and adapting our manufacturing and quality assurance/quality control processes for a scale-up of manufacturing capability for validation studies. A successful outcome of this proposal will lead to a rapid lead test with sensitivity comparable to laboratory testing, an accessible and easy-to-use device format with a companion mobile app, and pilot-scale production to validate our lead sensing technology in the laboratory and in the field. This work will enable manufacturing and commercial distribution of a highly sensitive and rapid lead biosensor, which will help address the growing water quality crisis in the United States and beyond.

项目摘要/摘要 安全饮用水对公众健康至关重要，但日益受到人为活动和 老化的基础设施，用重金属和其他毒素污染它。在美国最值得注意的是 饮用水受到铅的污染，铅是一种重金属，普遍存在于美国的水利基础设施中 还有室内管道。长期接触铅会导致许多不利的健康和社会后果，以及 是一种扩大不平等的环境不公正。一旦发现，铅污染可以通过以下方式减轻 改变饮用水水源、冲厕和现有的过滤技术。然而，随着最近发生的事件，如 正如密西西比州弗林特或新泽西州纽瓦克的危机所表明的那样，管理不当可能会导致重大的公共卫生威胁 通过在整个社区范围内暴露于危险的高铅水平。饮用水中的铅污染 由于陈旧的基础设施和严重依赖的国内管道系统，在美国各地普遍存在 领头。经常监测饮用水中是否存在铅污染是解决方案的一部分。它可以 发现问题所在，及时提醒消费者，告知风险缓解和补救措施 战略。然而，可靠的检测仍然局限于耗费时间的分析化学技术。 耗费巨大，需要大量的实验室基础设施和技术专长。这使大型的- 解决饮用水中铅危机所需的检测规模，是水常规检测的障碍 由消费者提供。在这里，我们建议通过进入下一阶段的发展来解决这些问题 我们的技术平台将实现可靠、廉价的现场和按需监控销售线索 在饮用水中。我们的技术是建立在合成生物学的最新创新基础上的，这些创新使我们能够重新定位 生物传感器蛋白，可检测特定的有毒配体，如重金属，进入“无细胞”反应， 当铅存在时，产生可检测到的信号。这些生化反应是 安全且可嵌入 用于长期储存和分发的纸质设备。向这些纸质设备中添加水会激活 在有毒化合物存在的情况下，发生生化反应并产生视觉信号。这是第二阶段 提案详细说明了一系列互为补充的目标，以提高此线索的特异性和敏感度 测试设备，使用以人为中心的设计过程来改进测试操作和结果解释，以及 调整我们的制造和质量保证/质量控制流程，以扩大制造规模 进行验证研究的能力。这一提议的成功结果将导致灵敏的快速铅测试 与实验室测试相比，这是一种易于访问和易于使用的设备格式，带有配套的移动应用程序， 并进行中试生产，在实验室和现场验证我们的铅传感技术。这部作品 将使高灵敏和快速的铅生物传感器的制造和商业销售成为可能，这将 帮助解决美国及其他地区日益严重的水质危机。