Bio-Based "Molectronic" Devices for Bidirectional Molecular-to-Electronic Signal Transduction

用于双向分子到电子信号转导的生物基“分子”器件

• 批准号: 1805274
• 负责人: William Bentley
• 金额: $ 38.36万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1805274&HistoricalAwards=false
• 关键词: Bio; Based; Molectronic; Devices; Bidirectional

Recent revelations have linked the human microbiome of the gastrointestinal tract to disease, behavior, and even mental health. Yet, there are few methodologies that enable study of these linkages, particularly the molecular signaling processes between the molecules, cells, and tissues involved, let alone their connection to behavior. Human and animal studies are expensive and time consuming, and they typically do not provide information at the molecular level. Importantly, it is at this level that information is needed. Culturing human cells and tissues on miniature microfluidic devices to mimic actual systems in the human body has been considered as one of the most promising alternatives to human or animal studies. While potentially transformative, these devices can be complex, as they sometimes include nutrient supplies, cells, actuators, pumps, valves, and even detector systems. To simplify, the principal investigator (PI) proposes a modular approach comprised of optimally designed subsystems. Their approach will also provide new efficient avenues for manipulating these cells and understanding their responses to molecular signals. Microelectrodes will be integrated and directly connected to cells and tissues for stimulating and interrogating cellular responses. Because the biological systems are "wired" to electrodes, this enables "programmed" function and highly accurate assessment of responses.Previously the PI's group has developed methods to electronically actuate and record signaling processes among bacteria and epithelial cells of human GI tract. While information processing in biology is accomplished by the secretion and perception of molecules, information processing within electronic devices is accomplished using electrons. The methodologies they have developed interconvert information content as it flows from molecules to electrons and back. To do this, they use synthetic biology and thin film microfabrication methodologies to assemble "smart" interfaces between biological systems and microelectronic devices. They base their methods on redox-based signals that uniquely span communication modalities. There are three specific aims in the proposed work. In Aim 1, the PIs will develop actuator devices that transduce electrical inputs to molecular signaling molecules, specifically bacterial quorum sensing autoinducers that regulate behavior. In Aim 2, they will develop sensor devices that communicate in the opposite direction - biomolecular information will be converted to electrical outputs. The researchers will determine molecular concentrations electronically, both directly and with the aid of enzymes and engineered cells that are incorporated into the devices. In Aim 3, these sensor/actuator modules will be integrated into a complete "animal-on-a-chip" system. Using this modular approach, the complexity of the current systems will be reduced, the throughput of these devices will be increased, and the efficiency of the entire process will be dramatically enhanced. The PIs expect these studies will vastly improve our ability to understand the ?communication? between molecules, cells, and tissues in the human body. Most importantly, the proposed work creates a new vantage point for interrogating biology at the length and time scales associated with its function. Equally importantly, because these systems incorporate techniques and methods from several disciplines, and because the perceived benefits to society are so great, they attract energetic and talented students who will become the innovators and leaders of the future.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

最近的发现将人类胃肠道微生物组与疾病，行为甚至心理健康联系起来。然而，很少有方法能够研究这些联系，特别是所涉及的分子、细胞和组织之间的分子信号传导过程，更不用说它们与行为的联系了。人类和动物研究既昂贵又耗时，而且通常不能提供分子水平的信息。重要的是，这一级需要信息。在微型微流体装置上培养人类细胞和组织以模拟人体中的实际系统已被认为是人类或动物研究的最有前途的替代方案之一。虽然这些设备可能具有变革性，但它们可能很复杂，因为它们有时包括营养供应，细胞，致动器，泵，阀门甚至检测器系统。为了简化，主要研究者（PI）提出了一种由优化设计的子系统组成的模块化方法。他们的方法还将为操纵这些细胞和理解它们对分子信号的反应提供新的有效途径。微电极将被集成并直接连接到细胞和组织，用于刺激和询问细胞反应。由于生物系统与电极“连接”，这使得“程序化”功能和高度准确的反应评估成为可能。此前，PI的团队已经开发出电子驱动和记录人类胃肠道细菌和上皮细胞之间信号过程的方法。虽然生物学中的信息处理是通过分子的分泌和感知来完成的，但电子设备内的信息处理是使用电子来完成的。他们开发的方法学在信息内容从分子流向电子并返回时相互转换。为此，他们使用合成生物学和薄膜微制造方法来组装生物系统和微电子设备之间的“智能”接口。他们的方法基于基于氧化还原的信号，这些信号独特地跨越了通信模式。拟议工作有三个具体目标。在目标1中，PI将开发致动器设备，将电输入转换为分子信号分子，特别是调节行为的细菌群体感应自诱导物。 在目标2中，他们将开发在相反方向上通信的传感器设备-生物分子信息将被转换为电输出。研究人员将以电子方式确定分子浓度，包括直接和借助酶和纳入设备的工程细胞。在目标3中，这些传感器/执行器模块将被集成到一个完整的“动物芯片”系统中。使用这种模块化方法，将降低当前系统的复杂性，增加这些设备的吞吐量，并大大提高整个过程的效率。PI希望这些研究将大大提高我们理解的能力？沟通？分子、细胞和组织之间的相互作用。最重要的是，这项工作为在与其功能相关的长度和时间尺度上询问生物学创造了一个新的Vantage位置。同样重要的是，由于这些系统融合了多个学科的技术和方法，而且对社会的感知效益如此之大，因此它们吸引了充满活力和才华的学生，他们将成为未来的创新者和领导者。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Homologous Quorum Sensing Regulatory Circuit: A Dual-Input Genetic Controller for Modulating Quorum Sensing-Mediated Protein Expression in E. coli.

• DOI: 10.1021/acssynbio.0c00179
• 发表时间: 2020-10-16
• 期刊: ACS synthetic biology
• 影响因子: 4.7
• 作者: Hauk P;Stephens K;Virgile C;VanArsdale E;Pottash AE;Schardt JS;Jay SM;Sintim HO;Bentley WE
• 通讯作者: Bentley WE

Catechol Patterned Film Enables the Enzymatic Detection of Glucose with Cell Phone Imaging

• DOI: 10.1021/acssuschemeng.1c04896
• 发表时间: 2021-10
• 期刊: ACS Sustainable Chemistry & Engineering
• 影响因子: 8.4
• 作者: Si Wu;J. Rzasa;Eunkyoung Kim;Zhiling Zhao;Jinyang Li;W. Bentley;N. N. Payne-N.;Xiaowen Shi;G. Payne

Mediated Electrochemical Probing: A Systems-Level Tool for Redox Biology

介导电化学探测：氧化还原生物学的系统级工具

• DOI: 10.1021/acschembio.1c00267
• 发表时间: 2021
• 期刊: ACS Chemical Biology
• 影响因子: 4
• 作者: Zhao, Zhiling;Ozcan, Evrim E.;VanArsdale, Eric;Li, Jinyang;Kim, Eunkyoung;Sandler, Anthony D.;Kelly, Deanna L.;Bentley, William E.;Payne, Gregory F.
• 通讯作者: Payne, Gregory F.

Single-Step Synthesis of Alginate Microgels Enveloped with a Covalent Polymeric Shell: A Simple Way to Protect Encapsulated Cells

一步合成共价聚合物壳包裹的藻酸盐微凝胶：保护封装细胞的简单方法

• DOI: 10.1021/acsami.0c20613
• 发表时间: 2021
• 期刊: ACS Applied Materials & Interfaces
• 影响因子: 9.5
• 作者: Ahn, So Hyun;Rath, Medha;Tsao, Chen-Yu;Bentley, William E.;Raghavan, Srinivasa R.
• 通讯作者: Raghavan, Srinivasa R.

Hydrogel Patterning with Catechol Enables Networked Electron Flow

• DOI: 10.1002/adfm.202007709
• 发表时间: 2021-01
• 期刊: Advanced Functional Materials
• 影响因子: 19
• 作者: Si Wu;Zhiling Zhao;J. Rzasa;Eunkyoung Kim;Jinyang Li;Eric VanArsdale;W. Bentley;Xiaowen Shi;G. Payne