Accessing molecular communication via synthetic biology and microelectronics – gut on a chip model

通过合成生物学和微电子学 - 芯片模型肠道进行分子通讯

• 批准号: 9455959
• 负责人: WILLIAM E. BENTLEY
• 金额: $ 22.52万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-22 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9455959
• 关键词: Address; Anaerobic Bacteria; Animals; Bacteria; Behavior; Benign; Biological; Biological Process; Biology; Catechols; Cells; Chemical Engineering; Chemicals; Chitosan; Coculture Techniques; Communication; Communities; Complex; Cues; DNA Microarray Chip; Development; Device Designs; Devices; Diagnosis; Diagnostic; Disease; Dopa; Electrocardiogram; Electrodes; Electronics; Electrons; Elements; Endoscopy; Engineering; Environment; Enzyme Activation; Enzymes; Epithelial Cells; Equipment; Escherichia coli; Feedback; Film; Gastrointestinal tract structure; Gene Expression; Genetic; Geometry; Glucose; Goals; Health; Homeostasis; Human; Hydrogels; Hydrogen Peroxide; Image; In Situ; In Vitro; Intestines; Ions; Language; Length; Link; Liquid substance; Measurement; Measures; Mechanics; Mediating; Mediator of activation protein; Methodology; Methods; Microfabrication; Microfluidic Microchips; Microfluidics; Modeling; Molecular; Molecular Probes; Mono-S; Nature; Optics; Organ; Output; Oxidation-Reduction; Oxides; Oxygen; Performance; Phenotype; Photons; Polysaccharides; Process; Proteins; Pseudomonas aeruginosa; Pyocyanine; Reporting; Reproducibility; Research Personnel; Resolution; Sampling; Sepharose; Signal Transduction; Signaling Molecule; Specificity; Speed; System; Systems Integration; Technology; Testing; Time; VAI-2; Work; base; beta-Galactosidase; biofabrication; biological systems; calginat; cell growth; design; drug discovery; flexibility; glucose monitor; glucose oxidase; gut microbiome; human disease; innovation; insight; lithography; microorganism; molecular recognition; novel; quorum sensing; response; sensor; spatiotemporal; synthetic biology; tool; uptake

PROJECT SUMMARY Synthetic biologists develop tools and approaches to endow microorganisms with novel attributes and behaviors, as well as the ability to synthesize novel products. There have been few reports, however, wherein bacteria serve as components of devices created to transmit biological information to and from electronic devices. Information flow between biological systems and electronic devices is complicated by the fact that most of biological function is mediated by molecular or ionic cues, while devices are programmed by electrons and photons. Technologies that have facilitated the bio/device intersection have changed our lives (e.g., EKG). Our objective is to rewire bacteria to serve as information translators and to do this in a way that facilitates understanding of human health. The human gastrointestinal microbiome, often viewed as a complex organ itself, influences homeostasis and is implicated in many human diseases. GI tract geometry is complex and its microenvironments are widely varied. pH and oxygen levels exist from the most acidic to neutral, and from completely anaerobic to oxygen saturation levels, respectively. There are few methodologies that enable resolution of its signaling, cell growth, and chemical environments even at the macro length scale. In the last several years however, researchers have developed micro and meso systems for interrogating GI tract biology. Capsular endoscopy has enabled first-of-kind remote imaging. At the microscale, organ or animal-on-a-chip methodologies provide first-of-their kind access to biological function in user-controlled conditions. Both methodologies will open new avenues for diagnosis and treatment of human disease. Both methodologies, however, lack the ability to interrogate and modulate biological signaling at cellular length scales and in real time. The proposed studies will enlist synthetic biology to create `smart' hydrogels for interrogating molecular space. The innovation of this proposed study is the development of `biological lithography', where polyelectrolyte polysaccharides, doped with redox responsive catechols, will be layered with engineered cells for an expanded repertoire of molecular recognition and information transfer. Importantly, fabrication methodologies are simple and biologically benign so that these sensing materials can be assembled in situ in minutes and with no added mechanical equipment. To date, in vitro devices at both micro and meso scale do not provide molecular information at the length and time scales of the cells they interrogate. The significance of this work is its complementarity to animal-on-a-chip systems, capsular endoscopy devices, and other methodologies that have great promise for advancing diagnosis and treatment of disease but that lack access to molecular cues and information transfer.

项目摘要 合成生物学家开发了具有新型属性和行为的微生物的工具和方法 作为合成新产品的能力。然而，很少有报道，其中细菌用作成分 创建的设备是为了向电子设备传输生物学信息。生物学之间的信息流 由于大多数生物学功能都是由分子或离子介导的，因此系统和电子设备变得复杂 提示，而设备由电子和光子编程。促进生物/设备的技术 交叉路口改变了我们的生活（例如，心电图）。我们的目的是重新布线细菌作为信息翻译者和 以促进对人类健康的理解的方式来做到这一点。 人类胃肠道微生物组通常被视为复杂的器官本身，会影响体内平衡，并被牵连 在许多人类疾病中。胃肠道几何形状很复杂，其微环境广泛变化。 pH和氧气 从最酸性到中性的水平分别存在，分别从完全厌氧到氧饱和度。那里 很少有能够解决其信号传导，细胞生长和化学环境的方法学 长度尺度。然而，在过去的几年中，研究人员开发了用于询问GI的微型和中间系统 道生物学。囊膜内窥镜检查启用了首先远程成像。在微观，器官或芯片上的动物 在用户控制条件下，方法论提供了对生物学功能的首次访问。两种方法 将为诊断和治疗人类疾病开放新的途径。但是，这两种方法都缺乏能力 在细胞长度尺度和实时调查生物信号传导。 拟议的研究将吸引合成生物学，以创建“智能”水凝胶来询问分子空间。这 这项拟议的研究的创新是“生物光刻”的发展，在那里聚电解质多糖，其中 用氧化还原响应式儿茶素掺杂，将与工程细胞分层，以扩大分子库 识别和信息转移。重要的是，制造方法是简单且生物学上的，因此 这些传感材料可以在几分钟内原位组装，并且没有添加的机械设备。迄今为止，体外 微型和中索量表的设备都不提供细胞的长度和时间尺度的分子信息 审问。这项工作的意义在于它与芯片上的动物，囊膜内窥镜设备，互补性， 以及其他可以推进诊断和治疗疾病但缺乏进入的方法论 分子提示和信息传递。