An Immuno-Mimetic Sensor-Actuator using Novel Polymeric Vesicles as Artificial Lymphocytes

使用新型聚合物囊泡作为人工淋巴细胞的免疫模拟传感器致动器

• 批准号: 0242647
• 负责人: Maria Santore
• 金额: $ 29.26万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2005-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0242647&HistoricalAwards=false
• 关键词: Immuno; Mimetic; Sensor; Actuator; using

An Immuno-Mimetic Sensor-Actuator using Novel Polymeric Vesicles as Artificial LymphocytesIn this program the principal investigator will develop a breakthrough sensor-actuator, mimicking the immune system to identify, amplify signal from, and respond to low levels of multiple target compounds ina wet environment. This compact (and potentially chip-based), smart system will continuouslymonitor a test space and provide independent real time chemical feedback to multiple stimuli.Microelectronics could be integrated into this stand-alone device for added functions.The proposed technology exploits novel polymeric vesicles that will act as artificiallymphocytes, a type of white blood cell. The polymeric vesicles are a new invention, made oftough membranes that will encapsulate amplification or response molecules. Different surfacereceptors on different vesicles will code for target compounds that, when present in the testingenvironment, will activate particular vesicles. The test solution flows through an amplificationcascade (a rough mimic of bone marrow) to replicate only the activated vesicles. Replicatedvesicles (a crude mimic of plasma cells) will return to the test space to release response compoundssuch as drugs or inhibitors to counteract the target compound(s) detected.The replicator cascade is like a photomultiplier tube (PMT), with amplification occurring oneach of several stages. The proposed device is, however, more advanced because, of the manytarget compounds cataloged, only those in the test space will be amplified. In the device, specificadhesive interactions facilitate separation of activated vesicles from those not yet activated. Whilethe latter are recycled, activated vesicles are lyzed to release each test compound (or analogthereof), at a concentration higher than that at the stage inlet. This solution passes to the next stagewhere the process repeats, giving a powerlaw dependence of amplification on the stage number.This program will conduct the science and device development necessary to form the basisof a single stage that later could be combined with others to produce the cascade. At the stagelevel, the goal is to maximize amplification, maintaining selectivity for activated vesicles (nottriggering the non-activated ones.) To accomplish this, the scientific investigation will addresshow adhesive interactions between receptors on vesicle and separator surfaces could be tunedthrough receptor placement and macroscopic parameters. Fundamental adhesive behavior will beassessed using micropipette aspiration methods (paralleling studies of cell adhesion) and comparedwith adhesive performance in device prototypes. Results will be interpreted using formalismsestablished for cell adhesion, appropriate for specific adhesive groups on a membrane capsule in aflowing solution.The specialized vesicles and their replication cascade form a sensor-actuator system whoseend applications bridge a number of industries, from biomedical uses to chemical process controland environmental monitoring (closed bodies of water) and response. The proposed scientificinvestigation targets designs that meet the constraints for a robust technology that will beimplantable or submersible. The scientific team bridges academic disciplines and specialty areas tocombine expertise in polymer interfaces, biomimetics, adhesion, and MEMS. Graduate andundergraduate students from different engineering and scientific backgrounds will benefit from thissynergistic approach to research, which preserves fundamental rigor and emphasizes engineeringcreativity.

在这个项目中，首席研究员将开发一种突破性的传感器执行器，模拟免疫系统来识别、放大信号，并对潮湿环境中低水平的多种目标化合物做出反应。这种紧凑（可能基于芯片）的智能系统将持续监测测试空间，并为多种刺激提供独立的实时化学反馈。微电子可以集成到这个独立的设备中，以增加功能。提出的技术利用新的聚合囊泡作为人工淋巴细胞，一种白细胞。聚合物囊泡是一项新发明，由坚韧的膜制成，可以包裹扩增或反应分子。不同囊泡上的不同表面受体将编码目标化合物，当这些化合物存在于测试环境中时，将激活特定的囊泡。测试溶液通过一个放大级联（骨髓的粗略模拟）来复制激活的囊泡。复制的囊泡（浆细胞的粗略模拟）将返回到测试空间释放反应化合物，如药物或抑制剂，以抵消检测到的目标化合物。复制子级联就像一个光电倍增管（PMT），放大发生在几个阶段中的每一个阶段。然而，所提出的设备更先进，因为在编目的许多目标化合物中，只有测试空间中的那些将被放大。在该装置中，特定的粘合剂相互作用促进了活化囊泡与未活化囊泡的分离。当后者被回收时，活化的囊泡被分解以释放每个测试化合物（或其类似物），其浓度高于级入口的浓度。这个解决方案传递到下一个阶段，在那里这个过程重复，给出一个幂律的放大依赖于阶段数。该计划将进行必要的科学和设备开发，以形成单个阶段的基础，以后可以与其他阶段结合起来产生级联。在阶段水平上，目标是最大化扩增，保持激活囊泡的选择性（不触发非激活囊泡）。为了实现这一目标，科学研究将解决囊泡和分离器表面上受体之间的粘附相互作用可以通过受体放置和宏观参数进行调整。基本的粘附行为将使用微移液管吸吸方法（细胞粘附的平行研究）进行评估，并与设备原型中的粘附性能进行比较。结果将使用为细胞粘附建立的形式来解释，适用于下列溶液中膜胶囊上的特定粘附组。专门的囊泡及其复制级联形成了一个传感器-执行器系统，其最终应用连接了许多行业，从生物医学用途到化学过程控制、环境监测（封闭水体）和响应。拟议的科学研究目标是满足可植入或可潜水的强大技术的限制。科学团队将学科和专业领域结合在聚合物界面，仿生学，粘附和MEMS方面的专业知识。来自不同工程和科学背景的研究生和本科生将受益于这种协同的研究方法，这种方法既保留了基本的严谨性，又强调了工程的创造力。