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

本项目的主要研究者将开发一种突破性的传感器-致动器，模仿免疫系统来识别、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。这种紧凑的（可能是基于芯片的）智能系统将持续监测测试空间，并为多种刺激提供独立的真实的化学反馈。微电子学可以集成到这种独立的设备中以增加功能。拟议的技术利用了新型聚合物囊泡，它将充当人工淋巴细胞，一种白色血细胞。聚合物囊泡是一项新发明，由坚韧的膜制成，可以封装扩增或反应分子。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。测试溶液流经一个扩增级联（一种粗略的骨髓模拟物），只复制激活的囊泡。复制囊泡（浆细胞的一种粗糙模拟物）将返回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。复制级联就像光电倍增管（PMT），在几个阶段的每一个阶段都发生放大。然而，拟议中的设备更先进，因为在编目的许多目标化合物中，只有那些在测试空间中的化合物会被放大。在该装置中，特异性的粘附相互作用促进了活化的囊泡与未活化的囊泡的分离。当后者被再循环时，活化的囊泡被裂解以释放每种测试化合物（或其类似物），其浓度高于阶段入口处的浓度。这个解决方案传递到下一个阶段，在那里重复这个过程，给出放大率对级数的幂律依赖性。这个计划将进行必要的科学和设备开发，以形成一个单一的阶段，以后可以与其他人相结合，以产生级联的基础。在阶段水平上，目标是最大化扩增，保持对活化囊泡的选择性（不触发非活化囊泡）。为了实现这一点，科学研究将致力于显示囊泡和分离器表面上的受体之间的粘附相互作用可以通过受体的位置和宏观参数来调节。基本的粘附行为将使用微量吸液管抽吸方法（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。结果将解释使用formalisestablished为细胞粘附，适用于特定的粘附基团膜囊在流动solution.The专门的囊泡和他们的复制级联形式的传感器-致动器系统whoseend应用桥梁的一些行业，从生物医学用途，化学过程控制和环境监测（封闭的水体）和响应。拟议中的科学调查的目标设计，满足一个强大的技术，将植入或潜水的限制。科学团队将学术学科和专业领域联系起来，将聚合物界面、仿生学、粘附和MEMS方面的专业知识结合起来。来自不同工程和科学背景的研究生和本科生将从这种协同研究方法中受益，这种方法保留了基本的严谨性并强调工程创造力。

An Immuno-Mimetic Sensor-Actuatorusing Novel Polymeric Vesicles as Artificial LymphocytesProject SummaryIn 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.