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

利用新型聚合物囊泡作为人工淋巴细胞的免疫模拟传感器-执行器项目概述在这个项目中，主要研究人员将开发一种突破性的传感器-执行器，模拟免疫系统在潮湿环境中识别、放大信号并对低水平的多目标化合物做出反应。这个紧凑的(可能基于芯片的)智能系统将持续监测测试空间，并为多个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实现附加功能。该技术利用新型聚合囊泡作为人工淋巴细胞，这是一种白细胞。聚合物囊泡是一项新发明，由坚韧的膜制成，它将包裹放大分子或反应分子。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。测试溶液流经扩增级联反应(粗略模拟骨髓)，仅复制激活的小泡。复制的囊泡(一种粗制的浆细胞模拟物)将返回测试空间，释放响应化合物，如药物或抑制剂，以中和检测到的目标化合物(S)。复制器级联就像一个光电倍增管(PMT)，在几个阶段的每一个阶段都进行放大。然而，拟议的设备更先进，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将被放大。在该设备中，特定的粘附剂相互作用有助于将激活的囊泡与尚未激活的囊泡分开。当后者被回收时，激活的囊泡被裂解以释放每个测试化合物(或其类似物)，浓度高于级入口的浓度。这一解决方案进入下一阶段，在那里重复这一过程，使放大依赖于阶段编号。该计划将进行必要的科学和设备开发，以形成单一阶段的基础，随后该阶段可以与其他阶段结合起来产生级联。在阶段水平上，目标是最大化放大，保持激活小泡的选择性(而不是触发非激活的小泡)。为了实现这一点，科学研究将表明，囊泡和隔膜表面受体之间的粘附性相互作用可以通过受体的位置和宏观参数来调节。基本的粘合行为将使用微吸管吸入法(平行细胞粘合研究)进行评估，并与设备原型中的粘合性能进行比较。结果将使用为细胞黏附建立的形式来解释，适用于流动溶液中的膜胶囊上的特定粘附组。特殊的囊泡及其复制级联形成传感器-致动器系统，该系统的最终应用连接了从生物医学用途到化学过程控制和环境监测(闭合水体)和响应的多个行业。拟议的科学调查的目标是满足可植入或潜水的坚固技术的限制的设计。科学团队在学术学科和专业领域之间架起桥梁，将聚合物界面、生物仿生、粘合和MEMS方面的专业知识结合在一起。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的研究方法中受益，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.