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

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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.