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

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

An Immuno-Mimetic Sensor-Actuator using Novel Polymeric Vesicles as Artificial Lymphocytes In 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 in a wet environment. This compact (and potentially chip-based), smart system will continuously monitor 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 artificial lymphocytes, a type of white blood cell. The polymeric vesicles are a new invention, made of tough membranes that will encapsulate amplification or response molecules. Different surface receptors on different vesicles will code for target compounds that, when present in the testing environment, will activate particular vesicles. The test solution flows through an amplification cascade (a rough mimic of bone marrow) to replicate only the activated vesicles. Replicated vesicles (a crude mimic of plasma cells) will return to the test space to release response compounds such as drugs or inhibitors to counteract the target compound(s) detected. The replicator cascade is like a photomultiplier tube (PMT), with amplification occurring on each of several stages. The proposed device is, however, more advanced because, of the many target compounds cataloged, only those in the test space will be amplified. In the device, specific adhesive interactions facilitate separation of activated vesicles from those not yet activated. While the latter are recycled, activated vesicles are lyzed to release each test compound (or analog thereof), at a concentration higher than that at the stage inlet. This solution passes to the next stage where 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 basis of a single stage that later could be combined with others to produce the cascade. At the stage level, the goal is to maximize amplification, maintaining selectivity for activated vesicles (not triggering the non-activated ones.) To accomplish this, the scientific investigation will address how adhesive interactions between receptors on vesicle and separator surfaces could be tuned through receptor placement and macroscopic parameters. Fundamental adhesive behavior will be assessed using micropipette aspiration methods (paralleling studies of cell adhesion) and compared with adhesive performance in device prototypes. Results will be interpreted using formalisms established for cell adhesion, appropriate for specific adhesive groups on a membrane capsule in a flowing solution. The specialized vesicles and their replication cascade form a sensor-actuator system whose end applications bridge a number of industries, from biomedical uses to chemical process control and environmental monitoring (closed bodies of water) and response. The proposed scientific investigation targets designs that meet the constraints for a robust technology that will be implantable or submersible. The scientific team bridges academic disciplines and specialty areas to combine expertise in polymer interfaces, biomimetics, adhesion, and MEMS. Graduate and undergraduate students from different engineering and scientific backgrounds will benefit from this synergistic approach to research, which preserves fundamental rigor and emphasizes engineering creativity.