Integrated nanosystems for monitoring cell-signaling proteins.

Abstract

Components were developed for an integrated "lab-on-a-chip" that is intended to monitor how single cells respond to external stimuli such as toxins. At the largest length scale (of microns), the system contains a microfluidics platform that can capture single cells, provide them with nutrients, and expose them to toxins. At nanometer length scales, the system contains nanoporous electrodes that can be used to detect the proteins expressed by the captured cells when they are exposed to toxins. Capacitance changes induced on these electrodes can detect as few as four protein molecules per square micron of sensor electrode surface with a dynamic range for protein detection of around three orders of magnitude. At a molecular level, the sensor electrodes are coated with programmable self-assembled monolayers of the molecular host cyclodextrin. This film can be programmed using electrochemical signals to grab or release ferrocene molecules that are functionalized with antibodies. The antibodies are highly selective for adsorbing only those proteins of interest on the sensor surface. While the integration of the films, sensors, and fluidic systems was not completed, it is shown how these components could be used to follow the cell-signaling cascade in white blood cells that is critical to the inner workings of the human immune system. Monitoring the appearance of cytokines and other cellsignaling proteins is relevant to applications ranging from detecting pathogens for Homeland Defense to cellular-level studies that impact human health. 4 ACKNOWLEDGMENTS