GOALI: Dielectric Microwave Spectroscopy of Macromolecular Recognition Events in Differential Transmission Lines

University Of California-Davis, Davis CA

Investigators

Abstract

0245716 Knoesen The development of methods to detect and characterize interactions between biomolecules in their physiological environments, in real time, and without the use of extrinsic tags or markers such as fluorescent dyes or conjugated enzymes is of great interest to map biochemical pathways that lead to disease states, monitor patients for clinically relevant analytes, detect infectious agents and environmental toxins, and the development of drugs. It is also desirable to measure these interactions in heterogeneous media such as biocompatible nanoporous or microporous structured materials (e.g. silica, titania, alumina) since such media could, in principle, provide an exquisite level of sensor sensitivity as they provide high surface areas for increased attachment density of receptors, and the surface energy and pore sizes can be manipulated to provide selective adsorption. Current optical-based sensors (SPR and protein chips), however, require a planar configuration for detection and are not compatible with porous films because of the optical scattering invariably accompanying such materials. Recent improvements in the spectral purity, stability and tunability of microwave sources are creating the opportunity for highly sensitive magnitude and phase measurements of signals up to at least 20 GHz that can be used to detect subtle dielectric changes with high accuracy over a large dynamic range. Recently it was shown that specific molecular binding events occurring at an interface can be detected by microwave dielectric spectroscopy. If microwave structures could be optimized (design and materials) and used for unambiguous identification of specific binding of low concentration analytes without extrinsic tags, the technique has the potential to revolutionize biomolecular detection. Furthermore, as is proposed in this project, since microwaves can interrogate optically opaque regions, the technique has potential applications that cannot be addressed by optical means. While this initial development is promising, it raises several important questions: (i) what is the nature of the electromagnetic interaction that occurs in the microwave domain that leads to the detection and identification of a molecular event that occurs in an ultrathin macromolecular layer? (ii) can microwave structures be engineered and optimized to provide a competitive advantage over optical biosensors to directly detect and distinguish between different binding events? This proposal brings together the complementary strengths of three groups with the support of their institutions (UC Davis; microwave measurements and spectroscopy, IBM-Almaden; materials research, Agilent Laboratories; expertise in molecular detection and microwave instrumentation) with the goal of implementing, characterizing, and analyzing microwave structures to investigate real-time detection, differentiation and quantification of biomolecular binding at interfaces. This interdisciplinary team will develop planar microwave transmission line structures, integrated with meso-fluidic systems, that make use of model immunoprotein binding assays of increasing complexity to investigate the electromagnetic interactions which indicate specific binding events occurring at planar (2D) interfaces and inside porous materials (3D materials). Dual transmission line structures will be used to reduce external effects that could otherwise obscure the detection and identification of a binding event. The dielectric dispersion changes associated with binding events will be studied in various microporous materials and structures of which the morphology and surface energies have been controlled to stabilize receptors that can entrap specific biomolecules. This multi-disciplinary project immerses students in research that transcends the boundaries between microwave engineering, the life sciences and organic, inorganic and polymer chemistry. The students will be exposed to the philosophies of two major industrial research organizations (Agilent and IBM Almaden Research) and gain access to their personnel and resources.