Alan Heeger

Conjugated Polymers as Light Harvesting Materials for Biosensors: Forster Resonance Energy Transfer (FRET) and the "FRET Gate"

Thursday, 30 June 2005
15:00 - 17:00 CEST


The detection of biological macromolecules (proteins and DNA) plays a critical role in a wide range of applications including clinical diagnosis, environmental monitoring, forensic analysis and antiterrorism. This demand has motivated significant interest in the development of convenient, real-time biosensors. Biosensors are devices that transduce a bio-recognition event, such as an antibody-antigen binding or the formation of a DNA duplex, into measurable electronic or opto-electronic signals. As such, biosensors offer the potential to replace traditional biochemical assays in applications, such as those listed above, in which time and operational convenience are of paramount importance. In many biosensor architectures, signal magnitude is dependent on the efficiency of electron-transfer or energy-transfer between exogenous (non-biological, and therefore readily detected even in the presence of biological contaminants) donors and acceptors (D/A) attached to the biomolecule. Because these transfer efficiencies are a sensitive function of D/A distance -- Forster resonance energy transfer (FRET) efficiency falls off with the sixth power of distance and electron-transfer (ET) rates falls off exponentially -- the modulation of electron-transfer or energy-transfer processes provides a ready means of signal generation.

In this lecture, I will focus on recent efforts at the University of California, Santa Barbara, to rationally incorporate recognition-modulated ET/FRET in sensitive, real-time electronic and optical biosensors. I will start by describing the concept of “light harvesting” by semiconducting polymers. I will then summarize the physics behind FRET with emphasis on time resolving the energy transfer process. I will then describe the use of FRET to detect specific sequences of bases on DNA using water soluble semiconducting polymers and peptide nucleic acid probes. I will conclude with a discussion of electrochemical sensors for DNA sequence detection and electrochemical sensors for protein detection. These electrochemical biosensors are based upon conformational changes of individual molecules induced by bio-specific interactions. Thus, these electrochemical biosensors are specific, sensitive, elegant and inherently simple (and thus low cost). Our goal is to create a class of biosenors that can be made available for broad use in applications ranging from diagnostics to the prevention of bioterrorism to authentication as a means of prevention of counterfeit drugs.

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