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20 years ago Grischkowsky and coworkers began a revolution in the terahertz (THz) optical range [1]. Zhang and others extended this new field so that measurements unimagined previously became accessible in table top systems [2]. An immediate effort began to determine intramolecular dynamics of biomacromolecules such as RNA's and proteins. This talk will discuss how THz polarization techniques can be used to both fingerprint specific biomolecules and reveal their biologically important changes. I will also discuss challenges that must be addressed to fully realize THz light's impact on the biomedical community.

The terahertz dielectric response decreases with DNA hybridization and the temperature dependence goes from a single Arrhenius dependence to a double Arrhenius dependence, indicating sensitivity to both solvent interaction and molecular structure dynamics.

Recently compact frequency sensitive THz detection has been achieved using gated gratings on 2DEG structure. The method is based on the resonant absorption of the 2D plasmon dependence on tuning of carrier density by depletion gating. Here we demonstrate a method to improve detector sensitivity, tunability and remove polarization dependence through the development of a gated grid design. The requirement for imaging applications of device dimensions on the order of < 1 micron over a detector area of 4 mm2, suggest that standard lithographic approaches will be too costly for large scale detector production. Here we realize the gated grid plasmonic structure on 2DEG material by using nanosphere self-assembly lithography.

Using terahertz spectroscopy we show that “protein dynamical transition” has a critical size requirement. Poly-Alanine and Poly-Lysine have transition down to 5 peptides, but not below, suggesting the dynamics requires a larger scale hydration network.

Previously we reported the sensitivity of terahertz dielectric responses to the heme oxidation state for cytochrome c. Here we discuss measurements and calculations determining how correlated and diffusive motions give rise to this contrast.

THz dielectric response of ferri-cytochrome c films increases with increasing hydration with a turn over in the increase at 25% water by weight. Our calculated normal mode density shows a similar increase with increasing hydration.

Temperature-dependent THz dielectric response of hen egg-white lysozyme (HEWL) solution was measured using THz-TDS. We observe a dynamical transition at 200K, corresponding to greater protein flexibility as a function of increasing temperature.

Terahertz time domain spectroscopy reveals hydration and temperature dependent “dynamical transitions” in both native and denatured proteins. These transitions may arise from hydration dependent side chain motion with these picosecond transitions subsequently influencing tertiary dynamics.

Novel methods for obtaining infrared chemical images of materials and biological samples will be introduced and briefly reviewed.