The Vanderbilt University Free-Electron Laser Center was established to apply the free- electron laser to interdisciplinary research in medicine, biology, and materials science. The free-electron laser is tunable over the range from 2 to 8 micrometers , with an average power up to 11 W. In its first user period, the laser logged around 1500 hours and served more than 23 groups from around the world.

The Center for Free-Electron Laser Studies (CFELS) at UCSB has been established to pursue applications and development of far infrared free electron lasers. The FELs are driven by an electrostatic 6 MV Van De Graaf recirculating accelerator. Independent electron beam optics steer the electron beam through two static hybrid-type undulators. Tuneable radiation is provided from 2.5 mm to 63 micrometers wavelength. Under development is a third FEL, capable of lasing on the third harmonic and producing radiation from 60 micrometers to 30 micrometers . FIR experiments are carried out at the CFELS user facility where an evacuated transport system switches the FIR beam into one of seven ports. In addition, various ancillary equipment is available to facilitate research with the FELs.

The Duke Free Electron Laser (FEL) Laboratory is housed in a 52,000 square foot adjacent to the Physics and Math Building at Duke University. There will be several EELs in the laboratory. The first is the linear accelerator-based Mark ifi FEL which has been operational since February 1992 (see Fig. 1). It is capable of providing electron beam energies of up to 44 MeV with an optical output tunable from 1.7-9.1 microns. The infrared beam consists of a train of micropulses 0.5-3 psec duration at the RF frequency of 3 GH (350 psec separation of the micropulse). The RF is delivered in 2-6 ji. secpulses at a nominal repetition rate of 10 Hz. The repetition rate of the macropulses can be varied from 1-20 Hz.

The Stanford Picosecond Free Electron Laser (FEL) Center has been established to support a broad range of biomedical and materials science research. In addition to the FEL, the Center has several conventional lasers available for experiments with high power, picosecond pulses of light. The FEL and the conventional lasers provide wavelength coverage from the visible to 100 microns. A wide variety of equipment, instruments, and standardized optical setups provide users with a flexible and powerful environment for research. This paper lists the facilities available at the FEL Center, and discusses the challenges encountered in developing a new user facility.

Electrons in semiconductor nanostructures such as quantum wells can exhibit a highly nonlinear response to far-infrared radiation of sufficient intensity, such as can be supplied by the free-electron lasers (FELs) at UCSB. Several different physical mechanisms can cause nonlinear behavior in nanostructures. Experimental results at UCSB demonstrate that transport, absorption, and harmonic generation can be used as probes of nonlinear response. In the future, it may be possible to use the UCSB-FELs to observe completely new nonlinear phenomena, such as non-perturbative quantum resonances in quantum wells driven by intense far-infrared radiation.

Carriers confined in quantum well structures in the GaAs-Al_xGa_1-xAs and InAs-AlSb systems have strongly nonlinear response at far-infrared (FIR) frequencies: they are strong harmonic generators. To date, studies of FIR frequency harmonic generation from heterostructures have been limited primarily to discrete frequencies accessible by molecular gas lasers (MGL). Because the mechanisms responsible for harmonic generation are expected to have frequency dependence in the FIR, the broad, continuous frequency coverage of the free electron lasers (FEL) at UCSB (4 cm^-1 - 25 cm^-1 for the millimeter FEL, and 32 cm^-1 to 155 cm^-1 for the FIR FEL) make them ideal sources for studies of free carrier nonlinearities in heterostructures. Quantitative experiments on harmonic generation must distinguish the small harmonic signals generated by the samples from the fundamental, and from the harmonic content of the incident FEL light. Here we discuss strategies for achieving the required selectivity, preliminary data taken with an MGL on heterostructure samples, and data taken with the FEL for a suitable calibration sample, LiNbO₃.

We have measured the broad band terahertz response of state of the art InGaAs/AlAs and InAs/AlSb resonant tunneling diodes from 180 GHz to 3.6 THz using the free-electron lasers at UCSB. A tungsten whisker antenna in a conventional probe station is used to couple the far- infrared radiation into the device. Normalizing the resonant tunneling response with the off- resonant response allows us to circumvent the much slower RC time constant of the device and consequently enables a measurement of the relaxation time due to the quantum inductance.

This paper describes the results of novel experiments made possible by the recently commissioned Vanderbilt Free-Electron Laser (VU-FEL_, the brightest tunable midinfrared FEL in the world. We emphasize two classes of experiments, novel semiconductor spectroscopies and wavelength-dependent laser ablation studies. Both take advantage of the high brightness and the tunability of the FEL. We have recently demonstrated the feasibility of measuring semiconductor heterojunction band discontinuities using the internal photoemission (IPE) technique and report the results for the cases of GaAs/GaAlAs and a-Ge/GaAs. The basic physical mechanism of IPE is that a photocurrent is produced by optically pumping electrons over the conduction band discontinuity (Delta) E_c. A photocurrent threshold is observed when the photon energy exceeds (Delta) E_c. Because IPE is optical in nature, (Delta) E_c can be determined with unprecedented accuracy (5 meV). By comparison, the best known direct method of measuring band discontinuities (UPS or XPS) achieves accuracies of only 100 meV.

Strong enhancement in the second harmonic generation signal is observed in the mid-infrared in ultra-narrow p-type asymmetric GaAs quantum wells. The experiments have been performed with the high power, tunable free electron laser located at Stanford University

In this paper we examine the use of a high-power, tunable free-electron laser (FEL) source to measure photoluminescence (PL) and photoluminescence excitation (PLE) spectra in two classes of disordered semiconductors, amorphous semiconductors and partially ordered III-V ternary semiconductors. The source must be tunable to follow the absorption continuously across the region of the optical energy gap, and the source must be of high power to provide enough absorbed photons in this relatively transparent spectral region so that PL processes can be measured. The usefulness of PLE spectroscopy in these semiconducting thin films lies in the fact that if the quantum efficiency (eta) for the PL process is independent of energy, then the PLE spectrum is a measure of the optical absorption. In addition, disordered semiconductors often exhibit enhanced absorption below the optical gap due to the disorder itself. PLE measurements that probe regions where the absorption coefficient (alpha) is small ((alpha) < < 10³ cm^-1) are most important because in these regions (alpha) is dominated by the electronic states introduced by the disorder.

The first infrared vibrational photon echo experiments conducted in a liquid and a glass are reported. The experiments were performed on the CO stretching mode of tungsten hexacarbonyl at 5.1 micrometers (1960 cm^-1) in 2-methyltetrahydrofuran over the temperature range 300 K to 16 K using picosecond pulses from the free electron laser at Stanford University. In addition, the first vibrational population relaxation measurements spanning a temperature range that takes a system from a liquid to a supercooled liquid to a glass are reported.

There has been a significant financial effort poured into the technology of the Free Electron Laser (FEL) over the last 15 years or so. Much of that money was spent in the hopes that the FEL would be a key element in the Strategic Defense Initiative, but a small fraction of money was allocated for the Medical FEL program. The Medical FELs program was aimed at exploring how the unique capabilities of the FEL could be utilized in medical applications. Part of the Medical FEl effort has been in clinical applications, but some of the effort has also been put into exploring applications of the FEL for fundamental biological physics. It is the purpose of this brief text to outline some of the fundamental biophysics I have done, and some plans we have for the future. Since the FEL is (still) considered to be an avant garde device, the reader should not be surprised to find that much of the work proposed here is also rather radical and avant garde.

The vibrational dynamics of O-H groups in fused silica have been examined by a time- resolved pump-probe technique using the Vanderbilt Free Electron Laser (FEL). We consider two effects, local heating and transient thermal lensing, which can influence measured T₁ values in one color pump-probe measurements. The dependence of these two effects on both the micropulse spacing and the total number of micropulses delivered to the sample are analyzed in detail for the O-H/SiO₂ system. The results indicate that transient thermal lensing can significantly influence the measured probe signal. The local heating may cause thermally induced changes in the ground state population of the absorber, thereby complicating the analysis of the relaxation dynamics.

Sequencing the human genome requires an interdisciplinary approach combining aspects of biology, chemistry, physics, and engineering applied at the molecular level. One potentially interesting approach involves the use of matrix-assisted laser desorption-ionization mass spectroscopy (MALDI-MS), because of its high sensitivity, high speed, great accuracy, and ease of automation. However, while MALDI-MS has been successful in mass analysis of proteins and many large biomolecules, attempts to apply the technique to DNA sequencing have proven notoriously difficult. Because the choice of matrix materials for MALDI-MS is severely constrained by the application of conventional UV and visible laser sources, we are investigating the application of a tunable infrared free-electron laser to test the potential of infrared MALDI-MS for DNA sequencing. We describe the advantages of using tunable IR laser sources to choose matrix materials with optimal desorption, ionization, and thermomechanical properties, while avoiding the photochemical effects induced by ultraviolet and visible lasers. We also show the results of preliminary MALDI-MS experiments on small organic molecules using the Vanderbilt free-electron laser.

Ultra-fast time-resolved infrared spectroscopy is discussed as a tool for investigating protein dynamics. Due to continuing developments in laser technology, researchers have recently begun to take advantage of the utility of vibrational spectroscopies as structural probes in studying the fast timescale dynamics of complex macromolecular systems. The structural complexity of proteins necessitates a wide range of infrared frequencies and timescales in order to obtain a detailed understanding of their conformational dynamics. Free electron lasers are uniquely well suited to this task, as designs are possible which provide ultra-short coherent light pulses throughout the infrared spectral region. Studies planned for the Stanford Picosecond FEL Center on reaction dynamics in the trans-membrane cytochrome oxidase proteins and protein folding in polypeptides are described. These serve as examples of the contributions free electron lasers will make in the fields of biochemistry and biophysics.

Sapphire and fluoride glass fiber optics were tested for their ability to deliver pulsed infrared laser energy. Commercial fluorozirconate fibers were found to deteriorate under pulsed laser irradiation when the wavelength was near the absorption peak of water at 2.94 micrometers. Irradiation of these fibers with modest fluences (30 mJ/cm²) of Er:YAG at 2.94 micrometers (200 microsecond(s) pulses at 6 Hz) or free electron laser (FEL) pulses (2 ps pulses in 2 microsecond(s) bursts delivered at 10 Hz) caused damage to the end faces within 30 minutes. The observations suggest a process capable of integrating energy. Because of the high transmission, no heat builds up in the fiber, but small (sub-micron) absorption sites may form due to possible chemical reactions.

The Vanderbilt Free Electron Laser operating at wavelengths from 2.8 to 5.0 micrometers was focused and used to ablate samples of human temporal bone from cadavers, swatches of leather, and Plexiglas. The ablation efficiency, energy density necessary for ablation, and thermal damage to the surrounding tissue was investigated in all three samples. Comparisons are made between the different wavelength and the light interaction with tissue. At the highest intensities, a plasma is formed at the air tissue interface. The ablation process at these intensities is strongly influenced by the plasma, and the rate of ablation appears to become nearly independent of the laser wavelength. At lower intensities, the laser light interacts with the tissue in a more traditional fashion.

A free-electron laser (FEL) microscope has been constructed to perform spatially and spectrally resolved pump/probe experiments in single living cells. Picosecond infrared FEL pulses are absorbed by the sample and rapidly converted to heat. Excitation of localized fluorescent reporter molecules using a UV/VIS probe beam leads to thermally induced alterations in the radiative signal. Fluorescence-detected infrared (FDIR) spectra are generated from regions proximal to reporter molecules by varying the FEL pump wavelength. Sub- wavelength spatial resolution is a composite function of media thermal properties and probe selectivity.

The Free Electron laser was used to explore ablative and toxic effects of infrared irradiation of the cornea at wavelengths ranging from 2.5 - 4.0 micrometers including the peak absorptive wavelength for water of 2.94 micrometers . The macropulse length was 6 microsecond(s) . Effects were studied by visible light and scanning electron microscopies. Ablation was noted at a threshold fluence of 550 - 750 mJ(DOT)cm^-2 and above at a wavelength of 2.94 micrometers . Ablation was accompanied by a distinct zone of tissue denaturation extending up to 12 micrometers into the adjacent tissue. Thermal denaturation appears to be a significant effect of infrared free-electron irradiation on the cornea and appears to be a consequence of the relatively long macropulse duration.

The therapeutic applications of laser-induced stress waves have been limited to the disruption of noncellular material such as renal stones, atheromatous plaque, vitreous strands and other ocular membranes. Recent experiments at the Wellman Laboratories of Photomedicine have demonstrated that there is also potential therapeutic applications of laser-induced stress waves for cellular processes. It has been established that stress waves can lead to selective killing of the cell cultures. The present studies are designed to investigate in a coherent way the parameters of the stress waves that can most efficiently cause cell death. This work coupled with the characterization of laser-induced pressure waves determine whether the scheme of selective killing of cells meditated by stress waves is a valid concept as a treatment. Laser- induced stress wave generation has unique properties when compared to other methods of generating pressure transients, particularly, ultrasound. These properties allow for the isolation of stress waves some of the other physical phenomena that occur during ultrasound and which frequently overwhelm the more subtle and potentially useful effects of the pressure transients. In combination with drugs, the laser-induced stress waves may offer a unique treatment regimen.