John A. Kozub

Free-electron lasers: reliability, performance, and beam delivery

The Vanderbilt free-electron laser (FEL) is a continuously tunable source of pulsed, mid-infrared radiation. FEL applications research has been underway for a decade. Recent experimental advances in FEL ablation of soft tissue indicate the potential for FEL-based protocols in surgery and medicine. In anticipation of these medical applications, the Vanderbilt FEL is being upgraded to meet the reliability and performance standards for a medical laser. Facilities for laser surgery have been constructed and equipped and medical delivery systems are being developed for pre-clinical and clinical research.

Laser-Induced Current Transients in Silicon-Germanium HBTs

Device-level current transients are induced by injecting carriers using two-photon absorption from a subbandgap pulsed laser and recorded using wideband transmission and measurement equipment. These transients exhibit three distinct temporal trends that depend on laser pulse energy as well as the transverse and vertical charge generation location. The nature of the current transient is controlled by both the behavior of the subcollector-substrate junction and isolation biasing. However, substrate potential modulation, due to deformation of the subcollector-substrate depletion region, is the dominant mechanism affecting transient characteristics.

The effect of free-electron laser pulse structure on mid-infrared soft-tissue ablation: biological effects

Previous studies have shown that changing the pulse structure of the free electron laser (FEL) from 1 to 200 ps and thus reducing the peak irradiance of the micropulse by 200 times had little or no effect on both the ablation threshold radiant exposure and the ablated crater depth for a defined radiant exposure. This study focuses on the ablation mechanism at 6.1 and 6.45 microm with an emphasis on the role of the FEL pulse structure. Three different experiments were performed to gain insight into this mechanism. The first was an analysis of the ablation plume dynamics observed for a 1 ps micropulse compared with a 200 ps micropulse as seen through bright-field analysis. Negligible differences are seen in the size, but not the dynamics of ablation, as a result of this imaging. The second experiment was a histological analysis of corneal and dermal tissue to determine whether there is less thermal damage associated with one micropulse duration versus another. No significant difference was seen in the extent of thermal damage on either canine cornea or mouse dermis for the micropulse durations studied at either wavelength. The final set of experiments involved the use of mass spectrometry to determine whether amide bond breakage could occur in the proteins present in tissue as a result of direct absorptions of mid-infrared light into the amide I and amide II absorption bands. This analysis showed that there was no amide bond breakage due to irradiation at 6.45 microm on protein.

Raman-shifted alexandrite laser for soft tissue ablation in the 6- to 7-µm wavelength range

Prior work with free-electron lasers (FELs) showed that wavelengths in the 6- to 7-µm range could ablate soft tissues efficiently with little collateral damage; however, FELs proved too costly and too complex for widespread surgical use. Several alternative 6- to 7-µm laser systems have demonstrated the ability to cut soft tissues cleanly, but at rates that were much too low for surgical applications. Here, we present initial results with a Raman-shifted, pulsed alexandrite laser that is tunable from 6 to 7 µm and cuts soft tissues cleanly—approximately 15 µm of thermal damage surrounding ablation craters in cornea—and does so with volumetric ablation rates of 2–5 × 10−3 mm3/s. These rates are comparable to those attained in prior successful surgical trials using the FEL for optic nerve sheath fenestration.

The effect of free-electron laser pulse structure on mid-infrared soft-tissue ablation: ablation metrics

Pulsed mid-infrared (6.45 microm) radiation has been shown to cut soft tissue with minimal collateral damage (<40 microm); however, the mechanism of ablation has not been elucidated to date. The goal of this research was to examine the role of the unique pulse structure of the Vanderbilt Mark-III free-electron laser (FEL) and its role in the efficient ablation of soft tissue with minimal collateral damage. The effect of the picosecond micropulse was examined by running the native FEL pulse structure through a pulse stretcher in order to increase the micropulse length from 1 ps up to approximately 200 ps. This allowed us to determine whether or not the picosecond train of micropulses played any role in the ablation process. The ablation threshold was determined for water and mouse dermis for each micropulse length. While the results of the analysis showed a statistically significant difference between 1 and 200 ps, the average per cent difference amounts to only 28% and is not proportional to the 200-fold drop in peak irradiance. The ablation efficiency was also measured on gelatin and mouse dermis for the different micropulse lengths. A small but statistically significant difference was observed between 1 and 200 ps, with the 200 ps pulse being more efficient on gelatin, and with the opposite trend for mouse dermis. We have shown that there is a small effect of micropulse duration of the FEL on the ablation process; however, this effect is negligible between 1 and 200 ps given that there is a 200-fold decrease in peak intensity. These results suggest that as we move forward in developing alternative laser sources for tissue ablation to replace the FEL, the picosecond micropulse structure is not a critical parameter that needs to be duplicated.

The Impact of Depletion Region Potential Modulation on Ion-Induced Current Transient Response

Transient capture measurements on an irradiated diode show the effect of increasing ion LET and varying strike location on transient current response. Significant modulation of the electrostatic potential in the device depletion region during and after the strike profoundly affects transient characteristics. The peak transient current tends to saturate with increasing ionization intensity. The saturation depends on device parameters and the applied bias. A previously developed analytical model is used to describe the mechanisms responsible for this trend. Ion strikes near the device contacts produce transients that are significantly different than strikes away from the contacts, but still in the active region of the device. This is attributed to well potential modulation effects. Device-level simulations, broadbeam heavy-ion measurements, and two-photon absorption single-event effects testing are used to investigate these phenomena. The implications of these results for highly-scaled technologies are also discussed.

Interplay of wavelength, fluence and spot-size in free-electron laser ablation of cornea

Infrared free-electron lasers ablate tissue with high efficiency and low collateral damage when tuned to the 6-microm range. This wavelength-dependence has been hypothesized to arise from a multi-step process following differential absorption by tissue water and proteins. Here, we test this hypothesis at wavelengths for which cornea has matching overall absorption, but drastically different differential absorption. We measure etch depth, collateral damage and plume images and find that the hypothesis is not confirmed. We do find larger etch depths for larger spot sizes--an effect that can lead to an apparent wavelength dependence. Plume imaging at several wavelengths and spot sizes suggests that this effect is due to increased post-pulse ablation at larger spots.

Miniature forward‐imaging B‐scan optical coherence tomography probe to guide real‐time laser ablation

Investigations have shown that pulsed lasers tuned to 6.1 µm in wavelength are capable of ablating ocular and neural tissue with minimal collateral damage. This study investigated whether a miniature B‐scan forward‐imaging optical coherence tomography (OCT) probe can be combined with the laser to provide real‐time visual feedback during laser incisions.

Comparison of OPO and Mark-III FEL for tissue ablation at 6.45 μm

We have investigated the experimental consequences of two picosecond infrared lasers, both tuned to 6.45micrometers and focused on ocular tissue. The exposure conditions were comparable, other than pulse repetition rate, where an optical parametric oscillator/amplifier laser (OPA) system operates at a kilohertz and the Mark-III FEL at 3 gigahertz. In both cases, the peak intensity was near 2x1014 W/m2 and the total delivered energy was approximately 125 mJ. The Mark-III consistently ablates tissue, while the OPA fails to ablate or to damage corneal tissue. In particular, there is no experimental evidence for protein denaturation due to OPA irradiation. WE account for these observations in terms of a theoretical model based on thermal diffusion and threshold conditions for superheating and chemical kinetics. We comment on the relevance of tissue geometry.

Pulse-Duration-Dependent Mid-Infrared Laser Ablation for Biological Applications

There are significant benefits to medical laser surgeries performed with mid-infrared wavelengths, including the ability to select laser parameters in order to minimize photochemical and thermal collateral damage. It has been shown that a wavelength of 6.1 μm is optimal when high ablation efficiency and minimal collateral damage is desired in biological soft tissues. Historically, free electron lasers were the only option for ablating tissue at this wavelength due to their ample pulse energy and average power. In recent years, new sources are being developed for this wavelength that can successfully ablate tissue. These alternative sources have different pulse structures and pulse durations than free electron lasers, motivating investigation of how these parameters affect the ablation process. Here, we present the pulse duration dependence for mid-IR laser ablation of biological tissues at a wavelength of 6.1 μm on a tissue phantom of cooked egg white. The crater shape, depth, and volume all changed in a significant, nonmonotonic manner as the laser pulse duration was increased from 100 ns to 5 μs.