Steven J. Davis

Pulsed diode laser-based monitor for singlet molecular oxygen

Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1Delta) are believed to be the species that destroys cancerous cells during PDT. Monitoring singlet oxygen produced by PDT may lead to more precise and effective PDT treatments. Our approach uses a pulsed diode laser-based monitor with optical fibers and a fast data acquisition system to monitor singlet oxygen during PDT. We present results of in vitro singlet oxygen detection in solutions and in a rat prostate cancer cell line as well as PDT mechanism modeling.

In-vivo singlet oxygen dosimetry of clinical 5-aminolevulinic acid photodynamic therapy.

Photodynamic therapy (PDT) is a viable treatment option for a wide range of applications, including oncology, dermatology, and ophthalmology. Singlet oxygen is believed to play a key role in the efficacy of PDT, and on-line monitoring of singlet oxygen during PDT could provide a methodology to establish and customize the treatment dose clinically. This work is the first report of monitoring singlet oxygen luminescence in vivo in human subjects during PDT, demonstrating the correlation of singlet oxygen levels during PDT with the post-PDT photobiological response.

Pulsed diode laser-based singlet oxygen monitor for photodynamic therapy: in vivo studies of tumor-laden rats.

Photodynamic therapy (PDT) is a promising cancer treatment that involves optical excitation of photosensitizers that promote oxygen molecules to the metastable O(2)(a(1)Delta) state (singlet oxygen). This species is believed to be responsible for the destruction of cancerous cells during PDT. We describe a fiber optic-coupled, pulsed diode laser-based diagnostic for singlet oxygen. We use both temporal and spectral filtering to enhance the detection of the weak O(2)(a-->X) emission near 1.27 microm. We present data that demonstrate real-time singlet oxygen production in tumor-laden rats with chlorin e6 and 5-aminolevulinic acid-induced protoporphyrin photosensitizers. We also observe a positive correlation between post-PDT treatment regression of the tumors and the relative amount of singlet oxygen measured. These results are promising for the development of the sensor as a real-time dosimeter for PDT.

Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema

Abstract. The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.

Laser-excitation studies of Br2. Collisional energy transfer involving resolved quantum states of excited Br2B3Π(0u+)

Selected ro-vibrational states (v′,J′) of excited Br2B3Π(0u+) were populated by absorption of radiation (570–600 nm) from a single-frequency c.w. dye laser, or from a 1 pm bandwidth pulsed dye laser. The rates of electronic, vibrational and rotational energy transfer within the B state of Br2 were studied, using Br2, Ar, He, N2 and Cl2 as collision partners.Wavelength-resolved fluorescence was analysed in the c.w. excitation studied. The results showed that Ar and N2 possessed large cross-sections for R–T transfer, whilst electronic quenching was slow. Collision efficiency of N2 for V–V transfer in Br2(B, ν′= 11–15) was ≈0.1, with Δv=+1 slower than Δv=–1. Minimal coupling of R–T and vibrational transfer in collisions with N2 found. When Δv′ quantum jumps occurred in vibrational transfer with N2, conservation of rotational quantum number J′ was observed, with a small amount of broadening of the initial rotational distribution. Collisions of Br2(B) with Br2(X) resulted in efficient electronic deactivation, with very little observed ro-vibrational energy transfer.Time-resolved undispersed fluorescence was analysed in the pulsed excitation studies. The rate constant for electronic self-deactivation of Br2(B, ν′= 14) was (4.2 ± 1.3)× 10–10 cm3 molecule–1 s–1 at 298 K. Electronic deactivation is assigned to collisional predissociation, which thus has a high efficiency.The results are interpreted in terms of a large cross-section for R–T transfer in collisions of Br2(B) with rare gas atoms, which lead to collision-induced predissociation and thus to depletion of Br2(B) population. Collisions with Cl2 also were found to give rapid collisional depletion of Br2(B). The elementary processes responsible in this case are probably a combination of electronic deactivation and rovibrational energy transfer, leading to predissociative loss of excited Br2(B). Electronic deactivation in collisions of Br2(B) with Ar and He is slow.

A MEMS Singlet Oxygen Generator—Part II: Experimental Exploration of the Performance Space

This paper reports the quantitative experimental exploration of the performance space of a microfabricated singlet oxygen generator (muSOG). SOGs are multiphase reactors that mix H2O2, KOH, and Cl2 to produce singlet delta oxygen, or O2 (a). A scaled-down SOG is being developed as the pump source for a microfabricated chemical oxygen-iodine laser system because scaling down a SOG yields improved performance compared to the macroscaled versions. The performance of the muSOG was characterized using O2 (a) yield, chlorine utilization, power in the flow, molar flow rate per unit of reactor volume, and steady-state operation as metrics. The performance of the muSOG is measured through a series of optical diagnostics and mass spectrometry. The test rig, which enables the monitoring of temperatures, pressures, and the molar flow rate of O2 (a), is described in detail. Infrared spectra and mass spectrometry confirm the steady-state operation of the device. Experimental results reveal O2 (a) concentrations in excess of 1017 cm-3, O2 (a) yield at the chip outlet approaching 80%, and molar flow rates of 02(a) per unit of reactor volume exceeding 600 times 10-4 mol/L/s.

Laser excitation dynamics of argon metastables generated in atmospheric pressure flows by microwave frequency microplasma arrays

The optically pumped rare-gas metastable laser is a chemically inert analogue to diode-pumped alkali (DPAL) and alkali-exciplex (XPAL) laser systems. Scaling of these devices requires efficient generation of electronically excited metastable atoms in a continuous-wave electric discharge in flowing gas mixtures at atmospheric pressure. This paper describes initial investigations of the use of linear microwave micro-discharge arrays to generate metastable rare-gas atoms at atmospheric pressure in optical pump-and-probe experiments for laser development. Power requirements to ignite and sustain the plasma at 1 atm are low, <30 W. We report on the laser excitation dynamics of argon metastables, Ar (4s, 1s5) (Paschen notation), generated in flowing mixtures of Ar and He at 1 atm. Tunable diode laser absorption measurements indicate Ar(1s5) concentrations near 3 × 1012 cm-3 at 1 atm. The metastables are optically pumped by absorption of a focused beam from a continuous-wave Ti:S laser, and spectrally selected fluorescence is observed with an InGaAs camera and an InGaAs array spectrometer. We observe the optical excitation of the 1s5→2p9 transition at 811.5 nm and the corresponding laser-induced fluorescence on the 2p10→1s5 transition at 912.3 nm; the 2p10 state is efficiently populated by collisional energy transfer from 2p9. Using tunable diode laser absorption/gain spectroscopy, we observe small-signal gains of ~1 cm-1 over a 1.9 cm path. We also observe stable, continuous-wave laser oscillation at 912.3 nm, with preliminary optical efficiency ~55%. These results are consistent with efficient collisional coupling within the Ar(4s) manifold.

The Electric Oxygen-Iodine Laser: Chemical Kinetics of O2(a1 delta) Production and I(2P1/2) Excitation in Microwave Discharge Systems

Generation of singlet oxygen metastables, O2(a1Δ), in an electric discharge plasma offers the potential for development of compact electric oxygen-iodine laser (EOIL) systems using a recyclable, all-gas-phase medium. The primary technical challenge for this concept is to develop a high-power, scalable electric discharge configuration that can produce high yields and flow rates of O2(a) to support I(2P1/2->2P3/2) lasing at high output power. This paper discusses the chemical kinetics of the generation of O2(a) and the excitation of I(2P1/2) in discharge-flow reactors using microwave discharges at low power, 40-120 W, and moderate power, 1-2 kW. The relatively high E/N of the microwave discharge, coupled with the dilution of O2 with Ar and/or He, leads to increased O2(a) production rates, resulting in O2(a) yields in the range 20-40%. At elevated power, the optimum O2(a) yield occurs at higher total flow rates, resulting in O2(a) flow rates as large as 1 mmole/s (~100 W of O2(a) in the flow) for 1 kW discharge power. We perform the reacting flow measurements using a comprehensive suite of optical emission and absorption diagnostics to monitor the absolute concentrations of O2(a), O2(b), O(3P), I2, I(2P3/2), I(2P1/2), small-signal gain, and temperature. These measurements constrain the kinetics model of the system, and reveal the existence of new chemical loss mechanisms related to atomic oxygen. The results for O2(a) production at 1 kW have intriguing implications for the scaling of EOIL systems to high power.

High-power laser applications to medicine

Abstract In this paper, we briefly summarize the processes that occur during the coupling of laser energy to biological tissue and review the parameters that control this interaction. We then consider three separate and recent applications of lasers to medicine. First, we present the results of a series of numerical simulations of the use of CO2 lasers for surgical applications. Then, we discuss spectroscopic issues related to the use of hematoporphyrin derivative (HPD) as a selective laser absorber and diagnostic for treatment of tumors. Use of pulsed dye lasers to fragment kidney stones and gallstones is then reviewed, mechanisms that control the process identified, and an interaction model is suggested.

ElectricOIL discharge and post-discharge kinetics experiments and modeling

Laser oscillation at 1315 nm on the I(2P1/2) → I(2P3/2) transition of atomic iodine has been obtained by a near resonant energy transfer from O2(a1&Dgr;) produced using a low-pressure oxygen/helium/nitric-oxide discharge. In the electric discharge oxygen-iodine laser (ElectricOIL) the discharge production of atomic oxygen, ozone, and other excited species adds levels of complexity to the singlet oxygen generator (SOG) kinetics which are not encountered in a classic purely chemical O2(a1&Dgr;) generation system. The advanced model BLAZE-IV has been introduced in order to study the energy-transfer laser system dynamics and kinetics. Levels of singlet oxygen, oxygen atoms and ozone are measured experimentally and compared with calculations. The new BLAZE-IV model is in reasonable agreement with O3, O2(b1&Sgr;), and O atom, and gas temperature measurements, but is under-predicting the increase in O2(a1&Dgr;) concentration resulting from the presence of NO in the discharge. A key conclusion is that the removal of oxygen atoms by NOX species leads to a significant increase in O2(a1&Dgr;) concentrations downstream of the discharge in part via a recycling process, however there are still some important processes related to the NOX discharge kinetics that are missing from the present modeling. Further, the removal of oxygen atoms dramatically inhibits the production of ozone in the downstream kinetics.