Ambient Mass Spectrometry Imaging with Picosecond Infrared Laser Ablation Electrospray Ionization (PIR-LAESI).

A picosecond infrared laser (PIRL) is capable of cutting through biological tissues in the absence of significant thermal damage. As such, PIRL is a standalone surgical scalpel with the added bonus of minimal postoperative scar tissue formation. In this work, a tandem of PIRL ablation with electrospray ionization (PIR-LAESI) mass spectrometry is demonstrated and characterized for tissue molecular imaging, with a limit of detection in the range of 100 nM for reserpine or better than 5 nM for verapamil in aqueous solution. We characterized PIRL crater size using agar films containing Rhodamine. PIR-LAESI offers a 20-30 µm vertical resolution (∼3 µm removal per pulse) and a lateral resolution of ∼100 µm. We were able to detect 25 fmol of Rhodamine in agar ablation experiments. PIR-LAESI was used to map the distribution of endogenous methoxykaempferol glucoronide in zebra plant (Aphelandra squarrosa) leaves producing a localization map that is corroborated by the literature. PIR-LAESI was further used to image the distribution inside mouse kidneys of gadoteridol, an exogenous magnetic resonance contrast agent intravenously injected. Parallel mass spectrometry imaging (MSI) using desorption electrospray ionization (DESI) and matrix assisted laser desorption ionization (MALDI) were performed to corroborate PIR-LAESI images of the exogenous agent. We further show that PIR-LAESI is capable of desorption ionization of proteins as well as phospholipids. This comparative study illustrates that PIR-LAESI is an ion source for ambient mass spectrometry applications. As such, a future PIRL scalpel combined with secondary ionization such as ESI and mass spectrometry has the potential to provide molecular feedback to guide PIRL surgery.

Heat generation during ablation of porcine skin with erbium:YAG laser vs a novel picosecond infrared laser.

IMPORTANCE: Despite significant advances in surgery, most surgical tools remain basic. Lasers provide a means of precise surgical ablation, but their clinical use has remained limited because of undesired thermal, ionizing, or acoustic stress effects leading to tissue injury. A novel ultrafast, nonionizing, picosecond infrared laser (PIRL) system has recently been developed and is capable, in theory, of ablation with negligible thermal or acoustic stress effects. OBJECTIVE: To measure and compare heat generation by means of thermography during ablation of ex vivo porcine skin by conventional microsecond-pulsed erbium:YAG (Er:YAG) laser and picosecond infrared laser (PIRL). DESIGN AND SETTING: This study was conducted in an optics laboratory and used a pretest-posttest experimental design comparing 2 methods of laser ablation of tissue with each sample acting as its own control. INTERVENTION: Ex vivo porcine skin was ablated in a 5-mm line pattern with both Er:YAG laser and PIRL at fluence levels marginally above ablation threshold (2 J/cm² and 0.6 J/cm², respectively). MAIN OUTCOMES AND MEASURES: Peaks and maxima of skin temperature rises were determined using a thermography camera. Means of peak temperature rises were compared using the paired sample t test. Ablation craters were assessed by means of digital microscopy. RESULTS Mean peak rise in skin surface temperature for the Er:YAG laser and PIRL was 15.0°C and 1.68°C, respectively (P < .001). Maximum peak rise in skin surface temperature was 18.85°C for the Er:YAG laser and 2.05°C for the PIRL. Ablation craters were confirmed on digital microscopy. CONCLUSIONS AND RELEVANCE: Picosecond infrared laser ablation results in negligible heat generation, considerably less than Er:YAG laser ablation, which confirms the potential of this novel technology in minimizing undesirable thermal injury associated with lasers currently in clinical use.

Vibrationally excited ultrafast thermodynamic phase transitions at the water/air interface.

The extraordinary ability of the hydrogen-bond network of water in the condensed phase to thermalize vibrational excitations within several picoseconds, even under supercritical conditions, offers the possibility of creating highly excited thermodynamic states at water surfaces on ultrafast time scales using vibrationally resonant short infrared laser pulses. We experimentally and numerically studied such states created by depositing ~100 ps long pulses tuned to the 3400 cm(-1) O­H stretch vibration at the water/air interface using time-resolved dark-field imaging and time-resolved optical reflectivity. The results are reasonably well described by using a hydrodynamic ablation model under the assumption of impulsive heat deposition. The large thermoelastic stress amplitudes on the order of 1 GPa created within 100 ps by depositing laser pulses with ~1 J cm(-2) fluence were inferred from the numerical simulations. Stresses of this magnitude drive the excited water layer into a very fast expansion resulting in rapid adiabatic cooling and thorough vaporization within a few nanoseconds. The spatial and temporal lengths scales of the ablation plume are nearly ideal for ejecting molecules into the gas phase with minimum perturbation for applications ranging from mass spectrometry and laser surgery to the development of extremely high pressure molecular beams.

Laser selective cutting of biological tissues by impulsive heat deposition through ultrafast vibrational excitations.

Mechanical and thermodynamic responses of biomaterials after impulsive heat deposition through vibrational excitations (IHDVE) are investigated and discussed. Specifically, we demonstrate highly efficient ablation of healthy tooth enamel using 55 ps infrared laser pulses tuned to the vibrational transition of interstitial water and hydroxyapatite around 2.95 microm. The peak intensity at 13 GW/cm(2) was well below the plasma generation threshold and the applied fluence 0.75 J/cm(2) was significantly smaller than the typical ablation thresholds observed with nanosecond and microsecond pulses from Er:YAG lasers operating at the same wavelength. The ablation was performed without adding any superficial water layer at the enamel surface. The total energy deposited per ablated volume was several times smaller than previously reported for non-resonant ultrafast plasma driven ablation with similar pulse durations. No micro-cracking of the ablated surface was observed with a scanning electron microscope. The highly efficient ablation is attributed to an enhanced photomechanical effect due to ultrafast vibrational relaxation into heat and the scattering of powerful ultrafast acoustic transients with random phases off the mesoscopic heterogeneous tissue structures.