Mid infrared sources for enhanced mass spectrometry imaging
File(s)
Author(s)
Battle, Ronan
Type
Thesis
Abstract
Pulsed mid-infrared laser sources can be used to precisely ablate biological tissue. This thesis describes progress towards exploiting mid-infrared sources at λ = 3 µm to perform laser-ablation based mass spectrometry imaging of biological tissues under ambient conditions. We developed picosecond duration 3 µm pulse sources based on parametric frequency conversion techniques and deployed them for molecular imaging using rapid evaporative ionisation mass spectrometry (REIMS).
A cascaded parametric architecture was developed to generate picosecond duration pulses based on four-wave mixing in photonic crystal fibre followed by difference frequency generation in periodically poled lithium niobate. This design provides a simple and flexible method of generating ultrafast mid-infrared pulses that could be used to realise compact and rugged laser sources. We used the cascaded architecture, as well as continuous-wave seeded optical parametric amplification, to build 3 µm sources that delivered MHz repetition-rate pulses with 100 mW level average powers. We then deployed these sources for tissue ablation. Owing to the high beam quality and temporal characteristics of these sources, ablation craters with a diameter <10 µm were achieved. REIMS analysis of the ablated tissue enabled us to perform single-cell level (10 µm) spatial resolution molecular imaging of varied tissue samples in ambient conditions without requiring complex sample preparation. Compared to the previous state of the art, an improvement in sensitivity (mass spectrometry signal per unit volume of tissue ablated) of up to 2 orders of magnitude was achieved by using the picosecond laser sources.
The ablation mechanism and REIMS imaging performance limits which arise from using high repetition rate mid-infrared picosecond pulses were then investigated. A highly configurable pulse picking module was installed on the optical parametric amplifier 3 µm laser source. Photothermal laser-tissue interactions were shown to drive the ablation for the focusing conditions and pulse energies used in this work.
A cascaded parametric architecture was developed to generate picosecond duration pulses based on four-wave mixing in photonic crystal fibre followed by difference frequency generation in periodically poled lithium niobate. This design provides a simple and flexible method of generating ultrafast mid-infrared pulses that could be used to realise compact and rugged laser sources. We used the cascaded architecture, as well as continuous-wave seeded optical parametric amplification, to build 3 µm sources that delivered MHz repetition-rate pulses with 100 mW level average powers. We then deployed these sources for tissue ablation. Owing to the high beam quality and temporal characteristics of these sources, ablation craters with a diameter <10 µm were achieved. REIMS analysis of the ablated tissue enabled us to perform single-cell level (10 µm) spatial resolution molecular imaging of varied tissue samples in ambient conditions without requiring complex sample preparation. Compared to the previous state of the art, an improvement in sensitivity (mass spectrometry signal per unit volume of tissue ablated) of up to 2 orders of magnitude was achieved by using the picosecond laser sources.
The ablation mechanism and REIMS imaging performance limits which arise from using high repetition rate mid-infrared picosecond pulses were then investigated. A highly configurable pulse picking module was installed on the optical parametric amplifier 3 µm laser source. Photothermal laser-tissue interactions were shown to drive the ablation for the focusing conditions and pulse energies used in this work.
Version
Open Access
Date Issued
2023-07-19
Date Awarded
01/03/2024
License URL
Advisor
Murray, Robert T
Taylor, James Roy
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Department of Physics
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)