Raman spectroscopy for unlabelled detection and quantification of drugs in tissue

Raman spectroscopy is an optical analysis technique for chemical analysis of samples. Inthis thesis, we have assessed its applicability in quantitative detection of drugs within animal tissue. This involved the design, construction, and optimisation of a Raman microscope for this application, consid...

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Main Author: Woodhouse, Nathan
Format: Thesis (University of Nottingham only)
Language:English
Published: 2023
Subjects:
Online Access:https://eprints.nottingham.ac.uk/72363/
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author Woodhouse, Nathan
author_facet Woodhouse, Nathan
author_sort Woodhouse, Nathan
building Nottingham Research Data Repository
collection Online Access
description Raman spectroscopy is an optical analysis technique for chemical analysis of samples. Inthis thesis, we have assessed its applicability in quantitative detection of drugs within animal tissue. This involved the design, construction, and optimisation of a Raman microscope for this application, considering the specific requirements of the samples. A Raman microscope was designed to efficiently measure Raman spectra from thin (16 μm) tissue sections with >1 cm field-of-view. Two of these were built, one with a 671 nm and one with a 785 nm wavelength excitation laser, to assess the relative benefits of each for drug detection specifically in the Raman silent region of the Raman spectrum (~ 1800 – 2800 cm-1), in both low and highly autofluorescing tissue. These instruments, and the acquisition parameters used, were optimised to maximise Raman throughput while minimising the effects of noise on the measurements from autofluorescence. Control tissue cryosections with drug solution pipetted on top was used as a feasibility test for qualitative detection of drugs in tissue. A model for prediction of the spectra and required measurement times for detection of different drug/tissue combinations at different concentrations was developed. The most promising drugs from this study were then used to generate mimetic tissue models, homogenous mixtures of drug and tissue with known mass ratios, to assess the quantifiability of Raman spectroscopy in drug detection in tissue. Detection limits as low as 18 μg/g were calculated for ponatinib in rat brain mimetic tissue models with 2-hour measurement times, and 34 μg/g for the ponatinib in rat liver mimetic tissue models.
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format Thesis (University of Nottingham only)
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spelling nottingham-723632025-02-28T12:27:07Z https://eprints.nottingham.ac.uk/72363/ Raman spectroscopy for unlabelled detection and quantification of drugs in tissue Woodhouse, Nathan Raman spectroscopy is an optical analysis technique for chemical analysis of samples. Inthis thesis, we have assessed its applicability in quantitative detection of drugs within animal tissue. This involved the design, construction, and optimisation of a Raman microscope for this application, considering the specific requirements of the samples. A Raman microscope was designed to efficiently measure Raman spectra from thin (16 μm) tissue sections with >1 cm field-of-view. Two of these were built, one with a 671 nm and one with a 785 nm wavelength excitation laser, to assess the relative benefits of each for drug detection specifically in the Raman silent region of the Raman spectrum (~ 1800 – 2800 cm-1), in both low and highly autofluorescing tissue. These instruments, and the acquisition parameters used, were optimised to maximise Raman throughput while minimising the effects of noise on the measurements from autofluorescence. Control tissue cryosections with drug solution pipetted on top was used as a feasibility test for qualitative detection of drugs in tissue. A model for prediction of the spectra and required measurement times for detection of different drug/tissue combinations at different concentrations was developed. The most promising drugs from this study were then used to generate mimetic tissue models, homogenous mixtures of drug and tissue with known mass ratios, to assess the quantifiability of Raman spectroscopy in drug detection in tissue. Detection limits as low as 18 μg/g were calculated for ponatinib in rat brain mimetic tissue models with 2-hour measurement times, and 34 μg/g for the ponatinib in rat liver mimetic tissue models. 2023-07-26 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/72363/1/%5BThesis%5D%20Nathan%20Woodhouse%20With%20Corrections.pdf Woodhouse, Nathan (2023) Raman spectroscopy for unlabelled detection and quantification of drugs in tissue. PhD thesis, University of Nottingham. Raman spectroscopy MALDI spectroscopy microscopy drug detection quantitative Matrix-assisted laser desorption/ionization spectrometry
spellingShingle Raman spectroscopy
MALDI spectroscopy
microscopy
drug detection
quantitative
Matrix-assisted laser desorption/ionization spectrometry
Woodhouse, Nathan
Raman spectroscopy for unlabelled detection and quantification of drugs in tissue
title Raman spectroscopy for unlabelled detection and quantification of drugs in tissue
title_full Raman spectroscopy for unlabelled detection and quantification of drugs in tissue
title_fullStr Raman spectroscopy for unlabelled detection and quantification of drugs in tissue
title_full_unstemmed Raman spectroscopy for unlabelled detection and quantification of drugs in tissue
title_short Raman spectroscopy for unlabelled detection and quantification of drugs in tissue
title_sort raman spectroscopy for unlabelled detection and quantification of drugs in tissue
topic Raman spectroscopy
MALDI spectroscopy
microscopy
drug detection
quantitative
Matrix-assisted laser desorption/ionization spectrometry
url https://eprints.nottingham.ac.uk/72363/