I was awarded my postgradute degree on the "Detection of cocaine and respective metabolites using fingerprints" from the University of Surrey in April 2017. Currently working at the University of Surrey's Ion Beam Centre (http://www.ionbeamcentre.co.uk/) as a Liaison Fellow. Here are the Ion Beam Centre we are world leading in the field of ion beam modification and ion beam analysis.
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- Surrey's Ion Beam Centre Liaison Fellow
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06 FEB 2020
Experimental fingerprint test can distinguish between those who have taken or handled cocaine
Direct analyte-probed nano-extraction (DAPNe) is a method of extracting material from a microscale region of a sample and provides the opportunity for detailed mass spectrometry analysis of extracted analytes from a small area. The technique has been shown to provide enhanced sensitivity compared with bulk analysis by selectively removing analytes from their matrix and has been applied for selective analysis of single cells and even single organelles. However, the quantitative capabilities of the technique are yet to be fully evaluated. In this study, various normalisation techniques were investigated in order to improve the quantitative capabilities of the technique. Two methods of internal standard incorporation were applied to test substrates, which were designed to replicate biological sample matrices. Additionally, normalisation to the extraction spot area and matrix compounds were investigated for suitability in situations when an internal standard is not available. The variability observed can be significantly reduced by using a sprayed internal standard, and in some cases, by normalising to the extracted area.
Elemental and molecular imaging play a crucial role in understanding disease pathogenesis. To accurately correlate elemental and molecular markers, it is desirable to perform sequential elemental and molecular imaging on a single tissue section. However, very little is known about the impact of performing these measurements in sequence. In this work, we highlight some of the challenges and successes associated with performing elemental mapping in sequence with mass spectrometry imaging. Specifically, the feasibility of molecular mapping using the mass spectrometry imaging (MSI) techniques matrix assisted laser desorption ionisation (MALDI) and desorption electrospray ionisation (DESI) in sequence with the elemental mapping technique particle induced X-ray emission (PIXE) is explored. Challenges for integration include substrate compatibility, as well as delocalisation and spectral changes. We demonstrate that whilst sequential imaging comes with some compromises, sequential DESI-PIXE imaging is sufficient to correlate sulphur, iron and lipid markers in a single tissue section at the 50-micrometre scale.
BACKGROUND: Paper spray mass spectrometry6 is a technique that has recently emerged and has shown excellent analytical sensitivity to a number of drugs in blood. As an alternative to blood, fingerprints have been shown to provide a noninvasive and traceable sampling matrix. Our goal was to validate the use of fingerprint samples to detect cocaine use. METHODS: Samples were collected on triangular pieces (168 mm2) of washed Whatman Grade I chromatography paper. Following application of internal standard, spray solvent and a voltage were applied to the paper before mass spectrometry detection. A fingerprint visualization step was incorporated into the analysis procedure by addition of silver nitrate solution and exposing the sample to ultraviolet light. RESULTS: Limits of detection for cocaine, benzoylecgonine, and methylecgonine were 1, 2, and 31 ng/mL respectively, with relative standard deviations of less than 33%. No matrix effects were observed. Analysis of 239 fingerprint samples yielded a 99% true-positive rate and a 2.5% false-positive rate, based on the detection of cocaine, benzoylecgonine, or methylecgonine with use of a single fingerprint. CONCLUSIONS: The method offers a qualitative and noninvasive screening test for cocaine use. The analysis method developed is rapid (4 min/sample) and requires no sample preparation.
Fingerprints have been proposed as a promising new matrix for drug testing. In previous work it has been shown that a fingerprint can be used to distinguish between drug users and non-users. Herein, we look at the possibility of using a fingerprint to distinguish between dermal contact and administration of heroin. Fingerprint samples were collected from (a) 10 patients attending a drug rehabilitation clinic (b) 50 non-drug users (c) participants who touched 2 mg street heroin, before and after various hand cleaning procedures. Oral fluid was also taken from the patients. All samples were analysed using a liquid chromatography – high resolution mass spectrometry (LC-HRMS) method validated in previous work for heroin and 6-AM. The HRMS data was analysed retrospectively for morphine, codeine, 6-acetylcodeine and noscapine. Heroin and 6-AM were detected in all fingerprint samples produced from contact with heroin, even after handwashing. In contrast, morphine, acetylcodeine and noscapine were successfully removed after handwashing. In patient samples, the detection of morphine, noscapine and acetylcodeine (alongside heroin and 6-AM) gave a closer agreement to patient testimony on whether they had recently used heroin use than the detection of heroin and 6-AM alone. This research highlights the importance of washing hands prior to donating a fingerprint sample to distinguish recent contact with heroin from heroin use.
Direct analyte probed nanoextraction (DAPNe) is a technique that allows extraction of drug and endogenous compounds from a discrete location on a tissue sample using a nano capillary filled with solvent. Samples can be extracted from a spot diameters as low as 6 µm. Studies previously undertaken by our group have shown that the technique can provide good precision (5%) for analysing drug molecules in 150 µm diameter areas of homogenised tissue, provided an internal standard is sprayed on to the tissue prior to analysis. However, without an isotopically labelled standard, the repeatability is poor, even after normalisation to and the spot area or matrix compounds. By application to tissue homogenates spiked with drug compounds, we can demonstrate that it is possible to significantly improve the repeatability of the technique by incorporating a liquid chromatography separation step. Liquid chromatography is a technique for separating compounds prior to mass spectrometry (LC-MS) which enables separation of isomeric compounds that cannot be discriminated using mass spectrometry alone, as well as reducing matrix interferences. Conventionally, LC-MS is carried out on bulk or homogenised samples, which means analysis is essentially an average of the sample and does not take into account discrete areas. This work opens a new opportunity for spatially resolved liquid chromatography mass spectrometry with precision better than 20%.
The use of synthetic stimulants, including designer cathinones, remains a significant concern worldwide. Thus, the detection and identification of synthetic cathinones in biological matrices is of paramount importance for clinical and forensic laboratories. In this study, distribution of mephedrone and its metabolites was investigated in fingerprints. Following a controlled human mephedrone administration (100 mg nasally insufflated), two mass spectrometry-based methods for fingerprint analysis have been evaluated. The samples deposited on triangular pieces of chromatography paper were directly analysed under ambient conditions by paper spray-mass spectrometry (PS-MS) while those deposited on glass cover slips were extracted and analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS method was 5–6 times more sensitive than PS-MS but required sample preparation and longer analysis time. Mephedrone was detected in 62% and in 38% of all post-administration samples analysed by LC-MS/MS and PS-MS, respectively. Nor-mephedrone was the only metabolite detected in 3.8% of all samples analysed by LC-MS/MS. A large inter- and intra-subject variation was observed for mephedrone which may be due to several factors, such as the applied finger pressure, angle and duration of contact with the deposition surface and inability to control the ‘amount’ of collected fingerprint deposits. Until these limitations are addressed, we suggest that the sole use of fingerprints can be a useful diagnostic tool in qualitative rather than quantitative analysis, and requires a confirmatory analysis in a different biological matrix.
Paper spray mass spectrometry is a rapid and sensitive tool for explosives detection but has so far only been demonstrated using high resolution mass spectrometry, which bears too high a cost for many practical applications. Here we explore the potential for paper spray to be implemented in field applications with portable mass spectrometry. This involved (a) replacing the paper substrate with a swabbing material (which we call “swab spray”) for compatibility with standard collection materials; (b) collection of explosives from surfaces; (c) an exploration of interferences within a ± 0.5 m/z window; and (d) demonstration of the use of high-field assisted waveform ion mobility spectrometer (FAIMS) for enhanced selectivity. We show that paper and Nomex® are viable collection materials, with Nomex providing cleaner spectra and therefore greater potential for integration with portable mass spectrometers. We show that sensitive detection using swab spray will require a mass spectrometer with a mass resolving power of 4000 or more. We show that by coupling the swab spray ionisation source with FAIMS, it is possible to reduce background interferences, thereby facilitating the use of a low resolving power (e.g. quadrupole) mass spectrometer.
The radical ring-opening polymerization (RROP) of thionolactones provides access to thioester backbone-functional copolymers but has, to date, only been demonstrated on acrylic copolymers. Herein, the thionolactone dibenzo[c,e]oxepane-5-thione (DOT) was subjected to azobisisobutyronitrile (AIBN)-initiated free-radical homopolymerization, which produced a thioester-functional homopolymer with a glass-transition temperature of 95 °C and the ability to degrade exclusively into predetermined small molecules. However, the homopolymerization was impractically slow and precluded the introduction of functionality. Conversely, the reversible addition–fragmentation chain-transfer (RAFT)-mediated copolymerization of DOT with N-methylmaleimide (MeMI), N-phenylmaleimide (PhMI), and N-2,3,4,5,6-pentafluorophenylmaleimide (PFPMI) rapidly produced well-defined copolymers with the tendency to form alternating sequences increasing in the order MeMI ≪ PhMI < PFPMI, with estimated reactivity ratios of rDOT = 0.198 and rPFPMI = 0.0078 for the latter system. Interestingly, defects in the alternating structure were more likely caused by (degradable) DOT–DOT sequences rather than (nondegradable) MI–MI sequences, which was confirmed through the paper spray mass spectrometric analysis of the products from aminolytic degradation. Upon the aminolysis of backbone thioesters, maleimide repeating units were ring-opened, forming bisamide structures. Conversely, copolymer degradation through a thiolate did not result in imide substitution but nucleophilic para-fluoro substitution on PFPMI comonomer units, indicating the ability of DOT–MI copolymers to degrade under different conditions and to form differently functional products. The RROP of thionolactones has distinct advantages over the RROP of cyclic ketene acetals and is anticipated to find use in the development of well-defined degradable polymer materials.
Surface mass spectrometry methods can be difficult to use effectively with low cost, portable mass spectrometers. This is because commercially available portable (single quadrupole) mass spectrometers lack the mass resolution to confidently differentiate between analyte and background signals. Additionally, current surface analysis methods provide no facility for chromatographic separation and therefore are vulnerable to ion suppression. Here we present a new analytical method where analytes are extracted from a sample using a solvent flushed across the surface under high pressure, separated using a chromatography column and then analysed using a portable mass spectrometer. The use of chromatography reduces ion suppression effects and this, used in combination with in-source fragmentation, increases selectivity, thereby allowing high sensitivity to be achieved with a portable and affordable quadrupole mass spectrometer. We demonstrate the efficacy of the method for the quantitative detection of cocaine and benzoylecgonine in urine and oral fluid. The method gives relative standard deviations below 15% (with one exception), and R2 values above 0.998. The limits of detection for these analytes in oral fluid and urine are
Porphyry-type deposits are the world’s main source of copper and molybdenum and provide a large proportion of gold and other metals. However, the mechanism by which mineralising fluids are extracted from source magmas and transported upwards into the ore-forming environment is not clearly understood. Here we use field, micro-textural and geochemical techniques to investigate field relationships and samples from a circa 8 km deep cross-section through the archetypal Yerington porphyry district, Nevada. We identify an interconnected network of relatively low-temperature hydrothermal quartz that is connected to mineralised miarolitic cavities within aplite dykes. We propose that porphyry-deposit-forming fluids migrated from evolved, more water-rich internal regions of the underlying Luhr Hill granite via these aplite dykes which contained a permeable magmatic crystal mush of feldspar and quartz. The textures we describe provide petrographic evidence for the transport of fluids through crystal mush dykes. We suggest that this process should be considered in future models for the formation of porphyry- and similar-type deposits.
We have calibrated on-site WD-XRF (wavelength-dispersive X-ray fluorescence) measurements of GeSbTe:N (GST:N) stoichiometry with off-site accurate ion beam analysis (IBA). N is determined by elastic backscattering spectrometry (EBS) using the resonance at 3.7 MeV in the 14N(a, a)14N reaction. Ge and Sb+Te are determined by Rutherford backscattering spectrometry (RBS) separately but self-consistently with the resonant EBS: the Sb/Te ratio can be determined by RBS but not with useful precision. The XRF instrumental function is determined using pure metal standards and the spectra are quantified using Fundamental Parameters code. We find that, as expected, for both Ge and (Sb+Te) the heavy elements are determined accurately by XRF (within the uncertainties), but for N the standardless XRF has non-linear errors around 10%. Using the absolute N content determined by IBA a calibration curve is obtained allowing N determination by WD-XRF at a precision of about 1% and an absolute accuracy (traceable through IBA) of about 4 % for GST films with N content between 4-20 at%. The IBA measurement precision of the N content of the GST-N XRF calibration samples is 0.4 at% (that is, a relative precision ranging from 10 % to 2 % for N contents between 4-20 at%).
The use of a low aerosol dispersion ablation chamber within a LA-ICP-MS set up allows for high-resolution, high-speed imaging of the distribution of elements within a sample. Here we show how this enhanced capability creates new analytical problems and solutions. We report the distribution of platinum at the cellular level in non-small cell lung cancer (NSCLC) explant models after treatment with clinically relevant doses of cisplatin. This revealed for the first time a correlation between the platinum signal and the presence of carbon deposits within lung tissue. We show how complementary ion beam analysis techniques, particle induced X-ray emission (PIXE) and elastic backscattering spectrometry (EBS) can be used to explore potential matrix effects in LA-ICP-MS data. For these samples, it was confirmed that the enhancement was unlikely to have resulted from a matrix effect alone. Thus, the presence of carbon deposits within tissue has potential implications for the effective distribution of the cisplatin drug.
BACKGROUND: Recent publications have explored the possibility of using fingerprints to confirm drug use, but none has yet dealt with environmental contamination from fingertips. Here we explored the possibility of establishing an environmental cutoff for drug testing from a single fingerprint. METHODS: Fingerprint samples (n=100) were collected from the hands of 50 nondrug users before and after handwashing to establish separate environmental cutoff values and testing protocols for cocaine, benzoylecgonine, heroin, and 6-monoacetylmorphine. The cutoff was challenged by testing the fingerprints of drug-free volunteers after shaking hands with drug users. Fingerprints from patients who testified to taking cocaine (n = 32) and heroin (n = 24) were also collected and analyzed. RESULTS: A different cutoff value needed to be applied, depending on whether the fingerprints were collected as presented or after handwashing. Applying these cutoffs gave a 0%false-positive rate from the drug-free volunteers. After application of the cutoff, the detection rate (compared to patient testimony) for washed hands of patients was 87.5% for cocaine use and 100% for heroin use. CONCLUSIONS: Fingerprints show enhanced levels of cocaine, heroin, and their respective metabolites in patients who testified to taking the substances, compared with the population of naı¨ve drug users surveyed, and a cutoff (decision level) can be established. The cutoff is robust enough to account for small increases in analyte observed after secondary transfer.
Liquid Extraction Surface Analysis (LESA) is a new, high throughput tool for ambient mass spectrometry. A solvent droplet is deposited from a pipette tip onto a surface and maintains contact with both the surface and the pipette tip for a few seconds before being re-aspirated. The technique is particularly suited to the analysis of trace materials on surfaces due to its high sensitivity and low volume of sample removal. In this work, we assess the suitability of LESA for obtaining detailed chemical profiles of fingerprints, oral fluid and urine, which may be used in future for rapid medical diagnostics or metabolomics studies. We further show how LESA can be used to detect illicit drugs and their metabolites in urine, oral fluid and fingerprints. This makes LESA a potentially useful tool in the growing field of fingerprint chemical analysis, which is relevant not only to forensics but also to medical diagnostics. Finally, we show how LESA can be used to detect the explosive material RDX in contaminated artificial fingermarks.
The finding that drugs and metabolites can be detected from fingerprints is of potential relevance to forensic science and as well as toxicology and clinical testing. However, discriminating between dermal contact and ingestion of drugs has never been verified experimentally. The inability to interpret the result of finding a drug or metabolite in a fingerprint has prevented widespread adoption of fingerprints in drug testing and limits the probative value of detecting drugs in fingermarks. A commonly held belief is that the detection of metabolites of drugs of abuse in fingerprints can be used to confirm a drug has been ingested. However, we show here that cocaine and its primary metabolite, benzoylecgonine, can be detected in fingerprints of non-drug users after contact with cocaine. Additionally, cocaine was found to persist above environmental levels for up to 48 hours after contact. Therefore the detection of cocaine and benzoylecgonine (BZE) in fingermarks can be forensically significant, but do not demonstrate that a person has ingested the substance. In contrast, the data here shows that a drug test from a fingerprint (where hands can be washed prior to donating a sample) CAN distinguish between contact and ingestion of cocaine. If hands were washed prior to giving a fingerprint, BZE was detected only after the administration of cocaine. Therefore BZE can be used to distinguish cocaine contact from cocaine ingestion, provided donors wash their hands prior to sampling. A test based on the detection of BZE in at least one of two donated fingerprint samples has accuracy 95%, sensitivity 90% and specificity of 100% (n = 86).
RATIONALE: Paper spray offers a rapid screening test without the need for sample preparation. The incomplete extraction of paper spray allows for further testing using more robust, selective and sensitive techniques such as liquid chromatography mass spectrometry (LC-MS). Here we develop a two-step process of paper spray followed by LC-MS to (1) rapidly screen a large number of samples and (2) confirm any disputed results. This demonstrates the applicability for testing medication adherence from a fingerprint. METHODS: Following paper spray analysis, drugs of abuse samples were analysed using LC-MS. All analyses were completed using a Q Exactive™ Plus Orbitrap™ mass spectrometer. This two-step procedure was applied to fingerprints collected from patients on a maintained dose of the antipsychotic drug quetiapine. RESULTS: The extraction efficiency of paper spray for two drugs of abuse and metabolites was found to be between 15-35% (analyte dependent). For short acquisition times, the extraction efficiency was found to vary between replicates by less than 30%, enabling subsequent analysis by LC-MS. This two-step process was then applied to fingerprints collected from two patients taking the antipsychotic drug quetiapine, which demonstrates how a negative screening result from paper spray can be resolved using LC-MS. CONCLUSIONS: We have shown for the first time the sequential analysis of the same sample using paper spray and LC-MS, as well as the detection of an antipsychotic drug from a fingerprint. We propose that this workflow may also be applied to any type of sample compatible with paper spray, and will be especially convenient where only one sample is available for analysis.
The rapid emergence of antibiotic resistant bacterial pathogens constitutes a critical problem in healthcare and requires the development of novel treatments. Potential strategies include the exploitation of microbial social interactions based on public goods, which are produced at a fitness cost by cooperative microorganisms, but can be exploited by cheaters that do not produce these goods. Cheater invasion has been proposed as a 'Trojan horse' approach to infiltrate pathogen populations with strains deploying built-in weaknesses (e.g., sensitiveness to antibiotics). However, previous attempts have been often unsuccessful because population invasion by cheaters was prevented by various mechanisms including the presence of spatial structure (e.g., growth in biofilms), which limits the diffusion and exploitation of public goods. Here we followed an alternative approach and examined whether the manipulation of public good uptake and not its production could result in potential 'Trojan horses' suitable for population invasion. We focused on the siderophore pyoverdine produced by the human pathogen Pseudomonas aeruginosa MPAO1 and manipulated its uptake by deleting and/or overexpressing the pyoverdine primary (FpvA) and secondary (FpvB) receptors. We found that receptor synthesis feeds back on pyoverdine production and uptake rates, which led to strains with altered pyoverdine-associated costs and benefits. Moreover, we found that the receptor FpvB was advantageous under iron-limited conditions but revealed hidden costs in the presence of an antibiotic stressor (gentamicin). As a consequence, FpvB mutants became the fittest strain under gentamicin exposure, displacing the wildtype in liquid cultures, and in biofilms and during infections of the wax moth larvae Galleria mellonella, which both represent structured environments. Our findings reveal that an evolutionary trade-off associated with the costs and benefits of a versatile pyoverdine uptake strategy can be harnessed for devising a Trojan-horse candidate for medical interventions.