Bioanalysis Zone

2014 Young Investigator Finalist: Cristina Guallar Hoyas




Nominee: Cristina Guallar Hoyas, Imperial College, UK

Nominated By: CL Paul Thomas, Loughborough University, UK


Supporting Comments: Dr Guallar Hoyas worked with me and Prof Ian Wilson to establish non-invasive metabolomic approaches to biomarker discovery and next generation diagnostics as we set up a Centre for Analytical Science here at Loughborough. Her PhD programme successfully evaluated and developed a work-flow for volatile organic compound profiling; new candidate markers for stress and childhood asthma were subsequently reported. The key detail in this project was that although Dr Guallar’s focus was breath, her research unlocked approaches into skin and saliva and that has led to new toxicity screening methods and new routes to non-invasive marker discovery studies. On completion of her PhD, Dr Guallar Hoyas took up a research post in the department of surgery and cancer at imperial College working on the agenda setting iknife project, combining advanced sampling MS and clinical science. It is my judgement that Dr Guallar embodies the skills and spirit of our next generation of analytical scientists. She works in a multidisciplinary space that requires flexible and collaborative cross-disciplinary approaches. To date Dr Guallar’s has worked in clinical chemometric, mass spectrometric and analytical science research spaces, creating new bio analytical approaches and new research pathways for biomarker prospecting and discovery.

What made you choose a career in bioanalysis?

One of the main reasons to choose my career in bioanalysis is the fast development on the technologies that are used to quantify and qualify the biomarkers that are associated with diseases in biofluids and biomatrices. The applicability of bioanalysis is an important step within translational medicine that can improve the understanding of the metabolic processes that occur in the body. The opportunity of working in bioanalysis has opened my views on the different ways samples can be prepared, extracted or analyzed, depending on the aim of the analysis and the analytes you are looking for.

Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community.

During my PhD I developed a work-flow for the analysis of human breath using hyphenated techniques for the qualitative determination of biomarkers in respiratory diseases. The work-flow involved meticulous breath sample collection, a validated analysis using thermal desorption GC coupled in parallel to MS and differential mobility spectrometry, and a painstaking data processing method to identify the whole VOC profile in exhaled breath. The integration of this technology in medicinal chemistry has the potential to provide a critical improvement over the current fluid and image-based testing techniques which are invasive and expensive to carry out.

Describe the most difficult challenge you have encountered in the laboratory and how you overcame it.

One of the most difficult challenges was the collection of breath samples from a large cohort of participants that took over a year to obtain. The stability of these samples was not well defined and rapid analysis after sampling was mandatory. During the year, retention time shifts due to the high water levels in breath gradually degrading the GC stationary phase were an important confounding factor. Until this was solved molecules could not be reliably tracked across the samples, and this prevented effective chemometric modelling. I developed a method that aligned and tracked all exhaled breath volatiles across the cohort. I developed a secondary retention index where the key was the realization that the retention index relationships of ubiquitous siloxanes present in all samples could be exploited to correct for shifts in retention time. Thermal desorption is a destructive sample introduction technique and samples are difficult to manipulate. Solving this vital data challenge was a breakthrough moment. It enabled breath volatiles to be coded by retention index and mass spectrum. This was essential to the subsequent creation of a breath data base and the breath matrix approach that has since been used successfully in multivariate analysis.

Where do you see your career in bioanalysis taking you?

I can see a career in which the combination of analytical techniques will be necessary to deliver a better understanding of the biochemistry associated with interacting processes within our bodies. Robust methods, reliable instrumentation and a complete understanding of metabolic processes are necessary to introduce bioanalysis in clinical laboratories. Each technique can provide complementary information with the potential of improving clinical outcomes for patients and the implementation of personalized medicine strategies. Marker discovery and stratified measurements is my goal.

How do you envisage the field of bioanalysis evolving in the future?

I can conceive a future where the non-invasive analysis of biofluids enables compliance, guidance and characterization requirements determined by regulation authorities to be fulfilled. I anticipate a complete analysis workflow where full genotoxic and carcinogenic screens, at the lower detection limits required, will deliver personalized measurements, and that such measurements will maximize the clinical information obtained from our samples. These protocols will constitute the fundamental steps in all analysis carried out on food, drugs or biofluids.

Please list 5 of your recent publications, and select one that best highlights your career to date in the field of bioanalysis.

1.  Guallar-Hoyas C, Beardsmore C, Pandya H, Thomas CLP, Gahleitner F. Metabolomic pilot study to identify volatile organic compound markers of childhood asthma in exhaled breath. Bioanalysis 5, 2239–2247 (2013).

2. Guallar-Hoyas C, Turner MA, Blackburn GJ, Wilson ID, Thomas CLP. A workflow for the metabolomic/metabonomic investigation of exhaled breath using thermal desorption GG-MS. Bioanalysis 4, 2227–2237 (2012).

3. Huo R, Agapiou A, Bocos-Bintintan V et al. The trapped human experiment. J. Breath Res. 5 (2011).

4. Geenen S, Guallar-Hoyas C, Michopoulos F et al. HPLC-MS/MS methods for the quantitative analysis of 5-oxoproline (pyroglutamate) in rat plasma and hepatic cell line culture medium. J. Pharm. Biomed. Anal. 56, 655–663 (2011).

5. Reynolds JC, Blackburn GJ, Guallar-Hoyas C et al. Detection of volatile organic compounds in breath using thermal desorption electrospray ionisation-ion mobility-mass spectrometry. Anal. Chem. 8, 22139–2144 (2010)

First choice: Guallar-Hoyas C, Turner MA, Blackburn GJ, Wilson ID, Thomas CLP. A workflow for the metabolomic/metabonomic investigation of exhaled breath using thermal desorption GG-MS. Bioanalysis 4, 2227–2237 (2012).

Reasoning: This is the best paper that highlights my career in bioanalysis as it reflects the stages followed for a rigorous collection, analysis and processing of exhaled breath samples. Every step is described meticulously so that the markers found to be responsible of disease are due to the actual disease and not due to a mistake during sample collection, instrumental variability or data processing.


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