Agilent QQQ systems enable ground-breaking research on use of metabolite biomarkers to predict a common pregnancy complication
Tiffany Payne, Agilent Clinical Diagnostic Analytical Instruments Director of Marketing
Preeclampsia is a serious disorder of later pregnancy that kills thousands of women and babies each year. Symptoms of preeclampsia occur after 20 weeks of pregnancy and may include mother’s high blood pressure and protein in the mother’s urine. While treatments exist for women who are at high risk of preeclampsia, you cannot apply early interventions unless you know a woman’s risk profile. [1,2] Now, scientists at Metabolomic Diagnostics in Cork, Ireland are using Agilent 6400 Series Triple Quadrupole LC/MS systems to develop an accurate, reliable way to predict preeclampsia risk early in pregnancy.
To learn about this research, we spoke with two members of the Metabolomic Diagnostics team: Charles Garvey, CEO and Robin Tuytten, Vice President of Research and Development. They explained their research question: Can we use metabolite biomarkers that are present in the blood in early pregnancy to predict complications that will occur later in the pregnancy? Specifically, can we use them to predict preeclampsia?
The challenge: find biomarkers for a disease with multiple causes
Garvey explained the complexity of their research:
“There are multiple causes of the disease, so we always knew you weren’t really going to pick up a single biomarker that was going to give you the answer. You needed a panel of biomarkers, and different markers will be sensitive to different causes of the disease.”
The team at Metabolomic Diagnostics realized early that to develop a test that could be widely deployed to predict preeclampsia, you needed an analysis that was simple, robust, and enabled high throughput. The analysis also needed to unambiguously measure a wide range of metabolites, with extremely straightforward sample preparation.
Garvey stated, “So we wanted to develop a test that essentially could use mass spectrometry to measure multiple biomarkers in a single pass. But we’re a small startup with limited funding to do this work, and so we reached out to Agilent and told them our story. We’ve had a relationship with Agilent going back over three years where they’ve provided us with technical expertise and equipment to support us in our work.”
Figure 1. The team at Metabolomic Diagnostics uses Agilent Triple Quadrupole LC/MS systems for ground-breaking research.
Tuytten described their need for rigorous sample analysis with selective detection:
“We are using our systems to analyze up to 40 metabolites, and we have minimal sample prep. So we need very good instruments that compensate for this lack of sample prep optimization.”
“In our laboratories, we operate two systems. We have a 1260 Infinity LC System, which is commonly available and very robust. We have that hyphenated with a 6460 Triple Quadruple LC/MS equipped with an Agilent Jet Stream source. We use this electrospray source because we have compounds across a very broad range of polarities, and our electrospray source allows us to do polarity switching.”
“We operate these instruments in a daily fashion, and we are very happy that the sources are very robust.”
“And then the other instrument we use is an Agilent 6495 Triple Quadrupole LC/MS. It’s a more recent triple quad instrument that features the iFunnel technology and the more optimized ion optics with a curved and tapered collision cell. While both instruments deliver what we need, the 6495 compensates more for our lack of optimized sample preparation and our need to look at many putative biomarkers at the same time.”
“So we operate these instruments in a daily fashion, and we are very happy that the sources are very robust. They can take good flow rates, so we can use standard columns rather than nano LC columns.”
Successful research leads to hope for early medical intervention
Garvey added, “And we have succeeded using that equipment to measure the biomarkers that we need to measure, and we can actually risk-stratify women for preeclampsia.”
When asked whether he would recommend Agilent LC/MS instruments, Garvey was emphatic. “Yes, we would certainly recommend Agilent, because the platform is very suited to the work we’re doing, and the company has been extremely supportive. And what we’re doing is definitely challenging, because we’re measuring large numbers of biomarkers of different types in different areas of the spectrum in a single pass. So we’re challenging the instrument quite significantly, and it’s been delivering.”
Tuytten added, “I’m very convinced that LC/MS will play a very big role in diagnostics of the future. We already delivered a proof of concept that shows what we can do with it. “
For Research Use Only. Not for use in diagnostic procedures.
Michael L. LeFevre, MD, MSPH, “Low-Dose Aspirin Use for the Prevention of Morbidity and Mortality from Preeclampsia: U.S. Preventive Services Task Force Recommendation Statement,” Annals of Internal Medicine, Sept. 2014.
Erika F. Werner, MD, Alisse K. Hauspurg, MD, and Dwight J. Rouse, MD, “A Cost–Benefit Analysis of Low-Dose Aspirin Prophylaxis for the Prevention of Preeclampsia in the United States,” The American College of Obstetricians and Gynecologists, published by Wolters Kluwer Health, Inc., Dec. 2015.
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